Effects of MDMA on the human body
Encyclopedia
The effects of MDMA on the human brain and body are complex, interacting with several neurochemical systems. It induces serotonin
, dopamine
, and norepinephrine
release, and can act directly on a number of receptors, including α2-adrenergic (adrenaline) and 5HT2A(serotonin) receptors. MDMA promotes the release of several hormones including prolactin
, oxytocin
, ACTH, dehydroepiandrosterone
(DHEA), and the antidiuretic hormone vasopressin
(which may be important in its occasional production of water intoxication
or hyponatremia
).
It's not fully understood why MDMA induces these unusual psychoactive effects. Most explanations focus on serotonin release. MDMA causes serotonin
vesicles
in the neurons to release quantities of serotonin into the synapse
s. Studies using pretreatment with an SSRI to block the ability of MDMA to release serotonin in volunteers suggest serotonin release is necessary for most effects of MDMA in humans. Released serotonin is believed to stimulate several receptors that contribute to the experiential effects of MDMA. Laboratory rodent experiments have shown MDMA to activate oxytocin
-containing neurons in the hypothalamus
by stimulating 5-HT1A receptors. This appears to contribute to some of the social effects of MDMA: upon administering a drug that blocked brain receptors for oxytocin, the effects of the drug on social behavior were reduced. A second serotonin receptor, 5-HT2A receptors (which are important for the effects of hallucinogens), makes mild contributions to MDMA effects. When the receptor was blocked, volunteers given MDMA reported decreases in MDMA-induced perceptual changes, emotional excitation, and acute adverse responses. In contrast, blocking these 5-HT2A receptors had little effect on MDMA-induced positive mood, well-being, extroversion, and most short-term sequelae. One possible explanation for some of these 5-HTA-mediated effects is that 5-HT2A stimulation inhibits dopamine release.
Although serotonin is important to the effects of MDMA, other drugs that release serotonin, such as fenfluramine
, do not have effects like MDMA. This indicates that other neurochemical systems must be important for the MDMA experience. In addition to serotonin, dopamine and noradrenaline may play important roles in producing MDMA effects. The dopaminergic D2 receptor antagonist haloperidol selectively reduced the euphoric effects of MDMA in volunteers while increasing feelings of anxiety. Although not yet examined in humans, several studies in rodents, indicate the noradrenergic mechanisms contribute to the stimulating effects of MDMA. Finally, currently unexplored effects of MDMA may turn out to be important, such as trace amine receptors.
The effects of MDMA on regional cerebral blood flow (CBF) have been studied in humans using [H215O]-Positron Emission Tomography (PET) MDMA was found to produce alteration of brain activity in cortical, limbic, and paralimbic structures. The dose of MDMA, 1.7 mg/kg, was psychoactive and participants reported heightened mood, increased extroversion, feelings of altered reality, and mild perceptual alterations. Feelings of "extroversion" correlated with CBF in the temporal cortex, amygdala, and orbitofrontal cortex.
Short-term experiential effects, which tend to last less than 4 hours, include:
Effects beginning after the main effects of MDMA have ended, which can last several days, include:
, Brugada
, and Jervell and Lange–Nielsen Syndromes
).
Serious adverse events in MDMA users may also be caused by drugs sold as "ecstasy", but which are not actually MDMA. Dangerous overheating, sometimes fatal, is associated with drugs such as PMA
or 4-MTA
. To help mitigate risks associated with the consumption of MDMA, certain organizations have created screening test kits to prevent the consumption of more harmful substances such as PMA, Methamphetamine, 2C analogs, BZP and TFMPP.
, low blood sodium levels as a result of drinking too much water. While it is important to avoid becoming dehydrated, especially when out dancing in a hot environment, there have been a number of users suffering from water intoxication
and associated hyponatremia
(dilution of the blood that can cause swelling
of the brain
). Although many cases of this clearly involved individuals drinking large amounts of water, there are cases where there is no evidence of excessive water consumption. Their cases may be caused by MDMA inducing release of the antidiuretic hormone vasopressin
by the pituitary gland. The action of vasopressin on the renal tubules leads to the retention of water, resulting in users producing less urine. (This is unrelated to having difficulty passing urine, a phenomenon known colloquially as E-wee). Hyponatremia also affects marathon runners and bodybuilders, who have been known to die from similar causes, as a result of drinking too much water and sweating out too much salt. It affects women more than men.
Hyponatremia is preventable by drinking fluid containing sodium, such as that contained in sports drinks (typically ~20mM NaCl).
, which is where too much serotonin is released into the brain. This can occur with MDMA if too much 5HTP
or other serotonergic drugs are consumed together. 50–200 mg of 5HTP is believed by some users to make MDMA work better and last longer, but anecdotally more than 300 mg 5HTP may increase risk of serotonin syndrome , which can lead into lethal hyperthermia if it becomes too severe. It has been suggested that hyperthyroidism
may also increase risk of ecstasy-related hyperthermia.
Note that this is different from normal hyperthermia. Dance parties are an obvious hyperthermia risk environment, the venue often being hot and crowded, and the attending public dancing whilst on stimulant drugs. Ideally the temperature inside the dance rooms should be maintained in the range 24–27°C; ecstasy affects the body's ability to regulate temperature and it is easy to become either too hot or too cold if the temperature is outside of this range.
Mild hyperthermia and/or dehydration can occur from dancing too long, and users may recover with administration of fluids and rest in a cooler environment. However, if the user expresses concern about how hot they feel, or if their body temperature is still rising even when they have stopped dancing and are in a cooler environment, and their skin is hot and dry to the touch, then they may be developing more dangerous drug-induced hyperthermia, and these cases should be taken to and handled by a medical professional immediately. Treatment is most effective the sooner it is given, as with all adverse drug reactions. Hyperthermia is a particular concern if MDMA use is combined with other substances, such as 5HTP, or if additional stimulants are involved, such as methamphetamine
or cocaine
. MDMA is also implicated in affecting the mechanism of uncoupling protein
(UCP), more specifically UCP3 in mitochondria which can lead to the abnormal thermogenic response.
In animal studies, a combination of prazosin
(alpha 1 adrenergic antagonist) and pindolol
(5HT1A antagonist/beta blocker) quickly and completely terminates drug-induced hyperthermia. Another drug, the migraine medicine pizotyline
has also been shown to be useful in treating MDMA overdose in animals. However, neither of these treatments are approved for use in humans.
MDMA appears to decrease heat loss in the body by causing constriction of blood vessels near the skin. In addition, it can increase heat production by muscles and the brain. These effects may be amplified in people who become dehydrated and are therefore unable to cool by sweating. On top of this, MDMA can mask the body's normal thirst and exhaustion responses, particularly if a user is dancing or is otherwise physically active for long periods of time without hydration. Because of these effects, MDMA can temporarily reduce the body's ability to regulate its core temperature so that high-temperature surroundings (e.g. clubs) combined with physical exertion may lead to hyperpyrexia if precautions are not taken to remain cool. Sustained hyperpyrexia may lead to rhabdomyolysis
, which in turn can cause renal failure
and death. Depending on the initial cause of rhabdomyolysis, it may be successfully treated with dantrolene
if diagnosed early enough, but often the characteristic symptoms may not be apparent until the condition is already severe.
The standard treatment for ecstasy overdose given in hospitals includes a range of drugs such as cyproheptadine
or chlorpromazine
but these are often of limited efficacy. MDMA overdose mainly results in hyperthermia
and hyponatremia
, which leads onto convulsions from the hyponatremia and rhabdomyolysis
(toxic muscle breakdown) from the hyperthermia. These complications can be treated; benzodiazepines such as diazepam
or lorazepam
are used to control convulsions and dantrolene
blocks rhabdomyolysis.
