Home      Discussion      Topics      Dictionary      Almanac
Signup       Login
Methylenedioxymethamphetamine

Methylenedioxymethamphetamine

Discussion
Ask a question about 'Methylenedioxymethamphetamine'
Start a new discussion about 'Methylenedioxymethamphetamine'
Answer questions from other users
Full Discussion Forum
 
Encyclopedia
MDMA is an entactogenic drug of the phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...

 and amphetamine
Substituted amphetamine
Substituted amphetamines are a chemical class of stimulants, entactogens, hallucinogens, and other drugs. They feature a phenethylamine core with a methyl group attached to the alpha carbon resulting in amphetamine, along with additional substitutions...

 class of drugs
Chemical classification
Chemical classification systems attempt to classify as elements or compounds according to certain chemical functional or structural properties. Whereas the structural properties are largely intrinsic, functional properties and the derived classifications depend to a certain degree on the type of...

. In popular culture, MDMA has become widely known as "ecstasy" ("E", "X" or "XTC"), usually referring to its street pill form, although this term may also include the presence of possible adulterants. The terms "molly" or "mandy" can colloquially refer to MDMA in crystalline or powder form.

MDMA can induce euphoria
Euphoria
Euphoria is an emotional and mental state defined as a sense of great elation and well being.Euphoria may also refer to:* Euphoria , a genus of scarab beetles* Euphoria, a genus name previously used for the longan and other trees...

, a sense of intimacy with others, and diminished anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

. Many studies, particularly in the fields of psychology
Psychology
Psychology is the study of the mind and behavior. Its immediate goal is to understand individuals and groups by both establishing general principles and researching specific cases. For many, the ultimate goal of psychology is to benefit society...

 and cognitive therapy
Cognitive therapy
Cognitive behavioral therapy is a psychotherapeutic approach: a talking therapy. CBT aims to solve problems concerning dysfunctional emotions, behaviors and cognitions through a goal-oriented, systematic procedure in the present...

, have suggested that MDMA has therapeutic benefits and facilitates therapy sessions in certain individuals, a practice for which it had formally been used in the past. Clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...

s are now testing the therapeutic potential of MDMA for post-traumatic stress disorder
Post-traumatic stress disorder
Posttraumaticstress disorder is a severe anxiety disorder that can develop after exposure to any event that results in psychological trauma. This event may involve the threat of death to oneself or to someone else, or to one's own or someone else's physical, sexual, or psychological integrity,...

 (PTSD) and anxiety associated with terminal cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

.

MDMA is criminalized
Criminalization
Criminalization or criminalisation, in criminology, is "the process by which behaviors and individuals are transformed into crime and criminals". Previously legal acts may be transformed into crimes by legislation or judicial decision...

 in most countries under a United Nations
United Nations
The United Nations is an international organization whose stated aims are facilitating cooperation in international law, international security, economic development, social progress, human rights, and achievement of world peace...

 (UN) agreement, and its possession
Drug possession
Drug possession is the crime of having one or more illegal drugs in one's possession, either for personal use, distribution, sale or otherwise. Illegal drugs fall into different categories and sentences vary depending on the amount, type of drug, circumstances, and jurisdiction.A person has...

, manufacture
Clandestine chemistry
Clandestine chemistry is chemistry carried out in secret, and particularly in illegal drug laboratories. Larger labs are usually run by gangs or organized crime intending to produce for distribution on the black market...

, or sale
Illegal drug trade
The illegal drug trade is a global black market, dedicated to cultivation, manufacture, distribution and sale of those substances which are subject to drug prohibition laws. Most jurisdictions prohibit trade, except under license, of many types of drugs by drug prohibition laws.A UN report said the...

 may result in criminal prosecution, although some limited exceptions exist for scientific and medical research. MDMA is one of the most widely used recreational drugs
Recreational drug use
Recreational drug use is the use of a drug, usually psychoactive, with the intention of creating or enhancing recreational experience. Such use is controversial, however, often being considered to be also drug abuse, and it is often illegal...

 in the world and is taken in a variety of contexts far removed from its roots in psychotherapeutic settings. It is commonly associated with dance parties (or "raves") and electronic dance music
Electronic dance music
Electronic dance music is electronic music produced primarily for the purposes of use within a nightclub setting, or in an environment that is centered upon dance-based entertainment...

.

Regulatory authorities in several locations around the world have approved scientific studies administering MDMA to humans to examine its therapeutic potential and its effects.

Medical uses


There have long been suggestions that MDMA might be useful in psychotherapy
Psychotherapy
Psychotherapy is a general term referring to any form of therapeutic interaction or treatment contracted between a trained professional and a client or patient; family, couple or group...

, facilitating self-examination with reduced fear. Indeed, some therapists, including Leo Zeff
Leo Zeff
Dr. Leo Zeff was an American psychologist and psychotherapist in Oakland, California who pioneered the use of ecstasy and other psychoactive drugs in psychotherapy in the 1970s....

, Claudio Naranjo
Claudio Naranjo
Claudio Naranjo is a Chilean psychiatrist who is considered a pioneer in integrating psychotherapy and the spiritual traditions. He is one of the three successors named by Fritz Perls , and a developer of the Enneagram of Personality and founder of the Seekers After Truth Institute...

, George Greer, Joseph Downing, and Philip Wolfson, used MDMA in their practices until it was made illegal. George Greer synthesized MDMA in the lab of Alexander Shulgin and administered it to about 80 of his clients over the course of the remaining years preceding MDMA's Schedule I placement in 1985. In a published summary of the effects, the authors reported patient
Patient
A patient is any recipient of healthcare services. The patient is most often ill or injured and in need of treatment by a physician, advanced practice registered nurse, veterinarian, or other health care provider....

s felt improved in various, mild psychiatric disorders and experienced other personal benefits, especially improved intimate communication with their significant others. In a subsequent publication on the treatment method, the authors reported that one patient with severe pain from terminal
Terminal illness
Terminal illness is a medical term popularized in the 20th century to describe a disease that cannot be cured or adequately treated and that is reasonably expected to result in the death of the patient within a short period of time. This term is more commonly used for progressive diseases such as...

 cancer experienced lasting pain relief
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....

 and improved quality of life
Quality of life
The term quality of life is used to evaluate the general well-being of individuals and societies. The term is used in a wide range of contexts, including the fields of international development, healthcare, and politics. Quality of life should not be confused with the concept of standard of...

.

Three neurobiological mechanisms for the therapeutic effects of MDMA have been suggested: "1) MDMA increases oxytocin levels, which may strengthen the therapeutic alliance; 2) MDMA increases ventromedial prefrontal activity and decreases amygdala activity, which may improve emotional regulation and decrease avoidance, and 3) MDMA increases norepinephrine release and circulating cortisol levels, which may facilitate emotional engagement and enhance extinction of learned fear associations."

The first phase-II double-blind randomized controlled clinical trial into the potential therapeutic benefits of using the drug as an augment to psychotherapy showed that most patients in the trial given psychotherapy treatment along with doses of MDMA experienced statistically significant reductions in the severity of their condition after two months, compared with a control group receiving psychotherapy and a placebo. The authors concludes "MDMA-assisted psychotherapy can be administered to posttraumatic stress disorder patients without evidence of harm, and it may be useful in patients refractory to other treatments."

The possible therapeutic potential of MDMA is being tested in several ongoing studies, some sponsored by the Multidisciplinary Association for Psychedelic Studies
Multidisciplinary Association for Psychedelic Studies
The Multidisciplinary Association for Psychedelic Studies is a membership-based 501 non-profit research and educational organization working to develop psychedelics and marijuana into legal prescription drugs...

 (MAPS). Studies in the U.S., Switzerland, and Israel are evaluating the efficacy of MDMA-assisted psychotherapy for treating those diagnosed with post-traumatic stress disorder
Post-traumatic stress disorder
Posttraumaticstress disorder is a severe anxiety disorder that can develop after exposure to any event that results in psychological trauma. This event may involve the threat of death to oneself or to someone else, or to one's own or someone else's physical, sexual, or psychological integrity,...

 (PTSD) or anxiety related to cancer.

Small doses of MDMA are used as an entheogen to enhance meditation by some Buddhist Monks.

Recreational use


The European Monitoring Centre for Drugs and Drug Addiction
European Monitoring Centre for Drugs and Drug Addiction
The European Monitoring Centre for Drugs and Drug Addiction is an agency of the European Union. Established in 1993, the EMCDDA is located in Lisbon, Portugal.-Mission and role:...

 notes that, although there are some reports of tablets being sold for as little as €1, most countries in Europe now report typical retail prices in the range of €3 to €9 per tablet. The United Nations Office on Drugs and Crime
United Nations Office on Drugs and Crime
The United Nations Office on Drugs and Crime is a United Nations agency that was established in 1997 as the Office for Drug Control and Crime Prevention by combining the United Nations International Drug Control Program and the Crime Prevention and Criminal Justice Division in the United Nations...

 claimed in its 2008 World Drug Report that typical U.S. retail prices are lower, costing $10 to $15 per tablet, or from $4 to $6 per tablet if bought in batches. MDMA is expensive in Australia, costing A$
Australian dollar
The Australian dollar is the currency of the Commonwealth of Australia, including Christmas Island, Cocos Islands, and Norfolk Island, as well as the independent Pacific Island states of Kiribati, Nauru and Tuvalu...

20–A$50 per tablet, but in the Asian community it is A$20–30, depending on the size. In terms of purity data for Australian MDMA, the average is around 34%, ranging from less than 1% to about 85%. The majority of tablets contain 70–85 mg of MDMA. Most MDMA enters Australia from different markets, the Netherlands, the UK, Asia, and the U.S.

Polysubstance use



MDMA is occasionally known for being taken in conjunction with psychedelic drugs, such as LSD
LSD
Lysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed and open eye visuals, synaesthesia, an...

 or psilocybin mushrooms, or even common drugs such as cannabis
Cannabis (drug)
Cannabis, also known as marijuana among many other names, refers to any number of preparations of the Cannabis plant intended for use as a psychoactive drug or for medicinal purposes. The English term marijuana comes from the Mexican Spanish word marihuana...

. As this practice has become more prevalent, most of the more common combinations have been given nicknames, such as "candy flipping", for MDMA combined with LSD
LSD
Lysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed and open eye visuals, synaesthesia, an...

, "hippy flipping", for MDMA with psilocybin
Psilocybin
Psilocybin is a naturally occurring psychedelic prodrug, with mind-altering effects similar to those of LSD and mescaline, after it is converted to psilocin. The effects can include altered thinking processes, perceptual distortions, an altered sense of time, and spiritual experiences, as well as...

, or "kitty flipping" for MDMA with Ketamine
Ketamine
Ketamine is a drug used in human and veterinary medicine. Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist...

. Many users use mentholated products while taking MDMA for its cooling sensation while experiencing the drug's effects. Examples include menthol cigarette
Cigarette
A cigarette is a small roll of finely cut tobacco leaves wrapped in a cylinder of thin paper for smoking. The cigarette is ignited at one end and allowed to smoulder; its smoke is inhaled from the other end, which is held in or to the mouth and in some cases a cigarette holder may be used as well...

s, Vick's Vapo Rub, NyQuil
NyQuil
NyQuil is a brand of over the counter medication which is intended to relieve various symptoms of the common cold. Because all of the medications within the NyQuil imprint contain sedating antihistamines, hypnotics, and/or alcohol, they are intended to be taken before sleep...

, and lozenges
Throat lozenge
A throat lozenge, cough drop, troche, or cough sweet is a small, medicated tablet intended to be dissolved slowly in the mouth to temporarily stop coughs and lubricate and soothe irritated tissues of the throat , possibly from the common cold or influenza...

.

Subjective effects


The primary effects attributable to MDMA consumption are predictable and fairly consistent among users. In general, users report feeling effects within 30–60 minutes of consumption, hitting a peak at approximately 1–1.5 hours, reaching a plateau that lasts about 2–3 hours, followed by a comedown
Comedown (drugs)
Comedown refers to the after effects of heavy recreational stimulant use, usually ecstasy, amphetamine, methylphenidate, cocaine, alcohol, and occasionally cannabis. It can be characterized by depression, apathy, dysphoria, anxiety, fatigue, intense hunger, paranoia and insomnia. These effects are...

 of a few hours, which may be accompanied by fatigue and minor effects.

The most common effect
Therapeutic effect
A therapeutic effect is a consequence of a medical treatment of any kind, the results of which are judged to be desirable and beneficial. This is true whether the result was expected, unexpected, or even an unintended consequence of the treatment...

s reported by users include:
  • A general and subjective alteration in consciousness
    Altered state of consciousness
    An altered state of consciousness , also named altered state of mind, is any condition which is significantly different from a normal waking beta wave state. The expression was used as early as 1966 by Arnold M. Ludwig and brought into common usage from 1969 by Charles Tart: it describes induced...

  • A strong sense of inner peace
    Inner peace
    Inner peace refers to a state of being mentally and spiritually at peace, with enough knowledge and understanding to keep oneself strong in the face of discord or stress. Being "at peace" is considered by many to be healthy and the opposite of being stressed or anxious...

     and self-acceptance
    Self-acceptance
    Self-acceptance is defined as affirmation or acceptance of self in spite of weaknesses or deficiencies.Although this term has been often understood in a common sense way, researchers have defined it formally in terms of positive and negative self-concepts...

  • Diminished aggression
    Aggression
    In psychology, as well as other social and behavioral sciences, aggression refers to behavior between members of the same species that is intended to cause humiliation, pain, or harm. Ferguson and Beaver defined aggressive behavior as "Behavior which is intended to increase the social dominance of...

    , hostility
    Hostility
    Hostility is a form of angry internal rejection or denial in psychology. It is a part of personal construct psychology, developed by George Kelly...

    , and jealousy
    Jealousy
    Jealousy is a second emotion and typically refers to the negative thoughts and feelings of insecurity, fear, and anxiety over an anticipated loss of something that the person values, particularly in reference to a human connection. Jealousy often consists of a combination of presenting emotions...

  • Diminished fear
    Fear
    Fear is a distressing negative sensation induced by a perceived threat. It is a basic survival mechanism occurring in response to a specific stimulus, such as pain or the threat of danger...

    , anxiety
    Anxiety
    Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

    , and insecurity
  • Extreme mood
    Mood (psychology)
    A mood is a relatively long lasting emotional state. Moods differ from emotions in that they are less specific, less intense, and less likely to be triggered by a particular stimulus or event....

     lift with accompanying euphoria
    Euphoria
    Euphoria is an emotional and mental state defined as a sense of great elation and well being.Euphoria may also refer to:* Euphoria , a genus of scarab beetles* Euphoria, a genus name previously used for the longan and other trees...

  • Feelings of empathy
    Empathy
    Empathy is the capacity to recognize and, to some extent, share feelings that are being experienced by another sapient or semi-sapient being. Someone may need to have a certain amount of empathy before they are able to feel compassion. The English word was coined in 1909 by E.B...

    , compassion
    Compassion
    Compassion is a virtue — one in which the emotional capacities of empathy and sympathy are regarded as a part of love itself, and a cornerstone of greater social interconnection and humanism — foundational to the highest principles in philosophy, society, and personhood.There is an aspect of...

    , and forgiveness
    Forgiveness
    Forgiveness is typically defined as the process of concluding resentment, indignation or anger as a result of a perceived offense, difference or mistake, or ceasing to demand punishment or restitution. The Oxford English Dictionary defines forgiveness as 'to grant free pardon and to give up all...

     toward others
  • Feelings of intimacy and even love
    Love
    Love is an emotion of strong affection and personal attachment. In philosophical context, love is a virtue representing all of human kindness, compassion, and affection. Love is central to many religions, as in the Christian phrase, "God is love" or Agape in the Canonical gospels...

     for others
  • Improved self-confidence
    Self-confidence
    The socio-psychological concept of self-confidence relates to self-assuredness in one's personal judgment, ability, power, etc., sometimes manifested excessively.Being confident in yourself is infectious if you present yourself well, others will want to follow in your foot steps towards...

  • The ability to discuss normally anxiety
    Anxiety
    Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

    -provoking topics with marked ease
  • An intensification of all of the bodily senses (hearing, touch, smell, vision, taste)
  • Substantial enhancement of the appreciation of music quality
  • Mild psychedelia, consisting of mental imagery and auditory
    Hearing (sense)
    Hearing is the ability to perceive sound by detecting vibrations through an organ such as the ear. It is one of the traditional five senses...

     and visual distortion
    Distortion
    A distortion is the alteration of the original shape of an object, image, sound, waveform or other form of information or representation. Distortion is usually unwanted, and often many methods are employed to minimize it in practice...

    s
  • Stimulation
    Stimulation
    Stimulation is the action of various agents on nerves, muscles, or a sensory end organ, by which activity is evoked; especially, the nervous impulse produced by various agents on nerves, or a sensory end organ, by which the part connected with the nerve is thrown into a state of activity.The word...

    , arousal
    Arousal
    Arousal is a physiological and psychological state of being awake or reactive to stimuli. It involves the activation of the reticular activating system in the brain stem, the autonomic nervous system and the endocrine system, leading to increased heart rate and blood pressure and a condition of...

    , and hyperactivity (e.g., many users get an "uncontrollable urge to dance" while under the influence)
  • Increased energy
    Energy (psychological)
    Mental or psychic energy or activity is the concept of a principle of activity powering the operation of the mind or psyche. Many modern psychologists or neuroscientists would equate it with increased metabolism in neurons of the brain....

     and endurance
    Endurance
    Endurance is the ability for a human or animal to exert itself and remain active for a long period of time, as well as its ability to resist, withstand, recover from, and have immunity to trauma, wounds, or fatigue. In humans, it is usually used in aerobic or anaerobic exercise...

  • Increased alertness
    Alertness
    Alertness is the state of paying close and continuous attention, being watchful and prompt to meet danger or emergency, or being quick to perceive and act. It is related to psychology as well as to physiology...

    , awareness
    Awareness
    Awareness is the state or ability to perceive, to feel, or to be conscious of events, objects or sensory patterns. In this level of consciousness, sense data can be confirmed by an observer without necessarily implying understanding. More broadly, it is the state or quality of being aware of...

    , and wakefulness
  • Increased desire
    Desire (emotion)
    Desire is a sense of longing for a person or object or hoping for an outcome. Desire is the fire that sets action aflame. The same sense is expressed by emotions such as "craving" or "hankering". When a person desires something or someone, their sense of longing is excited by the enjoyment or the...

    , drive
    Motivation
    Motivation is the driving force by which humans achieve their goals. Motivation is said to be intrinsic or extrinsic. The term is generally used for humans but it can also be used to describe the causes for animal behavior as well. This article refers to human motivation...

    , and motivation
    Motivation
    Motivation is the driving force by which humans achieve their goals. Motivation is said to be intrinsic or extrinsic. The term is generally used for humans but it can also be used to describe the causes for animal behavior as well. This article refers to human motivation...

  • Analgesia or decreased pain
    Pain
    Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...

     sensitivity
    Stimulus (physiology)
    In physiology, a stimulus is a detectable change in the internal or external environment. The ability of an organism or organ to respond to external stimuli is called sensitivity....


Adverse effects


In January 2001, an overview of the subjective side-effects of MDMA was published by Liechti, Gamma, and Vollenweider in the journal Psychopharmacology. Their paper was based on clinical research conducted over several years involving 74 healthy volunteers. The researchers found that there were a number of common side-effects and that many of the effects seemed to occur in different amounts based on gender. The top side-effects reported were difficulty concentrating, jaw clenching, grinding of the teeth
Bruxism
Bruxism is characterized by the grinding of the teeth and typically includes the clenching of the jaw. It is an oral parafunctional activity that occurs in most humans at some time in their lives. In most people, bruxism is mild enough not to be a health problem...

 during sleep, lack of appetite, and dry mouth/thirst (all occurring in more than 50% of the 74 volunteers). Liechti, et al. also measured some of the test subjects for blood pressure, heart rate, and body temperature against a placebo control but no statistically significant changes were seen.

A 2011 study carried out by Harvard Medical School and published in the journal Addiction found no signs of cognitive impairment due to ecstasy use, and that it did not decrease mental ability. The report also raised concerns that previous methods used to conduct that research on ecstasy had been flawed, and the experiments overstated the cognitive differences between ecstasy users and nonusers.

After-effects


Effects reported by some users once the acute
Acute (medicine)
In medicine, an acute disease is a disease with either or both of:# a rapid onset, as in acute infection# a short course ....

 effects of MDMA have worn off include:
  • Psychological
    • Anxiety and paranoia
    • Depression
    • Irritability
    • Fatigue
    • Impaired attention, focus, and concentration, as well as drive and motivation (due to depleted serotonin levels)
    • Residual feelings of empathy, emotional sensitivity, and a sense of closeness to others (afterglow
      Afterglow (drug culture)
      When used with regard to recreational drug use, afterglow refers to positive physical and mental effects that linger after the main effects of a drug have subsided, or after the peak experience has subsided. This state is often characterized by feelings of detachment or increased psychological...

      )

  • Physiological
    • Dizziness, lightheadedness, or vertigo
    • Loss of appetite
    • Gastrointestinal disturbances, such as diarrhea or constipation
    • Insomnia
    • Aches and pains, usually from excessive physical activity (e.g., dancing)
    • Exhaustion
    • Jaw soreness, from trismus
      Trismus
      -Common causes:*Pericoronitis is the most common cause of trismus.*Inflammation of muscles of mastication. It is a frequent sequel to surgical removal of mandibular third molars . The condition is usually resolved on its own in 10–14 days, during which time eating and oral hygiene are compromised...

       or bruxism
      Bruxism
      Bruxism is characterized by the grinding of the teeth and typically includes the clenching of the jaw. It is an oral parafunctional activity that occurs in most humans at some time in their lives. In most people, bruxism is mild enough not to be a health problem...



A slang term given to the depressive period following MDMA consumption is Tuesday Blues (or "Suicide Tuesday"), referring to the low mood that can be experienced midweek by depleted serotonin levels following weekend MDMA use. Some users report that consuming 5-HTP, L-Tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...

, vitamin
Vitamin
A vitamin is an organic compound required as a nutrient in tiny amounts by an organism. In other words, an organic chemical compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on...

s, and/or magnesium
Magnesium in biology
Magnesium is an essential element in biological systems. Magnesium occurs typically as the Mg2+ ion. It is an essential mineral nutrient for life and is present in every cell type in every organism. For example, ATP , the main source of energy in cells, must be bound to a magnesium ion in order to...

 supplements the day after use can reduce the depressive effect by replenishing serotonin levels.

Overdose


Upon overdose, the potentially serious serotonin syndrome
Serotonin syndrome
Serotonin syndrome is a potentially life-threatening adverse drug reaction that may occur following therapeutic drug use, inadvertent interactions between drugs, overdose of particular drugs, or the recreational use of certain drugs...

, stimulant psychosis, and/or hypertensive crisis, among other dangerous adverse reaction
Adverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...

s, may come to prominence, the symptoms of which can include the following:
  • Psychological
    • Disorientation and/or confusion
      Mental confusion
      Confusion of a pathological degree usually refers to loss of orientation sometimes accompanied by disordered consciousness and often memory Confusion (from Latin confusĭo, -ōnis, noun of action from confundere "to pour together", also "to confuse") of a pathological degree usually refers to loss...

    • Anxiety
      Anxiety
      Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

      , paranoia
      Paranoia
      Paranoia [] is a thought process believed to be heavily influenced by anxiety or fear, often to the point of irrationality and delusion. Paranoid thinking typically includes persecutory beliefs, or beliefs of conspiracy concerning a perceived threat towards oneself...

      , and/or panic attack
      Panic attack
      Panic attacks are periods of intense fear or apprehension that are of sudden onset and of relatively brief duration. Panic attacks usually begin abruptly, reach a peak within 10 minutes, and subside over the next several hours...

      s
    • Hypervigilance
      Hypervigilance
      Hypervigilance is an enhanced state of sensory sensitivity accompanied by an exaggerated intensity of behaviors whose purpose is to detect threats. Hypervigilance is also accompanied by a state of increased anxiety which can cause exhaustion. Other symptoms include: abnormally increased arousal, a...

       or increased sensitivity to perceptual stimuli
      Stimulus (physiology)
      In physiology, a stimulus is a detectable change in the internal or external environment. The ability of an organism or organ to respond to external stimuli is called sensitivity....

      , accompanied by significantly increased threat
      Coercion
      Coercion is the practice of forcing another party to behave in an involuntary manner by use of threats or intimidation or some other form of pressure or force. In law, coercion is codified as the duress crime. Such actions are used as leverage, to force the victim to act in the desired way...

       detection
    • Hypomania
      Hypomania
      Hypomania is a mood state characterized by persistent and pervasive elevated or irritable mood, as well as thoughts and behaviors that are consistent with such a mood state...

       or full-blown mania
      Mania
      Mania, the presence of which is a criterion for certain psychiatric diagnoses, is a state of abnormally elevated or irritable mood, arousal, and/ or energy levels. In a sense, it is the opposite of depression...

    • Derealization
      Derealization
      Derealization is an alteration in the perception or experience of the external world so that it seems unreal. Other symptoms include feeling as though one's environment is lacking in spontaneity, emotional coloring and depth. It is a dissociative symptom of many conditions, such as psychiatric and...

       and/or depersonalization
      Depersonalization
      Depersonalization is an anomaly of the mechanism by which an individual has self-awareness. It is a feeling of watching oneself act, while having no control over a situation. Sufferers feel they have changed, and the world has become less real, vague, dreamlike, or lacking in significance...

    • Hallucination
      Hallucination
      A hallucination, in the broadest sense of the word, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid,...

      s and/or delusion
      Delusion
      A delusion is a false belief held with absolute conviction despite superior evidence. Unlike hallucinations, delusions are always pathological...

      s
    • Thought disorder
      Thought disorder
      In psychiatry, thought disorder or formal thought disorder is a term used to describe incomprehensible language, either speech or writing, that is presumed to reflect thinking. There are different types...

       or disorganized thinking
      Thought disorder
      In psychiatry, thought disorder or formal thought disorder is a term used to describe incomprehensible language, either speech or writing, that is presumed to reflect thinking. There are different types...

    • Cognitive and memory impairment
      Cognitive deficit
      Cognitive deficit, also known as cognitive impairment is an inclusive term to describe any characteristic that acts as a barrier to cognitive performance...

       potentially to the point of retrograde
      Retrograde amnesia
      Retrograde amnesia is a loss of access to events that occurred, or information that was learned, before an injury or the onset of a disease....

       or anterograde amnesia
      Anterograde amnesia
      Anterograde amnesia is a loss of the ability to create new memories after the event that caused the amnesia, leading to a partial or complete inability to recall the recent past, while long-term memories from before the event remain intact. This is in contrast to retrograde amnesia, where memories...

    • Acute delirium
      Delirium
      Delirium or acute confusional state is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attentional deficits and generalized severe disorganization of behavior...


  • Physiological
    • Myoclonus
      Myoclonus
      Myoclonus is brief, involuntary twitching of a muscle or a group of muscles. It describes a medical sign and, generally, is not a diagnosis of a disease. Brief twitches are perfectly normal. The myoclonic twitches are usually caused by sudden muscle contractions; they also can result from brief...

       or involuntary and intense muscle twitching
    • Nystagmus
      Nystagmus
      Nystagmus is a condition of involuntary eye movement, acquired in infancy or later in life, that may result in reduced or limited vision.There are two key forms of Nystagmus: pathological and physiological, with variations within each type. Nystagmus may be caused by congenital disorders,...

       or involuntary eye movements
    • Hyperreflexia
      Hyperreflexia
      Hyperreflexia is defined as overactive or overresponsive reflexes. Examples of this can include twitching or spastic tendencies, which are indicative of upper motor neuron disease as well as the lessening or loss of control ordinarily exerted by higher brain centers of lower neural pathways...

       or overresponsive or overreactive reflex
      Reflex
      A reflex action, also known as a reflex, is an involuntary and nearly instantaneous movement in response to a stimulus. A true reflex is a behavior which is mediated via the reflex arc; this does not apply to casual uses of the term 'reflex'.-See also:...

      es
    • Tachypnoea or rapid breathing
      Breathing
      Breathing is the process that moves air in and out of the lungs. Aerobic organisms require oxygen to release energy via respiration, in the form of the metabolism of energy-rich molecules such as glucose. Breathing is only one process that delivers oxygen to where it is needed in the body and...

       and/or dyspnea
      Dyspnea
      Dyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...

       or shortness of breath
    • Palpitation
      Palpitation
      A palpitation is an abnormality of heartbeat that causes a conscious awareness of its beating, whether it is too slow, too fast, irregular, or at its normal frequency. The word may also refer to this sensation itself...

      s or abnormal awareness of the beating of the heart
      Cardiac cycle
      The cardiac cycle is a term referring to all or any of the events related to the flow or blood pressure that occurs from the beginning of one heartbeat to the beginning of the next. The frequency of the cardiac cycle is described by the heart rate. Each beat of the heart involves five major stages...

    • Angina pectoris or severe chest pain
      Chest pain
      Chest pain may be a symptom of a number of serious conditions and is generally considered a medical emergency. Even though it may be determined that the pain is non-cardiac in origin, this is often a diagnosis of exclusion made after ruling out more serious causes of the pain.-Differential...

      , as well as pulmonary hypertension
      Pulmonary hypertension
      In medicine, pulmonary hypertension is an increase in blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion...

       (PH)
    • Cardiac arrhythmia or abnormal electrical activity
      Electrical conduction system of the heart
      The normal intrinsic electrical conduction of the heart allows electrical propagation to be transmitted from the Sinoatrial Node through both atria and forward to the Atrioventricular Node. Normal/baseline physiology allows further propagation from the AV node to the ventricle or Purkinje Fibers...

       of the heart
    • Circulatory shock or cardiogenic shock
      Cardiogenic shock
      Cardiogenic shock is based upon an inadequate circulation of blood due to primary failure of the ventricles of the heart to function effectively....

    • Vasculitis
      Vasculitis
      Vasculitis refers to a heterogeneous group of disorders that are characterized by inflammatory destruction of blood vessels. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis...

       or destruction
      Toxicity
      Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...

       of blood vessel
      Blood vessel
      The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...

      s
    • Cardiotoxicity
      Cardiotoxicity
      Cardiotoxicity is the occurrence of heart electrophysiology dysfunction or/and muscle damage. The heart becomes weaker and is not as efficient in pumping and therefore circulating blood...

       or damage to the heart
    • Cardiac dysfunction, arrest, myocardial infarction
      Myocardial infarction
      Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...

      , and/or heart failure
    • Hemorrhage and/or stroke
    • Severe hyperthermia
      Hyperthermia
      Hyperthermia is an elevated body temperature due to failed thermoregulation. Hyperthermia occurs when the body produces or absorbs more heat than it can dissipate...

      , potentially resulting in organ failure
      Organ failure
      Organ dysfunction is a condition where an organ does not perform its expected function. Organ failure is organ dysfunction to such a degree that normal homeostasis cannot be maintained without external clinical intervention.It is not a diagnosis...


  • Miscellaneous
    • Syncope
      Syncope (medicine)
      Syncope , the medical term for fainting, is precisely defined as a transient loss of consciousness and postural tone characterized by rapid onset, short duration, and spontaneous recovery due to global cerebral hypoperfusion that most often results from hypotension.Many forms of syncope are...

       or fainting or loss of consciousness
    • Organ failure
      Organ failure
      Organ dysfunction is a condition where an organ does not perform its expected function. Organ failure is organ dysfunction to such a degree that normal homeostasis cannot be maintained without external clinical intervention.It is not a diagnosis...

       (as mentioned above)
    • Possible brain damage
    • Coma or death

Chronic use


Some studies indicate that repeated recreational users of MDMA have increased rates of depression and anxiety, even after quitting the drug. A Meta-analytic review of the published literature on memory show that ecstasy users may suffer short-term and long-term verbal memory impairment—with 70–80% of ecstasy users displaying impaired memory, although the results of this study may have been confounded by concurrent cannabis use. Moreover, this research shows the amount of doses consumed does not significantly predict memory performance. Other meta analyses have reported possibility of impairment of executive functioning. Despite these findings many factors including total lifetime MDMA consumption, the duration of abstinence between uses, dosage, the environment of use, poly-drug use/abuse, quality of mental health
Mental health
Mental health describes either a level of cognitive or emotional well-being or an absence of a mental disorder. From perspectives of the discipline of positive psychology or holism mental health may include an individual's ability to enjoy life and procure a balance between life activities and...

, various lifestyle choices, and predispositions to develop clinical depression and other disorders have made the results of many studies difficult to verify. A study that attempted to eliminate these confounding factors was published in February, 2011 by Addiction, and found few differences in the cognitive functioning of MDMA-using ravers versus non-MDMA-using ravers, "In a study designed to minimize limitations found in many prior investigations, we failed to demonstrate marked residual cognitive effects in ecstasy users. This finding contrasts with many previous findings-including our own-and emphasizes the need for continued caution in interpreting field studies of cognitive function in illicit ecstasy users." MDMA use has been occasionally associated with liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 damage, excessive wear of teeth, and (very rarely) hallucinogen persisting perception disorder
Hallucinogen persisting perception disorder
Hallucinogen persisting perception disorder is a disorder characterized by a continual presence of visual disturbances that are reminiscent of those generated by the ingestion of hallucinogenic substances. Previous use of hallucinogens by the person is needed, though not sufficient, for...

.


Short-term health concerns


Short-term physical health risks of MDMA consumption include hyperthermia
Hyperthermia
Hyperthermia is an elevated body temperature due to failed thermoregulation. Hyperthermia occurs when the body produces or absorbs more heat than it can dissipate...

, and hyponatremia
Hyponatremia
Hyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal. In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodium and is not due to sodium deficiency. Sodium is the dominant extracellular...

. Continuous activity without sufficient rest or rehydration may cause body temperature to rise to dangerous levels, and loss of fluid via excessive perspiration puts the body at further risk as the stimulatory and euphoric qualities of the drug may render the user oblivious to their energy expenditure for quite some time. Diuretics such as alcohol may exacerbate these risks further.

Long-term effects on serotonin and dopamine


MDMA causes a reduction in the concentration of serotonin transporter
Serotonin transporter
The serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...

s (SERTs) in the brain. The rate at which the brain recovers from serotonergic changes is unclear. One study demonstrated lasting serotonergic changes in some animals exposed to MDMA. Other studies have suggested that the brain may recover from serotonergic damage.

Some studies show that MDMA may be neurotoxic
Neurotoxicity
Neurotoxicity occurs when the exposure to natural or artificial toxic substances, which are called neurotoxins, alters the normal activity of the nervous system in such a way as to cause damage to nervous tissue. This can eventually disrupt or even kill neurons, key cells that transmit and process...

 in humans. Other studies, however, suggest that any potential brain damage may be at least partially reversible following prolonged abstinence from MDMA. However, other studies suggest that SERT-depletion arises from long-term MDMA use due to receptor down-regulation, rather than true neurotoxicity.
Depression and deficits in memory have been shown to occur more frequently in long-term MDMA users. However, some recent studies have suggested that MDMA use may not be associated with chronic depression.

One study on MDMA toxicity, by George A. Ricaurte
George A. Ricaurte
George A. Ricaurte is a controversial neurology researcher who works at the Johns Hopkins School of Medicine in the Department of Neurology. He received his MD from Northwestern University Medical School and his Ph.D. from the University of Chicago.His research focuses on Parkinson's disease and...

 of Johns Hopkins School of Medicine, which claimed that a single recreational dose of MDMA could cause Parkinson's Disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...

 in later life due to severe dopaminergic stress, was actually retracted by Ricaurte himself after he discovered his lab had administered not MDMA but methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...

, which is known to cause dopaminergic changes similar to the serotonergic changes caused by MDMA. Ricaurte blamed this mistake on a labeling error by the chemical supply company that sold the material to his lab, but the supply company responded that there was no evidence of a labeling error on their end. Most studies have found that levels of the dopamine transporter
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 (or other markers of dopamine function) in MDMA users deserve further study or are normal.

Several studies have indicated a possible mechanism for neurotoxicity in a metabolite of MDMA, through the reaction of Alpha-Methyldopamine
Alpha-Methyldopamine
α-Methyldopamine , also known as 3,4-dihydroxyamphetamine , is a neurotoxin and research chemical of the phenethylamine and amphetamine chemical classes...

, a principal metabolite, and glutathione
Glutathione
Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...

, the major antioxidant in the human body. One possible product of this reaction, 2,5-bis-(glutathion-S-yl)-alpha-methyldopamine, has been demonstrated to produce the same toxic effects observed in MDMA, while MDMA, and alpha-methyldopamine themselves have been shown to be non-neurotoxic. It is, however, impossible to avoid the metabolism of MDMA in the body, and the production of this toxic metabolite. Some studies have demonstrated possible ways to minimize the production of this particular metabolite, though evidence at this point is sparse at best.

Purity and dosage of "ecstasy"



Another concern associated with MDMA use is toxicity from chemicals other than MDMA in ecstasy tablets. Due to its near-universal illegality, the purity of a substance sold as ecstasy is unknown to the typical user. The MDMA content of tablets varies widely between regions and different brands of pills and fluctuates somewhat each year. Pills may contain other active substances meant to stimulate in a way similar to MDMA, such as amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...

, methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...

, ephedrine
Ephedrine
Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....

, caffeine
Caffeine
Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...

, all of which may be comparatively cheap to produce and can help to boost overall profits. In some cases, tablets sold as ecstasy do not even contain any MDMA. Instead they may contain an assortment of undesirable drugs and substances, such as paracetamol
Paracetamol
Paracetamol INN , or acetaminophen USAN , is a widely used over-the-counter analgesic and antipyretic . It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies...

, ibuprofen
Ibuprofen
Ibuprofen is a nonsteroidal anti-inflammatory drug used for relief of symptoms of arthritis, fever, as an analgesic , especially where there is an inflammatory component, and dysmenorrhea....

, talcum powder, etc.

There have been a number of deaths attributed to para-Methoxyamphetamine (PMA), a potent and highly neurotoxic hallucinogenic amphetamine, being sold as ecstasy. PMA is unique in its ability to quickly elevate body temperature and heart rate at relatively low doses, especially in comparison to MDMA. Hence, a user believing he is consuming two 120 mg pills of MDMA could actually be consuming a dose of PMA that is potentially lethal, depending on the purity of the pill. Not only does PMA cause the release of serotonin but it also acts as a monoamine oxidase inhibitor, MAOI
Monoamine oxidase inhibitor
Monoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....

. When combined with an MDMA or an MDMA-like substance, serotonin syndrome
Serotonin syndrome
Serotonin syndrome is a potentially life-threatening adverse drug reaction that may occur following therapeutic drug use, inadvertent interactions between drugs, overdose of particular drugs, or the recreational use of certain drugs...

 can result. Combining MAO inhibitors with certain legal prescription and over the counter medications can also lead to (potentially fatal) serotonin syndrome.

Harm assessment


The UK study placed great weight on the risk for acute physical harm, the propensity for physical and psychological dependency on the drug, and the negative familial and societal impacts of the drug. They did not evaluate or rate the negative impact of ecstasy on the cognitive health of ecstasy users, e.g., impaired memory and concentration. Based on these factors, the study placed MDMA at number 18 in the list of 20 popular drugs.

David Nutt
David Nutt
David John Nutt is a British psychiatrist and neuropsychopharmacologist specialising in the research of drugs that affect the brain and conditions such as addiction, anxiety and sleep. He was until 2009 a professor at the University of Bristol heading their Psychopharmacology Unit...

, a former chairman of the UK Advisory Council on the Misuse of Drugs
Advisory Council on the Misuse of Drugs
The Advisory Council on the Misuse of Drugs is a statutory and non-executive non-departmental British public body, which was established under the UK's Misuse of Drugs Act 1971.-Mandate:Its terms of reference, according to the Act, are as follows:...

, stated in the Journal of Psychopharmacology in January 2009 that ecstasy use compared favorably with horse riding in terms of risk, with ecstasy leading to around 30 deaths a year in the UK compared to about 10 from horse riding, and "acute harm to person" occurring in approximately 1 in 10,000 episodes of ecstasy use compared to about 1 in 350 episodes of horse riding. Dr. Nutt notes the lack of a balanced risk assessment in public discussions of MDMA:

The general public, especially the younger generation, are disillusioned with the lack of balanced political debate about drugs. This lack of rational debate can undermine the trust in government in relation to drug misuse and thereby undermining the government's message in public information campaigns. The media in general seem to have an interest in scare stories about illicit drugs, though there are some exceptions (Horizon, 2008). A telling review of 10-year media reporting of drug deaths in Scotland illustrates the distorted media perspective very well (Forsyth, 2001). During this decade, the likelihood of a newspaper reporting a death from paracetamol was in per 250 deaths, for diazepam it was 1 in 50, whereas for amphetamine it was 1 in 3 and for ecstasy every associated death was reported.

A spokesperson for the ACMD said that "The recent article by Professor David Nutt published in the Journal of Psychopharmacology was done in respect of his academic work and not as chair of the ACMD."

The most carefully designed study so far was published in February 2011 in the journal Addiction, comparing the effect on cognitive skills in 52 ecstasy users against 59 very closely matched non-users. The study, performed by the group of Prof. Halpern of Harvard Medical School, eliminated potential confounding factors like the use of other drugs and history of drug-use. The study found no short- or long-term differences in cognitive skills in the test group (users) versus the control group (non-users).

Drug interactions


There are a number of reported potentially dangerous possible interactions between MDMA and other drugs, including serotonergic
Serotonergic
Serotonergic or serotoninergic means "related to the neurotransmitter serotonin". A synapse is serotonergic if it uses serotonin as its neurotransmitter...

 drugs. Several cases have been reported of death in individuals who ingested MDMA while taking ritonavir
Ritonavir
Ritonavir, with trade name Norvir , is an antiretroviral drug from the protease inhibitor class used to treat HIV infection and AIDS....

 (Norvir), which inhibits multiple CYP450 enzymes. Toxicity or death has also been reported in people who took MDMA in combination with certain monoamine oxidase inhibitor
Monoamine oxidase inhibitor
Monoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....

s (MAOIs) such as phenelzine
Phenelzine
Phenelzine is a non-selective and irreversible monoamine oxidase inhibitor of the hydrazine class which is used as an antidepressant and anxiolytic...

 (Nardil), tranylcypromine
Tranylcypromine
Tranylcypromine is a drug of the substituted phenethylamine and amphetamine classes which acts as a monoamine oxidase inhibitor —it is a non-selective and irreversible inhibitor of the enzyme monoamine oxidase...

 (Parnate), or moclobemide
Moclobemide
Moclobemide is a monoamine oxidase inhibitor drug primarily used to treat depression and social anxiety. Although clinical trials with the medicine began in 1977, it is not approved for use in the United States...

 (Aurorix, Manerix). On the other hand, MAOB
Monoamine oxidase B
Monoamine oxidase B, also known as MAOB, is a protein that in humans is encoded by the MAOB gene.The protein encoded by this gene belongs to the flavin monoamine oxidase family. It is an enzyme located in the mitochondrial outer membrane...

 inhibitors like selegiline
Selegiline
Selegiline is a drug used for the treatment of early-stage Parkinson's disease, depression and senile dementia. In normal clinical doses it is a selective irreversible MAO-B inhibitor, however in larger doses it loses its specificity and also inhibits MAO-A...

 (Deprenyl; Eldepryl, Zelapar, Emsam) do not seem to carry these risks when taken at selective doses, and have been used to completely block neurotoxicity in rats.

Commercial sassafras oil generally is a by-product of camphor
Camphor
Camphor is a waxy, white or transparent solid with a strong, aromatic odor. It is a terpenoid with the chemical formula C10H16O. It is found in wood of the camphor laurel , a large evergreen tree found in Asia and also of Dryobalanops aromatica, a giant of the Bornean forests...

 production in Asia
Asia
Asia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...

 or comes from related trees in Brazil
Brazil
Brazil , officially the Federative Republic of Brazil , is the largest country in South America. It is the world's fifth largest country, both by geographical area and by population with over 192 million people...

. Safrole is a precursor for the clandestine manufacture
Clandestine chemistry
Clandestine chemistry is chemistry carried out in secret, and particularly in illegal drug laboratories. Larger labs are usually run by gangs or organized crime intending to produce for distribution on the black market...

 of MDMA
Methylenedioxymethamphetamine
MDMA is an entactogenic drug of the phenethylamine and amphetamine class of drugs. In popular culture, MDMA has become widely known as "ecstasy" , usually referring to its street pill form, although this term may also include the presence of possible adulterants...

 (ecstasy), and as such, its transport is monitored internationally.
Roots of Sassafras can also be steeped to make tea and were used in the flavoring of traditional root beer
Root beer
Root beer is a carbonated, sweetened beverage, originally made using the root of a sassafras plant as the primary flavor. Root beer, popularized in North America, comes in two forms: alcoholic and soft drink. The historical root beer was analogous to small beer in that the process provided a drink...

 until being banned for mass production by the FDA. Laboratory animals that were given oral doses of sassafras tea or sassafras oil that contained large doses of safrole developed permanent liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 damage or various types of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

. In humans liver damage can take years to develop and it may not have obvious signs.

Chemistry


Safrole
Safrole
Safrole, also known as shikimol, is a phenylpropene. It is a colorless or slightly yellow oily liquid. It is typically extracted from the root-bark or the fruit of sassafras plants in the form of sassafras oil , or synthesized from other related methylenedioxy...

, a colorless or slightly black oil, extracted from the root-bark or the fruit of sassafras
Sassafras
Sassafras is a genus of three extant and one extinct species of deciduous trees in the family Lauraceae, native to eastern North America and eastern Asia.-Overview:...

 plants is the primary precursor for all manufacture of MDMA. There are numerous synthetic methods available in the literature to convert safrole into MDMA via different intermediates. One common route is via the MDP2P
MDP2P
3,4-phenyl-2-propanone , is a chemical compound consisting of a phenylacetone moiety substituted with a methylenedioxy functional group, an entactogen and stimulant of the phenethylamine, amphetamine, and cathinone classes...

 (3,4-methylenedioxy
Methylenedioxy
Methylenedioxy in the field of chemistry, particularly in organic chemistry, is the name for a functional group with the structural formula R-O-CH2-O-R' which is connected to the rest of a molecule by two chemical bonds. The methylenedioxy group consists of two oxygen atoms connected to a methylene...

phenyl-2-propanone, also known as piperonyl acetone) intermediate. This intermediate can be produced in at least two different ways. One method is to isomerize safrole to isosafrole
Isosafrole
Isosafrole is a phenylpropene, a type of aromatic organic chemical with a smell similar to anise or licorice. It is found in small amounts in various essential oils, but is most commonly obtained by isomerizing the plant oil safrole....

 in the presence of a strong base and then oxidize isosafrole
Isosafrole
Isosafrole is a phenylpropene, a type of aromatic organic chemical with a smell similar to anise or licorice. It is found in small amounts in various essential oils, but is most commonly obtained by isomerizing the plant oil safrole....

 to MDP2P. Another, reportedly better, method is to make use of the Wacker process
Wacker process
The Wacker process or the Hoechst-Wacker process originally referred to the oxidation of ethylene to acetaldehyde by oxygen in water in the presence of a tetrachloropalladate catalyst...

 to oxidize safrole directly to the MDP2P (3,4-methylenedioxy phenyl-2-propanone) intermediate. This can be done with a palladium
Palladium
Palladium is a chemical element with the chemical symbol Pd and an atomic number of 46. It is a rare and lustrous silvery-white metal discovered in 1803 by William Hyde Wollaston. He named it after the asteroid Pallas, which was itself named after the epithet of the Greek goddess Athena, acquired...

 catalyst. Once the MDP2P intermediate has been prepared, a reductive amination
Reductive amination
Reductive amination is a form of amination that involves the conversion of a carbonyl group to an amine via an intermediate imine...

 leads to MDMA, a racemate {1:1 mixture of (R)-1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine and (S)-1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine}.
Another method for the synthesis of racemic
Racemic
In chemistry, a racemic mixture, or racemate , is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule. The first known racemic mixture was "racemic acid", which Louis Pasteur found to be a mixture of the two enantiomeric isomers of tartaric acid.- Nomenclature :A...

 MDMA is addition of hydrogen bromide to safrole and reaction of the adduct with methylamine.


Relatively small quantities of essential oil are required to make large numbers of MDMA pills. The essential oil of Ocotea cymbarum
Ocotea cymbarum
Ocotea cymbarum is a species of plant in the Lauraceae family. It is found in Brazil, Colombia, French Guiana, Guyana, Suriname, and Venezuela.-References:* World Conservation Monitoring Centre 1998. . Downloaded on 22 August 2007....

typically contains between 80 and 94% safrole. This would allow 500 ml of the oil, which retails at between $20 and $100, to be used to produce an estimated 1,300 to 2,800 tablets containing approximately 120 mg of MDMA each.

Pharmacology


MDMA acts as a releasing agent
Releasing agent
A releasing agent , or simply releaser, is a drug that induces the release of a neurotransmitter from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitter. Many drugs use neurotransmitter release to exert their psychological and...

 of serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

, norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

, and dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

. It enters neurons via carriage by the monoamine transporter
Monoamine transporter
Monoamine transporters are protein structures that function as integral plasma membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. Three major classes of MATs are responsible for the reuptake of their associated amine neurotransmitters...

s. Once inside, MDMA inhibits the vesicular monoamine transporter
Vesicular monoamine transporter
The vesicular monoamine transporter is a transport protein integrated into the membrane of intracellular vesicles of presynaptic neurons. It acts to transport monoamines into the synaptic vesicles.-Monoamines:...

, which results in increased concentrations of serotonin, norepinephrine, and dopamine in the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...

, and induces their release by reversing
Transporter reversal
Transporter reversal is the action of reversing a plasmalemmal transporter via a process known as phosphorylation. Neurotransmitter transporters normally function as part of the reuptake process, by carrying neurotransmitter chemicals from the extracellular space into the cytoplasm of a...

 their respective transporters through a process known as phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....

. It also acts as a weak 5-HT1
5-HT1 receptor
The 5-HT1 receptors are a subfamily of 5-HT receptors that bind the endogenous neurotransmitter serotonin . The 5-HT1 subfamily consists of five G protein-coupled receptors that are coupled to Gi/Go and mediate inhibitory neurotransmission, including 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F...

 and 5-HT2 receptor
5-HT2 receptor
The 5-HT2 receptors are a subfamily of 5-HT receptors that bind the endogenous neurotransmitter serotonin . The 5-HT2 subfamily consists of three G protein-coupled receptors which are coupled to Gq/G11 and mediate excitatory neurotransmission, including 5-HT2A, 5-HT2B, and 5-HT2C...

 agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...

, and its more efficacious metabolite MDA
3,4-Methylenedioxyamphetamine
3,4-Methylenedioxyamphetamine , also known as tenamfetamine , is a psychedelic and entactogenic drug of the phenethylamine and amphetamine chemical classes...

 likely augments this action.

MDMA's unusual entactogenic effects have been hypothesized to be, at least partly, the result of indirect oxytocin
Oxytocin
Oxytocin is a mammalian hormone that acts primarily as a neuromodulator in the brain.Oxytocin is best known for its roles in sexual reproduction, in particular during and after childbirth...

 secretion via activation of the serotonin system. Oxytocin is a hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

 released following events like hugging, orgasm
Orgasm
Orgasm is the peak of the plateau phase of the sexual response cycle, characterized by an intense sensation of pleasure...

, and childbirth
Childbirth
Childbirth is the culmination of a human pregnancy or gestation period with the birth of one or more newborn infants from a woman's uterus...

, and is thought to facilitate bonding
Pair bond
In biology, a pair bond is the strong affinity that develops in some species between the males and females in a pair, potentially leading to breeding. Pair-bonding is a term coined in the 1940s that is frequently used in sociobiology and evolutionary psychology circles...

 and the establishment of trust. Based on studies in rats, MDMA is believed to cause the release of oxytocin, at least in part, by both directly and indirectly agonizing the serotonin 5-HT1A receptor
5-HT1A receptor
The 5-HT1A receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gi/Go and mediates inhibitory neurotransmission...

. A placebo-controlled study in 15 human volunteers found that 100 mg MDMA increased blood levels of oxytocin, and the amount of oxytocin increase was correlated with the subjective prosocial effects of MDMA.

Pharmacokinetics


MDMA reaches maximal concentration
Concentration
In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...

s in the blood stream between 1.5 and 3 hours after ingestion
Ingestion
Ingestion is the consumption of a substance by an organism. In animals, it normally is accomplished by taking in the substance through the mouth into the gastrointestinal tract, such as through eating or drinking...

. It is then slowly metabolized
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

 and excreted
Excretion
Excretion is the process by which waste products of metabolism and other non-useful materials are eliminated from an organism. This is primarily carried out by the lungs, kidneys and skin. This is in contrast with secretion, where the substance may have specific tasks after leaving the cell...

, with levels decreasing to half their peak concentration over approximately 8 hours. Thus, there are still high MDMA levels in the body when the experiential effects have mostly ended, indicating that acute tolerance has developed to the actions of MDMA. Taking additional supplements of MDMA at this point, therefore, produces higher concentrations of MDMA in the blood and brain than might be expected based on the perceived effects.

Metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...

s of MDMA that have been identified in humans include 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxy-methamphetamine (HMMA), 4-hydroxy-3-methoxyamphetamine (HMA), 3,4-dihydroxyamphetamine (DHA) (also called alpha-methyldopamine (α-Me-DA)), 3,4-methylenedioxyphenylacetone
MDP2P
3,4-phenyl-2-propanone , is a chemical compound consisting of a phenylacetone moiety substituted with a methylenedioxy functional group, an entactogen and stimulant of the phenethylamine, amphetamine, and cathinone classes...

 (MDP2P), and N-hydroxy-3,4-methylenedioxyamphetamine (MDOH). The contributions of these metabolites to the psychoactive and toxic effects of MDMA are an area of active research. Sixty-five percent of MDMA is excreted unchanged in the urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...

 (in addition, 7% is metabolized into MDA) during the 24 hours after ingestion.

MDMA is known to be metabolized by two main metabolic pathway
Metabolic pathway
In biochemistry, metabolic pathways are series of chemical reactions occurring within a cell. In each pathway, a principal chemical is modified by a series of chemical reactions. Enzymes catalyze these reactions, and often require dietary minerals, vitamins, and other cofactors in order to function...

s: (1) O-demethylenation followed by catechol-O-methyltransferase
Catechol-O-methyl transferase
Catechol-O-methyltransferase is one of several enzymes that degrade catecholamines such as dopamine, epinephrine, and norepinephrine. In humans, catechol-O-methyltransferase protein is encoded by the COMT gene...

 (COMT)-catalyzed methylation and/or glucuronide/sulfate conjugation; and (2) N-dealkylation, deamination, and oxidation to the corresponding benzoic acid
Benzoic acid
Benzoic acid , C7H6O2 , is a colorless crystalline solid and the simplest aromatic carboxylic acid. The name derived from gum benzoin, which was for a long time the only source for benzoic acid. Its salts are used as a food preservative and benzoic acid is an important precursor for the synthesis...

 derivatives conjugated with glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...

. The metabolism may be primarily by cytochrome P450
Cytochrome P450 oxidase
The cytochrome P450 superfamily is a large and diverse group of enzymes. The function of most CYP enzymes is to catalyze the oxidation of organic substances. The substrates of CYP enzymes include metabolic intermediates such as lipids and steroidal hormones, as well as xenobiotic substances...

 (CYP450) enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s (CYP2D6
CYP2D6
Cytochrome P450 2D6 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. Also, many substances are bioactivated by CYP2D6 to form their active compounds...

 (in humans, but CYP2D1 in mice
MICE
-Fiction:*Mice , alien species in The Hitchhiker's Guide to the Galaxy*The Mice -Acronyms:* "Meetings, Incentives, Conferencing, Exhibitions", facilities terminology for events...

), and CYP3A4
CYP3A4
Cytochrome P450 3A4 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. CYP3A4 is involved in the oxidation of the largest range of substrates of all the CYPs. As a result, CYP3A4 is present in...