It has been argued that "the seriousness of the effects can be dependent on environmental factors other than the drug concentration", as blood concentrations of the drug spanned a large range in cases of death in MDMA users. This not-with-standing, "most of the cases of serious toxicity or fatality have involved blood levels... up to 40 times higher than the usual recreational range."
Quoted from Dr. Julie Holland:
"Not only are MDMA related cases a small percentage of all drug-related emergency room visits, but a large percentage of MDMA cases are not life-threatening. In a recent study conducted by the physicians in the Emergency Department of Bellevue, (Rella, Int J Med Toxicol 2000; 3(5): 28) regional hospital ecstasy cases phoned into the New York City poison control center were analyzed. There were 191 cases reported during the years 1993 to 1999 inclusive. This is a rate of fewer than thirty cases per year. 139 cases (73%) were mild and experienced minor or no toxicity. The most commonly reported symptoms were increased heart rate (22%), agitation (19%), and nausea and vomiting (12%). In these seven years, only one ecstasy-related death was reported, which was due to hyperthermia, or overheating. Ecstasy is simply not the "killer drug" the media would like us to believe."
(teeth grinding) and trismus (jaw clenching) as a short-term effect from the drug. Many users of MDMA alleviate this by using chewing gum
, or chewing on improvised mouth guards (such as a small plastic glow stick or pacifier
). Temporary jaw ache often results from jaw clenching or excessive chewing. Some users consume supplemental magnesium
tablets to relax the jaw muscles and relieve clenching, although this practice has not been formally studied. In extreme cases, ecstasy use has been associated with excessive wear of teeth and resulting dental problems.
Liver damage, which may have an immunological cause, has been seen in a small number of users. It is not clear to what extent liver toxicity is caused by MDMA or other compounds found in ecstasy tablets. Animal studies suggest MDMA can cause liver damage and that the risk and extent of liver damage is increased by high body temperature.
While there has been an urban legend that having an allergy to penicillin
or related antibiotics means one is allergic to MDMA, this myth is baseless, as the two drugs are far too different for an allergy
to one to translate into an allergy to the other. There are also no known cases of anyone ever having an allergic reaction to MDMA. It's probably too small of a molecule for the immune system
to react to it and cause an allergy.
In very rare cases, MDMA has been associated with serious neurological problems such as subarachnoid hemorrhage
, intracranial bleeding, or cerebral infarction
. Similar problems have been noted with amphetamines. The mechanisms are thought to involve the short-term hypertension
leading to damage of cerebral blood vessels, especially in patients with pre-existing conditions such as arteriovenous malformation
s or cerebral angiomas.
While users sometimes report increased sexual desire, there are many reports of difficulty achieving both erection
and orgasm
while on the drug. It has been said that, "[MDMA] is a love drug but not a sex drug for most people." This is the rationale behind the use of sextasy (combining MDMA with Viagra).
In addition to these main areas of research, there have been a number of animal studies suggesting MDMA can cause other possible neurological changes, including apoptosis
, non-serotonergic neurotoxicity in the somatosensory cortex, and increased expression and altered processing of amyloid precursor protein.
s. In these studies, the brains of animals who are given high or repeated doses of MDMA show long-term decreases in all measures of serotonergic functioning, including concentrations of serotonin, tryptophan hydroxylase, and binding of the serotonin transporter protein. Although measures of serotonin are decreased, there are no decreases in the number of cells in the dorsal raphe, which indicates that the serotonin neurons have not died. Limited studies attempting to stain and photograph serotonergic axons shortly after high-dose MDMA exposure have reported that axons appear swollen and misshapen, as if they might be degenerating. However, few studies have attempted to stain and examine axons and with the measures commonly used in MDMA studies it is difficult or impossible to distinguish axon loss from decreases in production of markers of serotonin.
Animal studies show that there is recovery of serotonergic markers. However, if axons are actually regrowing, there is no assurance that they will reform their original connections. While rats show extensive recovery that sometimes appears complete, some primate studies show evidence of lasting alterations in serotonergic measures. Human studies, discussed below, show recovery, but these studies use indirect measures that may lack sensitivity for detecting subtle changes.
It is not known what dose(s) of MDMA would produce similar toxic effects in humans. This is because there are some difficulties in translating animal MDMA toxicity studies to humans. Firstly, it is difficult to equate rat doses to human doses, because rats metabolize MDMA twice as fast as humans and often larger doses or multiple doses are administered to simulate human plasma levels. Second, if the neurotoxicity of MDMA depends on its metabolites (Jones 2004;), it may be difficult or impossible to translate an MDMA dose between species since different species metabolize MDMA to different extents. Therefore, it is difficult to say what dose in humans would produce the effects seen in animals.
Keeping these limitations in mind, comparisons of MDMA exposures can be made between animal neurotoxicity studies and human clinical studies. One (uncertain) estimate suggests that the neurotoxic dose may be only moderately higher than amounts given in clinical studies (1.5 or 1.7 mg/kg, about 100 or 120 mg). That published comparison was made based on data from rats.
Further comparisons can be made using monkey data. In a recent study by Mechan et al. (2006), the lowest repeated dose regimen that produced serotonergic effects, detectable after 2 weeks, in squirrel monkeys was 2.4 mg/kg given orally three times in a row (every 3 hours). The peak plasma MDMA concentrations seen after that dose was 787 ± 129 ng/ml (mean ± SEM, range: 654 to 1046 ng/ml) and the Area Under the Concentration vs. Time-Curve (AUC, a measure of overall drug exposure) was 3451 ± 103 hr*ng/ml. In comparison, 1.6 mg/kg oral (112 mg in a 70 kg / person) in humans produces peak MDMA concentrations of 291.8 ± 76.5 ng/ml (range: 190 - 465 ng/ml) and an AUC of 3485.3 ± 760.1 hr*ng/ml (Kolbrich et al. 2008). Thus, a typical human dose produces peak MDMA concentrations that are about 37% of a known neurotoxic dose and has a very similar AUC. Because MDMA has nonlinear kinetics, it is likely that fewer than three of these doses would be needed to produce an exposure in humans greater than the dose schedule that produced decreased brain serotonin and decreased serotonin transporter binding in monkeys.
are formed, also called free radicals. These molecules have an unpaired electron that makes them highly reactive. They pull strongly on the electrons of neighboring molecules and destabilize the electrical balance of those molecules, sometimes causing those molecules to fall apart. This can become a chain reaction.
In normal functioning, there are antioxidants in the system that act as free radical scavengers. These are molecules with an extra electron that they are willing to give up to the free radicals, making both the free radical and the antioxidant more stable. MDMA rapidly increases the levels of free radicals in the system, which is thought to overwhelm the reserves of scavengers. The radicals then damage cell walls, reduce the flexibility of blood vessels, destroy enzymes, and cause other molecular damage in the neurological pathways. (Erowid, 2001) It has been shown that MDMA's neurotoxic effects in rodents are increased by a hyperthermic environment and decreased by a hypothermic one. (Yeh, 1997)
Studies have suggested that the neurotoxic molecules are not hydroxyl free radicals, but superoxide free radicals. When rats are injected with salicylate, a molecule that scavenges hydroxyl free radicals, the neurotoxic effects of MDMA are not attenuated, but actually potentiated. Further evidence of this superoxide theory comes from the observation that CuZn-superoxide dismutase transgenic mice (mice with excess human antioxidant enzyme) demonstrate neuroprotective mechanisms that protect the mice from MDMA-induced depletion of 5-HT (serotonin) and 5-HIAA and lethal effects. (Baggott, 2001 and Yeh, 1997)
MDMA itself does not seem to be neurotoxic as infusing it into an animal's brain does not produce long-term serotonergic changes. This suggests that another molecule may be triggering the oxidative stress. Earlier scientists have suggested that dopamine might be important for initiating the cascade of oxidative stress. However, it needs to be a chemical which is not produced in the brain, but produced systemically, so this seems to rule out dopamine. More recent scientists suggest an MDMA metabolite (such as 3,4-dihydroxy-methamphetamine) may be responsible.