) and COMT. Complex, nonlinear pharmacokinetics
Pharmacokinetics
Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism...

 arise via autoinhibition of CYP2D6
CYP2D6
Cytochrome P450 2D6 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. Also, many substances are bioactivated by CYP2D6 to form their active compounds...

 and CYP2D8, resulting in zeroth order kinetics
Rate equation
The rate law or rate equation for a chemical reaction is an equation that links the reaction rate with concentrations or pressures of reactants and constant parameters . To determine the rate equation for a particular system one combines the reaction rate with a mass balance for the system...

 at higher doses. It is thought that this can result in sustained and higher concentration
Concentration
In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...

s of MDMA if the user takes consecutive doses of the drug.

Because the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 CYP2D6
CYP2D6
Cytochrome P450 2D6 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. Also, many substances are bioactivated by CYP2D6 to form their active compounds...

 is deficient or totally absent in some people, it was once hypothesized that these people might have elevated risk when taking MDMA. However, there is still no evidence for this theory and available evidence argues against it. It is now thought that the contribution of CYP2D6 to MDMA metabolism in humans is less than 30% of the metabolism. Indeed, an individual lacking CYP2D6 was given MDMA in a controlled clinical setting and a larger study gave MDMA to healthy volunteers after inhibiting CYP2D6 with paroxetine
Paroxetine
Paroxetine is an SSRI antidepressant. Marketing of the drug began in 1992 by the pharmaceutical company SmithKline Beecham, now GlaxoSmithKline...

. Lack of the enzyme caused a modest increase in drug exposure and decreases in some metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...

s, but physical effects did not appear appreciably elevated. While there is little or no evidence that low CYP2D6 activity increases risks from MDMA, it is likely that MDMA-induced CYP2D inhibition will increase risk of those prescription drugs that are metabolized by this enzyme. MDMA-induced CYP2D inhibition appears to last for up to a week after MDMA exposure.

MDMA and metabolites are primarily excreted as conjugates, such as sulfates and glucuronides.
MDMA is a chiral
Chirality (chemistry)
A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....

 compound and has been almost exclusively administered as a racemate
Racemic
In chemistry, a racemic mixture, or racemate , is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule. The first known racemic mixture was "racemic acid", which Louis Pasteur found to be a mixture of the two enantiomeric isomers of tartaric acid.- Nomenclature :A...

. However, an early uncontrolled report suggests that the (S)-enantiomer
Enantiomer
In chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable , much as one's left and right hands are the same except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...

 is significantly more potent
Potency (pharmacology)
In the field of pharmacology, potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. A highly potent drug evokes a larger response at low concentrations, while a drug of lower potency evokes a small response at low concentrations...

 in humans than the (R)-enantiomer indicate that the disposition of MDMA is stereoselective, with the S-enantiomer having a shorter elimination half-life and greater excretion than the R-enantiomer. For example, Fallon et al. reported that the area under the blood plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...

 concentration versus time curve (AUC) was two to four times higher for the (R)-enantiomer than the (S)-enantiomer after a 40 mg oral dose in human volunteers. Likewise, the plasma half-life of (R)-MDMA was significantly longer than that of the (S)-enantiomer (5.8 ± 2.2 hours vs 3.6 ± 0.9 hours). However, because MDMA has dose dependent kinetics, it is likely that these half-lives would be higher at more typical doses (100 mg is sometimes considered a typical dose). Given as the racemate, MDMA has a half-life
Half-life
Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...

 of around 8 hours.

Detection of use


MDMA and MDA may be quantitated in blood, plasma or urine to monitor for abuse, confirm a diagnosis of poisoning or assist in the forensic investigation of a traffic or other criminal violation or a sudden death. Some drug abuse screening programs rely on hair, saliva, or sweat as specimens. Most commercial amphetamine immunoassay screening tests cross-react significantly with MDMA or its major metabolites, but chromatographic techniques can easily distinguish and separately measure each of these substances. The concentrations of MDA in the blood or urine of a person who has taken only MDMA are, in general, less than 10% those of the parent drug.

History



MDMA was first synthesized in 1912 by Merck
Merck KGaA
Merck KGaA is a German chemical and pharmaceutical company. Merck, also known as “German Merck” and “Merck Darmstadt”, was founded in Darmstadt, Germany, in 1668, making it the world's oldest operating chemical and pharmaceutical company. The company was privately owned until going public in 1995...

 chemist Anton Köllisch
Anton Kollisch
Anton Köllisch was the German chemist who, whilst working at Darmstadt for pharmaceutical giant Merck, first synthesized the chemical MDMA that would later come to be known as "ecstasy"....

. At the time, Merck was interested in developing substances that stopped abnormal bleeding. Merck wanted to evade an existing patent, held by Bayer
Bayer
Bayer AG is a chemical and pharmaceutical company founded in Barmen , Germany in 1863. It is headquartered in Leverkusen, North Rhine-Westphalia, Germany and well known for its original brand of aspirin.-History:...

, for one such compound: hydrastinine
Hydrastinine
Hydrastinine is a semisynthetic alkaloid from the hydrolysis of the alkaloid hydrastine, which was found naturally in small quantities in Hydrastis canadensis L. . Hydrastinine was produced by oxidative splitting of hydrastine hydrochloride with nitric acid in good yield...

. At the behest of his superiors Walther Beckh and Otto Wolfes, Köllisch developed a preparation of a hydrastinine analogue, methylhydrastinine. MDMA was an intermediate compound
Reaction intermediate
A reaction intermediate or an intermediate is a molecular entity that is formed from the reactants and reacts further to give the directly observed products of a chemical reaction. Most chemical reactions are stepwise, that is they take more than one elementary step to complete...

 in the synthesis of methylhydrastinine, and Merck was not interested in its properties at the time. On 24 December 1912, Merck filed two patent applications that described the synthesis of MDMA and its subsequent conversion to methylhydrastinine.

Over the following 65 years, MDMA was largely forgotten. Merck records indicate that its researcher
Researcher
A researcher is somebody who performs research, the search for knowledge or in general any systematic investigation to establish facts. Researchers can work in academic, industrial, government, or private institutions.-Examples of research institutions:...

s returned to the compound sporadically. In 1927, Max Oberlin studied the pharmacology of MDMA and observed that its effects on blood sugar
Blood sugar
The blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal. Normally in mammals, the body maintains the blood glucose level at a reference range between about 3.6 and 5.8 mM , or 64.8 and 104.4 mg/dL...

 and smooth muscle
Smooth muscle
Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...

s were similar to ephedrine
Ephedrine
Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....

's. Researchers at Merck conducted experiments with MDMA in 1952 and 1959. In 1953 and 1954, the United States Army
United States Army
The United States Army is the main branch of the United States Armed Forces responsible for land-based military operations. It is the largest and oldest established branch of the U.S. military, and is one of seven U.S. uniformed services...

 commissioned a study of toxicity
Toxicity
Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...

 and behavioral effects in animals of injected mescaline
Mescaline
Mescaline or 3,4,5-trimethoxyphenethylamine is a naturally occurring psychedelic alkaloid of the phenethylamine class used mainly as an entheogen....

 and several analogues, including MDMA. These originally classified investigations were declassified and published in 1973. The first scientific paper on MDMA appeared in 1958 in Yakugaku Zasshi, the Journal of the Pharmaceutical Society of Japan. In this paper, Yutaka Kasuya described the synthesis of MDMA, a part of his research on antispasmodics.

MDMA was being used recreationally in the United States by 1970. In the mid-1970s, Alexander Shulgin
Alexander Shulgin
Alexander "Sasha" Theodore Shulgin is an American pharmacologist, chemist, artist, and drug developer.Shulgin is credited with the popularization of MDMA, commonly known as ecstasy, in the late 1970s and early 1980s, especially for psychopharmaceutical use and the treatment of depression and...

, then at University of California, Berkeley
University of California, Berkeley
The University of California, Berkeley , is a teaching and research university established in 1868 and located in Berkeley, California, USA...

, heard from his students about unusual effects of MDMA; among others, the drug had helped one of them to overcome his stutter. Intrigued, Shulgin synthesized MDMA and tried it himself in 1976. Two years later, he and David E. Nichols
David E. Nichols
David E. Nichols is an American pharmacologist and medicinal chemist.Presently the Robert C. and Charlotte P. Anderson Distinguished Chair in Pharmacology at Purdue University, Nichols has worked in the field of psychoactive drugs since 1969...

 published the first report on the drug's psychotropic effect in humans. They described "altered state of consciousness with emotional and sensual overtones" that can be compared "to marijuana, and to psilocybin
Psilocybin
Psilocybin is a naturally occurring psychedelic prodrug, with mind-altering effects similar to those of LSD and mescaline, after it is converted to psilocin. The effects can include altered thinking processes, perceptual distortions, an altered sense of time, and spiritual experiences, as well as...

 devoid of the hallucinatory component".

Shulgin took to occasionally using MDMA for relaxation, referring to it as "my low-calorie martini", and giving the drug to his friends, researchers, and other people who he thought could benefit from it. One such person was psychotherapist Leo Zeff
Leo Zeff
Dr. Leo Zeff was an American psychologist and psychotherapist in Oakland, California who pioneered the use of ecstasy and other psychoactive drugs in psychotherapy in the 1970s....

, who had been known to use psychedelic
Psychedelic drug
A psychedelic substance is a psychoactive drug whose primary action is to alter cognition and perception. Psychedelics are part of a wider class of psychoactive drugs known as hallucinogens, a class that also includes related substances such as dissociatives and deliriants...

s in his practice. Zeff was so impressed with the effects of MDMA that he came out of his semi-retirement to proselytize for it. Over the following years, Zeff traveled around the U.S. and occasionally to Europe, training other psychotherapists in the use of MDMA. Among underground psychotherapists, MDMA developed a reputation for enhancing communication during clinical sessions, reducing patients' psychological defenses, and increasing capacity for therapeutic introspection
Introspection
Introspection is the self-observation and reporting of conscious inner thoughts, desires and sensations. It is a conscious and purposive process relying on thinking, reasoning, and examining one's own thoughts, feelings, and, in more spiritual cases, one's soul...

.

In the early 1980s in the U.S., MDMA rose to prominence as "Adam" in trendy nightclubs and gay dance clubs in the Dallas area. From there, use spread to rave
Rave
Rave, rave dance, and rave party are parties that originated mostly from acid house parties, which featured fast-paced electronic music and light shows. At these parties people dance and socialize to dance music played by disc jockeys and occasionally live performers...

s in major cities around the country, and then to mainstream society. The drug was first proposed for scheduling
Controlled Substances Act
The Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...

 by the Drug Enforcement Administration
Drug Enforcement Administration
The Drug Enforcement Administration is a federal law enforcement agency under the United States Department of Justice, tasked with combating drug smuggling and use within the United States...

 (DEA) in July 1984 and was classified as a Schedule I controlled substance in the U.S. on 31 May 1985.

In the late 1980s MDMA, known by that time as "ecstasy", began to be widely used in the UK and other parts of Europe, becoming an integral element of rave culture and other psychedelic-influenced music scenes. Spreading along with rave culture, illicit MDMA use became increasingly widespread among young adults in universities and later in high schools. MDMA became one of the four most widely used illicit drugs in the U.S., along with cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...

, heroin, and cannabis
Cannabis (drug)
Cannabis, also known as marijuana among many other names, refers to any number of preparations of the Cannabis plant intended for use as a psychoactive drug or for medicinal purposes. The English term marijuana comes from the Mexican Spanish word marihuana...

.
According to some estimates as of 2004, only marijuana attracts more first time users in the U.S.

After MDMA was criminalized, most medical use stopped, although some therapists continued to prescribe the drug illegally. Later Charles Grob initiated an ascending-dose safety study in healthy volunteers. Subsequent legally-approved MDMA studies in humans have taken place in the U.S. in Detroit (Wayne State University
Wayne State University
Wayne State University is a public research university located in Detroit, Michigan, United States, in the city's Midtown Cultural Center Historic District. Founded in 1868, WSU consists of 13 schools and colleges offering more than 400 major subject areas to over 32,000 graduate and...

), Chicago (University of Chicago
University of Chicago
The University of Chicago is a private research university in Chicago, Illinois, USA. It was founded by the American Baptist Education Society with a donation from oil magnate and philanthropist John D. Rockefeller and incorporated in 1890...

), San Francisco (UCSF and California Pacific Medical Center
California Pacific Medical Center
California Pacific Medical Center is one of the largest private, non-profit, academic medical centers in Northern California. The Medical Center is a combination of four of San Francisco's oldest medical institutions: Pacific Presbyterian Hospital, Children's Hospital of San Francisco, Davies...

), Baltimore
Baltimore
Baltimore is the largest independent city in the United States and the largest city and cultural center of the US state of Maryland. The city is located in central Maryland along the tidal portion of the Patapsco River, an arm of the Chesapeake Bay. Baltimore is sometimes referred to as Baltimore...

 (NIDA
National Institute on Drug Abuse
The National Institute on Drug Abuse is a United States federal-government research institute whose mission is to "lead the Nation in bringing the power of science to bear on drug abuse and addiction."-History:...

–NIH Intramural Program), and South Carolina
South Carolina
South Carolina is a state in the Deep South of the United States that borders Georgia to the south, North Carolina to the north, and the Atlantic Ocean to the east. Originally part of the Province of Carolina, the Province of South Carolina was one of the 13 colonies that declared independence...

, as well as in Switzerland (University Hospital of Psychiatry, Zürich
Zürich
Zurich is the largest city in Switzerland and the capital of the canton of Zurich. It is located in central Switzerland at the northwestern tip of Lake Zurich...

), the Netherlands (Maastricht University), and Spain (Universitat Autònoma de Barcelona).

In 2010, the BBC reported that use of MDMA had decreased in the UK in previous years. This is thought to be due to increased seizures and decreased production of the precursor chemicals used to manufacture MDMA. The availability of legal alternatives to MDMA such as mephedrone, or methylone, is also thought to have contributed to its decrease in popularity.

Legal status


MDMA is legally controlled in most of the world under the UN Convention on Psychotropic Substances
Convention on Psychotropic Substances
The Convention on Psychotropic Substances of 1971 is a United Nations treaty designed to control psychoactive drugs such as amphetamines, barbiturates, benzodiazepines, and psychedelics signed at Vienna on February 21, 1971...

 and other international agreements, although exceptions exist for research. In general, the unlicensed use, sale or manufacture of MDMA are all criminal offenses.

United Kingdom


MDMA was made illegal in 1977 by a modification order to the existing Misuse of Drugs Act 1971
Misuse of Drugs Act 1971
The Misuse of Drugs Act 1971 is an Act of Parliament which represents UK action in line with treaty commitments under the Single Convention on Narcotic Drugs, the Convention on Psychotropic Substances, and the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic...

. Although MDMA was not named explicitly in this legislation, the order extended the definition of Class A drugs to include various ring-substituted phenethylamines, thereby making it illegal to sell, buy, or possess the drug without a license. Penalties include a maximum of seven years and/or unlimited fine for possession; life and/or unlimited fine for production or trafficking. See list of drugs illegal in the UK for more information. In February 2009 an official independent scientific advisory board to the UK government recommended that MDMA be re-classified to Class B, but this recommendation was immediately rejected by the government (see Recommendation to downgrade MDMA). This 2009 report on MDMA stated:
In 2000, the UK Police Foundation issued the Runciman Report
Runciman Report
The Runciman Report was a 2000 Police Foundation inquiry into the United Kingdom's Misuse of Drugs Act 1971 authored by Viscountess Runciman.-Recommendations:...

, which reviewed the medical and social harms of MDMA and recommended: "Ecstasy and related compounds should be transferred from Class A to Class B." In 2002, the Home Affairs Committee of the UK House of Commons, issued a report, The Government's Drugs Policy: Is it working?, which also recommended that MDMA should be reclassified to a Class B drug. The UK government rejected both recommendations, saying that re-classification of MDMA would not be considered without a recommendation from the Advisory Council on the Misuse of Drugs, the official UK scientific advisory board on drug abuse issues.
MDMA (3,4-Methylenedioxymethamphetamine) is an entactogenic drug of the phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...

 and amphetamine
Substituted amphetamine
Substituted amphetamines are a chemical class of stimulants, entactogens, hallucinogens, and other drugs. They feature a phenethylamine core with a methyl group attached to the alpha carbon resulting in amphetamine, along with additional substitutions...

 class of drugs
Chemical classification
Chemical classification systems attempt to classify as elements or compounds according to certain chemical functional or structural properties. Whereas the structural properties are largely intrinsic, functional properties and the derived classifications depend to a certain degree on the type of...

. In popular culture, MDMA has become widely known as "ecstasy" ("E", "X" or "XTC"), usually referring to its street pill form, although this term may also include the presence of possible adulterants. The terms "molly" or "mandy" can colloquially refer to MDMA in crystalline or powder form.

MDMA can induce euphoria
Euphoria
Euphoria is an emotional and mental state defined as a sense of great elation and well being.Euphoria may also refer to:* Euphoria , a genus of scarab beetles* Euphoria, a genus name previously used for the longan and other trees...

, a sense of intimacy with others, and diminished anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

. Many studies, particularly in the fields of psychology
Psychology
Psychology is the study of the mind and behavior. Its immediate goal is to understand individuals and groups by both establishing general principles and researching specific cases. For many, the ultimate goal of psychology is to benefit society...

 and cognitive therapy
Cognitive therapy
Cognitive behavioral therapy is a psychotherapeutic approach: a talking therapy. CBT aims to solve problems concerning dysfunctional emotions, behaviors and cognitions through a goal-oriented, systematic procedure in the present...

, have suggested that MDMA has therapeutic benefits and facilitates therapy sessions in certain individuals, a practice for which it had formally been used in the past. Clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...

s are now testing the therapeutic potential of MDMA for post-traumatic stress disorder
Post-traumatic stress disorder
Posttraumaticstress disorder is a severe anxiety disorder that can develop after exposure to any event that results in psychological trauma. This event may involve the threat of death to oneself or to someone else, or to one's own or someone else's physical, sexual, or psychological integrity,...

 (PTSD) and anxiety associated with terminal cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

.Ecstasy to be tested on terminal cancer patients, Associated Press, 12/28/2004

MDMA is criminalized
Criminalization
Criminalization or criminalisation, in criminology, is "the process by which behaviors and individuals are transformed into crime and criminals". Previously legal acts may be transformed into crimes by legislation or judicial decision...

 in most countries under a United Nations
United Nations
The United Nations is an international organization whose stated aims are facilitating cooperation in international law, international security, economic development, social progress, human rights, and achievement of world peace...

 (UN) agreement,"Where is Ecstasy Legal?". Ecstasy.org. Retrieved on 2011-06-11. and its possession
Drug possession
Drug possession is the crime of having one or more illegal drugs in one's possession, either for personal use, distribution, sale or otherwise. Illegal drugs fall into different categories and sentences vary depending on the amount, type of drug, circumstances, and jurisdiction.A person has...

, manufacture
Clandestine chemistry
Clandestine chemistry is chemistry carried out in secret, and particularly in illegal drug laboratories. Larger labs are usually run by gangs or organized crime intending to produce for distribution on the black market...

, or sale
Illegal drug trade
The illegal drug trade is a global black market, dedicated to cultivation, manufacture, distribution and sale of those substances which are subject to drug prohibition laws. Most jurisdictions prohibit trade, except under license, of many types of drugs by drug prohibition laws.A UN report said the...

 may result in criminal prosecution, although some limited exceptions exist for scientific and medical research. MDMA is one of the most widely used recreational drugs
Recreational drug use
Recreational drug use is the use of a drug, usually psychoactive, with the intention of creating or enhancing recreational experience. Such use is controversial, however, often being considered to be also drug abuse, and it is often illegal...

 in the world and is taken in a variety of contexts far removed from its roots in psychotherapeutic settings. It is commonly associated with dance parties (or "raves") and electronic dance music
Electronic dance music
Electronic dance music is electronic music produced primarily for the purposes of use within a nightclub setting, or in an environment that is centered upon dance-based entertainment...

.

Regulatory authorities in several locations around the world have approved scientific studies administering MDMA to humans to examine its therapeutic potential and its effects.Psychedelic Research Worldwide. MAPS. Retrieved on 2011-06-11.

Medical uses


There have long been suggestions that MDMA might be useful in psychotherapy
Psychotherapy
Psychotherapy is a general term referring to any form of therapeutic interaction or treatment contracted between a trained professional and a client or patient; family, couple or group...

, facilitating self-examination with reduced fear.Greer G. Tolbert R. "The Therapeutic Use of MDMA in Ecstasy: The Clinical, Pharmacological, and Neurotoxicological Effects of the Drug MDMA." 1990 (ed Peroutka, SJ) Boston, p. 21-36. (PDF) . Retrieved on 2011-06-11. Indeed, some therapists, including Leo Zeff
Leo Zeff
Dr. Leo Zeff was an American psychologist and psychotherapist in Oakland, California who pioneered the use of ecstasy and other psychoactive drugs in psychotherapy in the 1970s....

, Claudio Naranjo
Claudio Naranjo
Claudio Naranjo is a Chilean psychiatrist who is considered a pioneer in integrating psychotherapy and the spiritual traditions. He is one of the three successors named by Fritz Perls , and a developer of the Enneagram of Personality and founder of the Seekers After Truth Institute...

, George Greer, Joseph Downing, and Philip Wolfson, used MDMA in their practices until it was made illegal. George Greer synthesized MDMA in the lab of Alexander Shulgin and administered it to about 80 of his clients over the course of the remaining years preceding MDMA's Schedule I placement in 1985. In a published summary of the effects, the authors reported patient
Patient
A patient is any recipient of healthcare services. The patient is most often ill or injured and in need of treatment by a physician, advanced practice registered nurse, veterinarian, or other health care provider....

s felt improved in various, mild psychiatric disorders and experienced other personal benefits, especially improved intimate communication with their significant others. In a subsequent publication on the treatment method, the authors reported that one patient with severe pain from terminal
Terminal illness
Terminal illness is a medical term popularized in the 20th century to describe a disease that cannot be cured or adequately treated and that is reasonably expected to result in the death of the patient within a short period of time. This term is more commonly used for progressive diseases such as...

 cancer experienced lasting pain relief
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....

 and improved quality of life
Quality of life
The term quality of life is used to evaluate the general well-being of individuals and societies. The term is used in a wide range of contexts, including the fields of international development, healthcare, and politics. Quality of life should not be confused with the concept of standard of...

.

Three neurobiological mechanisms for the therapeutic effects of MDMA have been suggested: "1) MDMA increases oxytocin levels, which may strengthen the therapeutic alliance; 2) MDMA increases ventromedial prefrontal activity and decreases amygdala activity, which may improve emotional regulation and decrease avoidance, and 3) MDMA increases norepinephrine release and circulating cortisol levels, which may facilitate emotional engagement and enhance extinction of learned fear associations."

The first phase-II double-blind randomized controlled clinical trial into the potential therapeutic benefits of using the drug as an augment to psychotherapy showed that most patients in the trial given psychotherapy treatment along with doses of MDMA experienced statistically significant reductions in the severity of their condition after two months, compared with a control group receiving psychotherapy and a placebo. The authors concludes "MDMA-assisted psychotherapy can be administered to posttraumatic stress disorder patients without evidence of harm, and it may be useful in patients refractory to other treatments."

The possible therapeutic potential of MDMA is being tested in several ongoing studies, some sponsored by the Multidisciplinary Association for Psychedelic Studies
Multidisciplinary Association for Psychedelic Studies
The Multidisciplinary Association for Psychedelic Studies is a membership-based 501 non-profit research and educational organization working to develop psychedelics and marijuana into legal prescription drugs...

 (MAPS). Studies in the U.S., Switzerland, and Israel are evaluating the efficacy of MDMA-assisted psychotherapy for treating those diagnosed with post-traumatic stress disorder
Post-traumatic stress disorder
Posttraumaticstress disorder is a severe anxiety disorder that can develop after exposure to any event that results in psychological trauma. This event may involve the threat of death to oneself or to someone else, or to one's own or someone else's physical, sexual, or psychological integrity,...

 (PTSD) or anxiety related to cancer.

Small doses of MDMA are used as an entheogen to enhance meditation by some Buddhist Monks.MDMA and Religion. CSP. Retrieved on 2011-06-11.

Recreational use


The European Monitoring Centre for Drugs and Drug Addiction
European Monitoring Centre for Drugs and Drug Addiction
The European Monitoring Centre for Drugs and Drug Addiction is an agency of the European Union. Established in 1993, the EMCDDA is located in Lisbon, Portugal.-Mission and role:...

 notes that, although there are some reports of tablets being sold for as little as €1, most countries in Europe now report typical retail prices in the range of €3 to €9 per tablet. The United Nations Office on Drugs and Crime
United Nations Office on Drugs and Crime
The United Nations Office on Drugs and Crime is a United Nations agency that was established in 1997 as the Office for Drug Control and Crime Prevention by combining the United Nations International Drug Control Program and the Crime Prevention and Criminal Justice Division in the United Nations...

 claimed in its 2008 World Drug Report that typical U.S. retail prices are lower, costing $10 to $15 per tablet, or from $4 to $6 per tablet if bought in batches. MDMA is expensive in Australia, costing A$
Australian dollar
The Australian dollar is the currency of the Commonwealth of Australia, including Christmas Island, Cocos Islands, and Norfolk Island, as well as the independent Pacific Island states of Kiribati, Nauru and Tuvalu...

20–A$50 per tablet, but in the Asian community it is A$20–30, depending on the size. In terms of purity data for Australian MDMA, the average is around 34%, ranging from less than 1% to about 85%. The majority of tablets contain 70–85 mg of MDMA. Most MDMA enters Australia from different markets, the Netherlands, the UK, Asia, and the U.S.Drugtext – 10 years of ecstasy and other party drug use in Australia: What have we done and what is there left to do?. Drugtext.org. Retrieved on 2011-06-11.

Polysubstance use



MDMA is occasionally known for being taken in conjunction with psychedelic drugs, such as LSD
LSD
Lysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed and open eye visuals, synaesthesia, an...

 or psilocybin mushrooms, or even common drugs such as cannabis
Cannabis (drug)
Cannabis, also known as marijuana among many other names, refers to any number of preparations of the Cannabis plant intended for use as a psychoactive drug or for medicinal purposes. The English term marijuana comes from the Mexican Spanish word marihuana...

. As this practice has become more prevalent, most of the more common combinations have been given nicknames, such as "candy flipping", for MDMA combined with LSD
LSD
Lysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed and open eye visuals, synaesthesia, an...

, "hippy flipping", for MDMA with psilocybin
Psilocybin
Psilocybin is a naturally occurring psychedelic prodrug, with mind-altering effects similar to those of LSD and mescaline, after it is converted to psilocin. The effects can include altered thinking processes, perceptual distortions, an altered sense of time, and spiritual experiences, as well as...

, or "kitty flipping" for MDMA with Ketamine
Ketamine
Ketamine is a drug used in human and veterinary medicine. Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist...

. Many users use mentholated products while taking MDMA for its cooling sensation while experiencing the drug's effects. Examples include menthol cigarette
Cigarette
A cigarette is a small roll of finely cut tobacco leaves wrapped in a cylinder of thin paper for smoking. The cigarette is ignited at one end and allowed to smoulder; its smoke is inhaled from the other end, which is held in or to the mouth and in some cases a cigarette holder may be used as well...

s, Vick's Vapo Rub, NyQuil
NyQuil
NyQuil is a brand of over the counter medication which is intended to relieve various symptoms of the common cold. Because all of the medications within the NyQuil imprint contain sedating antihistamines, hypnotics, and/or alcohol, they are intended to be taken before sleep...

, and lozenges
Throat lozenge
A throat lozenge, cough drop, troche, or cough sweet is a small, medicated tablet intended to be dissolved slowly in the mouth to temporarily stop coughs and lubricate and soothe irritated tissues of the throat , possibly from the common cold or influenza...

.

Subjective effects


The primary effects attributable to MDMA consumption are predictable and fairly consistent among users. In general, users report feeling effects within 30–60 minutes of consumption, hitting a peak at approximately 1–1.5 hours, reaching a plateau that lasts about 2–3 hours, followed by a comedown
Comedown (drugs)
Comedown refers to the after effects of heavy recreational stimulant use, usually ecstasy, amphetamine, methylphenidate, cocaine, alcohol, and occasionally cannabis. It can be characterized by depression, apathy, dysphoria, anxiety, fatigue, intense hunger, paranoia and insomnia. These effects are...

 of a few hours, which may be accompanied by fatigue and minor effects.

The most common effect
Therapeutic effect
A therapeutic effect is a consequence of a medical treatment of any kind, the results of which are judged to be desirable and beneficial. This is true whether the result was expected, unexpected, or even an unintended consequence of the treatment...

s reported by users include:
  • A general and subjective alteration in consciousness
    Altered state of consciousness
    An altered state of consciousness , also named altered state of mind, is any condition which is significantly different from a normal waking beta wave state. The expression was used as early as 1966 by Arnold M. Ludwig and brought into common usage from 1969 by Charles Tart: it describes induced...

  • A strong sense of inner peace
    Inner peace
    Inner peace refers to a state of being mentally and spiritually at peace, with enough knowledge and understanding to keep oneself strong in the face of discord or stress. Being "at peace" is considered by many to be healthy and the opposite of being stressed or anxious...

     and self-acceptance
    Self-acceptance
    Self-acceptance is defined as affirmation or acceptance of self in spite of weaknesses or deficiencies.Although this term has been often understood in a common sense way, researchers have defined it formally in terms of positive and negative self-concepts...

  • Diminished aggression
    Aggression
    In psychology, as well as other social and behavioral sciences, aggression refers to behavior between members of the same species that is intended to cause humiliation, pain, or harm. Ferguson and Beaver defined aggressive behavior as "Behavior which is intended to increase the social dominance of...

    , hostility
    Hostility
    Hostility is a form of angry internal rejection or denial in psychology. It is a part of personal construct psychology, developed by George Kelly...

    , and jealousy
    Jealousy
    Jealousy is a second emotion and typically refers to the negative thoughts and feelings of insecurity, fear, and anxiety over an anticipated loss of something that the person values, particularly in reference to a human connection. Jealousy often consists of a combination of presenting emotions...

  • Diminished fear
    Fear
    Fear is a distressing negative sensation induced by a perceived threat. It is a basic survival mechanism occurring in response to a specific stimulus, such as pain or the threat of danger...

    , anxiety
    Anxiety
    Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

    , and insecurity
  • Extreme mood
    Mood (psychology)
    A mood is a relatively long lasting emotional state. Moods differ from emotions in that they are less specific, less intense, and less likely to be triggered by a particular stimulus or event....

     lift with accompanying euphoria
    Euphoria
    Euphoria is an emotional and mental state defined as a sense of great elation and well being.Euphoria may also refer to:* Euphoria , a genus of scarab beetles* Euphoria, a genus name previously used for the longan and other trees...

  • Feelings of empathy
    Empathy
    Empathy is the capacity to recognize and, to some extent, share feelings that are being experienced by another sapient or semi-sapient being. Someone may need to have a certain amount of empathy before they are able to feel compassion. The English word was coined in 1909 by E.B...

    , compassion
    Compassion
    Compassion is a virtue — one in which the emotional capacities of empathy and sympathy are regarded as a part of love itself, and a cornerstone of greater social interconnection and humanism — foundational to the highest principles in philosophy, society, and personhood.There is an aspect of...

    , and forgiveness
    Forgiveness
    Forgiveness is typically defined as the process of concluding resentment, indignation or anger as a result of a perceived offense, difference or mistake, or ceasing to demand punishment or restitution. The Oxford English Dictionary defines forgiveness as 'to grant free pardon and to give up all...

     toward others
  • Feelings of intimacy and even love
    Love
    Love is an emotion of strong affection and personal attachment. In philosophical context, love is a virtue representing all of human kindness, compassion, and affection. Love is central to many religions, as in the Christian phrase, "God is love" or Agape in the Canonical gospels...

     for others
  • Improved self-confidence
    Self-confidence
    The socio-psychological concept of self-confidence relates to self-assuredness in one's personal judgment, ability, power, etc., sometimes manifested excessively.Being confident in yourself is infectious if you present yourself well, others will want to follow in your foot steps towards...

  • The ability to discuss normally anxiety
    Anxiety
    Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

    -provoking topics with marked ease
  • An intensification of all of the bodily senses (hearing, touch, smell, vision, taste)
  • Substantial enhancement of the appreciation of music quality
  • Mild psychedelia, consisting of mental imagery and auditory
    Hearing (sense)
    Hearing is the ability to perceive sound by detecting vibrations through an organ such as the ear. It is one of the traditional five senses...

     and visual distortion
    Distortion
    A distortion is the alteration of the original shape of an object, image, sound, waveform or other form of information or representation. Distortion is usually unwanted, and often many methods are employed to minimize it in practice...

    s
  • Stimulation
    Stimulation
    Stimulation is the action of various agents on nerves, muscles, or a sensory end organ, by which activity is evoked; especially, the nervous impulse produced by various agents on nerves, or a sensory end organ, by which the part connected with the nerve is thrown into a state of activity.The word...

    , arousal
    Arousal
    Arousal is a physiological and psychological state of being awake or reactive to stimuli. It involves the activation of the reticular activating system in the brain stem, the autonomic nervous system and the endocrine system, leading to increased heart rate and blood pressure and a condition of...

    , and hyperactivity (e.g., many users get an "uncontrollable urge to dance" while under the influence)
  • Increased energy
    Energy (psychological)
    Mental or psychic energy or activity is the concept of a principle of activity powering the operation of the mind or psyche. Many modern psychologists or neuroscientists would equate it with increased metabolism in neurons of the brain....

     and endurance
    Endurance
    Endurance is the ability for a human or animal to exert itself and remain active for a long period of time, as well as its ability to resist, withstand, recover from, and have immunity to trauma, wounds, or fatigue. In humans, it is usually used in aerobic or anaerobic exercise...

  • Increased alertness
    Alertness
    Alertness is the state of paying close and continuous attention, being watchful and prompt to meet danger or emergency, or being quick to perceive and act. It is related to psychology as well as to physiology...

    , awareness
    Awareness
    Awareness is the state or ability to perceive, to feel, or to be conscious of events, objects or sensory patterns. In this level of consciousness, sense data can be confirmed by an observer without necessarily implying understanding. More broadly, it is the state or quality of being aware of...

    , and wakefulness
  • Increased desire
    Desire (emotion)
    Desire is a sense of longing for a person or object or hoping for an outcome. Desire is the fire that sets action aflame. The same sense is expressed by emotions such as "craving" or "hankering". When a person desires something or someone, their sense of longing is excited by the enjoyment or the...

    , drive
    Motivation
    Motivation is the driving force by which humans achieve their goals. Motivation is said to be intrinsic or extrinsic. The term is generally used for humans but it can also be used to describe the causes for animal behavior as well. This article refers to human motivation...

    , and motivation
    Motivation
    Motivation is the driving force by which humans achieve their goals. Motivation is said to be intrinsic or extrinsic. The term is generally used for humans but it can also be used to describe the causes for animal behavior as well. This article refers to human motivation...

  • Analgesia or decreased pain
    Pain
    Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...

     sensitivity
    Stimulus (physiology)
    In physiology, a stimulus is a detectable change in the internal or external environment. The ability of an organism or organ to respond to external stimuli is called sensitivity....


Adverse effects


In January 2001, an overview of the subjective side-effects of MDMA was published by Liechti, Gamma, and Vollenweider in the journal Psychopharmacology. Their paper was based on clinical research conducted over several years involving 74 healthy volunteers. The researchers found that there were a number of common side-effects and that many of the effects seemed to occur in different amounts based on gender. The top side-effects reported were difficulty concentrating, jaw clenching, grinding of the teeth
Bruxism
Bruxism is characterized by the grinding of the teeth and typically includes the clenching of the jaw. It is an oral parafunctional activity that occurs in most humans at some time in their lives. In most people, bruxism is mild enough not to be a health problem...

 during sleep, lack of appetite, and dry mouth/thirst (all occurring in more than 50% of the 74 volunteers). Liechti, et al. also measured some of the test subjects for blood pressure, heart rate, and body temperature against a placebo control but no statistically significant changes were seen.Erowid (September 2001). Short-Term Side Effects of MDMA.

A 2011 study carried out by Harvard Medical School and published in the journal Addiction found no signs of cognitive impairment due to ecstasy use, and that it did not decrease mental ability. The report also raised concerns that previous methods used to conduct that research on ecstasy had been flawed, and the experiments overstated the cognitive differences between ecstasy users and nonusers.Addiction (February 2011). "New study finds no cognitive impairment among ecstasy users".

After-effects


Effects reported by some users once the acute
Acute (medicine)
In medicine, an acute disease is a disease with either or both of:# a rapid onset, as in acute infection# a short course ....

 effects of MDMA have worn off include:
  • Psychological
    • Anxiety and paranoia
    • Depression
    • Irritability
    • Fatigue
    • Impaired attention, focus, and concentration, as well as drive and motivation (due to depleted serotonin levels)
    • Residual feelings of empathy, emotional sensitivity, and a sense of closeness to others (afterglow
      Afterglow (drug culture)
      When used with regard to recreational drug use, afterglow refers to positive physical and mental effects that linger after the main effects of a drug have subsided, or after the peak experience has subsided. This state is often characterized by feelings of detachment or increased psychological...

      )

  • Physiological
    • Dizziness, lightheadedness, or vertigo
    • Loss of appetite
    • Gastrointestinal disturbances, such as diarrhea or constipation
    • Insomnia
    • Aches and pains, usually from excessive physical activity (e.g., dancing)
    • Exhaustion
    • Jaw soreness, from trismus
      Trismus
      -Common causes:*Pericoronitis is the most common cause of trismus.*Inflammation of muscles of mastication. It is a frequent sequel to surgical removal of mandibular third molars . The condition is usually resolved on its own in 10–14 days, during which time eating and oral hygiene are compromised...

       or bruxism
      Bruxism
      Bruxism is characterized by the grinding of the teeth and typically includes the clenching of the jaw. It is an oral parafunctional activity that occurs in most humans at some time in their lives. In most people, bruxism is mild enough not to be a health problem...



A slang term given to the depressive period following MDMA consumption is Tuesday Blues (or "Suicide Tuesday"), referring to the low mood that can be experienced midweek by depleted serotonin levels following weekend MDMA use. Some users report that consuming 5-HTP, L-Tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...

, vitamin
Vitamin
A vitamin is an organic compound required as a nutrient in tiny amounts by an organism. In other words, an organic chemical compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on...

s, and/or magnesium
Magnesium in biology
Magnesium is an essential element in biological systems. Magnesium occurs typically as the Mg2+ ion. It is an essential mineral nutrient for life and is present in every cell type in every organism. For example, ATP , the main source of energy in cells, must be bound to a magnesium ion in order to...

 supplements the day after use can reduce the depressive effect by replenishing serotonin levelsMolly Flannagan, Ecstasy: Neurotoxicity and How It Can Be Reduced, 2001.

Overdose


Upon overdose, the potentially serious serotonin syndrome
Serotonin syndrome
Serotonin syndrome is a potentially life-threatening adverse drug reaction that may occur following therapeutic drug use, inadvertent interactions between drugs, overdose of particular drugs, or the recreational use of certain drugs...

, stimulant psychosis, and/or hypertensive crisis, among other dangerous adverse reaction
Adverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...

s, may come to prominence, the symptoms of which can include the following:
  • Psychological
    • Disorientation and/or confusion
      Mental confusion
      Confusion of a pathological degree usually refers to loss of orientation sometimes accompanied by disordered consciousness and often memory Confusion (from Latin confusĭo, -ōnis, noun of action from confundere "to pour together", also "to confuse") of a pathological degree usually refers to loss...

    • Anxiety
      Anxiety
      Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

      , paranoia
      Paranoia
      Paranoia [] is a thought process believed to be heavily influenced by anxiety or fear, often to the point of irrationality and delusion. Paranoid thinking typically includes persecutory beliefs, or beliefs of conspiracy concerning a perceived threat towards oneself...

      , and/or panic attack
      Panic attack
      Panic attacks are periods of intense fear or apprehension that are of sudden onset and of relatively brief duration. Panic attacks usually begin abruptly, reach a peak within 10 minutes, and subside over the next several hours...

      s
    • Hypervigilance
      Hypervigilance
      Hypervigilance is an enhanced state of sensory sensitivity accompanied by an exaggerated intensity of behaviors whose purpose is to detect threats. Hypervigilance is also accompanied by a state of increased anxiety which can cause exhaustion. Other symptoms include: abnormally increased arousal, a...

       or increased sensitivity to perceptual stimuli
      Stimulus (physiology)
      In physiology, a stimulus is a detectable change in the internal or external environment. The ability of an organism or organ to respond to external stimuli is called sensitivity....

      , accompanied by significantly increased threat
      Coercion
      Coercion is the practice of forcing another party to behave in an involuntary manner by use of threats or intimidation or some other form of pressure or force. In law, coercion is codified as the duress crime. Such actions are used as leverage, to force the victim to act in the desired way...

       detection
    • Hypomania
      Hypomania
      Hypomania is a mood state characterized by persistent and pervasive elevated or irritable mood, as well as thoughts and behaviors that are consistent with such a mood state...

       or full-blown mania
      Mania
      Mania, the presence of which is a criterion for certain psychiatric diagnoses, is a state of abnormally elevated or irritable mood, arousal, and/ or energy levels. In a sense, it is the opposite of depression...

    • Derealization
      Derealization
      Derealization is an alteration in the perception or experience of the external world so that it seems unreal. Other symptoms include feeling as though one's environment is lacking in spontaneity, emotional coloring and depth. It is a dissociative symptom of many conditions, such as psychiatric and...

       and/or depersonalization
      Depersonalization
      Depersonalization is an anomaly of the mechanism by which an individual has self-awareness. It is a feeling of watching oneself act, while having no control over a situation. Sufferers feel they have changed, and the world has become less real, vague, dreamlike, or lacking in significance...

    • Hallucination
      Hallucination
      A hallucination, in the broadest sense of the word, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid,...

      s and/or delusion
      Delusion
      A delusion is a false belief held with absolute conviction despite superior evidence. Unlike hallucinations, delusions are always pathological...

      s
    • Thought disorder
      Thought disorder
      In psychiatry, thought disorder or formal thought disorder is a term used to describe incomprehensible language, either speech or writing, that is presumed to reflect thinking. There are different types...

       or disorganized thinking
      Thought disorder
      In psychiatry, thought disorder or formal thought disorder is a term used to describe incomprehensible language, either speech or writing, that is presumed to reflect thinking. There are different types...

    • Cognitive and memory impairment
      Cognitive deficit
      Cognitive deficit, also known as cognitive impairment is an inclusive term to describe any characteristic that acts as a barrier to cognitive performance...

       potentially to the point of retrograde
      Retrograde amnesia
      Retrograde amnesia is a loss of access to events that occurred, or information that was learned, before an injury or the onset of a disease....

       or anterograde amnesia
      Anterograde amnesia
      Anterograde amnesia is a loss of the ability to create new memories after the event that caused the amnesia, leading to a partial or complete inability to recall the recent past, while long-term memories from before the event remain intact. This is in contrast to retrograde amnesia, where memories...

    • Acute delirium
      Delirium
      Delirium or acute confusional state is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attentional deficits and generalized severe disorganization of behavior...


  • Physiological
    • Myoclonus
      Myoclonus
      Myoclonus is brief, involuntary twitching of a muscle or a group of muscles. It describes a medical sign and, generally, is not a diagnosis of a disease. Brief twitches are perfectly normal. The myoclonic twitches are usually caused by sudden muscle contractions; they also can result from brief...

       or involuntary and intense muscle twitching
    • Nystagmus
      Nystagmus
      Nystagmus is a condition of involuntary eye movement, acquired in infancy or later in life, that may result in reduced or limited vision.There are two key forms of Nystagmus: pathological and physiological, with variations within each type. Nystagmus may be caused by congenital disorders,...

       or involuntary eye movements
    • Hyperreflexia
      Hyperreflexia
      Hyperreflexia is defined as overactive or overresponsive reflexes. Examples of this can include twitching or spastic tendencies, which are indicative of upper motor neuron disease as well as the lessening or loss of control ordinarily exerted by higher brain centers of lower neural pathways...

       or overresponsive or overreactive reflex
      Reflex
      A reflex action, also known as a reflex, is an involuntary and nearly instantaneous movement in response to a stimulus. A true reflex is a behavior which is mediated via the reflex arc; this does not apply to casual uses of the term 'reflex'.-See also:...

      es
    • Tachypnoea or rapid breathing
      Breathing
      Breathing is the process that moves air in and out of the lungs. Aerobic organisms require oxygen to release energy via respiration, in the form of the metabolism of energy-rich molecules such as glucose. Breathing is only one process that delivers oxygen to where it is needed in the body and...

       and/or dyspnea
      Dyspnea
      Dyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...

       or shortness of breath
    • Palpitation
      Palpitation
      A palpitation is an abnormality of heartbeat that causes a conscious awareness of its beating, whether it is too slow, too fast, irregular, or at its normal frequency. The word may also refer to this sensation itself...

      s or abnormal awareness of the beating of the heart
      Cardiac cycle
      The cardiac cycle is a term referring to all or any of the events related to the flow or blood pressure that occurs from the beginning of one heartbeat to the beginning of the next. The frequency of the cardiac cycle is described by the heart rate. Each beat of the heart involves five major stages...

    • Angina pectoris or severe chest pain
      Chest pain
      Chest pain may be a symptom of a number of serious conditions and is generally considered a medical emergency. Even though it may be determined that the pain is non-cardiac in origin, this is often a diagnosis of exclusion made after ruling out more serious causes of the pain.-Differential...

      , as well as pulmonary hypertension
      Pulmonary hypertension
      In medicine, pulmonary hypertension is an increase in blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion...

       (PH)
    • Cardiac arrhythmia or abnormal electrical activity
      Electrical conduction system of the heart
      The normal intrinsic electrical conduction of the heart allows electrical propagation to be transmitted from the Sinoatrial Node through both atria and forward to the Atrioventricular Node. Normal/baseline physiology allows further propagation from the AV node to the ventricle or Purkinje Fibers...

       of the heart
    • Circulatory shock or cardiogenic shock
      Cardiogenic shock
      Cardiogenic shock is based upon an inadequate circulation of blood due to primary failure of the ventricles of the heart to function effectively....

    • Vasculitis
      Vasculitis
      Vasculitis refers to a heterogeneous group of disorders that are characterized by inflammatory destruction of blood vessels. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis...

       or destruction
      Toxicity
      Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...

       of blood vessel
      Blood vessel
      The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...

      s
    • Cardiotoxicity
      Cardiotoxicity
      Cardiotoxicity is the occurrence of heart electrophysiology dysfunction or/and muscle damage. The heart becomes weaker and is not as efficient in pumping and therefore circulating blood...

       or damage to the heart
    • Cardiac dysfunction, arrest, myocardial infarction
      Myocardial infarction
      Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...

      , and/or heart failure
    • Hemorrhage and/or stroke
    • Severe hyperthermia
      Hyperthermia
      Hyperthermia is an elevated body temperature due to failed thermoregulation. Hyperthermia occurs when the body produces or absorbs more heat than it can dissipate...

      , potentially resulting in organ failure
      Organ failure
      Organ dysfunction is a condition where an organ does not perform its expected function. Organ failure is organ dysfunction to such a degree that normal homeostasis cannot be maintained without external clinical intervention.It is not a diagnosis...


  • Miscellaneous
    • Syncope
      Syncope (medicine)
      Syncope , the medical term for fainting, is precisely defined as a transient loss of consciousness and postural tone characterized by rapid onset, short duration, and spontaneous recovery due to global cerebral hypoperfusion that most often results from hypotension.Many forms of syncope are...

       or fainting or loss of consciousness
    • Organ failure
      Organ failure
      Organ dysfunction is a condition where an organ does not perform its expected function. Organ failure is organ dysfunction to such a degree that normal homeostasis cannot be maintained without external clinical intervention.It is not a diagnosis...

       (as mentioned above)
    • Possible brain damage
    • Coma or death

Chronic use


Some studies indicate that repeated recreational users of MDMA have increased rates of depression and anxiety, even after quitting the drug. A Meta-analytic review of the published literature on memory show that ecstasy users may suffer short-term and long-term verbal memory impairment—with 70–80% of ecstasy users displaying impaired memory, although the results of this study may have been confounded by concurrent cannabis use. Moreover, this research shows the amount of doses consumed does not significantly predict memory performance. Other meta analyses have reported possibility of impairment of executive functioning. Despite these findings many factors including total lifetime MDMA consumption, the duration of abstinence between uses, dosage, the environment of use, poly-drug use/abuse, quality of mental health
Mental health
Mental health describes either a level of cognitive or emotional well-being or an absence of a mental disorder. From perspectives of the discipline of positive psychology or holism mental health may include an individual's ability to enjoy life and procure a balance between life activities and...

, various lifestyle choices, and predispositions to develop clinical depression and other disorders have made the results of many studies difficult to verify. A study that attempted to eliminate these confounding factors was published in February, 2011 by Addiction, and found few differences in the cognitive functioning of MDMA-using ravers versus non-MDMA-using ravers, "In a study designed to minimize limitations found in many prior investigations, we failed to demonstrate marked residual cognitive effects in ecstasy users. This finding contrasts with many previous findings-including our own-and emphasizes the need for continued caution in interpreting field studies of cognitive function in illicit ecstasy users." MDMA use has been occasionally associated with liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 damage, excessive wear of teeth, and (very rarely) hallucinogen persisting perception disorder
Hallucinogen persisting perception disorder
Hallucinogen persisting perception disorder is a disorder characterized by a continual presence of visual disturbances that are reminiscent of those generated by the ingestion of hallucinogenic substances. Previous use of hallucinogens by the person is needed, though not sufficient, for...

.


Short-term health concerns


Short-term physical health risks of MDMA consumption include hyperthermia
Hyperthermia
Hyperthermia is an elevated body temperature due to failed thermoregulation. Hyperthermia occurs when the body produces or absorbs more heat than it can dissipate...

, and hyponatremia
Hyponatremia
Hyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal. In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodium and is not due to sodium deficiency. Sodium is the dominant extracellular...

. Continuous activity without sufficient rest or rehydration may cause body temperature to rise to dangerous levels, and loss of fluid via excessive perspiration puts the body at further risk as the stimulatory and euphoric qualities of the drug may render the user oblivious to their energy expenditure for quite some time. Diuretics such as alcohol may exacerbate these risks further.

Long-term effects on serotonin and dopamine


MDMA causes a reduction in the concentration of serotonin transporter
Serotonin transporter
The serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...

s (SERTs) in the brain. The rate at which the brain recovers from serotonergic changes is unclear. One study demonstrated lasting serotonergic changes in some animals exposed to MDMA. Other studies have suggested that the brain may recover from serotonergic damage.

Some studies show that MDMA may be neurotoxic
Neurotoxicity
Neurotoxicity occurs when the exposure to natural or artificial toxic substances, which are called neurotoxins, alters the normal activity of the nervous system in such a way as to cause damage to nervous tissue. This can eventually disrupt or even kill neurons, key cells that transmit and process...

 in humans.Neurotoxicity at Dancesafe.orgDoes MDMA Cause Brain Damage?, Matthew Baggott, and John Mendelson Other studies, however, suggest that any potential brain damage may be at least partially reversible following prolonged abstinence from MDMA.Research on Ecstasy Is Clouded by Errors, Donald G. McNeil Jr., New York Times, 2 December 2003. However, other studies suggest that SERT-depletion arises from long-term MDMA use due to receptor down-regulation, rather than true neurotoxicity."p-Chlorophenylalanine Changes Serotonin Transporter mRNA Levels and Expression of the Gene Product", Journal of Neurochemistry
Journal of Neurochemistry
The Journal of Neurochemistry is a peer-reviewed scientific journal established by the International Society for Neurochemistry in 1956. The journal covers a variety of subjects within the field of neuroscience, but focuses in particular on the "molecular and cellular aspects of the nervous system,...

, 1996. Online copy (pdf)

Depression and deficits in memory have been shown to occur more frequently in long-term MDMA users.Depression at DanceSafe.org However, some recent studies have suggested that MDMA use may not be associated with chronic depression.Study claims recreational ecstasy use and depression unrelated, Wikinews,
26 April 2006


One study on MDMA toxicity, by George A. Ricaurte
George A. Ricaurte
George A. Ricaurte is a controversial neurology researcher who works at the Johns Hopkins School of Medicine in the Department of Neurology. He received his MD from Northwestern University Medical School and his Ph.D. from the University of Chicago.His research focuses on Parkinson's disease and...

 of Johns Hopkins School of Medicine, which claimed that a single recreational dose of MDMA could cause Parkinson's Disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...

 in later life due to severe dopaminergic stress, was actually retracted by Ricaurte himself after he discovered his lab had administered not MDMA but methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...

, which is known to cause dopaminergic changes similar to the serotonergic changes caused by MDMA.Ecstasy Study Botched, Retracted, Kristen Philipkoski, Wired.com, 09.05.03 Ricaurte blamed this mistake on a labeling error by the chemical supply company that sold the material to his lab, but the supply company responded that there was no evidence of a labeling error on their end. Most studies have found that levels of the dopamine transporter
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 (or other markers of dopamine function) in MDMA users deserve further study or are normal.Aghajanian & Liebermann (2001) 'Caveat Emptor: Reseearchers Beware' Neuropsychopharmacology 24,3:335–6

Several studies have indicated a possible mechanism for neurotoxicity in a metabolite of MDMA, through the reaction of Alpha-Methyldopamine
Alpha-Methyldopamine
α-Methyldopamine , also known as 3,4-dihydroxyamphetamine , is a neurotoxin and research chemical of the phenethylamine and amphetamine chemical classes...

, a principal metabolite, and glutathione
Glutathione
Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...

, the major antioxidant in the human body. One possible product of this reaction, 2,5-bis-(glutathion-S-yl)-alpha-methyldopamine, has been demonstrated to produce the same toxic effects observed in MDMA, while MDMA, and alpha-methyldopamine themselves have been shown to be non-neurotoxic. It is, however, impossible to avoid the metabolism of MDMA in the body, and the production of this toxic metabolite. Some studies have demonstrated possible ways to minimize the production of this particular metabolite, though evidence at this point is sparse at best.

Purity and dosage of "ecstasy"



Another concern associated with MDMA use is toxicity from chemicals other than MDMA in ecstasy tablets. Due to its near-universal illegality, the purity of a substance sold as ecstasy is unknown to the typical user. The MDMA content of tablets varies widely between regions and different brands of pills and fluctuates somewhat each year. Pills may contain other active substances meant to stimulate in a way similar to MDMA, such as amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...

, methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...

, ephedrine
Ephedrine
Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....

, caffeine
Caffeine
Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...

, all of which may be comparatively cheap to produce and can help to boost overall profits. In some cases, tablets sold as ecstasy do not even contain any MDMA. Instead they may contain an assortment of undesirable drugs and substances, such as paracetamol
Paracetamol
Paracetamol INN , or acetaminophen USAN , is a widely used over-the-counter analgesic and antipyretic . It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies...

, ibuprofen
Ibuprofen
Ibuprofen is a nonsteroidal anti-inflammatory drug used for relief of symptoms of arthritis, fever, as an analgesic , especially where there is an inflammatory component, and dysmenorrhea....

, talcum powder, etc.http://ecstasydata.org/datastats.php?row=Summary&percent=1

There have been a number of deaths attributed to para-Methoxyamphetamine (PMA), a potent and highly neurotoxic hallucinogenic amphetamine, being sold as ecstasy. PMA is unique in its ability to quickly elevate body temperature and heart rate at relatively low doses, especially in comparison to MDMA. Hence, a user believing he is consuming two 120 mg pills of MDMA could actually be consuming a dose of PMA that is potentially lethal, depending on the purity of the pill. Not only does PMA cause the release of serotonin but it also acts as a monoamine oxidase inhibitor, MAOI
Monoamine oxidase inhibitor
Monoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....