The most obvious strategy is reducing dose. Long-term serotonergic changes are dose dependent in animals. Taking higher or repeated doses of MDMA is therefore likely to increase chances of similar changes in people. Although the threshold dose to cause toxicity is unknown in humans, lower doses are almost certainly less risky.
Studies in rats also find that environments or activities that increase the animals' body temperature increase serotonergic changes. However, this finding has not been replicated in primates, possibly because rodents are less able to regulate body temperature than primates. Nonetheless, it is possible that higher body temperature also increases serotonergic changes in people.
Antioxidants may decrease possible MDMA-induced serotonergic changes. Studies in rats have shown that injections of ascorbic acid, alpha lipoic acid, or some other radical scavengers are effective in reducing oxidative stress caused by MDMA. (Erowid, 2001) It has been speculated that humans may be able to similarly achieve protection using a combination of antioxidants, such as Vitamin A, C, and E or multivitamins including selenium, riboflavin, zinc, carotenoids, etc. may help reduce oxidative damage. No published studies have confirmed that this works. In addition, many of these vitamins, though, are water soluble, and are quickly excreted from the body. The typical MDMA user is psychoactive for 4–6 hours and may not have an appetite from the time of taking until the following sleep cycle or many hours later. Damage occurs in the absence of these antioxidants.
There are problems in trying to translate studies of neuroprotection with antioxidants from animal studies to humans. The effective doses of antioxidants given to these animals are much higher than humans would ever take both in its method of administration (injected vs. oral) and in its dosage. Both the neurotoxic and neuroprotective effects may be maximized in these animal studies, and it is not possible to know what doses or patterns of use (if any) would produce the same effects in people.
Selective serotonin reuptake inhibitors (SSRIs) have been shown to decrease or block MDMA neurotoxicity in rodents, even if they are given several hours after MDMA. Because of this, some MDMA users administer an SSRI while, or shortly after taking MDMA, in an attempt to prevent possible neurotoxicity
. These SSRIs are typically antidepressant
s such as fluoxetine
or sertraline
. The theory of some scientists is that SSRIs prevent dopamine
or a neurotoxic MDMA metabolite from entering through the serotonin
reuptake
transporter, where it is theorized that it may contribute to formation of reactive oxygen species, including hydrogen peroxide
. There are several concerns with taking SSRIs with MDMA. On a practical level, administration of SSRIs will block the desired effects of the drug if taken too early. This blocking effect can last several weeks, depending on the half-life of the SSRI. In addition, MDMA and the SSRI will often mutually reduce each other's metabolism, causing them to last longer in the body. Theoretically, this might increase risk of overdosing on the SSRI, leading to serotonin syndrome
. Although this appears to occur rarely (if ever), it is considered a theoretical possibility.
More significant risks occur if MDMA is taken with some other prescription drugs, including antidepressants that act as Monoamine oxidase inhibitor
. This can lead to serotonin syndrome
and the possibility of life-threatening hypertension.
Many users also attempt to replenish the hypothesized deficit of serotonin
that is thought to follow the use of MDMA by administering 5-HTP, in an attempt to reduce the depressed mood and unpleasant symptoms in the days following MDMA usage (including the immediate "come-down" and what is known as "suicide Tuesday" or "mid-week blues"). The serotonin
precursor 5-HTP, which is commercially available as a dietary supplement, supplies the user with more of the raw materials to synthesize the neurotransmitter
, theoretically reducing the negative psychological effects of depleted serotonin. (Note that normal dietary sources of serotonin precursors may have less than normal effects if tryptophan hydroxylase
levels have been reduced by MDMA.) Varied reports indicate that the perceived impact of pre-loading is dependent upon a number of factors and while it has not been shown to reliably increase the subjective effects of MDMA, your mileage may vary.
One difficulty in interpreting these studies is that it is difficult to know if serotonergic differences predated MDMA use. In addition, none of these studies can address whether any changes are neurotoxicity proper or neuroadaptation. A recent review concluded that "the current state of neuroimaging in human MDMA users does not permit conclusions regarding the long-term effects of MDMA exposure".
Although they are often studied in the same people or animals, possible serotonergic changes may have different risk, mechanisms, and recovery compared to possible cognitive and behavioral changes occurring after MDMA exposure. Studies in animals and humans have generally failed to correlate these two domains.
There does not seem to be a single type of cognitive task that is consistently altered in the different studies. Tasks that have shown differences include ones measuring attention, learning, memory, and executive function. Many of the findings, which are more commonly reported in people with more extensive ecstasy use histories (or even abuse diagnoses), may simply reflect preexisting differences between people who are drawn to use drugs like ecstasy frequently and those who do not.
In addition, mood is sometimes found to be worse and impulsivity greater in ecstasy users. At least two meta-analyses
of these studies have been completed (Morgan 2000; Sumnall & Cole 2005). Morgan's analysis of 17 studies showed that ecstasy users had a slight tendency to be more impulsive and have lower mood than controls. Sumnall and Cole's analysis showed a slight increase in the prevalence of depressive symptoms in ecstasy users over controls. (Mood measured in these studies does not indicate clinical levels of depression, which has not been associated with MDMA use.) Of course, studies like these raise a cause-consequence question: did these impulsive and depressed people use ecstasy to self-medicate or did otherwise normal people become depressed and impulsive after using ecstasy? This question has not been conclusively answered and both possibilities may be true in individual cases.
There are a growing number of longitudinal or prospective studies, looking at users and nonusers at several points in time. Published prospective studies tend to report subtle difference between users and nonusers with performance within normal range. These difference tend to persist (Reneman et al. 2006; Gouzoulis-Mayfrank et al. 2005; Thomasius et al. 2006) or increase across time (Zakzanis and Young 2001; Zakzanis and Campbell 2006). While persisting differences are consistent with differences predating ecstasy use, increases may indicate worsening due to drug exposure.
A recent important study (the NeXT Netherlands XTC toxicity study) prospectively examined 25 people before and after their first episode of ecstasy use (mean 2.0 ± 1.4 ecstasy pills, on average 11.1 ± 12.9 weeks since last ecstasy use). The study measured working memory, selective attention, and associative memory using fMRI. No significant effects were found of the reportedly modest dose(s) of ecstasy on any of these measures, suggesting that the first few exposures to ecstasy typically do not cause significant residual toxicity. Thus, if ecstasy does cause cognitive-behavioral changes, it would likely require repeated use for these changes to occur (or become detectable). Contrary to this another recent report has shown that a single exposure to MDMA can result in cognitive-behavioral changes. The study took a group of people who have never used MDMA and had them perform cognitive tests. The participants were then exposed to a low dose of MDMA and underwent the same cognitive tests three years later. It was found that scores on immediate and delayed verbal recall and verbal recognition were significantly lower in the group of incident Ecstasy users compared with persistent Ecstasy-naive subjects. The authors did recognize there were limitations to their study but it shows that MDMA most likely does cause cognitive-behavioral effects after one exposure.
In addition to concerns about neurotoxicity, several published reports have described hallucinogen persisting perception disorder
in MDMA users. This appears to be very rare and published cases have been complicated by use of other drugs, in concurrence with MDMA use.
is controversial. Some studies indicate that many users may be addicted, but this depends on the definition of addiction; while many ecstasy users may take the drug regularly and develop significant tolerance to its effects, relatively few users exhibit cravings or physical symptoms of dependence
, or find it difficult to stop using the drug when they decide to do so. Cottler et al. (2001)
interviewed 52 users and found that 43% met standard criteria for dependence. However, some of these people may have been inappropriately diagnosed with dependence because they reported tolerance or after effects from MDMA. Tolerance and after effects ("withdrawal
" effects) are symptoms of dependence for many drugs, but seem to occur in some MDMA users who are actually not dependent. For example, studies in Switzerland
in which MDMA was given to people who had never used it before documented after effects. When people are classified as addicted to MDMA, it is not clear if that indicates a difficulty in quitting the drug. In a prospective study in Germany
, many who were initially categorized as addicted, spontaneously 'improved' without any treatment for the alleged addiction. Given the complexities in classifying MDMA users as addicted, conclusions about the addictive potential of MDMA are less reliable than those about nicotine addiction. Cases have been reported of addictive personality
types abusing MDMA as they would with alcohol, tobacco, or other drugs, taking excessively high doses against the natural recommendations, and taking it too frequently and even daily, against recommendations. However they typically end up abandoning MDMA for drugs more suitable to addictive behavior after a period of time, and the tolerance issues of MDMA make it naturally antagonistic to long term daily addiction.
at Johns Hopkins University
implicated MDMA as a cause of Parkinson's-like brain abnormalities in monkeys, suggesting that a single use of MDMA caused permanent and serious damage to dopamine neurons. This controversial finding was subsequently retracted with the researchers stating that they had inadvertently injected their experimental animals with methamphetamine
instead of MDMA.
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...
, 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...
, and norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
release, and can act directly on a number of receptors, including α2-adrenergic (adrenaline) and 5HT2A(serotonin) receptors. MDMA promotes the release of several hormones including prolactin
Prolactin
Prolactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen...
, 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...
, ACTH, dehydroepiandrosterone
Dehydroepiandrosterone
5-Dehydroepiandrosterone is a 19-carbon endogenous steroid hormone. It is the major secretory steroidal product of the adrenal glands and is also produced by the gonads and the brain. DHEA is the most abundant circulating steroid in humans....
(DHEA), and the antidiuretic hormone vasopressin
Vasopressin
Arginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
(which may be important in its occasional production of water intoxication
Water intoxication
Water intoxication, also known as water poisoning, is a potentially fatal disturbance in brain functions that results when the normal balance of electrolytes in the body is pushed outside of safe limits by over-consumption of water....
or 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...
).
It's not fully understood why MDMA induces these unusual psychoactive effects. Most explanations focus on serotonin release. MDMA causes 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...
vesicles
Vesicle (biology)
A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...
in the neurons to release quantities of serotonin into the synapse
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
s. Studies using pretreatment with an SSRI to block the ability of MDMA to release serotonin in volunteers suggest serotonin release is necessary for most effects of MDMA in humans. Released serotonin is believed to stimulate several receptors that contribute to the experiential effects of MDMA. Laboratory rodent experiments have shown MDMA to activate 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...
-containing neurons in the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
by stimulating 5-HT1A receptors. This appears to contribute to some of the social effects of MDMA: upon administering a drug that blocked brain receptors for oxytocin, the effects of the drug on social behavior were reduced. A second serotonin receptor, 5-HT2A receptors (which are important for the effects of hallucinogens), makes mild contributions to MDMA effects. When the receptor was blocked, volunteers given MDMA reported decreases in MDMA-induced perceptual changes, emotional excitation, and acute adverse responses. In contrast, blocking these 5-HT2A receptors had little effect on MDMA-induced positive mood, well-being, extroversion, and most short-term sequelae. One possible explanation for some of these 5-HTA-mediated effects is that 5-HT2A stimulation inhibits dopamine release.
Although serotonin is important to the effects of MDMA, other drugs that release serotonin, such as fenfluramine
Fenfluramine
Fenfluramine is a drug that was part of the Fen-Phen anti-obesity medication . Fenfluramine was introduced on the U.S. market in 1973. It is the racemic mixture of two enantiomers, dextrofenfluramine and levofenfluramine...
, do not have effects like MDMA. This indicates that other neurochemical systems must be important for the MDMA experience. In addition to serotonin, dopamine and noradrenaline may play important roles in producing MDMA effects. The dopaminergic D2 receptor antagonist haloperidol selectively reduced the euphoric effects of MDMA in volunteers while increasing feelings of anxiety. Although not yet examined in humans, several studies in rodents, indicate the noradrenergic mechanisms contribute to the stimulating effects of MDMA. Finally, currently unexplored effects of MDMA may turn out to be important, such as trace amine receptors.
The effects of MDMA on regional cerebral blood flow (CBF) have been studied in humans using [H215O]-Positron Emission Tomography (PET) MDMA was found to produce alteration of brain activity in cortical, limbic, and paralimbic structures. The dose of MDMA, 1.7 mg/kg, was psychoactive and participants reported heightened mood, increased extroversion, feelings of altered reality, and mild perceptual alterations. Feelings of "extroversion" correlated with CBF in the temporal cortex, amygdala, and orbitofrontal cortex.
Subjective effects
- Mental and physical euphoriaEuphoriaEuphoria 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 general well-being and contentedness
- Decreased negative emotion and behavior such as stress, anxietyAnxietyAnxiety 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,...
, fearFearFear 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...
, and paranoiaParanoiaParanoia [] 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... - Increased sociability and feelings of communication being easy or simple
- Increased urge to communicate with others
- Increased empathyEmpathyEmpathy 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...
and feelings of closeness or connection with others - Reduced insecurity, defensiveness, and fear of emotional injury
- Decreased irritability, aggression, anger, and jealousy
- A sense of increased insightfulness and introspectionIntrospectionIntrospection 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...
- Mild psychedelia (colors and sounds are enhanced, mild closed-eye visuals, improved pattern recognition, etc.)
- Enhanced tactile sensations (touching, hugHugA hug is a form of physical intimacy, that usually involves closing or holding the arms around the neck, back, or waist of another person; if more than two persons are involved, this is referred to as a group hug. A hug, sometimes in association with a kiss, eye contact or other gestures, is a...
ging, and sexSexIn biology, sex is a process of combining and mixing genetic traits, often resulting in the specialization of organisms into a male or female variety . Sexual reproduction involves combining specialized cells to form offspring that inherit traits from both parents...
for example all feel more pleasant)
Effects beginning after the main effects of MDMA have ended, which can last several days, include:
- Lowered mood or even depressionDepression (mood)Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
(comedown) after the effects have worn off - Increased anxiety, stress, and other negative emotions
- Residual feelings of empathy, emotional sensitivity, and a sense of closeness to others (afterglow)
Other short-term effects
Acute physiological effects include:- Increased heart rateHeart rateHeart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....
and blood pressureBlood pressureBlood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies... - Increased body temperatureThermoregulationThermoregulation is the ability of an organism to keep its body temperature within certain boundaries, even when the surrounding temperature is very different...
- Increased perspiration and sweating
- Pupil dilationMydriasisMydriasis is a dilation of the pupil due to disease, trauma or the use of drugs. Normally, the pupil dilates in the dark and constricts in the light to respectively improve vividity at night and to protect the retina from sunlight damage during the day...
- Blurred visionBlurred vision-Causes:There are many causes of blurred vision:* Use of atropine or other anticholinergics* Presbyopia -- Difficulty focusing on objects that are close. The elderly are common victims....
- Nystagmus (rapid involuntary eye movements and jittering)
- TrismaTrismus-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...
(jaw-clenching) and bruxiaBruxismBruxism 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...
(grinding of the teeth) - Difficulty sleepingInsomniaInsomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
- Loss of appetiteAppetiteThe appetite is the desire to eat food, felt as hunger. Appetite exists in all higher life-forms, and serves to regulate adequate energy intake to maintain metabolic needs. It is regulated by a close interplay between the digestive tract, adipose tissue and the brain. Decreased desire to eat is...
- NauseaNauseaNausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and emesis - Urinary retentionUrinary retentionUrinary retention, also known as ischuria, is a lack of ability to urinate. It is a common complication of benign prostatic hyperplasia , although it can also be caused by nerve dysfunction, constipation, infection, or medications...