. When combined with an MDMA or an MDMA-like substance, serotonin syndrome
Serotonin syndrome
Serotonin syndrome is a potentially life-threatening adverse drug reaction that may occur following therapeutic drug use, inadvertent interactions between drugs, overdose of particular drugs, or the recreational use of certain drugs...

 can result.J Pharm Pharmacol. 1980 Apr;32(4):262-6. Combining MAO inhibitors with certain legal prescription and over the counter medications can also lead to (potentially fatal) serotonin syndrome.

Harm assessment


The UK study placed great weight on the risk for acute physical harm, the propensity for physical and psychological dependency on the drug, and the negative familial and societal impacts of the drug. They did not evaluate or rate the negative impact of ecstasy on the cognitive health of ecstasy users, e.g., impaired memory and concentration. Based on these factors, the study placed MDMA at number 18 in the list of 20 popular drugs.Scientists want new drug rankings, BBC News, 23 March 2007

David Nutt
David Nutt
David John Nutt is a British psychiatrist and neuropsychopharmacologist specialising in the research of drugs that affect the brain and conditions such as addiction, anxiety and sleep. He was until 2009 a professor at the University of Bristol heading their Psychopharmacology Unit...

, a former chairman of the UK Advisory Council on the Misuse of Drugs
Advisory Council on the Misuse of Drugs
The Advisory Council on the Misuse of Drugs is a statutory and non-executive non-departmental British public body, which was established under the UK's Misuse of Drugs Act 1971.-Mandate:Its terms of reference, according to the Act, are as follows:...

, stated in the Journal of Psychopharmacology in January 2009 that ecstasy use compared favorably with horse riding in terms of risk, with ecstasy leading to around 30 deaths a year in the UK compared to about 10 from horse riding, and "acute harm to person" occurring in approximately 1 in 10,000 episodes of ecstasy use compared to about 1 in 350 episodes of horse riding. Dr. Nutt notes the lack of a balanced risk assessment in public discussions of MDMA:

The general public, especially the younger generation, are disillusioned with the lack of balanced political debate about drugs. This lack of rational debate can undermine the trust in government in relation to drug misuse and thereby undermining the government's message in public information campaigns. The media in general seem to have an interest in scare stories about illicit drugs, though there are some exceptions (Horizon, 2008). A telling review of 10-year media reporting of drug deaths in Scotland illustrates the distorted media perspective very well (Forsyth, 2001). During this decade, the likelihood of a newspaper reporting a death from paracetamol was in per 250 deaths, for diazepam it was 1 in 50, whereas for amphetamine it was 1 in 3 and for ecstasy every associated death was reported.

A spokesperson for the ACMD said that "The recent article by Professor David Nutt published in the Journal of Psychopharmacology was done in respect of his academic work and not as chair of the ACMD."Ecstasy 'not worse than riding', BBC News, 7 February 2009

The most carefully designed study so far was published in February 2011Halpern et. al, Addiction, 2011 in the journal Addiction, comparing the effect on cognitive skills in 52 ecstasy users against 59 very closely matched non-users. The study, performed by the group of Prof. Halpern of Harvard Medical School, eliminated potential confounding factors like the use of other drugs and history of drug-use. The study found no short- or long-term differences in cognitive skills in the test group (users) versus the control group (non-users).

Drug interactions


There are a number of reported potentially dangerous possible interactions between MDMA and other drugs, including serotonergic
Serotonergic
Serotonergic or serotoninergic means "related to the neurotransmitter serotonin". A synapse is serotonergic if it uses serotonin as its neurotransmitter...

 drugs.http://www.ncbi.nlm.nih.gov/pubmed/17620161 Qualitative review of serotonin syndrome, ecstasy (MDMA) and the use of other serotonergic substances: hierarchy of risk (by Silins E, Copeland J, Dillon P.)] Several cases have been reported of death in individuals who ingested MDMA while taking ritonavir
Ritonavir
Ritonavir, with trade name Norvir , is an antiretroviral drug from the protease inhibitor class used to treat HIV infection and AIDS....

 (Norvir), which inhibits multiple CYP450 enzymes. Toxicity or death has also been reported in people who took MDMA in combination with certain monoamine oxidase inhibitor
Monoamine oxidase inhibitor
Monoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....

s (MAOIs) such as phenelzine
Phenelzine
Phenelzine is a non-selective and irreversible monoamine oxidase inhibitor of the hydrazine class which is used as an antidepressant and anxiolytic...

 (Nardil), tranylcypromine
Tranylcypromine
Tranylcypromine is a drug of the substituted phenethylamine and amphetamine classes which acts as a monoamine oxidase inhibitor —it is a non-selective and irreversible inhibitor of the enzyme monoamine oxidase...

 (Parnate), or moclobemide
Moclobemide
Moclobemide is a monoamine oxidase inhibitor drug primarily used to treat depression and social anxiety. Although clinical trials with the medicine began in 1977, it is not approved for use in the United States...

 (Aurorix, Manerix). On the other hand, MAOB
Monoamine oxidase B
Monoamine oxidase B, also known as MAOB, is a protein that in humans is encoded by the MAOB gene.The protein encoded by this gene belongs to the flavin monoamine oxidase family. It is an enzyme located in the mitochondrial outer membrane...

 inhibitors like selegiline
Selegiline
Selegiline is a drug used for the treatment of early-stage Parkinson's disease, depression and senile dementia. In normal clinical doses it is a selective irreversible MAO-B inhibitor, however in larger doses it loses its specificity and also inhibits MAO-A...

 (Deprenyl; Eldepryl, Zelapar, Emsam) do not seem to carry these risks when taken at selective doses, and have been used to completely block neurotoxicity in rats.The Prozac Misunderstanding, at TheDEA.org

Commercial sassafras oil generally is a by-product of camphor
Camphor
Camphor is a waxy, white or transparent solid with a strong, aromatic odor. It is a terpenoid with the chemical formula C10H16O. It is found in wood of the camphor laurel , a large evergreen tree found in Asia and also of Dryobalanops aromatica, a giant of the Bornean forests...

 production in Asia
Asia
Asia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...

 or comes from related trees in Brazil
Brazil
Brazil , officially the Federative Republic of Brazil , is the largest country in South America. It is the world's fifth largest country, both by geographical area and by population with over 192 million people...

. Safrole is a precursor for the clandestine manufacture
Clandestine chemistry
Clandestine chemistry is chemistry carried out in secret, and particularly in illegal drug laboratories. Larger labs are usually run by gangs or organized crime intending to produce for distribution on the black market...

 of MDMA
Methylenedioxymethamphetamine
MDMA is an entactogenic drug of the phenethylamine and amphetamine class of drugs. In popular culture, MDMA has become widely known as "ecstasy" , usually referring to its street pill form, although this term may also include the presence of possible adulterants...

 (ecstasy), and as such, its transport is monitored internationally.
Roots of Sassafras can also be steeped to make tea and were used in the flavoring of traditional root beer
Root beer
Root beer is a carbonated, sweetened beverage, originally made using the root of a sassafras plant as the primary flavor. Root beer, popularized in North America, comes in two forms: alcoholic and soft drink. The historical root beer was analogous to small beer in that the process provided a drink...

 until being banned for mass production by the FDA. Laboratory animals that were given oral doses of sassafras tea or sassafras oil that contained large doses of safrole developed permanent liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 damage or various types of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

. In humans liver damage can take years to develop and it may not have obvious signs.

Chemistry


Safrole
Safrole
Safrole, also known as shikimol, is a phenylpropene. It is a colorless or slightly yellow oily liquid. It is typically extracted from the root-bark or the fruit of sassafras plants in the form of sassafras oil , or synthesized from other related methylenedioxy...

, a colorless or slightly black oil, extracted from the root-bark or the fruit of sassafras
Sassafras
Sassafras is a genus of three extant and one extinct species of deciduous trees in the family Lauraceae, native to eastern North America and eastern Asia.-Overview:...

 plants is the primary precursor for all manufacture of MDMA. There are numerous synthetic methods available in the literature to convert safrole into MDMA via different intermediates.Reductive aminations of carbonyl compounds with borohydride and borane reducing agents. Baxter, Ellen W.; Reitz, Allen B. Organic Reactions (Hoboken, New Jersey, United States) (2002), 59 One common route is via the MDP2P
MDP2P
3,4-phenyl-2-propanone , is a chemical compound consisting of a phenylacetone moiety substituted with a methylenedioxy functional group, an entactogen and stimulant of the phenethylamine, amphetamine, and cathinone classes...

 (3,4-methylenedioxy
Methylenedioxy
Methylenedioxy in the field of chemistry, particularly in organic chemistry, is the name for a functional group with the structural formula R-O-CH2-O-R' which is connected to the rest of a molecule by two chemical bonds. The methylenedioxy group consists of two oxygen atoms connected to a methylene...

phenyl-2-propanone, also known as piperonyl acetone) intermediate. This intermediate can be produced in at least two different ways. One method is to isomerize safrole to isosafrole
Isosafrole
Isosafrole is a phenylpropene, a type of aromatic organic chemical with a smell similar to anise or licorice. It is found in small amounts in various essential oils, but is most commonly obtained by isomerizing the plant oil safrole....

 in the presence of a strong base and then oxidize isosafrole
Isosafrole
Isosafrole is a phenylpropene, a type of aromatic organic chemical with a smell similar to anise or licorice. It is found in small amounts in various essential oils, but is most commonly obtained by isomerizing the plant oil safrole....

 to MDP2P. Another, reportedly better, method is to make use of the Wacker process
Wacker process
The Wacker process or the Hoechst-Wacker process originally referred to the oxidation of ethylene to acetaldehyde by oxygen in water in the presence of a tetrachloropalladate catalyst...

 to oxidize safrole directly to the MDP2P (3,4-methylenedioxy phenyl-2-propanone) intermediate. This can be done with a palladium
Palladium
Palladium is a chemical element with the chemical symbol Pd and an atomic number of 46. It is a rare and lustrous silvery-white metal discovered in 1803 by William Hyde Wollaston. He named it after the asteroid Pallas, which was itself named after the epithet of the Greek goddess Athena, acquired...

 catalyst. Once the MDP2P intermediate has been prepared, a reductive amination
Reductive amination
Reductive amination is a form of amination that involves the conversion of a carbonyl group to an amine via an intermediate imine...

 leads to MDMA, a racemate {1:1 mixture of (R)-1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine and (S)-1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine}.
Another method for the synthesis of racemic
Racemic
In chemistry, a racemic mixture, or racemate , is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule. The first known racemic mixture was "racemic acid", which Louis Pasteur found to be a mixture of the two enantiomeric isomers of tartaric acid.- Nomenclature :A...

 MDMA is addition of hydrogen bromide to safrole and reaction of the adduct with methylamine.


Relatively small quantities of essential oil are required to make large numbers of MDMA pills. The essential oil of Ocotea cymbarum
Ocotea cymbarum
Ocotea cymbarum is a species of plant in the Lauraceae family. It is found in Brazil, Colombia, French Guiana, Guyana, Suriname, and Venezuela.-References:* World Conservation Monitoring Centre 1998. . Downloaded on 22 August 2007....

typically contains between 80 and 94% safrole. This would allow 500 ml of the oil, which retails at between $20 and $100, to be used to produce an estimated 1,300 to 2,800 tablets containing approximately 120 mg of MDMA each.Nov 2005 DEA Microgram newsletter. Usdoj.gov (2005-11-11). Retrieved on 2011-06-11.

Pharmacology


MDMA acts as a releasing agent
Releasing agent
A releasing agent , or simply releaser, is a drug that induces the release of a neurotransmitter from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitter. Many drugs use neurotransmitter release to exert their psychological and...

 of serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

, norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

, and dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

. It enters neurons via carriage by the monoamine transporter
Monoamine transporter
Monoamine transporters are protein structures that function as integral plasma membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. Three major classes of MATs are responsible for the reuptake of their associated amine neurotransmitters...

s. Once inside, MDMA inhibits the vesicular monoamine transporter
Vesicular monoamine transporter
The vesicular monoamine transporter is a transport protein integrated into the membrane of intracellular vesicles of presynaptic neurons. It acts to transport monoamines into the synaptic vesicles.-Monoamines:...

, which results in increased concentrations of serotonin, norepinephrine, and dopamine in the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...

, and induces their release by reversing
Transporter reversal
Transporter reversal is the action of reversing a plasmalemmal transporter via a process known as phosphorylation. Neurotransmitter transporters normally function as part of the reuptake process, by carrying neurotransmitter chemicals from the extracellular space into the cytoplasm of a...

 their respective transporters through a process known as phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....

. It also acts as a weak 5-HT1
5-HT1 receptor
The 5-HT1 receptors are a subfamily of 5-HT receptors that bind the endogenous neurotransmitter serotonin . The 5-HT1 subfamily consists of five G protein-coupled receptors that are coupled to Gi/Go and mediate inhibitory neurotransmission, including 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F...

 and 5-HT2 receptor
5-HT2 receptor
The 5-HT2 receptors are a subfamily of 5-HT receptors that bind the endogenous neurotransmitter serotonin . The 5-HT2 subfamily consists of three G protein-coupled receptors which are coupled to Gq/G11 and mediate excitatory neurotransmission, including 5-HT2A, 5-HT2B, and 5-HT2C...

 agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...

, and its more efficacious metabolite MDA
3,4-Methylenedioxyamphetamine
3,4-Methylenedioxyamphetamine , also known as tenamfetamine , is a psychedelic and entactogenic drug of the phenethylamine and amphetamine chemical classes...

 likely augments this action.

MDMA's unusual entactogenic effects have been hypothesized to be, at least partly, the result of indirect oxytocin
Oxytocin
Oxytocin is a mammalian hormone that acts primarily as a neuromodulator in the brain.Oxytocin is best known for its roles in sexual reproduction, in particular during and after childbirth...

 secretion via activation of the serotonin system. Oxytocin is a hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

 released following events like hugging, orgasm
Orgasm
Orgasm is the peak of the plateau phase of the sexual response cycle, characterized by an intense sensation of pleasure...

, and childbirth
Childbirth
Childbirth is the culmination of a human pregnancy or gestation period with the birth of one or more newborn infants from a woman's uterus...

, and is thought to facilitate bonding
Pair bond
In biology, a pair bond is the strong affinity that develops in some species between the males and females in a pair, potentially leading to breeding. Pair-bonding is a term coined in the 1940s that is frequently used in sociobiology and evolutionary psychology circles...

 and the establishment of trust. Based on studies in rats, MDMA is believed to cause the release of oxytocin, at least in part, by both directly and indirectly agonizing the serotonin 5-HT1A receptor
5-HT1A receptor
The 5-HT1A receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gi/Go and mediates inhibitory neurotransmission...

. A placebo-controlled study in 15 human volunteers found that 100 mg MDMA increased blood levels of oxytocin, and the amount of oxytocin increase was correlated with the subjective prosocial effects of MDMA.

Pharmacokinetics


MDMA reaches maximal concentration
Concentration
In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...

s in the blood stream between 1.5 and 3 hours after ingestion
Ingestion
Ingestion is the consumption of a substance by an organism. In animals, it normally is accomplished by taking in the substance through the mouth into the gastrointestinal tract, such as through eating or drinking...

. It is then slowly metabolized
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

 and excreted
Excretion
Excretion is the process by which waste products of metabolism and other non-useful materials are eliminated from an organism. This is primarily carried out by the lungs, kidneys and skin. This is in contrast with secretion, where the substance may have specific tasks after leaving the cell...

, with levels decreasing to half their peak concentration over approximately 8 hours. Thus, there are still high MDMA levels in the body when the experiential effects have mostly ended, indicating that acute tolerance has developed to the actions of MDMA. Taking additional supplements of MDMA at this point, therefore, produces higher concentrations of MDMA in the blood and brain than might be expected based on the perceived effects.

Metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...

s of MDMA that have been identified in humans include 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxy-methamphetamine (HMMA), 4-hydroxy-3-methoxyamphetamine (HMA), 3,4-dihydroxyamphetamine (DHA) (also called alpha-methyldopamine (α-Me-DA)), 3,4-methylenedioxyphenylacetone
MDP2P
3,4-phenyl-2-propanone , is a chemical compound consisting of a phenylacetone moiety substituted with a methylenedioxy functional group, an entactogen and stimulant of the phenethylamine, amphetamine, and cathinone classes...

 (MDP2P), and N-hydroxy-3,4-methylenedioxyamphetamine (MDOH). The contributions of these metabolites to the psychoactive and toxic effects of MDMA are an area of active research. Sixty-five percent of MDMA is excreted unchanged in the urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...

 (in addition, 7% is metabolized into MDA) during the 24 hours after ingestion.

MDMA is known to be metabolized by two main metabolic pathway
Metabolic pathway
In biochemistry, metabolic pathways are series of chemical reactions occurring within a cell. In each pathway, a principal chemical is modified by a series of chemical reactions. Enzymes catalyze these reactions, and often require dietary minerals, vitamins, and other cofactors in order to function...

s: (1) O-demethylenation followed by catechol-O-methyltransferase
Catechol-O-methyl transferase
Catechol-O-methyltransferase is one of several enzymes that degrade catecholamines such as dopamine, epinephrine, and norepinephrine. In humans, catechol-O-methyltransferase protein is encoded by the COMT gene...

 (COMT)-catalyzed methylation and/or glucuronide/sulfate conjugation; and (2) N-dealkylation, deamination, and oxidation to the corresponding benzoic acid
Benzoic acid
Benzoic acid , C7H6O2 , is a colorless crystalline solid and the simplest aromatic carboxylic acid. The name derived from gum benzoin, which was for a long time the only source for benzoic acid. Its salts are used as a food preservative and benzoic acid is an important precursor for the synthesis...

 derivatives conjugated with glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...

. The metabolism may be primarily by cytochrome P450
Cytochrome P450 oxidase
The cytochrome P450 superfamily is a large and diverse group of enzymes. The function of most CYP enzymes is to catalyze the oxidation of organic substances. The substrates of CYP enzymes include metabolic intermediates such as lipids and steroidal hormones, as well as xenobiotic substances...

 (CYP450) enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s (CYP2D6
CYP2D6
Cytochrome P450 2D6 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. Also, many substances are bioactivated by CYP2D6 to form their active compounds...

 (in humans, but CYP2D1 in mice
MICE
-Fiction:*Mice , alien species in The Hitchhiker's Guide to the Galaxy*The Mice -Acronyms:* "Meetings, Incentives, Conferencing, Exhibitions", facilities terminology for events...

), and CYP3A4
CYP3A4
Cytochrome P450 3A4 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. CYP3A4 is involved in the oxidation of the largest range of substrates of all the CYPs. As a result, CYP3A4 is present in...

) and COMT. Complex, nonlinear pharmacokinetics
Pharmacokinetics
Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism...

 arise via autoinhibition of CYP2D6
CYP2D6
Cytochrome P450 2D6 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. Also, many substances are bioactivated by CYP2D6 to form their active compounds...

 and CYP2D8, resulting in zeroth order kinetics
Rate equation
The rate law or rate equation for a chemical reaction is an equation that links the reaction rate with concentrations or pressures of reactants and constant parameters . To determine the rate equation for a particular system one combines the reaction rate with a mass balance for the system...

 at higher doses. It is thought that this can result in sustained and higher concentration
Concentration
In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...

s of MDMA if the user takes consecutive doses of the drug.

Because the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 CYP2D6
CYP2D6
Cytochrome P450 2D6 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. Also, many substances are bioactivated by CYP2D6 to form their active compounds...

 is deficient or totally absent in some people,eMedicine – Toxicity, MDMA: Article by David Yew. Emedicine.com. Retrieved on 2011-06-11. it was once hypothesized that these people might have elevated risk when taking MDMA. However, there is still no evidence for this theory and available evidence argues against it. It is now thought that the contribution of CYP2D6 to MDMA metabolism in humans is less than 30% of the metabolism. Indeed, an individual lacking CYP2D6 was given MDMA in a controlled clinical setting and a larger study gave MDMA to healthy volunteers after inhibiting CYP2D6 with paroxetine
Paroxetine
Paroxetine is an SSRI antidepressant. Marketing of the drug began in 1992 by the pharmaceutical company SmithKline Beecham, now GlaxoSmithKline...

. Lack of the enzyme caused a modest increase in drug exposure and decreases in some metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...

s, but physical effects did not appear appreciably elevated. While there is little or no evidence that low CYP2D6 activity increases risks from MDMA, it is likely that MDMA-induced CYP2D inhibition will increase risk of those prescription drugs that are metabolized by this enzyme. MDMA-induced CYP2D inhibition appears to last for up to a week after MDMA exposure.

MDMA and metabolites are primarily excreted as conjugates, such as sulfates and glucuronides.
MDMA is a chiral
Chirality (chemistry)
A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....

 compound and has been almost exclusively administered as a racemate
Racemic
In chemistry, a racemic mixture, or racemate , is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule. The first known racemic mixture was "racemic acid", which Louis Pasteur found to be a mixture of the two enantiomeric isomers of tartaric acid.- Nomenclature :A...

. However, an early uncontrolled report suggests that the (S)-enantiomer
Enantiomer
In chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable , much as one's left and right hands are the same except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...

 is significantly more potent
Potency (pharmacology)
In the field of pharmacology, potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. A highly potent drug evokes a larger response at low concentrations, while a drug of lower potency evokes a small response at low concentrations...

 in humans than the (R)-enantiomer indicate that the disposition of MDMA is stereoselective, with the S-enantiomer having a shorter elimination half-life and greater excretion than the R-enantiomer. For example, Fallon et al. reported that the area under the blood plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...

 concentration versus time curve (AUC) was two to four times higher for the (R)-enantiomer than the (S)-enantiomer after a 40 mg oral dose in human volunteers. Likewise, the plasma half-life of (R)-MDMA was significantly longer than that of the (S)-enantiomer (5.8 ± 2.2 hours vs 3.6 ± 0.9 hours). However, because MDMA has dose dependent kinetics, it is likely that these half-lives would be higher at more typical doses (100 mg is sometimes considered a typical dose). Given as the racemate, MDMA has a half-life
Half-life
Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...

 of around 8 hours.

Detection of use


MDMA and MDA may be quantitated in blood, plasma or urine to monitor for abuse, confirm a diagnosis of poisoning or assist in the forensic investigation of a traffic or other criminal violation or a sudden death. Some drug abuse screening programs rely on hair, saliva, or sweat as specimens. Most commercial amphetamine immunoassay screening tests cross-react significantly with MDMA or its major metabolites, but chromatographic techniques can easily distinguish and separately measure each of these substances. The concentrations of MDA in the blood or urine of a person who has taken only MDMA are, in general, less than 10% those of the parent drug.Kolbrich EA, Goodwin RS, Gorelick DA, Hayes RJ, Stein EA, Huestis MA. Plasma pharmacokinetics of 3,4-methylenedioxymethamphetamine after controlled oral administration to young adults. Ther. Drug Monit. 30: 320–332, 2008.R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 9th edition, Biomedical Publications, Seal Beach, California, 2011, pp. 1078–1080.

History



MDMA was first synthesized in 1912 by Merck
Merck KGaA
Merck KGaA is a German chemical and pharmaceutical company. Merck, also known as “German Merck” and “Merck Darmstadt”, was founded in Darmstadt, Germany, in 1668, making it the world's oldest operating chemical and pharmaceutical company. The company was privately owned until going public in 1995...

 chemist Anton Köllisch
Anton Kollisch
Anton Köllisch was the German chemist who, whilst working at Darmstadt for pharmaceutical giant Merck, first synthesized the chemical MDMA that would later come to be known as "ecstasy"....

. At the time, Merck was interested in developing substances that stopped abnormal bleeding. Merck wanted to evade an existing patent, held by Bayer
Bayer
Bayer AG is a chemical and pharmaceutical company founded in Barmen , Germany in 1863. It is headquartered in Leverkusen, North Rhine-Westphalia, Germany and well known for its original brand of aspirin.-History:...

, for one such compound: hydrastinine
Hydrastinine
Hydrastinine is a semisynthetic alkaloid from the hydrolysis of the alkaloid hydrastine, which was found naturally in small quantities in Hydrastis canadensis L. . Hydrastinine was produced by oxidative splitting of hydrastine hydrochloride with nitric acid in good yield...

. At the behest of his superiors Walther Beckh and Otto Wolfes, Köllisch developed a preparation of a hydrastinine analogue, methylhydrastinine. MDMA was an intermediate compound
Reaction intermediate
A reaction intermediate or an intermediate is a molecular entity that is formed from the reactants and reacts further to give the directly observed products of a chemical reaction. Most chemical reactions are stepwise, that is they take more than one elementary step to complete...

 in the synthesis of methylhydrastinine, and Merck was not interested in its properties at the time. On 24 December 1912, Merck filed two patent applications that described the synthesis of MDMA and its subsequent conversion to methylhydrastinine.

Over the following 65 years, MDMA was largely forgotten. Merck records indicate that its researcher
Researcher
A researcher is somebody who performs research, the search for knowledge or in general any systematic investigation to establish facts. Researchers can work in academic, industrial, government, or private institutions.-Examples of research institutions:...

s returned to the compound sporadically. In 1927, Max Oberlin studied the pharmacology of MDMA and observed that its effects on blood sugar
Blood sugar
The blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal. Normally in mammals, the body maintains the blood glucose level at a reference range between about 3.6 and 5.8 mM , or 64.8 and 104.4 mg/dL...

 and smooth muscle
Smooth muscle
Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...

s were similar to ephedrine
Ephedrine
Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....

's. Researchers at Merck conducted experiments with MDMA in 1952 and 1959. In 1953 and 1954, the United States Army
United States Army
The United States Army is the main branch of the United States Armed Forces responsible for land-based military operations. It is the largest and oldest established branch of the U.S. military, and is one of seven U.S. uniformed services...

 commissioned a study of toxicity
Toxicity
Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...

 and behavioral effects in animals of injected mescaline
Mescaline
Mescaline or 3,4,5-trimethoxyphenethylamine is a naturally occurring psychedelic alkaloid of the phenethylamine class used mainly as an entheogen....

 and several analogues, including MDMA. These originally classified investigations were declassified and published in 1973. The first scientific paper on MDMA appeared in 1958 in Yakugaku Zasshi, the Journal of the Pharmaceutical Society of Japan. In this paper, Yutaka Kasuya described the synthesis of MDMA, a part of his research on antispasmodics.

MDMA was being used recreationally in the United States by 1970.The first confirmed sample was seized and identified by Chicago Police in 1970, see In the mid-1970s, Alexander Shulgin
Alexander Shulgin
Alexander "Sasha" Theodore Shulgin is an American pharmacologist, chemist, artist, and drug developer.Shulgin is credited with the popularization of MDMA, commonly known as ecstasy, in the late 1970s and early 1980s, especially for psychopharmaceutical use and the treatment of depression and...

, then at University of California, Berkeley
University of California, Berkeley
The University of California, Berkeley , is a teaching and research university established in 1868 and located in Berkeley, California, USA...

, heard from his students about unusual effects of MDMA; among others, the drug had helped one of them to overcome his stutter. Intrigued, Shulgin synthesized MDMA and tried it himself in 1976. Two years later, he and David E. Nichols
David E. Nichols
David E. Nichols is an American pharmacologist and medicinal chemist.Presently the Robert C. and Charlotte P. Anderson Distinguished Chair in Pharmacology at Purdue University, Nichols has worked in the field of psychoactive drugs since 1969...

 published the first report on the drug's psychotropic effect in humans. They described "altered state of consciousness with emotional and sensual overtones" that can be compared "to marijuana, and to psilocybin
Psilocybin
Psilocybin is a naturally occurring psychedelic prodrug, with mind-altering effects similar to those of LSD and mescaline, after it is converted to psilocin. The effects can include altered thinking processes, perceptual distortions, an altered sense of time, and spiritual experiences, as well as...

 devoid of the hallucinatory component".

Shulgin took to occasionally using MDMA for relaxation, referring to it as "my low-calorie martini", and giving the drug to his friends, researchers, and other people who he thought could benefit from it. One such person was psychotherapist Leo Zeff
Leo Zeff
Dr. Leo Zeff was an American psychologist and psychotherapist in Oakland, California who pioneered the use of ecstasy and other psychoactive drugs in psychotherapy in the 1970s....