- In males, possible erectile dysfunctionErectile dysfunctionErectile dysfunction is sexual dysfunction characterized by the inability to develop or maintain an erection of the penis during sexual performance....
Adverse effects
Also, serious adverse events in MDMA users may be an interaction of the drug with a preexisting medical condition. Risk of adverse event after MDMA consumption is thought to be increased by preexisting cardiovascular problems, such as cardiomyopathy, hypertension, viral myocarditis, and congenital cardiac conduction abnormalities (such as Wolff–Parkinson–White, Romano–WardRomano-Ward syndrome
Romano-Ward syndrome, is the major variant of long QT syndrome. It is a condition that causes a disruption of the heart's normal rhythm. This disorder is a form of long QT syndrome, which is a heart condition that causes the cardiac muscle to take longer than usual to recharge between beats...
, Brugada
Brugada syndrome
The Brugada syndrome is a genetic disease that is characterised by abnormal electrocardiogram findings and an increased risk of sudden cardiac death. It is named by the Spanish cardiologists Pedro Brugada and Josep Brugada...
, and Jervell and Lange–Nielsen Syndromes
Jervell and Lange-Nielsen syndrome
Jervell and Lange-Nielsen syndrome, a type of long QT syndrome, causes the cardiac muscle to take longer than usual to recharge between beats. If untreated, the irregular heartbeats, called arrhythmias, can lead to fainting, seizures, or sudden death...
).
Serious adverse events in MDMA users may also be caused by drugs sold as "ecstasy", but which are not actually MDMA. Dangerous overheating, sometimes fatal, is associated with drugs such as PMA
PMA
para-Methoxyamphetamine , also known as 4-methoxyamphetamine , is a serotonergic drug of the amphetamine class...
or 4-MTA
4-MTA
4-Methylthioamphetamine is an illicit drug and research chemical developed in the 1990s by a team led by David E. Nichols at Purdue University. It acts as a non-neurotoxic highly selective serotonin releasing agent in animals...
. To help mitigate risks associated with the consumption of MDMA, certain organizations have created screening test kits to prevent the consumption of more harmful substances such as PMA, Methamphetamine, 2C analogs, BZP and TFMPP.
Hyponatremia
An important cause of death following MDMA use is hyponatremiaHyponatremia
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...
, low blood sodium levels as a result of drinking too much water. While it is important to avoid becoming dehydrated, especially when out dancing in a hot environment, there have been a number of users suffering from water intoxication
Water intoxication
Water intoxication, also known as water poisoning, is a potentially fatal disturbance in brain functions that results when the normal balance of electrolytes in the body is pushed outside of safe limits by over-consumption of water....
and associated 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...
(dilution of the blood that can cause swelling
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
of the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
). Although many cases of this clearly involved individuals drinking large amounts of water, there are cases where there is no evidence of excessive water consumption. Their cases may be caused by MDMA inducing release of the antidiuretic hormone vasopressin
Vasopressin
Arginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
by the pituitary gland. The action of vasopressin on the renal tubules leads to the retention of water, resulting in users producing less urine. (This is unrelated to having difficulty passing urine, a phenomenon known colloquially as E-wee). Hyponatremia also affects marathon runners and bodybuilders, who have been known to die from similar causes, as a result of drinking too much water and sweating out too much salt. It affects women more than men.
Hyponatremia is preventable by drinking fluid containing sodium, such as that contained in sports drinks (typically ~20mM NaCl).
Hyperthermia
The primary acute risks of taking MDMA resemble those of other stimulant amphetamines. The second most important cause of death from MDMA use is hyperthermia, core body temperature rising too high until the major organs shut down at about 42°C. This is comparatively more problematic than blood salt imbalance, harder to treat and to avoid. Ecstasy-related hyperthermia may occur as a symptom of serotonin syndromeSerotonin 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...
, which is where too much serotonin is released into the brain. This can occur with MDMA if too much 5HTP
5-Hydroxytryptophan
5-Hydroxytryptophan , also known as oxitriptan , is a naturally occurring amino acid and chemical precursor as well as metabolic intermediate in the biosynthesis of the neurotransmitters serotonin and melatonin from tryptophan....
or other serotonergic drugs are consumed together. 50–200 mg of 5HTP is believed by some users to make MDMA work better and last longer, but anecdotally more than 300 mg 5HTP may increase risk of serotonin syndrome , which can lead into lethal hyperthermia if it becomes too severe. It has been suggested that hyperthyroidism
Hyperthyroidism
Hyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...
may also increase risk of ecstasy-related hyperthermia.
Note that this is different from normal hyperthermia. Dance parties are an obvious hyperthermia risk environment, the venue often being hot and crowded, and the attending public dancing whilst on stimulant drugs. Ideally the temperature inside the dance rooms should be maintained in the range 24–27°C; ecstasy affects the body's ability to regulate temperature and it is easy to become either too hot or too cold if the temperature is outside of this range.
Mild hyperthermia and/or dehydration can occur from dancing too long, and users may recover with administration of fluids and rest in a cooler environment. However, if the user expresses concern about how hot they feel, or if their body temperature is still rising even when they have stopped dancing and are in a cooler environment, and their skin is hot and dry to the touch, then they may be developing more dangerous drug-induced hyperthermia, and these cases should be taken to and handled by a medical professional immediately. Treatment is most effective the sooner it is given, as with all adverse drug reactions. Hyperthermia is a particular concern if MDMA use is combined with other substances, such as 5HTP, or if additional stimulants are involved, such as methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...
or 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...
. MDMA is also implicated in affecting the mechanism of uncoupling protein
Uncoupling protein
An uncoupling protein is a mitochondrial inner membrane protein that can dissipate the proton gradient before it can be used to provide the energy for oxidative phosphorylation.There are five types known in mammals:* UCP1, also known as thermogenin* UCP2...
(UCP), more specifically UCP3 in mitochondria which can lead to the abnormal thermogenic response.
In animal studies, a combination of prazosin
Prazosin
Prazosin, trade names Minipress, Vasoflex, Pressin and Hypovase, is a sympatholytic drug used to treat high blood pressure and Anxiety, PTSD and Panic Disorder. It belongs to the class of alpha-adrenergic blockers. Specifically, prazosin is selective for the alpha-1 receptors on vascular smooth...
(alpha 1 adrenergic antagonist) and pindolol
Pindolol
Pindolol is a beta blocker....
(5HT1A antagonist/beta blocker) quickly and completely terminates drug-induced hyperthermia. Another drug, the migraine medicine pizotyline
Pizotifen
Pizotifen or pizotyline , trade name Sandomigran, is a benzocycloheptene based drug used as a medicine, primarily as a preventative to reduce the frequency of recurrent migraine headaches.-Uses:...
has also been shown to be useful in treating MDMA overdose in animals. However, neither of these treatments are approved for use in humans.
MDMA appears to decrease heat loss in the body by causing constriction of blood vessels near the skin. In addition, it can increase heat production by muscles and the brain. These effects may be amplified in people who become dehydrated and are therefore unable to cool by sweating. On top of this, MDMA can mask the body's normal thirst and exhaustion responses, particularly if a user is dancing or is otherwise physically active for long periods of time without hydration. Because of these effects, MDMA can temporarily reduce the body's ability to regulate its core temperature so that high-temperature surroundings (e.g. clubs) combined with physical exertion may lead to hyperpyrexia if precautions are not taken to remain cool. Sustained hyperpyrexia may lead to rhabdomyolysis
Rhabdomyolysis
Rhabdomyolysis is a condition in which damaged skeletal muscle tissue breaks down rapidly. Breakdown products of damaged muscle cells are released into the bloodstream; some of these, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney failure...
, which in turn can cause renal failure
Renal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
and death. Depending on the initial cause of rhabdomyolysis, it may be successfully treated with dantrolene
Dantrolene
Dantrolene sodium is a muscle relaxant that acts by abolishing excitation-contraction coupling in muscle cells, probably by action on the ryanodine receptor. It is the only specific and effective treatment for malignant hyperthermia, a rare, life-threatening disorder triggered by general anesthesia...
if diagnosed early enough, but often the characteristic symptoms may not be apparent until the condition is already severe.
Overdose
Due to the difference between the recreational dose and the lethality dose, it is extremely rare for a death to be accredited just to the consumption of MDMA. While a typical recreational dose is roughly 100–150 mg (often being measured by eye and dealt with as fractions of a gram), this dose is often then repeated but remains well below the lethal dose. Consumption of the drug can be self-reinforcing while under the influence, and overdoses can occur. People who are grossly obese, or who have diabetes, high blood pressure or heart conditions have a greater risk of overdose death from any stimulant, and should generally avoid MDMA and similar drugs.The standard treatment for ecstasy overdose given in hospitals includes a range of drugs such as cyproheptadine
Cyproheptadine
Cyproheptadine , sold under the brand name Periactin, is a first-generation antihistamine with additional anticholinergic, antiserotonergic, and local anesthetic properties.- Indications :...
or chlorpromazine
Chlorpromazine
Chlorpromazine is a typical antipsychotic...
but these are often of limited efficacy. MDMA overdose mainly results in 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...
, which leads onto convulsions from the hyponatremia and rhabdomyolysis
Rhabdomyolysis
Rhabdomyolysis is a condition in which damaged skeletal muscle tissue breaks down rapidly. Breakdown products of damaged muscle cells are released into the bloodstream; some of these, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney failure...
(toxic muscle breakdown) from the hyperthermia. These complications can be treated; benzodiazepines such as diazepam
Diazepam
Diazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...
or lorazepam
Lorazepam
Lorazepam is a high-potency short-to-intermediate-acting 3-hydroxy benzodiazepine drug that has all five intrinsic benzodiazepine effects: anxiolytic, amnesic, sedative/hypnotic, anticonvulsant, antiemetic and muscle relaxant...
are used to control convulsions and dantrolene
Dantrolene
Dantrolene sodium is a muscle relaxant that acts by abolishing excitation-contraction coupling in muscle cells, probably by action on the ryanodine receptor. It is the only specific and effective treatment for malignant hyperthermia, a rare, life-threatening disorder triggered by general anesthesia...
blocks rhabdomyolysis.
It has been argued that "the seriousness of the effects can be dependent on environmental factors other than the drug concentration", as blood concentrations of the drug spanned a large range in cases of death in MDMA users. This not-with-standing, "most of the cases of serious toxicity or fatality have involved blood levels... up to 40 times higher than the usual recreational range."
Quoted from Dr. Julie Holland:
"Not only are MDMA related cases a small percentage of all drug-related emergency room visits, but a large percentage of MDMA cases are not life-threatening. In a recent study conducted by the physicians in the Emergency Department of Bellevue, (Rella, Int J Med Toxicol 2000; 3(5): 28) regional hospital ecstasy cases phoned into the New York City poison control center were analyzed. There were 191 cases reported during the years 1993 to 1999 inclusive. This is a rate of fewer than thirty cases per year. 139 cases (73%) were mild and experienced minor or no toxicity. The most commonly reported symptoms were increased heart rate (22%), agitation (19%), and nausea and vomiting (12%). In these seven years, only one ecstasy-related death was reported, which was due to hyperthermia, or overheating. Ecstasy is simply not the "killer drug" the media would like us to believe."
Other adverse effects
MDMA users almost always experience bruxismBruxism
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...
(teeth grinding) and trismus (jaw clenching) as a short-term effect from the drug. Many users of MDMA alleviate this by using chewing gum
Chewing gum
Chewing gum is a type of gum traditionally made of chicle, a natural latex product, or synthetic rubber known as polyisobutylene. For economical and quality reasons, many modern chewing gums use rubber instead of chicle...
, or chewing on improvised mouth guards (such as a small plastic glow stick or pacifier
Pacifier
A pacifier is a rubber, plastic, or silicone nipple given to an infant or other young child to suck upon. In its standard appearance it has a teat, mouth shield, and handle...
). Temporary jaw ache often results from jaw clenching or excessive chewing. Some users consume supplemental magnesium
Magnesium
Magnesium is a chemical element with the symbol Mg, atomic number 12, and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the Earth's crust and ninth in the known universe as a whole...
tablets to relax the jaw muscles and relieve clenching, although this practice has not been formally studied. In extreme cases, ecstasy use has been associated with excessive wear of teeth and resulting dental problems.
Liver damage, which may have an immunological cause, has been seen in a small number of users. It is not clear to what extent liver toxicity is caused by MDMA or other compounds found in ecstasy tablets. Animal studies suggest MDMA can cause liver damage and that the risk and extent of liver damage is increased by high body temperature.
While there has been an urban legend that having an allergy to penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....
or related antibiotics means one is allergic to MDMA, this myth is baseless, as the two drugs are far too different for an allergy
Allergy
An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
to one to translate into an allergy to the other. There are also no known cases of anyone ever having an allergic reaction to MDMA. It's probably too small of a molecule for the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
to react to it and cause an allergy.
In very rare cases, MDMA has been associated with serious neurological problems such as subarachnoid hemorrhage
Subarachnoid hemorrhage
A subarachnoid hemorrhage , or subarachnoid haemorrhage in British English, is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain...
, intracranial bleeding, or cerebral infarction
Cerebral infarction
A cerebral infarction is the ischemic kind of stroke due to a disturbance in the blood vessels supplying blood to the brain. It can be atherothrombotic or embolic. Stroke caused by cerebral infarction should be distinguished from two other kinds of stroke: cerebral hemorrhage and subarachnoid...
. Similar problems have been noted with amphetamines. The mechanisms are thought to involve the short-term hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
leading to damage of cerebral blood vessels, especially in patients with pre-existing conditions such as arteriovenous malformation
Arteriovenous malformation
Arteriovenous malformation or AVM is an abnormal connection between veins and arteries, usually congenital. This pathology is widely known because of its occurrence in the central nervous system, but can appear in any location. An arteriovenous malformation is a vascular anomaly. It is a...
s or cerebral angiomas.
While users sometimes report increased sexual desire, there are many reports of difficulty achieving both erection
Erection
Penile erection is a physiological phenomenon where the penis becomes enlarged and firm. Penile erection is the result of a complex interaction of psychological, neural, vascular and endocrine factors, and is usually, though not exclusively, associated with sexual arousal...
and orgasm
Orgasm
Orgasm is the peak of the plateau phase of the sexual response cycle, characterized by an intense sensation of pleasure...
while on the drug. It has been said that, "[MDMA] is a love drug but not a sex drug for most people." This is the rationale behind the use of sextasy (combining MDMA with Viagra).
Long-term adverse effects
Research on possible long-term adverse effects of MDMA has mainly focused on two areas. The first area is possible serotonergic neurotoxicity. The second area is psychiatric and behavioral problems that might result from MDMA use. These possible adverse effects may be independent. Studies finding serotonergic changes do not always find cognitive-behavioral changes and studies finding cognitive-behavioral changes do not always find serotonergic changes.In addition to these main areas of research, there have been a number of animal studies suggesting MDMA can cause other possible neurological changes, including apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
, non-serotonergic neurotoxicity in the somatosensory cortex, and increased expression and altered processing of amyloid precursor protein.