, who had been known to use psychedelic
Psychedelic drug
A psychedelic substance is a psychoactive drug whose primary action is to alter cognition and perception. Psychedelics are part of a wider class of psychoactive drugs known as hallucinogens, a class that also includes related substances such as dissociatives and deliriants...

s in his practice. Zeff was so impressed with the effects of MDMA that he came out of his semi-retirement to proselytize for it. Over the following years, Zeff traveled around the U.S. and occasionally to Europe, training other psychotherapists in the use of MDMA. Among underground psychotherapists, MDMA developed a reputation for enhancing communication during clinical sessions, reducing patients' psychological defenses, and increasing capacity for therapeutic introspection
Introspection
Introspection is the self-observation and reporting of conscious inner thoughts, desires and sensations. It is a conscious and purposive process relying on thinking, reasoning, and examining one's own thoughts, feelings, and, in more spiritual cases, one's soul...

. Doblin, Rick. A Clinical Plan for MDMA (Ecstasy) in the Treatment of Post-Traumatic Stress Disorder (PTSD): Partnering with the FDA. Referenced 2011-10-23 from http://www.maps.org/news-letters/v12n3/12305dob.html

In the early 1980s in the U.S., MDMA rose to prominence as "Adam" in trendy nightclubs and gay dance clubs in the Dallas area.''The Austin Chronicle'' – "Countdown to Ecstasy." by Marc Savlov. Weeklywire.com. Retrieved on 2011-06-11. From there, use spread to rave
Rave
Rave, rave dance, and rave party are parties that originated mostly from acid house parties, which featured fast-paced electronic music and light shows. At these parties people dance and socialize to dance music played by disc jockeys and occasionally live performers...

s in major cities around the country, and then to mainstream society. The drug was first proposed for scheduling
Controlled Substances Act
The Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...

 by the Drug Enforcement Administration
Drug Enforcement Administration
The Drug Enforcement Administration is a federal law enforcement agency under the United States Department of Justice, tasked with combating drug smuggling and use within the United States...

 (DEA) in July 1984 and was classified as a Schedule I controlled substance in the U.S. on 31 May 1985.Erowid MDMA Vault: Info #3 on Scheduling. Erowid.org. Retrieved on 2011-06-11.

In the late 1980s MDMA, known by that time as "ecstasy", began to be widely used in the UK and other parts of Europe, becoming an integral element of rave culture and other psychedelic-influenced music scenes. Spreading along with rave culture, illicit MDMA use became increasingly widespread among young adults in universities and later in high schools. MDMA became one of the four most widely used illicit drugs in the U.S., along with cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...

, heroin, and cannabis
Cannabis (drug)
Cannabis, also known as marijuana among many other names, refers to any number of preparations of the Cannabis plant intended for use as a psychoactive drug or for medicinal purposes. The English term marijuana comes from the Mexican Spanish word marihuana...

.
According to some estimates as of 2004, only marijuana attracts more first time users in the U.S.

After MDMA was criminalized, most medical use stopped, although some therapists continued to prescribe the drug illegally. Later Charles Grob initiated an ascending-dose safety study in healthy volunteers. Subsequent legally-approved MDMA studies in humans have taken place in the U.S. in Detroit (Wayne State University
Wayne State University
Wayne State University is a public research university located in Detroit, Michigan, United States, in the city's Midtown Cultural Center Historic District. Founded in 1868, WSU consists of 13 schools and colleges offering more than 400 major subject areas to over 32,000 graduate and...

), Chicago (University of Chicago
University of Chicago
The University of Chicago is a private research university in Chicago, Illinois, USA. It was founded by the American Baptist Education Society with a donation from oil magnate and philanthropist John D. Rockefeller and incorporated in 1890...

), San Francisco (UCSF and California Pacific Medical Center
California Pacific Medical Center
California Pacific Medical Center is one of the largest private, non-profit, academic medical centers in Northern California. The Medical Center is a combination of four of San Francisco's oldest medical institutions: Pacific Presbyterian Hospital, Children's Hospital of San Francisco, Davies...

), Baltimore
Baltimore
Baltimore is the largest independent city in the United States and the largest city and cultural center of the US state of Maryland. The city is located in central Maryland along the tidal portion of the Patapsco River, an arm of the Chesapeake Bay. Baltimore is sometimes referred to as Baltimore...

 (NIDA
National Institute on Drug Abuse
The National Institute on Drug Abuse is a United States federal-government research institute whose mission is to "lead the Nation in bringing the power of science to bear on drug abuse and addiction."-History:...

–NIH Intramural Program), and South Carolina
South Carolina
South Carolina is a state in the Deep South of the United States that borders Georgia to the south, North Carolina to the north, and the Atlantic Ocean to the east. Originally part of the Province of Carolina, the Province of South Carolina was one of the 13 colonies that declared independence...

, as well as in Switzerland (University Hospital of Psychiatry, Zürich
Zürich
Zurich is the largest city in Switzerland and the capital of the canton of Zurich. It is located in central Switzerland at the northwestern tip of Lake Zurich...

), the Netherlands (Maastricht University), and Spain (Universitat Autònoma de Barcelona).Bibliography of Psychadelic Research Studies. collected by the Multidisciplinary Association for Psychedelic Studies

In 2010, the BBC reported that use of MDMA had decreased in the UK in previous years. This is thought to be due to increased seizures and decreased production of the precursor chemicals used to manufacture MDMA. The availability of legal alternatives to MDMA such as mephedrone, or methylone, is also thought to have contributed to its decrease in popularity.

Legal status


MDMA is legally controlled in most of the world under the UN Convention on Psychotropic Substances
Convention on Psychotropic Substances
The Convention on Psychotropic Substances of 1971 is a United Nations treaty designed to control psychoactive drugs such as amphetamines, barbiturates, benzodiazepines, and psychedelics signed at Vienna on February 21, 1971...

 and other international agreements, although exceptions exist for research. In general, the unlicensed use, sale or manufacture of MDMA are all criminal offenses.

United Kingdom


MDMA was made illegal in 1977 by a modification order to the existing Misuse of Drugs Act 1971
Misuse of Drugs Act 1971
The Misuse of Drugs Act 1971 is an Act of Parliament which represents UK action in line with treaty commitments under the Single Convention on Narcotic Drugs, the Convention on Psychotropic Substances, and the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic...

. Although MDMA was not named explicitly in this legislation, the order extended the definition of Class A drugs to include various ring-substituted phenethylamines,Misuse of Drugs Act 1971. Statutelaw.gov.uk (1998-01-05). Retrieved on 2011-06-11. thereby making it illegal to sell, buy, or possess the drug without a license. Penalties include a maximum of seven years and/or unlimited fine for possession; life and/or unlimited fine for production or trafficking. See list of drugs illegal in the UK for more information. In February 2009 an official independent scientific advisory board to the UK government recommended that MDMA be re-classified to Class B, but this recommendation was immediately rejected by the government (see Recommendation to downgrade MDMA). This 2009 report on MDMA stated:
In 2000, the UK Police Foundation issued the Runciman Report
Runciman Report
The Runciman Report was a 2000 Police Foundation inquiry into the United Kingdom's Misuse of Drugs Act 1971 authored by Viscountess Runciman.-Recommendations:...

, which reviewed the medical and social harms of MDMA and recommended: "Ecstasy and related compounds should be transferred from Class A to Class B."Drugs and the law: Report of the inquiry into the Misuse of Drugs Act 1971 London: Police Foundation, 2000, Runciman Report
Runciman Report
The Runciman Report was a 2000 Police Foundation inquiry into the United Kingdom's Misuse of Drugs Act 1971 authored by Viscountess Runciman.-Recommendations:...

In 2002, the Home Affairs Committee of the UK House of Commons, issued a report, The Government's Drugs Policy: Is it working?, which also recommended that MDMA should be reclassified to a Class B drug."The Government's Drugs Policy: Is it working?" House of Commons, Home Affairs Committee, May 2002 The UK government rejected both recommendations, saying that re-classification of MDMA would not be considered without a recommendation from the Advisory Council on the Misuse of Drugs, the official UK scientific advisory board on drug abuse issues.
MDMA (3,4-Methylenedioxymethamphetamine) is an entactogenic drug of the phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...

 and amphetamine
Substituted amphetamine
Substituted amphetamines are a chemical class of stimulants, entactogens, hallucinogens, and other drugs. They feature a phenethylamine core with a methyl group attached to the alpha carbon resulting in amphetamine, along with additional substitutions...

 class of drugs
Chemical classification
Chemical classification systems attempt to classify as elements or compounds according to certain chemical functional or structural properties. Whereas the structural properties are largely intrinsic, functional properties and the derived classifications depend to a certain degree on the type of...

. In popular culture, MDMA has become widely known as "ecstasy" ("E", "X" or "XTC"), usually referring to its street pill form, although this term may also include the presence of possible adulterants. The terms "molly" or "mandy" can colloquially refer to MDMA in crystalline or powder form.

MDMA can induce euphoria
Euphoria
Euphoria is an emotional and mental state defined as a sense of great elation and well being.Euphoria may also refer to:* Euphoria , a genus of scarab beetles* Euphoria, a genus name previously used for the longan and other trees...

, a sense of intimacy with others, and diminished anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

. Many studies, particularly in the fields of psychology
Psychology
Psychology is the study of the mind and behavior. Its immediate goal is to understand individuals and groups by both establishing general principles and researching specific cases. For many, the ultimate goal of psychology is to benefit society...

 and cognitive therapy
Cognitive therapy
Cognitive behavioral therapy is a psychotherapeutic approach: a talking therapy. CBT aims to solve problems concerning dysfunctional emotions, behaviors and cognitions through a goal-oriented, systematic procedure in the present...

, have suggested that MDMA has therapeutic benefits and facilitates therapy sessions in certain individuals, a practice for which it had formally been used in the past. Clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...

s are now testing the therapeutic potential of MDMA for post-traumatic stress disorder
Post-traumatic stress disorder
Posttraumaticstress disorder is a severe anxiety disorder that can develop after exposure to any event that results in psychological trauma. This event may involve the threat of death to oneself or to someone else, or to one's own or someone else's physical, sexual, or psychological integrity,...

 (PTSD) and anxiety associated with terminal cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

.Ecstasy to be tested on terminal cancer patients, Associated Press, 12/28/2004

MDMA is criminalized
Criminalization
Criminalization or criminalisation, in criminology, is "the process by which behaviors and individuals are transformed into crime and criminals". Previously legal acts may be transformed into crimes by legislation or judicial decision...

 in most countries under a United Nations
United Nations
The United Nations is an international organization whose stated aims are facilitating cooperation in international law, international security, economic development, social progress, human rights, and achievement of world peace...

 (UN) agreement,"Where is Ecstasy Legal?". Ecstasy.org. Retrieved on 2011-06-11. and its possession
Drug possession
Drug possession is the crime of having one or more illegal drugs in one's possession, either for personal use, distribution, sale or otherwise. Illegal drugs fall into different categories and sentences vary depending on the amount, type of drug, circumstances, and jurisdiction.A person has...

, manufacture
Clandestine chemistry
Clandestine chemistry is chemistry carried out in secret, and particularly in illegal drug laboratories. Larger labs are usually run by gangs or organized crime intending to produce for distribution on the black market...

, or sale
Illegal drug trade
The illegal drug trade is a global black market, dedicated to cultivation, manufacture, distribution and sale of those substances which are subject to drug prohibition laws. Most jurisdictions prohibit trade, except under license, of many types of drugs by drug prohibition laws.A UN report said the...

 may result in criminal prosecution, although some limited exceptions exist for scientific and medical research. MDMA is one of the most widely used recreational drugs
Recreational drug use
Recreational drug use is the use of a drug, usually psychoactive, with the intention of creating or enhancing recreational experience. Such use is controversial, however, often being considered to be also drug abuse, and it is often illegal...

 in the world and is taken in a variety of contexts far removed from its roots in psychotherapeutic settings. It is commonly associated with dance parties (or "raves") and electronic dance music
Electronic dance music
Electronic dance music is electronic music produced primarily for the purposes of use within a nightclub setting, or in an environment that is centered upon dance-based entertainment...

.

Regulatory authorities in several locations around the world have approved scientific studies administering MDMA to humans to examine its therapeutic potential and its effects.Psychedelic Research Worldwide. MAPS. Retrieved on 2011-06-11.

Medical uses


There have long been suggestions that MDMA might be useful in psychotherapy
Psychotherapy
Psychotherapy is a general term referring to any form of therapeutic interaction or treatment contracted between a trained professional and a client or patient; family, couple or group...

, facilitating self-examination with reduced fear.Greer G. Tolbert R. "The Therapeutic Use of MDMA in Ecstasy: The Clinical, Pharmacological, and Neurotoxicological Effects of the Drug MDMA." 1990 (ed Peroutka, SJ) Boston, p. 21-36. (PDF) . Retrieved on 2011-06-11. Indeed, some therapists, including Leo Zeff
Leo Zeff
Dr. Leo Zeff was an American psychologist and psychotherapist in Oakland, California who pioneered the use of ecstasy and other psychoactive drugs in psychotherapy in the 1970s....

, Claudio Naranjo
Claudio Naranjo
Claudio Naranjo is a Chilean psychiatrist who is considered a pioneer in integrating psychotherapy and the spiritual traditions. He is one of the three successors named by Fritz Perls , and a developer of the Enneagram of Personality and founder of the Seekers After Truth Institute...

, George Greer, Joseph Downing, and Philip Wolfson, used MDMA in their practices until it was made illegal. George Greer synthesized MDMA in the lab of Alexander Shulgin and administered it to about 80 of his clients over the course of the remaining years preceding MDMA's Schedule I placement in 1985. In a published summary of the effects, the authors reported patient
Patient
A patient is any recipient of healthcare services. The patient is most often ill or injured and in need of treatment by a physician, advanced practice registered nurse, veterinarian, or other health care provider....

s felt improved in various, mild psychiatric disorders and experienced other personal benefits, especially improved intimate communication with their significant others. In a subsequent publication on the treatment method, the authors reported that one patient with severe pain from terminal
Terminal illness
Terminal illness is a medical term popularized in the 20th century to describe a disease that cannot be cured or adequately treated and that is reasonably expected to result in the death of the patient within a short period of time. This term is more commonly used for progressive diseases such as...

 cancer experienced lasting pain relief
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....

 and improved quality of life
Quality of life
The term quality of life is used to evaluate the general well-being of individuals and societies. The term is used in a wide range of contexts, including the fields of international development, healthcare, and politics. Quality of life should not be confused with the concept of standard of...

.

Three neurobiological mechanisms for the therapeutic effects of MDMA have been suggested: "1) MDMA increases oxytocin levels, which may strengthen the therapeutic alliance; 2) MDMA increases ventromedial prefrontal activity and decreases amygdala activity, which may improve emotional regulation and decrease avoidance, and 3) MDMA increases norepinephrine release and circulating cortisol levels, which may facilitate emotional engagement and enhance extinction of learned fear associations."

The first phase-II double-blind randomized controlled clinical trial into the potential therapeutic benefits of using the drug as an augment to psychotherapy showed that most patients in the trial given psychotherapy treatment along with doses of MDMA experienced statistically significant reductions in the severity of their condition after two months, compared with a control group receiving psychotherapy and a placebo. The authors concludes "MDMA-assisted psychotherapy can be administered to posttraumatic stress disorder patients without evidence of harm, and it may be useful in patients refractory to other treatments."

The possible therapeutic potential of MDMA is being tested in several ongoing studies, some sponsored by the Multidisciplinary Association for Psychedelic Studies
Multidisciplinary Association for Psychedelic Studies
The Multidisciplinary Association for Psychedelic Studies is a membership-based 501 non-profit research and educational organization working to develop psychedelics and marijuana into legal prescription drugs...

 (MAPS). Studies in the U.S., Switzerland, and Israel are evaluating the efficacy of MDMA-assisted psychotherapy for treating those diagnosed with post-traumatic stress disorder
Post-traumatic stress disorder
Posttraumaticstress disorder is a severe anxiety disorder that can develop after exposure to any event that results in psychological trauma. This event may involve the threat of death to oneself or to someone else, or to one's own or someone else's physical, sexual, or psychological integrity,...

 (PTSD) or anxiety related to cancer.

Small doses of MDMA are used as an entheogen to enhance meditation by some Buddhist Monks.MDMA and Religion. CSP. Retrieved on 2011-06-11.

Recreational use


The European Monitoring Centre for Drugs and Drug Addiction
European Monitoring Centre for Drugs and Drug Addiction
The European Monitoring Centre for Drugs and Drug Addiction is an agency of the European Union. Established in 1993, the EMCDDA is located in Lisbon, Portugal.-Mission and role:...

 notes that, although there are some reports of tablets being sold for as little as €1, most countries in Europe now report typical retail prices in the range of €3 to €9 per tablet. The United Nations Office on Drugs and Crime
United Nations Office on Drugs and Crime
The United Nations Office on Drugs and Crime is a United Nations agency that was established in 1997 as the Office for Drug Control and Crime Prevention by combining the United Nations International Drug Control Program and the Crime Prevention and Criminal Justice Division in the United Nations...

 claimed in its 2008 World Drug Report that typical U.S. retail prices are lower, costing $10 to $15 per tablet, or from $4 to $6 per tablet if bought in batches. MDMA is expensive in Australia, costing A$
Australian dollar
The Australian dollar is the currency of the Commonwealth of Australia, including Christmas Island, Cocos Islands, and Norfolk Island, as well as the independent Pacific Island states of Kiribati, Nauru and Tuvalu...

20–A$50 per tablet, but in the Asian community it is A$20–30, depending on the size. In terms of purity data for Australian MDMA, the average is around 34%, ranging from less than 1% to about 85%. The majority of tablets contain 70–85 mg of MDMA. Most MDMA enters Australia from different markets, the Netherlands, the UK, Asia, and the U.S.Drugtext – 10 years of ecstasy and other party drug use in Australia: What have we done and what is there left to do?. Drugtext.org. Retrieved on 2011-06-11.

Polysubstance use



MDMA is occasionally known for being taken in conjunction with psychedelic drugs, such as LSD
LSD
Lysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed and open eye visuals, synaesthesia, an...

 or psilocybin mushrooms, or even common drugs such as cannabis
Cannabis (drug)
Cannabis, also known as marijuana among many other names, refers to any number of preparations of the Cannabis plant intended for use as a psychoactive drug or for medicinal purposes. The English term marijuana comes from the Mexican Spanish word marihuana...

. As this practice has become more prevalent, most of the more common combinations have been given nicknames, such as "candy flipping", for MDMA combined with LSD
LSD
Lysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed and open eye visuals, synaesthesia, an...

, "hippy flipping", for MDMA with psilocybin
Psilocybin
Psilocybin is a naturally occurring psychedelic prodrug, with mind-altering effects similar to those of LSD and mescaline, after it is converted to psilocin. The effects can include altered thinking processes, perceptual distortions, an altered sense of time, and spiritual experiences, as well as...

, or "kitty flipping" for MDMA with Ketamine
Ketamine
Ketamine is a drug used in human and veterinary medicine. Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist...

. Many users use mentholated products while taking MDMA for its cooling sensation while experiencing the drug's effects. Examples include menthol cigarette
Cigarette
A cigarette is a small roll of finely cut tobacco leaves wrapped in a cylinder of thin paper for smoking. The cigarette is ignited at one end and allowed to smoulder; its smoke is inhaled from the other end, which is held in or to the mouth and in some cases a cigarette holder may be used as well...

s, Vick's Vapo Rub, NyQuil
NyQuil
NyQuil is a brand of over the counter medication which is intended to relieve various symptoms of the common cold. Because all of the medications within the NyQuil imprint contain sedating antihistamines, hypnotics, and/or alcohol, they are intended to be taken before sleep...

, and lozenges
Throat lozenge
A throat lozenge, cough drop, troche, or cough sweet is a small, medicated tablet intended to be dissolved slowly in the mouth to temporarily stop coughs and lubricate and soothe irritated tissues of the throat , possibly from the common cold or influenza...

.

Subjective effects


The primary effects attributable to MDMA consumption are predictable and fairly consistent among users. In general, users report feeling effects within 30–60 minutes of consumption, hitting a peak at approximately 1–1.5 hours, reaching a plateau that lasts about 2–3 hours, followed by a comedown
Comedown (drugs)
Comedown refers to the after effects of heavy recreational stimulant use, usually ecstasy, amphetamine, methylphenidate, cocaine, alcohol, and occasionally cannabis. It can be characterized by depression, apathy, dysphoria, anxiety, fatigue, intense hunger, paranoia and insomnia. These effects are...

 of a few hours, which may be accompanied by fatigue and minor effects.

The most common effect
Therapeutic effect
A therapeutic effect is a consequence of a medical treatment of any kind, the results of which are judged to be desirable and beneficial. This is true whether the result was expected, unexpected, or even an unintended consequence of the treatment...

s reported by users include:
  • A general and subjective alteration in consciousness
    Altered state of consciousness
    An altered state of consciousness , also named altered state of mind, is any condition which is significantly different from a normal waking beta wave state. The expression was used as early as 1966 by Arnold M. Ludwig and brought into common usage from 1969 by Charles Tart: it describes induced...

  • A strong sense of inner peace
    Inner peace
    Inner peace refers to a state of being mentally and spiritually at peace, with enough knowledge and understanding to keep oneself strong in the face of discord or stress. Being "at peace" is considered by many to be healthy and the opposite of being stressed or anxious...

     and self-acceptance
    Self-acceptance
    Self-acceptance is defined as affirmation or acceptance of self in spite of weaknesses or deficiencies.Although this term has been often understood in a common sense way, researchers have defined it formally in terms of positive and negative self-concepts...

  • Diminished aggression
    Aggression
    In psychology, as well as other social and behavioral sciences, aggression refers to behavior between members of the same species that is intended to cause humiliation, pain, or harm. Ferguson and Beaver defined aggressive behavior as "Behavior which is intended to increase the social dominance of...

    , hostility
    Hostility
    Hostility is a form of angry internal rejection or denial in psychology. It is a part of personal construct psychology, developed by George Kelly...

    , and jealousy
    Jealousy
    Jealousy is a second emotion and typically refers to the negative thoughts and feelings of insecurity, fear, and anxiety over an anticipated loss of something that the person values, particularly in reference to a human connection. Jealousy often consists of a combination of presenting emotions...

  • Diminished fear
    Fear
    Fear is a distressing negative sensation induced by a perceived threat. It is a basic survival mechanism occurring in response to a specific stimulus, such as pain or the threat of danger...

    , anxiety
    Anxiety
    Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

    , and insecurity
  • Extreme mood
    Mood (psychology)
    A mood is a relatively long lasting emotional state. Moods differ from emotions in that they are less specific, less intense, and less likely to be triggered by a particular stimulus or event....

     lift with accompanying euphoria
    Euphoria
    Euphoria is an emotional and mental state defined as a sense of great elation and well being.Euphoria may also refer to:* Euphoria , a genus of scarab beetles* Euphoria, a genus name previously used for the longan and other trees...

  • Feelings of empathy
    Empathy
    Empathy is the capacity to recognize and, to some extent, share feelings that are being experienced by another sapient or semi-sapient being. Someone may need to have a certain amount of empathy before they are able to feel compassion. The English word was coined in 1909 by E.B...

    , compassion
    Compassion
    Compassion is a virtue — one in which the emotional capacities of empathy and sympathy are regarded as a part of love itself, and a cornerstone of greater social interconnection and humanism — foundational to the highest principles in philosophy, society, and personhood.There is an aspect of...

    , and forgiveness
    Forgiveness
    Forgiveness is typically defined as the process of concluding resentment, indignation or anger as a result of a perceived offense, difference or mistake, or ceasing to demand punishment or restitution. The Oxford English Dictionary defines forgiveness as 'to grant free pardon and to give up all...

     toward others
  • Feelings of intimacy and even love
    Love
    Love is an emotion of strong affection and personal attachment. In philosophical context, love is a virtue representing all of human kindness, compassion, and affection. Love is central to many religions, as in the Christian phrase, "God is love" or Agape in the Canonical gospels...

     for others
  • Improved self-confidence
    Self-confidence
    The socio-psychological concept of self-confidence relates to self-assuredness in one's personal judgment, ability, power, etc., sometimes manifested excessively.Being confident in yourself is infectious if you present yourself well, others will want to follow in your foot steps towards...

  • The ability to discuss normally anxiety
    Anxiety
    Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

    -provoking topics with marked ease
  • An intensification of all of the bodily senses (hearing, touch, smell, vision, taste)
  • Substantial enhancement of the appreciation of music quality
  • Mild psychedelia, consisting of mental imagery and auditory
    Hearing (sense)
    Hearing is the ability to perceive sound by detecting vibrations through an organ such as the ear. It is one of the traditional five senses...

     and visual distortion
    Distortion
    A distortion is the alteration of the original shape of an object, image, sound, waveform or other form of information or representation. Distortion is usually unwanted, and often many methods are employed to minimize it in practice...

    s
  • Stimulation
    Stimulation
    Stimulation is the action of various agents on nerves, muscles, or a sensory end organ, by which activity is evoked; especially, the nervous impulse produced by various agents on nerves, or a sensory end organ, by which the part connected with the nerve is thrown into a state of activity.The word...

    , arousal
    Arousal
    Arousal is a physiological and psychological state of being awake or reactive to stimuli. It involves the activation of the reticular activating system in the brain stem, the autonomic nervous system and the endocrine system, leading to increased heart rate and blood pressure and a condition of...

    , and hyperactivity (e.g., many users get an "uncontrollable urge to dance" while under the influence)
  • Increased energy
    Energy (psychological)
    Mental or psychic energy or activity is the concept of a principle of activity powering the operation of the mind or psyche. Many modern psychologists or neuroscientists would equate it with increased metabolism in neurons of the brain....

     and endurance
    Endurance
    Endurance is the ability for a human or animal to exert itself and remain active for a long period of time, as well as its ability to resist, withstand, recover from, and have immunity to trauma, wounds, or fatigue. In humans, it is usually used in aerobic or anaerobic exercise...

  • Increased alertness
    Alertness
    Alertness is the state of paying close and continuous attention, being watchful and prompt to meet danger or emergency, or being quick to perceive and act. It is related to psychology as well as to physiology...

    , awareness
    Awareness
    Awareness is the state or ability to perceive, to feel, or to be conscious of events, objects or sensory patterns. In this level of consciousness, sense data can be confirmed by an observer without necessarily implying understanding. More broadly, it is the state or quality of being aware of...

    , and wakefulness
  • Increased desire
    Desire (emotion)
    Desire is a sense of longing for a person or object or hoping for an outcome. Desire is the fire that sets action aflame. The same sense is expressed by emotions such as "craving" or "hankering". When a person desires something or someone, their sense of longing is excited by the enjoyment or the...

    , drive
    Motivation
    Motivation is the driving force by which humans achieve their goals. Motivation is said to be intrinsic or extrinsic. The term is generally used for humans but it can also be used to describe the causes for animal behavior as well. This article refers to human motivation...

    , and motivation
    Motivation
    Motivation is the driving force by which humans achieve their goals. Motivation is said to be intrinsic or extrinsic. The term is generally used for humans but it can also be used to describe the causes for animal behavior as well. This article refers to human motivation...

  • Analgesia or decreased pain
    Pain
    Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...

     sensitivity
    Stimulus (physiology)
    In physiology, a stimulus is a detectable change in the internal or external environment. The ability of an organism or organ to respond to external stimuli is called sensitivity....


Adverse effects


In January 2001, an overview of the subjective side-effects of MDMA was published by Liechti, Gamma, and Vollenweider in the journal Psychopharmacology. Their paper was based on clinical research conducted over several years involving 74 healthy volunteers. The researchers found that there were a number of common side-effects and that many of the effects seemed to occur in different amounts based on gender. The top side-effects reported were difficulty concentrating, jaw clenching, grinding of the teeth
Bruxism
Bruxism is characterized by the grinding of the teeth and typically includes the clenching of the jaw. It is an oral parafunctional activity that occurs in most humans at some time in their lives. In most people, bruxism is mild enough not to be a health problem...

 during sleep, lack of appetite, and dry mouth/thirst (all occurring in more than 50% of the 74 volunteers). Liechti, et al. also measured some of the test subjects for blood pressure, heart rate, and body temperature against a placebo control but no statistically significant changes were seen.Erowid (September 2001). Short-Term Side Effects of MDMA.

A 2011 study carried out by Harvard Medical School and published in the journal Addiction found no signs of cognitive impairment due to ecstasy use, and that it did not decrease mental ability. The report also raised concerns that previous methods used to conduct that research on ecstasy had been flawed, and the experiments overstated the cognitive differences between ecstasy users and nonusers.Addiction (February 2011). "New study finds no cognitive impairment among ecstasy users".

After-effects


Effects reported by some users once the acute
Acute (medicine)
In medicine, an acute disease is a disease with either or both of:# a rapid onset, as in acute infection# a short course ....

 effects of MDMA have worn off include:
  • Psychological
    • Anxiety and paranoia
    • Depression
    • Irritability
    • Fatigue
    • Impaired attention, focus, and concentration, as well as drive and motivation (due to depleted serotonin levels)
    • Residual feelings of empathy, emotional sensitivity, and a sense of closeness to others (afterglow
      Afterglow (drug culture)
      When used with regard to recreational drug use, afterglow refers to positive physical and mental effects that linger after the main effects of a drug have subsided, or after the peak experience has subsided. This state is often characterized by feelings of detachment or increased psychological...

      )

  • Physiological
    • Dizziness, lightheadedness, or vertigo
    • Loss of appetite
    • Gastrointestinal disturbances, such as diarrhea or constipation
    • Insomnia
    • Aches and pains, usually from excessive physical activity (e.g., dancing)
    • Exhaustion
    • Jaw soreness, from trismus
      Trismus
      -Common causes:*Pericoronitis is the most common cause of trismus.*Inflammation of muscles of mastication. It is a frequent sequel to surgical removal of mandibular third molars . The condition is usually resolved on its own in 10–14 days, during which time eating and oral hygiene are compromised...

       or bruxism
      Bruxism
      Bruxism is characterized by the grinding of the teeth and typically includes the clenching of the jaw. It is an oral parafunctional activity that occurs in most humans at some time in their lives. In most people, bruxism is mild enough not to be a health problem...



A slang term given to the depressive period following MDMA consumption is Tuesday Blues (or "Suicide Tuesday"), referring to the low mood that can be experienced midweek by depleted serotonin levels following weekend MDMA use. Some users report that consuming 5-HTP, L-Tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...

, vitamin
Vitamin
A vitamin is an organic compound required as a nutrient in tiny amounts by an organism. In other words, an organic chemical compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on...

s, and/or magnesium
Magnesium in biology
Magnesium is an essential element in biological systems. Magnesium occurs typically as the Mg2+ ion. It is an essential mineral nutrient for life and is present in every cell type in every organism. For example, ATP , the main source of energy in cells, must be bound to a magnesium ion in order to...

 supplements the day after use can reduce the depressive effect by replenishing serotonin levelsMolly Flannagan, Ecstasy: Neurotoxicity and How It Can Be Reduced, 2001.

Overdose


Upon overdose, the potentially serious serotonin syndrome
Serotonin syndrome
Serotonin syndrome is a potentially life-threatening adverse drug reaction that may occur following therapeutic drug use, inadvertent interactions between drugs, overdose of particular drugs, or the recreational use of certain drugs...

, stimulant psychosis, and/or hypertensive crisis, among other dangerous adverse reaction
Adverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...

s, may come to prominence, the symptoms of which can include the following:
  • Psychological
    • Disorientation and/or confusion
      Mental confusion
      Confusion of a pathological degree usually refers to loss of orientation sometimes accompanied by disordered consciousness and often memory Confusion (from Latin confusĭo, -ōnis, noun of action from confundere "to pour together", also "to confuse") of a pathological degree usually refers to loss...

    • Anxiety
      Anxiety
      Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

      , paranoia
      Paranoia
      Paranoia [] is a thought process believed to be heavily influenced by anxiety or fear, often to the point of irrationality and delusion. Paranoid thinking typically includes persecutory beliefs, or beliefs of conspiracy concerning a perceived threat towards oneself...

      , and/or panic attack
      Panic attack
      Panic attacks are periods of intense fear or apprehension that are of sudden onset and of relatively brief duration. Panic attacks usually begin abruptly, reach a peak within 10 minutes, and subside over the next several hours...

      s
    • Hypervigilance
      Hypervigilance
      Hypervigilance is an enhanced state of sensory sensitivity accompanied by an exaggerated intensity of behaviors whose purpose is to detect threats. Hypervigilance is also accompanied by a state of increased anxiety which can cause exhaustion. Other symptoms include: abnormally increased arousal, a...

       or increased sensitivity to perceptual stimuli
      Stimulus (physiology)
      In physiology, a stimulus is a detectable change in the internal or external environment. The ability of an organism or organ to respond to external stimuli is called sensitivity....

      , accompanied by significantly increased threat
      Coercion
      Coercion is the practice of forcing another party to behave in an involuntary manner by use of threats or intimidation or some other form of pressure or force. In law, coercion is codified as the duress crime. Such actions are used as leverage, to force the victim to act in the desired way...

       detection
    • Hypomania
      Hypomania
      Hypomania is a mood state characterized by persistent and pervasive elevated or irritable mood, as well as thoughts and behaviors that are consistent with such a mood state...

       or full-blown mania
      Mania
      Mania, the presence of which is a criterion for certain psychiatric diagnoses, is a state of abnormally elevated or irritable mood, arousal, and/ or energy levels. In a sense, it is the opposite of depression...

    • Derealization
      Derealization
      Derealization is an alteration in the perception or experience of the external world so that it seems unreal. Other symptoms include feeling as though one's environment is lacking in spontaneity, emotional coloring and depth. It is a dissociative symptom of many conditions, such as psychiatric and...

       and/or depersonalization
      Depersonalization
      Depersonalization is an anomaly of the mechanism by which an individual has self-awareness. It is a feeling of watching oneself act, while having no control over a situation. Sufferers feel they have changed, and the world has become less real, vague, dreamlike, or lacking in significance...

    • Hallucination
      Hallucination
      A hallucination, in the broadest sense of the word, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid,...

      s and/or delusion
      Delusion
      A delusion is a false belief held with absolute conviction despite superior evidence. Unlike hallucinations, delusions are always pathological...

      s
    • Thought disorder
      Thought disorder
      In psychiatry, thought disorder or formal thought disorder is a term used to describe incomprehensible language, either speech or writing, that is presumed to reflect thinking. There are different types...

       or disorganized thinking
      Thought disorder
      In psychiatry, thought disorder or formal thought disorder is a term used to describe incomprehensible language, either speech or writing, that is presumed to reflect thinking. There are different types...

    • Cognitive and memory impairment
      Cognitive deficit
      Cognitive deficit, also known as cognitive impairment is an inclusive term to describe any characteristic that acts as a barrier to cognitive performance...

       potentially to the point of retrograde
      Retrograde amnesia
      Retrograde amnesia is a loss of access to events that occurred, or information that was learned, before an injury or the onset of a disease....

       or anterograde amnesia
      Anterograde amnesia
      Anterograde amnesia is a loss of the ability to create new memories after the event that caused the amnesia, leading to a partial or complete inability to recall the recent past, while long-term memories from before the event remain intact. This is in contrast to retrograde amnesia, where memories...

    • Acute delirium
      Delirium
      Delirium or acute confusional state is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attentional deficits and generalized severe disorganization of behavior...


  • Physiological
    • Myoclonus
      Myoclonus
      Myoclonus is brief, involuntary twitching of a muscle or a group of muscles. It describes a medical sign and, generally, is not a diagnosis of a disease. Brief twitches are perfectly normal. The myoclonic twitches are usually caused by sudden muscle contractions; they also can result from brief...

       or involuntary and intense muscle twitching
    • Nystagmus
      Nystagmus
      Nystagmus is a condition of involuntary eye movement, acquired in infancy or later in life, that may result in reduced or limited vision.There are two key forms of Nystagmus: pathological and physiological, with variations within each type. Nystagmus may be caused by congenital disorders,...

       or involuntary eye movements
    • Hyperreflexia
      Hyperreflexia
      Hyperreflexia is defined as overactive or overresponsive reflexes. Examples of this can include twitching or spastic tendencies, which are indicative of upper motor neuron disease as well as the lessening or loss of control ordinarily exerted by higher brain centers of lower neural pathways...

       or overresponsive or overreactive reflex
      Reflex
      A reflex action, also known as a reflex, is an involuntary and nearly instantaneous movement in response to a stimulus. A true reflex is a behavior which is mediated via the reflex arc; this does not apply to casual uses of the term 'reflex'.-See also:...

      es
    • Tachypnoea or rapid breathing
      Breathing
      Breathing is the process that moves air in and out of the lungs. Aerobic organisms require oxygen to release energy via respiration, in the form of the metabolism of energy-rich molecules such as glucose. Breathing is only one process that delivers oxygen to where it is needed in the body and...

       and/or dyspnea
      Dyspnea
      Dyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...

       or shortness of breath
    • Palpitation
      Palpitation
      A palpitation is an abnormality of heartbeat that causes a conscious awareness of its beating, whether it is too slow, too fast, irregular, or at its normal frequency. The word may also refer to this sensation itself...

      s or abnormal awareness of the beating of the heart
      Cardiac cycle
      The cardiac cycle is a term referring to all or any of the events related to the flow or blood pressure that occurs from the beginning of one heartbeat to the beginning of the next. The frequency of the cardiac cycle is described by the heart rate. Each beat of the heart involves five major stages...

    • Angina pectoris or severe chest pain
      Chest pain
      Chest pain may be a symptom of a number of serious conditions and is generally considered a medical emergency. Even though it may be determined that the pain is non-cardiac in origin, this is often a diagnosis of exclusion made after ruling out more serious causes of the pain.-Differential...

      , as well as pulmonary hypertension
      Pulmonary hypertension
      In medicine, pulmonary hypertension is an increase in blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion...

       (PH)
    • Cardiac arrhythmia or abnormal electrical activity
      Electrical conduction system of the heart
      The normal intrinsic electrical conduction of the heart allows electrical propagation to be transmitted from the Sinoatrial Node through both atria and forward to the Atrioventricular Node. Normal/baseline physiology allows further propagation from the AV node to the ventricle or Purkinje Fibers...

       of the heart
    • Circulatory shock or cardiogenic shock
      Cardiogenic shock
      Cardiogenic shock is based upon an inadequate circulation of blood due to primary failure of the ventricles of the heart to function effectively....

    • Vasculitis
      Vasculitis
      Vasculitis refers to a heterogeneous group of disorders that are characterized by inflammatory destruction of blood vessels. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis...

       or destruction
      Toxicity
      Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...

       of blood vessel
      Blood vessel
      The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...

      s
    • Cardiotoxicity
      Cardiotoxicity
      Cardiotoxicity is the occurrence of heart electrophysiology dysfunction or/and muscle damage. The heart becomes weaker and is not as efficient in pumping and therefore circulating blood...

       or damage to the heart
    • Cardiac dysfunction, arrest, myocardial infarction
      Myocardial infarction
      Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...

      , and/or heart failure
    • Hemorrhage and/or stroke
    • Severe hyperthermia
      Hyperthermia
      Hyperthermia is an elevated body temperature due to failed thermoregulation. Hyperthermia occurs when the body produces or absorbs more heat than it can dissipate...

      , potentially resulting in organ failure
      Organ failure
      Organ dysfunction is a condition where an organ does not perform its expected function. Organ failure is organ dysfunction to such a degree that normal homeostasis cannot be maintained without external clinical intervention.It is not a diagnosis...


  • Miscellaneous
    • Syncope
      Syncope (medicine)
      Syncope , the medical term for fainting, is precisely defined as a transient loss of consciousness and postural tone characterized by rapid onset, short duration, and spontaneous recovery due to global cerebral hypoperfusion that most often results from hypotension.Many forms of syncope are...

       or fainting or loss of consciousness
    • Organ failure
      Organ failure
      Organ dysfunction is a condition where an organ does not perform its expected function. Organ failure is organ dysfunction to such a degree that normal homeostasis cannot be maintained without external clinical intervention.It is not a diagnosis...

       (as mentioned above)
    • Possible brain damage
    • Coma or death

Chronic use


Some studies indicate that repeated recreational users of MDMA have increased rates of depression and anxiety, even after quitting the drug. A Meta-analytic review of the published literature on memory show that ecstasy users may suffer short-term and long-term verbal memory impairment—with 70–80% of ecstasy users displaying impaired memory, although the results of this study may have been confounded by concurrent cannabis use. Moreover, this research shows the amount of doses consumed does not significantly predict memory performance. Other meta analyses have reported possibility of impairment of executive functioning. Despite these findings many factors including total lifetime MDMA consumption, the duration of abstinence between uses, dosage, the environment of use, poly-drug use/abuse, quality of mental health
Mental health
Mental health describes either a level of cognitive or emotional well-being or an absence of a mental disorder. From perspectives of the discipline of positive psychology or holism mental health may include an individual's ability to enjoy life and procure a balance between life activities and...

, various lifestyle choices, and predispositions to develop clinical depression and other disorders have made the results of many studies difficult to verify. A study that attempted to eliminate these confounding factors was published in February, 2011 by Addiction, and found few differences in the cognitive functioning of MDMA-using ravers versus non-MDMA-using ravers, "In a study designed to minimize limitations found in many prior investigations, we failed to demonstrate marked residual cognitive effects in ecstasy users. This finding contrasts with many previous findings-including our own-and emphasizes the need for continued caution in interpreting field studies of cognitive function in illicit ecstasy users." MDMA use has been occasionally associated with liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 damage, excessive wear of teeth, and (very rarely) hallucinogen persisting perception disorder
Hallucinogen persisting perception disorder
Hallucinogen persisting perception disorder is a disorder characterized by a continual presence of visual disturbances that are reminiscent of those generated by the ingestion of hallucinogenic substances. Previous use of hallucinogens by the person is needed, though not sufficient, for...

.


Short-term health concerns


Short-term physical health risks of MDMA consumption include hyperthermia
Hyperthermia
Hyperthermia is an elevated body temperature due to failed thermoregulation. Hyperthermia occurs when the body produces or absorbs more heat than it can dissipate...

, and hyponatremia
Hyponatremia
Hyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal. In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodium and is not due to sodium deficiency. Sodium is the dominant extracellular...

. Continuous activity without sufficient rest or rehydration may cause body temperature to rise to dangerous levels, and loss of fluid via excessive perspiration puts the body at further risk as the stimulatory and euphoric qualities of the drug may render the user oblivious to their energy expenditure for quite some time. Diuretics such as alcohol may exacerbate these risks further.

Long-term effects on serotonin and dopamine


MDMA causes a reduction in the concentration of serotonin transporter
Serotonin transporter
The serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...

s (SERTs) in the brain. The rate at which the brain recovers from serotonergic changes is unclear. One study demonstrated lasting serotonergic changes in some animals exposed to MDMA. Other studies have suggested that the brain may recover from serotonergic damage.

Some studies show that MDMA may be neurotoxic
Neurotoxicity
Neurotoxicity occurs when the exposure to natural or artificial toxic substances, which are called neurotoxins, alters the normal activity of the nervous system in such a way as to cause damage to nervous tissue. This can eventually disrupt or even kill neurons, key cells that transmit and process...

 in humans.Neurotoxicity at Dancesafe.orgDoes MDMA Cause Brain Damage?, Matthew Baggott, and John Mendelson Other studies, however, suggest that any potential brain damage may be at least partially reversible following prolonged abstinence from MDMA.Research on Ecstasy Is Clouded by Errors, Donald G. McNeil Jr., New York Times, 2 December 2003. However, other studies suggest that SERT-depletion arises from long-term MDMA use due to receptor down-regulation, rather than true neurotoxicity."p-Chlorophenylalanine Changes Serotonin Transporter mRNA Levels and Expression of the Gene Product", Journal of Neurochemistry
Journal of Neurochemistry
The Journal of Neurochemistry is a peer-reviewed scientific journal established by the International Society for Neurochemistry in 1956. The journal covers a variety of subjects within the field of neuroscience, but focuses in particular on the "molecular and cellular aspects of the nervous system,...

, 1996. Online copy (pdf)

Depression and deficits in memory have been shown to occur more frequently in long-term MDMA users.Depression at DanceSafe.org However, some recent studies have suggested that MDMA use may not be associated with chronic depression.Study claims recreational ecstasy use and depression unrelated, Wikinews,
26 April 2006


One study on MDMA toxicity, by George A. Ricaurte
George A. Ricaurte
George A. Ricaurte is a controversial neurology researcher who works at the Johns Hopkins School of Medicine in the Department of Neurology. He received his MD from Northwestern University Medical School and his Ph.D. from the University of Chicago.His research focuses on Parkinson's disease and...

 of Johns Hopkins School of Medicine, which claimed that a single recreational dose of MDMA could cause Parkinson's Disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...

 in later life due to severe dopaminergic stress, was actually retracted by Ricaurte himself after he discovered his lab had administered not MDMA but methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...

, which is known to cause dopaminergic changes similar to the serotonergic changes caused by MDMA.Ecstasy Study Botched, Retracted, Kristen Philipkoski, Wired.com, 09.05.03 Ricaurte blamed this mistake on a labeling error by the chemical supply company that sold the material to his lab, but the supply company responded that there was no evidence of a labeling error on their end. Most studies have found that levels of the dopamine transporter
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

 (or other markers of dopamine function) in MDMA users deserve further study or are normal.Aghajanian & Liebermann (2001) 'Caveat Emptor: Reseearchers Beware' Neuropsychopharmacology 24,3:335–6

Several studies have indicated a possible mechanism for neurotoxicity in a metabolite of MDMA, through the reaction of Alpha-Methyldopamine
Alpha-Methyldopamine
α-Methyldopamine , also known as 3,4-dihydroxyamphetamine , is a neurotoxin and research chemical of the phenethylamine and amphetamine chemical classes...

, a principal metabolite, and glutathione
Glutathione
Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...

, the major antioxidant in the human body. One possible product of this reaction, 2,5-bis-(glutathion-S-yl)-alpha-methyldopamine, has been demonstrated to produce the same toxic effects observed in MDMA, while MDMA, and alpha-methyldopamine themselves have been shown to be non-neurotoxic. It is, however, impossible to avoid the metabolism of MDMA in the body, and the production of this toxic metabolite. Some studies have demonstrated possible ways to minimize the production of this particular metabolite, though evidence at this point is sparse at best.

Purity and dosage of "ecstasy"



Another concern associated with MDMA use is toxicity from chemicals other than MDMA in ecstasy tablets. Due to its near-universal illegality, the purity of a substance sold as ecstasy is unknown to the typical user. The MDMA content of tablets varies widely between regions and different brands of pills and fluctuates somewhat each year. Pills may contain other active substances meant to stimulate in a way similar to MDMA, such as amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...

, methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...

, ephedrine
Ephedrine
Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....

, caffeine
Caffeine
Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...

, all of which may be comparatively cheap to produce and can help to boost overall profits. In some cases, tablets sold as ecstasy do not even contain any MDMA. Instead they may contain an assortment of undesirable drugs and substances, such as paracetamol
Paracetamol
Paracetamol INN , or acetaminophen USAN , is a widely used over-the-counter analgesic and antipyretic . It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies...

, ibuprofen
Ibuprofen
Ibuprofen is a nonsteroidal anti-inflammatory drug used for relief of symptoms of arthritis, fever, as an analgesic , especially where there is an inflammatory component, and dysmenorrhea....

, talcum powder, etc.http://ecstasydata.org/datastats.php?row=Summary&percent=1

There have been a number of deaths attributed to para-Methoxyamphetamine (PMA), a potent and highly neurotoxic hallucinogenic amphetamine, being sold as ecstasy. PMA is unique in its ability to quickly elevate body temperature and heart rate at relatively low doses, especially in comparison to MDMA. Hence, a user believing he is consuming two 120 mg pills of MDMA could actually be consuming a dose of PMA that is potentially lethal, depending on the purity of the pill. Not only does PMA cause the release of serotonin but it also acts as a monoamine oxidase inhibitor, MAOI
Monoamine oxidase inhibitor
Monoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....

. When combined with an MDMA or an MDMA-like substance, serotonin syndrome
Serotonin syndrome
Serotonin syndrome is a potentially life-threatening adverse drug reaction that may occur following therapeutic drug use, inadvertent interactions between drugs, overdose of particular drugs, or the recreational use of certain drugs...

 can result.J Pharm Pharmacol. 1980 Apr;32(4):262-6. Combining MAO inhibitors with certain legal prescription and over the counter medications can also lead to (potentially fatal) serotonin syndrome.

Harm assessment


The UK study placed great weight on the risk for acute physical harm, the propensity for physical and psychological dependency on the drug, and the negative familial and societal impacts of the drug. They did not evaluate or rate the negative impact of ecstasy on the cognitive health of ecstasy users, e.g., impaired memory and concentration. Based on these factors, the study placed MDMA at number 18 in the list of 20 popular drugs.Scientists want new drug rankings, BBC News, 23 March 2007

David Nutt
David Nutt
David John Nutt is a British psychiatrist and neuropsychopharmacologist specialising in the research of drugs that affect the brain and conditions such as addiction, anxiety and sleep. He was until 2009 a professor at the University of Bristol heading their Psychopharmacology Unit...

, a former chairman of the UK Advisory Council on the Misuse of Drugs
Advisory Council on the Misuse of Drugs
The Advisory Council on the Misuse of Drugs is a statutory and non-executive non-departmental British public body, which was established under the UK's Misuse of Drugs Act 1971.-Mandate:Its terms of reference, according to the Act, are as follows:...

, stated in the Journal of Psychopharmacology in January 2009 that ecstasy use compared favorably with horse riding in terms of risk, with ecstasy leading to around 30 deaths a year in the UK compared to about 10 from horse riding, and "acute harm to person" occurring in approximately 1 in 10,000 episodes of ecstasy use compared to about 1 in 350 episodes of horse riding. Dr. Nutt notes the lack of a balanced risk assessment in public discussions of MDMA:

The general public, especially the younger generation, are disillusioned with the lack of balanced political debate about drugs. This lack of rational debate can undermine the trust in government in relation to drug misuse and thereby undermining the government's message in public information campaigns. The media in general seem to have an interest in scare stories about illicit drugs, though there are some exceptions (Horizon, 2008). A telling review of 10-year media reporting of drug deaths in Scotland illustrates the distorted media perspective very well (Forsyth, 2001). During this decade, the likelihood of a newspaper reporting a death from paracetamol was in per 250 deaths, for diazepam it was 1 in 50, whereas for amphetamine it was 1 in 3 and for ecstasy every associated death was reported.

A spokesperson for the ACMD said that "The recent article by Professor David Nutt published in the Journal of Psychopharmacology was done in respect of his academic work and not as chair of the ACMD."Ecstasy 'not worse than riding', BBC News, 7 February 2009

The most carefully designed study so far was published in February 2011Halpern et. al, Addiction, 2011 in the journal Addiction, comparing the effect on cognitive skills in 52 ecstasy users against 59 very closely matched non-users. The study, performed by the group of Prof. Halpern of Harvard Medical School, eliminated potential confounding factors like the use of other drugs and history of drug-use. The study found no short- or long-term differences in cognitive skills in the test group (users) versus the control group (non-users).

Drug interactions


There are a number of reported potentially dangerous possible interactions between MDMA and other drugs, including serotonergic
Serotonergic
Serotonergic or serotoninergic means "related to the neurotransmitter serotonin". A synapse is serotonergic if it uses serotonin as its neurotransmitter...

 drugs.http://www.ncbi.nlm.nih.gov/pubmed/17620161 Qualitative review of serotonin syndrome, ecstasy (MDMA) and the use of other serotonergic substances: hierarchy of risk (by Silins E, Copeland J, Dillon P.)] Several cases have been reported of death in individuals who ingested MDMA while taking ritonavir
Ritonavir
Ritonavir, with trade name Norvir , is an antiretroviral drug from the protease inhibitor class used to treat HIV infection and AIDS....

 (Norvir), which inhibits multiple CYP450 enzymes. Toxicity or death has also been reported in people who took MDMA in combination with certain monoamine oxidase inhibitor
Monoamine oxidase inhibitor
Monoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....

s (MAOIs) such as phenelzine
Phenelzine
Phenelzine is a non-selective and irreversible monoamine oxidase inhibitor of the hydrazine class which is used as an antidepressant and anxiolytic...

 (Nardil), tranylcypromine
Tranylcypromine
Tranylcypromine is a drug of the substituted phenethylamine and amphetamine classes which acts as a monoamine oxidase inhibitor —it is a non-selective and irreversible inhibitor of the enzyme monoamine oxidase...

 (Parnate), or moclobemide
Moclobemide
Moclobemide is a monoamine oxidase inhibitor drug primarily used to treat depression and social anxiety. Although clinical trials with the medicine began in 1977, it is not approved for use in the United States...

 (Aurorix, Manerix). On the other hand, MAOB
Monoamine oxidase B
Monoamine oxidase B, also known as MAOB, is a protein that in humans is encoded by the MAOB gene.The protein encoded by this gene belongs to the flavin monoamine oxidase family. It is an enzyme located in the mitochondrial outer membrane...

 inhibitors like selegiline
Selegiline
Selegiline is a drug used for the treatment of early-stage Parkinson's disease, depression and senile dementia. In normal clinical doses it is a selective irreversible MAO-B inhibitor, however in larger doses it loses its specificity and also inhibits MAO-A...

 (Deprenyl; Eldepryl, Zelapar, Emsam) do not seem to carry these risks when taken at selective doses, and have been used to completely block neurotoxicity in rats.The Prozac Misunderstanding, at TheDEA.org

Commercial sassafras oil generally is a by-product of camphor
Camphor
Camphor is a waxy, white or transparent solid with a strong, aromatic odor. It is a terpenoid with the chemical formula C10H16O. It is found in wood of the camphor laurel , a large evergreen tree found in Asia and also of Dryobalanops aromatica, a giant of the Bornean forests...

 production in Asia
Asia
Asia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...

 or comes from related trees in Brazil
Brazil
Brazil , officially the Federative Republic of Brazil , is the largest country in South America. It is the world's fifth largest country, both by geographical area and by population with over 192 million people...

. Safrole is a precursor for the clandestine manufacture
Clandestine chemistry
Clandestine chemistry is chemistry carried out in secret, and particularly in illegal drug laboratories. Larger labs are usually run by gangs or organized crime intending to produce for distribution on the black market...

 of MDMA
Methylenedioxymethamphetamine
MDMA is an entactogenic drug of the phenethylamine and amphetamine class of drugs. In popular culture, MDMA has become widely known as "ecstasy" , usually referring to its street pill form, although this term may also include the presence of possible adulterants...

 (ecstasy), and as such, its transport is monitored internationally.
Roots of Sassafras can also be steeped to make tea and were used in the flavoring of traditional root beer
Root beer
Root beer is a carbonated, sweetened beverage, originally made using the root of a sassafras plant as the primary flavor. Root beer, popularized in North America, comes in two forms: alcoholic and soft drink. The historical root beer was analogous to small beer in that the process provided a drink...

 until being banned for mass production by the FDA. Laboratory animals that were given oral doses of sassafras tea or sassafras oil that contained large doses of safrole developed permanent liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 damage or various types of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

. In humans liver damage can take years to develop and it may not have obvious signs.

Chemistry


Safrole
Safrole
Safrole, also known as shikimol, is a phenylpropene. It is a colorless or slightly yellow oily liquid. It is typically extracted from the root-bark or the fruit of sassafras plants in the form of sassafras oil , or synthesized from other related methylenedioxy...

, a colorless or slightly black oil, extracted from the root-bark or the fruit of sassafras
Sassafras
Sassafras is a genus of three extant and one extinct species of deciduous trees in the family Lauraceae, native to eastern North America and eastern Asia.-Overview:...

 plants is the primary precursor for all manufacture of MDMA. There are numerous synthetic methods available in the literature to convert safrole into MDMA via different intermediates.Reductive aminations of carbonyl compounds with borohydride and borane reducing agents. Baxter, Ellen W.; Reitz, Allen B. Organic Reactions (Hoboken, New Jersey, United States) (2002), 59 One common route is via the MDP2P
MDP2P
3,4-phenyl-2-propanone , is a chemical compound consisting of a phenylacetone moiety substituted with a methylenedioxy functional group, an entactogen and stimulant of the phenethylamine, amphetamine, and cathinone classes...