Serotonergic changes
Experiments indicate that both moderate and high dose or rapidly repeated MDMA exposure may lead to long-lasting changes in neurons that make serotonin. Serotonergic changes have been demonstrated experimentally in the brains of all mammalian species studied, with most studies involving ratRat
Rats are various medium-sized, long-tailed rodents of the superfamily Muroidea. "True rats" are members of the genus Rattus, the most important of which to humans are the black rat, Rattus rattus, and the brown rat, Rattus norvegicus...
s. In these studies, the brains of animals who are given high or repeated doses of MDMA show long-term decreases in all measures of serotonergic functioning, including concentrations of serotonin, tryptophan hydroxylase, and binding of the serotonin transporter protein. Although measures of serotonin are decreased, there are no decreases in the number of cells in the dorsal raphe, which indicates that the serotonin neurons have not died. Limited studies attempting to stain and photograph serotonergic axons shortly after high-dose MDMA exposure have reported that axons appear swollen and misshapen, as if they might be degenerating. However, few studies have attempted to stain and examine axons and with the measures commonly used in MDMA studies it is difficult or impossible to distinguish axon loss from decreases in production of markers of serotonin.
Animal studies show that there is recovery of serotonergic markers. However, if axons are actually regrowing, there is no assurance that they will reform their original connections. While rats show extensive recovery that sometimes appears complete, some primate studies show evidence of lasting alterations in serotonergic measures. Human studies, discussed below, show recovery, but these studies use indirect measures that may lack sensitivity for detecting subtle changes.
It is not known what dose(s) of MDMA would produce similar toxic effects in humans. This is because there are some difficulties in translating animal MDMA toxicity studies to humans. Firstly, it is difficult to equate rat doses to human doses, because rats metabolize MDMA twice as fast as humans and often larger doses or multiple doses are administered to simulate human plasma levels. Second, if the neurotoxicity of MDMA depends on its metabolites (Jones 2004;), it may be difficult or impossible to translate an MDMA dose between species since different species metabolize MDMA to different extents. Therefore, it is difficult to say what dose in humans would produce the effects seen in animals.
Keeping these limitations in mind, comparisons of MDMA exposures can be made between animal neurotoxicity studies and human clinical studies. One (uncertain) estimate suggests that the neurotoxic dose may be only moderately higher than amounts given in clinical studies (1.5 or 1.7 mg/kg, about 100 or 120 mg). That published comparison was made based on data from rats.
Further comparisons can be made using monkey data. In a recent study by Mechan et al. (2006), the lowest repeated dose regimen that produced serotonergic effects, detectable after 2 weeks, in squirrel monkeys was 2.4 mg/kg given orally three times in a row (every 3 hours). The peak plasma MDMA concentrations seen after that dose was 787 ± 129 ng/ml (mean ± SEM, range: 654 to 1046 ng/ml) and the Area Under the Concentration vs. Time-Curve (AUC, a measure of overall drug exposure) was 3451 ± 103 hr*ng/ml. In comparison, 1.6 mg/kg oral (112 mg in a 70 kg / person) in humans produces peak MDMA concentrations of 291.8 ± 76.5 ng/ml (range: 190 - 465 ng/ml) and an AUC of 3485.3 ± 760.1 hr*ng/ml (Kolbrich et al. 2008). Thus, a typical human dose produces peak MDMA concentrations that are about 37% of a known neurotoxic dose and has a very similar AUC. Because MDMA has nonlinear kinetics, it is likely that fewer than three of these doses would be needed to produce an exposure in humans greater than the dose schedule that produced decreased brain serotonin and decreased serotonin transporter binding in monkeys.
Mechanisms of serotonergic changes
The mechanism proposed for this apparent neurotoxicity involves the induction of oxidative stress. This stress results from an increase in free radicals and a decrease in antioxidants in the brain. (Shankaran, 2001) Oxidation is part of the normal metabolic processes of the body. As the cell goes about its life, by-products called oxidative radicalsRadical (chemistry)
Radicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...
are formed, also called free radicals. These molecules have an unpaired electron that makes them highly reactive. They pull strongly on the electrons of neighboring molecules and destabilize the electrical balance of those molecules, sometimes causing those molecules to fall apart. This can become a chain reaction.
In normal functioning, there are antioxidants in the system that act as free radical scavengers. These are molecules with an extra electron that they are willing to give up to the free radicals, making both the free radical and the antioxidant more stable. MDMA rapidly increases the levels of free radicals in the system, which is thought to overwhelm the reserves of scavengers. The radicals then damage cell walls, reduce the flexibility of blood vessels, destroy enzymes, and cause other molecular damage in the neurological pathways. (Erowid, 2001) It has been shown that MDMA's neurotoxic effects in rodents are increased by a hyperthermic environment and decreased by a hypothermic one. (Yeh, 1997)
Studies have suggested that the neurotoxic molecules are not hydroxyl free radicals, but superoxide free radicals. When rats are injected with salicylate, a molecule that scavenges hydroxyl free radicals, the neurotoxic effects of MDMA are not attenuated, but actually potentiated. Further evidence of this superoxide theory comes from the observation that CuZn-superoxide dismutase transgenic mice (mice with excess human antioxidant enzyme) demonstrate neuroprotective mechanisms that protect the mice from MDMA-induced depletion of 5-HT (serotonin) and 5-HIAA and lethal effects. (Baggott, 2001 and Yeh, 1997)
MDMA itself does not seem to be neurotoxic as infusing it into an animal's brain does not produce long-term serotonergic changes. This suggests that another molecule may be triggering the oxidative stress. Earlier scientists have suggested that dopamine might be important for initiating the cascade of oxidative stress. However, it needs to be a chemical which is not produced in the brain, but produced systemically, so this seems to rule out dopamine. More recent scientists suggest an MDMA metabolite (such as 3,4-dihydroxy-methamphetamine) may be responsible.
Possible neuroprotective strategies
There are a number of factors that have been shown to protect animals from long-term MDMA-induced serotonin changes. These include dose, temperature, antioxidants, and SSRIs. Some MDMA users have attempted to use analogous strategies to decrease their risks of long-term serotonin changes, although there is uncertainty as to how well this works in people.The most obvious strategy is reducing dose. Long-term serotonergic changes are dose dependent in animals. Taking higher or repeated doses of MDMA is therefore likely to increase chances of similar changes in people. Although the threshold dose to cause toxicity is unknown in humans, lower doses are almost certainly less risky.
Studies in rats also find that environments or activities that increase the animals' body temperature increase serotonergic changes. However, this finding has not been replicated in primates, possibly because rodents are less able to regulate body temperature than primates. Nonetheless, it is possible that higher body temperature also increases serotonergic changes in people.
Antioxidants may decrease possible MDMA-induced serotonergic changes. Studies in rats have shown that injections of ascorbic acid, alpha lipoic acid, or some other radical scavengers are effective in reducing oxidative stress caused by MDMA. (Erowid, 2001) It has been speculated that humans may be able to similarly achieve protection using a combination of antioxidants, such as Vitamin A, C, and E or multivitamins including selenium, riboflavin, zinc, carotenoids, etc. may help reduce oxidative damage. No published studies have confirmed that this works. In addition, many of these vitamins, though, are water soluble, and are quickly excreted from the body. The typical MDMA user is psychoactive for 4–6 hours and may not have an appetite from the time of taking until the following sleep cycle or many hours later. Damage occurs in the absence of these antioxidants.
There are problems in trying to translate studies of neuroprotection with antioxidants from animal studies to humans. The effective doses of antioxidants given to these animals are much higher than humans would ever take both in its method of administration (injected vs. oral) and in its dosage. Both the neurotoxic and neuroprotective effects may be maximized in these animal studies, and it is not possible to know what doses or patterns of use (if any) would produce the same effects in people.
Selective serotonin reuptake inhibitors (SSRIs) have been shown to decrease or block MDMA neurotoxicity in rodents, even if they are given several hours after MDMA. Because of this, some MDMA users administer an SSRI while, or shortly after taking MDMA, in an attempt to prevent possible neurotoxicity
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...