 (3,4-methylenedioxy
Methylenedioxy
Methylenedioxy in the field of chemistry, particularly in organic chemistry, is the name for a functional group with the structural formula R-O-CH2-O-R' which is connected to the rest of a molecule by two chemical bonds. The methylenedioxy group consists of two oxygen atoms connected to a methylene...

phenyl-2-propanone, also known as piperonyl acetone) intermediate. This intermediate can be produced in at least two different ways. One method is to isomerize safrole to isosafrole
Isosafrole
Isosafrole is a phenylpropene, a type of aromatic organic chemical with a smell similar to anise or licorice. It is found in small amounts in various essential oils, but is most commonly obtained by isomerizing the plant oil safrole....

 in the presence of a strong base and then oxidize isosafrole
Isosafrole
Isosafrole is a phenylpropene, a type of aromatic organic chemical with a smell similar to anise or licorice. It is found in small amounts in various essential oils, but is most commonly obtained by isomerizing the plant oil safrole....

 to MDP2P. Another, reportedly better, method is to make use of the Wacker process
Wacker process
The Wacker process or the Hoechst-Wacker process originally referred to the oxidation of ethylene to acetaldehyde by oxygen in water in the presence of a tetrachloropalladate catalyst...

 to oxidize safrole directly to the MDP2P (3,4-methylenedioxy phenyl-2-propanone) intermediate. This can be done with a palladium
Palladium
Palladium is a chemical element with the chemical symbol Pd and an atomic number of 46. It is a rare and lustrous silvery-white metal discovered in 1803 by William Hyde Wollaston. He named it after the asteroid Pallas, which was itself named after the epithet of the Greek goddess Athena, acquired...

 catalyst. Once the MDP2P intermediate has been prepared, a reductive amination
Reductive amination
Reductive amination is a form of amination that involves the conversion of a carbonyl group to an amine via an intermediate imine...

 leads to MDMA, a racemate {1:1 mixture of (R)-1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine and (S)-1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine}.
Another method for the synthesis of racemic
Racemic
In chemistry, a racemic mixture, or racemate , is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule. The first known racemic mixture was "racemic acid", which Louis Pasteur found to be a mixture of the two enantiomeric isomers of tartaric acid.- Nomenclature :A...

 MDMA is addition of hydrogen bromide to safrole and reaction of the adduct with methylamine.


Relatively small quantities of essential oil are required to make large numbers of MDMA pills. The essential oil of Ocotea cymbarum
Ocotea cymbarum
Ocotea cymbarum is a species of plant in the Lauraceae family. It is found in Brazil, Colombia, French Guiana, Guyana, Suriname, and Venezuela.-References:* World Conservation Monitoring Centre 1998. . Downloaded on 22 August 2007....

typically contains between 80 and 94% safrole. This would allow 500 ml of the oil, which retails at between $20 and $100, to be used to produce an estimated 1,300 to 2,800 tablets containing approximately 120 mg of MDMA each.Nov 2005 DEA Microgram newsletter. Usdoj.gov (2005-11-11). Retrieved on 2011-06-11.

Pharmacology


MDMA acts as a releasing agent
Releasing agent
A releasing agent , or simply releaser, is a drug that induces the release of a neurotransmitter from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitter. Many drugs use neurotransmitter release to exert their psychological and...

 of serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

, norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

, and dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

. It enters neurons via carriage by the monoamine transporter
Monoamine transporter
Monoamine transporters are protein structures that function as integral plasma membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. Three major classes of MATs are responsible for the reuptake of their associated amine neurotransmitters...

s. Once inside, MDMA inhibits the vesicular monoamine transporter
Vesicular monoamine transporter
The vesicular monoamine transporter is a transport protein integrated into the membrane of intracellular vesicles of presynaptic neurons. It acts to transport monoamines into the synaptic vesicles.-Monoamines:...

, which results in increased concentrations of serotonin, norepinephrine, and dopamine in the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...

, and induces their release by reversing
Transporter reversal
Transporter reversal is the action of reversing a plasmalemmal transporter via a process known as phosphorylation. Neurotransmitter transporters normally function as part of the reuptake process, by carrying neurotransmitter chemicals from the extracellular space into the cytoplasm of a...

 their respective transporters through a process known as phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....

. It also acts as a weak 5-HT1
5-HT1 receptor
The 5-HT1 receptors are a subfamily of 5-HT receptors that bind the endogenous neurotransmitter serotonin . The 5-HT1 subfamily consists of five G protein-coupled receptors that are coupled to Gi/Go and mediate inhibitory neurotransmission, including 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F...

 and 5-HT2 receptor
5-HT2 receptor
The 5-HT2 receptors are a subfamily of 5-HT receptors that bind the endogenous neurotransmitter serotonin . The 5-HT2 subfamily consists of three G protein-coupled receptors which are coupled to Gq/G11 and mediate excitatory neurotransmission, including 5-HT2A, 5-HT2B, and 5-HT2C...

 agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...

, and its more efficacious metabolite MDA
3,4-Methylenedioxyamphetamine
3,4-Methylenedioxyamphetamine , also known as tenamfetamine , is a psychedelic and entactogenic drug of the phenethylamine and amphetamine chemical classes...

 likely augments this action.

MDMA's unusual entactogenic effects have been hypothesized to be, at least partly, the result of indirect oxytocin
Oxytocin
Oxytocin is a mammalian hormone that acts primarily as a neuromodulator in the brain.Oxytocin is best known for its roles in sexual reproduction, in particular during and after childbirth...

 secretion via activation of the serotonin system. Oxytocin is a hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

 released following events like hugging, orgasm
Orgasm
Orgasm is the peak of the plateau phase of the sexual response cycle, characterized by an intense sensation of pleasure...

, and childbirth
Childbirth
Childbirth is the culmination of a human pregnancy or gestation period with the birth of one or more newborn infants from a woman's uterus...

, and is thought to facilitate bonding
Pair bond
In biology, a pair bond is the strong affinity that develops in some species between the males and females in a pair, potentially leading to breeding. Pair-bonding is a term coined in the 1940s that is frequently used in sociobiology and evolutionary psychology circles...

 and the establishment of trust. Based on studies in rats, MDMA is believed to cause the release of oxytocin, at least in part, by both directly and indirectly agonizing the serotonin 5-HT1A receptor
5-HT1A receptor
The 5-HT1A receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gi/Go and mediates inhibitory neurotransmission...

. A placebo-controlled study in 15 human volunteers found that 100 mg MDMA increased blood levels of oxytocin, and the amount of oxytocin increase was correlated with the subjective prosocial effects of MDMA.

Pharmacokinetics


MDMA reaches maximal concentration
Concentration
In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...

s in the blood stream between 1.5 and 3 hours after ingestion
Ingestion
Ingestion is the consumption of a substance by an organism. In animals, it normally is accomplished by taking in the substance through the mouth into the gastrointestinal tract, such as through eating or drinking...

. It is then slowly metabolized
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

 and excreted
Excretion
Excretion is the process by which waste products of metabolism and other non-useful materials are eliminated from an organism. This is primarily carried out by the lungs, kidneys and skin. This is in contrast with secretion, where the substance may have specific tasks after leaving the cell...

, with levels decreasing to half their peak concentration over approximately 8 hours. Thus, there are still high MDMA levels in the body when the experiential effects have mostly ended, indicating that acute tolerance has developed to the actions of MDMA. Taking additional supplements of MDMA at this point, therefore, produces higher concentrations of MDMA in the blood and brain than might be expected based on the perceived effects.

Metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...

s of MDMA that have been identified in humans include 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxy-methamphetamine (HMMA), 4-hydroxy-3-methoxyamphetamine (HMA), 3,4-dihydroxyamphetamine (DHA) (also called alpha-methyldopamine (α-Me-DA)), 3,4-methylenedioxyphenylacetone
MDP2P
3,4-phenyl-2-propanone , is a chemical compound consisting of a phenylacetone moiety substituted with a methylenedioxy functional group, an entactogen and stimulant of the phenethylamine, amphetamine, and cathinone classes...

 (MDP2P), and N-hydroxy-3,4-methylenedioxyamphetamine (MDOH). The contributions of these metabolites to the psychoactive and toxic effects of MDMA are an area of active research. Sixty-five percent of MDMA is excreted unchanged in the urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...

 (in addition, 7% is metabolized into MDA) during the 24 hours after ingestion.

MDMA is known to be metabolized by two main metabolic pathway
Metabolic pathway
In biochemistry, metabolic pathways are series of chemical reactions occurring within a cell. In each pathway, a principal chemical is modified by a series of chemical reactions. Enzymes catalyze these reactions, and often require dietary minerals, vitamins, and other cofactors in order to function...

s: (1) O-demethylenation followed by catechol-O-methyltransferase
Catechol-O-methyl transferase
Catechol-O-methyltransferase is one of several enzymes that degrade catecholamines such as dopamine, epinephrine, and norepinephrine. In humans, catechol-O-methyltransferase protein is encoded by the COMT gene...

 (COMT)-catalyzed methylation and/or glucuronide/sulfate conjugation; and (2) N-dealkylation, deamination, and oxidation to the corresponding benzoic acid
Benzoic acid
Benzoic acid , C7H6O2 , is a colorless crystalline solid and the simplest aromatic carboxylic acid. The name derived from gum benzoin, which was for a long time the only source for benzoic acid. Its salts are used as a food preservative and benzoic acid is an important precursor for the synthesis...

 derivatives conjugated with glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...

. The metabolism may be primarily by cytochrome P450
Cytochrome P450 oxidase
The cytochrome P450 superfamily is a large and diverse group of enzymes. The function of most CYP enzymes is to catalyze the oxidation of organic substances. The substrates of CYP enzymes include metabolic intermediates such as lipids and steroidal hormones, as well as xenobiotic substances...

 (CYP450) enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s (CYP2D6
CYP2D6
Cytochrome P450 2D6 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. Also, many substances are bioactivated by CYP2D6 to form their active compounds...

 (in humans, but CYP2D1 in mice
MICE
-Fiction:*Mice , alien species in The Hitchhiker's Guide to the Galaxy*The Mice -Acronyms:* "Meetings, Incentives, Conferencing, Exhibitions", facilities terminology for events...

), and CYP3A4
CYP3A4
Cytochrome P450 3A4 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. CYP3A4 is involved in the oxidation of the largest range of substrates of all the CYPs. As a result, CYP3A4 is present in...

) and COMT. Complex, nonlinear pharmacokinetics
Pharmacokinetics
Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism...

 arise via autoinhibition of CYP2D6
CYP2D6
Cytochrome P450 2D6 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. Also, many substances are bioactivated by CYP2D6 to form their active compounds...

 and CYP2D8, resulting in zeroth order kinetics
Rate equation
The rate law or rate equation for a chemical reaction is an equation that links the reaction rate with concentrations or pressures of reactants and constant parameters . To determine the rate equation for a particular system one combines the reaction rate with a mass balance for the system...

 at higher doses. It is thought that this can result in sustained and higher concentration
Concentration
In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...

s of MDMA if the user takes consecutive doses of the drug.

Because the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 CYP2D6
CYP2D6
Cytochrome P450 2D6 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. Also, many substances are bioactivated by CYP2D6 to form their active compounds...

 is deficient or totally absent in some people,eMedicine – Toxicity, MDMA: Article by David Yew. Emedicine.com. Retrieved on 2011-06-11. it was once hypothesized that these people might have elevated risk when taking MDMA. However, there is still no evidence for this theory and available evidence argues against it. It is now thought that the contribution of CYP2D6 to MDMA metabolism in humans is less than 30% of the metabolism. Indeed, an individual lacking CYP2D6 was given MDMA in a controlled clinical setting and a larger study gave MDMA to healthy volunteers after inhibiting CYP2D6 with paroxetine
Paroxetine
Paroxetine is an SSRI antidepressant. Marketing of the drug began in 1992 by the pharmaceutical company SmithKline Beecham, now GlaxoSmithKline...

. Lack of the enzyme caused a modest increase in drug exposure and decreases in some metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...

s, but physical effects did not appear appreciably elevated. While there is little or no evidence that low CYP2D6 activity increases risks from MDMA, it is likely that MDMA-induced CYP2D inhibition will increase risk of those prescription drugs that are metabolized by this enzyme. MDMA-induced CYP2D inhibition appears to last for up to a week after MDMA exposure.

MDMA and metabolites are primarily excreted as conjugates, such as sulfates and glucuronides.
MDMA is a chiral
Chirality (chemistry)
A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....

 compound and has been almost exclusively administered as a racemate
Racemic
In chemistry, a racemic mixture, or racemate , is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule. The first known racemic mixture was "racemic acid", which Louis Pasteur found to be a mixture of the two enantiomeric isomers of tartaric acid.- Nomenclature :A...

. However, an early uncontrolled report suggests that the (S)-enantiomer
Enantiomer
In chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable , much as one's left and right hands are the same except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...

 is significantly more potent
Potency (pharmacology)
In the field of pharmacology, potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. A highly potent drug evokes a larger response at low concentrations, while a drug of lower potency evokes a small response at low concentrations...

 in humans than the (R)-enantiomer indicate that the disposition of MDMA is stereoselective, with the S-enantiomer having a shorter elimination half-life and greater excretion than the R-enantiomer. For example, Fallon et al. reported that the area under the blood plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...

 concentration versus time curve (AUC) was two to four times higher for the (R)-enantiomer than the (S)-enantiomer after a 40 mg oral dose in human volunteers. Likewise, the plasma half-life of (R)-MDMA was significantly longer than that of the (S)-enantiomer (5.8 ± 2.2 hours vs 3.6 ± 0.9 hours). However, because MDMA has dose dependent kinetics, it is likely that these half-lives would be higher at more typical doses (100 mg is sometimes considered a typical dose). Given as the racemate, MDMA has a half-life
Half-life
Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...

 of around 8 hours.

Detection of use


MDMA and MDA may be quantitated in blood, plasma or urine to monitor for abuse, confirm a diagnosis of poisoning or assist in the forensic investigation of a traffic or other criminal violation or a sudden death. Some drug abuse screening programs rely on hair, saliva, or sweat as specimens. Most commercial amphetamine immunoassay screening tests cross-react significantly with MDMA or its major metabolites, but chromatographic techniques can easily distinguish and separately measure each of these substances. The concentrations of MDA in the blood or urine of a person who has taken only MDMA are, in general, less than 10% those of the parent drug.Kolbrich EA, Goodwin RS, Gorelick DA, Hayes RJ, Stein EA, Huestis MA. Plasma pharmacokinetics of 3,4-methylenedioxymethamphetamine after controlled oral administration to young adults. Ther. Drug Monit. 30: 320–332, 2008.R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 9th edition, Biomedical Publications, Seal Beach, California, 2011, pp. 1078–1080.

History



MDMA was first synthesized in 1912 by Merck
Merck KGaA
Merck KGaA is a German chemical and pharmaceutical company. Merck, also known as “German Merck” and “Merck Darmstadt”, was founded in Darmstadt, Germany, in 1668, making it the world's oldest operating chemical and pharmaceutical company. The company was privately owned until going public in 1995...

 chemist Anton Köllisch
Anton Kollisch
Anton Köllisch was the German chemist who, whilst working at Darmstadt for pharmaceutical giant Merck, first synthesized the chemical MDMA that would later come to be known as "ecstasy"....

. At the time, Merck was interested in developing substances that stopped abnormal bleeding. Merck wanted to evade an existing patent, held by Bayer
Bayer
Bayer AG is a chemical and pharmaceutical company founded in Barmen , Germany in 1863. It is headquartered in Leverkusen, North Rhine-Westphalia, Germany and well known for its original brand of aspirin.-History:...

, for one such compound: hydrastinine
Hydrastinine
Hydrastinine is a semisynthetic alkaloid from the hydrolysis of the alkaloid hydrastine, which was found naturally in small quantities in Hydrastis canadensis L. . Hydrastinine was produced by oxidative splitting of hydrastine hydrochloride with nitric acid in good yield...

. At the behest of his superiors Walther Beckh and Otto Wolfes, Köllisch developed a preparation of a hydrastinine analogue, methylhydrastinine. MDMA was an intermediate compound
Reaction intermediate
A reaction intermediate or an intermediate is a molecular entity that is formed from the reactants and reacts further to give the directly observed products of a chemical reaction. Most chemical reactions are stepwise, that is they take more than one elementary step to complete...

 in the synthesis of methylhydrastinine, and Merck was not interested in its properties at the time. On 24 December 1912, Merck filed two patent applications that described the synthesis of MDMA and its subsequent conversion to methylhydrastinine.

Over the following 65 years, MDMA was largely forgotten. Merck records indicate that its researcher
Researcher
A researcher is somebody who performs research, the search for knowledge or in general any systematic investigation to establish facts. Researchers can work in academic, industrial, government, or private institutions.-Examples of research institutions:...

s returned to the compound sporadically. In 1927, Max Oberlin studied the pharmacology of MDMA and observed that its effects on blood sugar
Blood sugar
The blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal. Normally in mammals, the body maintains the blood glucose level at a reference range between about 3.6 and 5.8 mM , or 64.8 and 104.4 mg/dL...

 and smooth muscle
Smooth muscle
Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...

s were similar to ephedrine
Ephedrine
Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....

's. Researchers at Merck conducted experiments with MDMA in 1952 and 1959. In 1953 and 1954, the United States Army
United States Army
The United States Army is the main branch of the United States Armed Forces responsible for land-based military operations. It is the largest and oldest established branch of the U.S. military, and is one of seven U.S. uniformed services...

 commissioned a study of toxicity
Toxicity
Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...

 and behavioral effects in animals of injected mescaline
Mescaline
Mescaline or 3,4,5-trimethoxyphenethylamine is a naturally occurring psychedelic alkaloid of the phenethylamine class used mainly as an entheogen....

 and several analogues, including MDMA. These originally classified investigations were declassified and published in 1973. The first scientific paper on MDMA appeared in 1958 in Yakugaku Zasshi, the Journal of the Pharmaceutical Society of Japan. In this paper, Yutaka Kasuya described the synthesis of MDMA, a part of his research on antispasmodics.

MDMA was being used recreationally in the United States by 1970.The first confirmed sample was seized and identified by Chicago Police in 1970, see In the mid-1970s, Alexander Shulgin
Alexander Shulgin
Alexander "Sasha" Theodore Shulgin is an American pharmacologist, chemist, artist, and drug developer.Shulgin is credited with the popularization of MDMA, commonly known as ecstasy, in the late 1970s and early 1980s, especially for psychopharmaceutical use and the treatment of depression and...

, then at University of California, Berkeley
University of California, Berkeley
The University of California, Berkeley , is a teaching and research university established in 1868 and located in Berkeley, California, USA...

, heard from his students about unusual effects of MDMA; among others, the drug had helped one of them to overcome his stutter. Intrigued, Shulgin synthesized MDMA and tried it himself in 1976. Two years later, he and David E. Nichols
David E. Nichols
David E. Nichols is an American pharmacologist and medicinal chemist.Presently the Robert C. and Charlotte P. Anderson Distinguished Chair in Pharmacology at Purdue University, Nichols has worked in the field of psychoactive drugs since 1969...

 published the first report on the drug's psychotropic effect in humans. They described "altered state of consciousness with emotional and sensual overtones" that can be compared "to marijuana, and to psilocybin
Psilocybin
Psilocybin is a naturally occurring psychedelic prodrug, with mind-altering effects similar to those of LSD and mescaline, after it is converted to psilocin. The effects can include altered thinking processes, perceptual distortions, an altered sense of time, and spiritual experiences, as well as...

 devoid of the hallucinatory component".

Shulgin took to occasionally using MDMA for relaxation, referring to it as "my low-calorie martini", and giving the drug to his friends, researchers, and other people who he thought could benefit from it. One such person was psychotherapist Leo Zeff
Leo Zeff
Dr. Leo Zeff was an American psychologist and psychotherapist in Oakland, California who pioneered the use of ecstasy and other psychoactive drugs in psychotherapy in the 1970s....

, who had been known to use psychedelic
Psychedelic drug
A psychedelic substance is a psychoactive drug whose primary action is to alter cognition and perception. Psychedelics are part of a wider class of psychoactive drugs known as hallucinogens, a class that also includes related substances such as dissociatives and deliriants...

s in his practice. Zeff was so impressed with the effects of MDMA that he came out of his semi-retirement to proselytize for it. Over the following years, Zeff traveled around the U.S. and occasionally to Europe, training other psychotherapists in the use of MDMA. Among underground psychotherapists, MDMA developed a reputation for enhancing communication during clinical sessions, reducing patients' psychological defenses, and increasing capacity for therapeutic introspection
Introspection
Introspection is the self-observation and reporting of conscious inner thoughts, desires and sensations. It is a conscious and purposive process relying on thinking, reasoning, and examining one's own thoughts, feelings, and, in more spiritual cases, one's soul...

. Doblin, Rick. A Clinical Plan for MDMA (Ecstasy) in the Treatment of Post-Traumatic Stress Disorder (PTSD): Partnering with the FDA. Referenced 2011-10-23 from http://www.maps.org/news-letters/v12n3/12305dob.html

In the early 1980s in the U.S., MDMA rose to prominence as "Adam" in trendy nightclubs and gay dance clubs in the Dallas area.''The Austin Chronicle'' – "Countdown to Ecstasy." by Marc Savlov. Weeklywire.com. Retrieved on 2011-06-11. From there, use spread to rave
Rave
Rave, rave dance, and rave party are parties that originated mostly from acid house parties, which featured fast-paced electronic music and light shows. At these parties people dance and socialize to dance music played by disc jockeys and occasionally live performers...

s in major cities around the country, and then to mainstream society. The drug was first proposed for scheduling
Controlled Substances Act
The Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...

 by the Drug Enforcement Administration
Drug Enforcement Administration
The Drug Enforcement Administration is a federal law enforcement agency under the United States Department of Justice, tasked with combating drug smuggling and use within the United States...

 (DEA) in July 1984 and was classified as a Schedule I controlled substance in the U.S. on 31 May 1985.Erowid MDMA Vault: Info #3 on Scheduling. Erowid.org. Retrieved on 2011-06-11.

In the late 1980s MDMA, known by that time as "ecstasy", began to be widely used in the UK and other parts of Europe, becoming an integral element of rave culture and other psychedelic-influenced music scenes. Spreading along with rave culture, illicit MDMA use became increasingly widespread among young adults in universities and later in high schools. MDMA became one of the four most widely used illicit drugs in the U.S., along with cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...

, heroin, and cannabis
Cannabis (drug)
Cannabis, also known as marijuana among many other names, refers to any number of preparations of the Cannabis plant intended for use as a psychoactive drug or for medicinal purposes. The English term marijuana comes from the Mexican Spanish word marihuana...

.
According to some estimates as of 2004, only marijuana attracts more first time users in the U.S.

After MDMA was criminalized, most medical use stopped, although some therapists continued to prescribe the drug illegally. Later Charles Grob initiated an ascending-dose safety study in healthy volunteers. Subsequent legally-approved MDMA studies in humans have taken place in the U.S. in Detroit (Wayne State University
Wayne State University
Wayne State University is a public research university located in Detroit, Michigan, United States, in the city's Midtown Cultural Center Historic District. Founded in 1868, WSU consists of 13 schools and colleges offering more than 400 major subject areas to over 32,000 graduate and...

), Chicago (University of Chicago
University of Chicago
The University of Chicago is a private research university in Chicago, Illinois, USA. It was founded by the American Baptist Education Society with a donation from oil magnate and philanthropist John D. Rockefeller and incorporated in 1890...

), San Francisco (UCSF and California Pacific Medical Center
California Pacific Medical Center
California Pacific Medical Center is one of the largest private, non-profit, academic medical centers in Northern California. The Medical Center is a combination of four of San Francisco's oldest medical institutions: Pacific Presbyterian Hospital, Children's Hospital of San Francisco, Davies...

), Baltimore
Baltimore
Baltimore is the largest independent city in the United States and the largest city and cultural center of the US state of Maryland. The city is located in central Maryland along the tidal portion of the Patapsco River, an arm of the Chesapeake Bay. Baltimore is sometimes referred to as Baltimore...

 (NIDA
National Institute on Drug Abuse
The National Institute on Drug Abuse is a United States federal-government research institute whose mission is to "lead the Nation in bringing the power of science to bear on drug abuse and addiction."-History:...

–NIH Intramural Program), and South Carolina
South Carolina
South Carolina is a state in the Deep South of the United States that borders Georgia to the south, North Carolina to the north, and the Atlantic Ocean to the east. Originally part of the Province of Carolina, the Province of South Carolina was one of the 13 colonies that declared independence...

, as well as in Switzerland (University Hospital of Psychiatry, Zürich
Zürich
Zurich is the largest city in Switzerland and the capital of the canton of Zurich. It is located in central Switzerland at the northwestern tip of Lake Zurich...

), the Netherlands (Maastricht University), and Spain (Universitat Autònoma de Barcelona).Bibliography of Psychadelic Research Studies. collected by the Multidisciplinary Association for Psychedelic Studies

In 2010, the BBC reported that use of MDMA had decreased in the UK in previous years. This is thought to be due to increased seizures and decreased production of the precursor chemicals used to manufacture MDMA. The availability of legal alternatives to MDMA such as mephedrone, or methylone, is also thought to have contributed to its decrease in popularity.

Legal status


MDMA is legally controlled in most of the world under the UN Convention on Psychotropic Substances
Convention on Psychotropic Substances
The Convention on Psychotropic Substances of 1971 is a United Nations treaty designed to control psychoactive drugs such as amphetamines, barbiturates, benzodiazepines, and psychedelics signed at Vienna on February 21, 1971...

 and other international agreements, although exceptions exist for research. In general, the unlicensed use, sale or manufacture of MDMA are all criminal offenses.

United Kingdom


MDMA was made illegal in 1977 by a modification order to the existing Misuse of Drugs Act 1971
Misuse of Drugs Act 1971
The Misuse of Drugs Act 1971 is an Act of Parliament which represents UK action in line with treaty commitments under the Single Convention on Narcotic Drugs, the Convention on Psychotropic Substances, and the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic...

. Although MDMA was not named explicitly in this legislation, the order extended the definition of Class A drugs to include various ring-substituted phenethylamines,Misuse of Drugs Act 1971. Statutelaw.gov.uk (1998-01-05). Retrieved on 2011-06-11. thereby making it illegal to sell, buy, or possess the drug without a license. Penalties include a maximum of seven years and/or unlimited fine for possession; life and/or unlimited fine for production or trafficking. See list of drugs illegal in the UK for more information. In February 2009 an official independent scientific advisory board to the UK government recommended that MDMA be re-classified to Class B, but this recommendation was immediately rejected by the government (see Recommendation to downgrade MDMA). This 2009 report on MDMA stated:
In 2000, the UK Police Foundation issued the Runciman Report
Runciman Report
The Runciman Report was a 2000 Police Foundation inquiry into the United Kingdom's Misuse of Drugs Act 1971 authored by Viscountess Runciman.-Recommendations:...

, which reviewed the medical and social harms of MDMA and recommended: "Ecstasy and related compounds should be transferred from Class A to Class B."Drugs and the law: Report of the inquiry into the Misuse of Drugs Act 1971 London: Police Foundation, 2000, Runciman Report
Runciman Report
The Runciman Report was a 2000 Police Foundation inquiry into the United Kingdom's Misuse of Drugs Act 1971 authored by Viscountess Runciman.-Recommendations:...

In 2002, the Home Affairs Committee of the UK House of Commons, issued a report, The Government's Drugs Policy: Is it working?, which also recommended that MDMA should be reclassified to a Class B drug."The Government's Drugs Policy: Is it working?" House of Commons, Home Affairs Committee, May 2002 The UK government rejected both recommendations, saying that re-classification of MDMA would not be considered without a recommendation from the Advisory Council on the Misuse of Drugs, the official UK scientific advisory board on drug abuse issues.
[Fifth Report], UK House of Commons, Science and Technology Committee, (July 2006)