. These SSRIs are typically antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
s such as fluoxetine
Fluoxetine
Fluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company...
or sertraline
Sertraline
Sertraline hydrochloride is an antidepressant of the selective serotonin reuptake inhibitor class. It was introduced to the market by Pfizer in 1991. Sertraline is primarily used to treat major depression in adult outpatients as well as obsessive–compulsive, panic, and social anxiety disorders in...
. The theory of some scientists is that SSRIs prevent 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...
or a neurotoxic MDMA metabolite from entering through the 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...
reuptake
Reuptake
Reuptake, or re-uptake, is the reabsorption of a neurotransmitter by a neurotransmitter transporter of a pre-synaptic neuron after it has performed its function of transmitting a neural impulse....
transporter, where it is theorized that it may contribute to formation of reactive oxygen species, including hydrogen peroxide
Hydrogen peroxide
Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...
. There are several concerns with taking SSRIs with MDMA. On a practical level, administration of SSRIs will block the desired effects of the drug if taken too early. This blocking effect can last several weeks, depending on the half-life of the SSRI. In addition, MDMA and the SSRI will often mutually reduce each other's metabolism, causing them to last longer in the body. Theoretically, this might increase risk of overdosing on the SSRI, leading to 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...
. Although this appears to occur rarely (if ever), it is considered a theoretical possibility.
More significant risks occur if MDMA is taken with some other prescription drugs, including antidepressants that act as 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....
. This can lead to 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...
and the possibility of life-threatening hypertension.
Many users also attempt to replenish the hypothesized deficit 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...
that is thought to follow the use of MDMA by administering 5-HTP, in an attempt to reduce the depressed mood and unpleasant symptoms in the days following MDMA usage (including the immediate "come-down" and what is known as "suicide Tuesday" or "mid-week blues"). The 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...
precursor 5-HTP, which is commercially available as a dietary supplement, supplies the user with more of the raw materials to synthesize the neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
, theoretically reducing the negative psychological effects of depleted serotonin. (Note that normal dietary sources of serotonin precursors may have less than normal effects if tryptophan hydroxylase
Tryptophan hydroxylase
Tryptophan hydroxylase is an enzyme involved in the synthesis of the neurotransmitter serotonin. TPH catalyzes the following chemical reactionIt employs one cofactor, iron.- Function :...
levels have been reduced by MDMA.) Varied reports indicate that the perceived impact of pre-loading is dependent upon a number of factors and while it has not been shown to reliably increase the subjective effects of MDMA, your mileage may vary.
Evidence for serotonergic changes in humans
Studies have used positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging methods to estimate brain serotonin transporter levels in ecstasy users. These studies have found reduced levels of the transporter in recently abstinent MDMA users as well as evidence of partial or full recovery with prolonged abstinence. However, the sensitivity of these methods is unknown and changes may not have been detected. Three studies of 5-HT2A receptors in human MDMA users have been published by one group of researchers (Reneman and colleagues). Together, these studies find possibly reduced receptor binding during active MDMA use and increased receptor binding in longer-abstinent subjects. The authors argue that long-lasting reductions in 5-HT release may have caused compensatory up-regulation of 5-HT2A receptors. Other studies have measured cerebrospinal fluid concentrations of the serotonin metabolite 5HIAA. Three of four published studies have reported concentrations to be lower in ecstasy users than non-users.One difficulty in interpreting these studies is that it is difficult to know if serotonergic differences predated MDMA use. In addition, none of these studies can address whether any changes are neurotoxicity proper or neuroadaptation. A recent review concluded that "the current state of neuroimaging in human MDMA users does not permit conclusions regarding the long-term effects of MDMA exposure".
Although they are often studied in the same people or animals, possible serotonergic changes may have different risk, mechanisms, and recovery compared to possible cognitive and behavioral changes occurring after MDMA exposure. Studies in animals and humans have generally failed to correlate these two domains.
Psychiatric and behavioral changes
Some studies find that repeated ecstasy use may lead to subtle decreases in learning, memory, attention, executive function, mood, and decision making. Considerable research has been done into these possible cognitive-behavioral deficits but studies are inconclusive. Most are retrospective, that is, they study people after they started using ecstasy. This makes it difficult to know if differences between users and non-users were preexisting.There does not seem to be a single type of cognitive task that is consistently altered in the different studies. Tasks that have shown differences include ones measuring attention, learning, memory, and executive function. Many of the findings, which are more commonly reported in people with more extensive ecstasy use histories (or even abuse diagnoses), may simply reflect preexisting differences between people who are drawn to use drugs like ecstasy frequently and those who do not.
In addition, mood is sometimes found to be worse and impulsivity greater in ecstasy users. At least two meta-analyses
Meta-analysis
In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...
of these studies have been completed (Morgan 2000; Sumnall & Cole 2005). Morgan's analysis of 17 studies showed that ecstasy users had a slight tendency to be more impulsive and have lower mood than controls. Sumnall and Cole's analysis showed a slight increase in the prevalence of depressive symptoms in ecstasy users over controls. (Mood measured in these studies does not indicate clinical levels of depression, which has not been associated with MDMA use.) Of course, studies like these raise a cause-consequence question: did these impulsive and depressed people use ecstasy to self-medicate or did otherwise normal people become depressed and impulsive after using ecstasy? This question has not been conclusively answered and both possibilities may be true in individual cases.
There are a growing number of longitudinal or prospective studies, looking at users and nonusers at several points in time. Published prospective studies tend to report subtle difference between users and nonusers with performance within normal range. These difference tend to persist (Reneman et al. 2006; Gouzoulis-Mayfrank et al. 2005; Thomasius et al. 2006) or increase across time (Zakzanis and Young 2001; Zakzanis and Campbell 2006). While persisting differences are consistent with differences predating ecstasy use, increases may indicate worsening due to drug exposure.
A recent important study (the NeXT Netherlands XTC toxicity study) prospectively examined 25 people before and after their first episode of ecstasy use (mean 2.0 ± 1.4 ecstasy pills, on average 11.1 ± 12.9 weeks since last ecstasy use). The study measured working memory, selective attention, and associative memory using fMRI. No significant effects were found of the reportedly modest dose(s) of ecstasy on any of these measures, suggesting that the first few exposures to ecstasy typically do not cause significant residual toxicity. Thus, if ecstasy does cause cognitive-behavioral changes, it would likely require repeated use for these changes to occur (or become detectable). Contrary to this another recent report has shown that a single exposure to MDMA can result in cognitive-behavioral changes. The study took a group of people who have never used MDMA and had them perform cognitive tests. The participants were then exposed to a low dose of MDMA and underwent the same cognitive tests three years later. It was found that scores on immediate and delayed verbal recall and verbal recognition were significantly lower in the group of incident Ecstasy users compared with persistent Ecstasy-naive subjects. The authors did recognize there were limitations to their study but it shows that MDMA most likely does cause cognitive-behavioral effects after one exposure.
In addition to concerns about neurotoxicity, several published reports have described 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...
in MDMA users. This appears to be very rare and published cases have been complicated by use of other drugs, in concurrence with MDMA use.
Addiction and tolerance
The potential of MDMA to produce addictionSubstance dependence
The section about substance dependence in the Diagnostic and Statistical Manual of Mental Disorders does not use the word addiction at all. It explains:...
is controversial. Some studies indicate that many users may be addicted, but this depends on the definition of addiction; while many ecstasy users may take the drug regularly and develop significant tolerance to its effects, relatively few users exhibit cravings or physical symptoms of dependence
Substance dependence
The section about substance dependence in the Diagnostic and Statistical Manual of Mental Disorders does not use the word addiction at all. It explains:...
, or find it difficult to stop using the drug when they decide to do so. Cottler et al. (2001)
interviewed 52 users and found that 43% met standard criteria for dependence. However, some of these people may have been inappropriately diagnosed with dependence because they reported tolerance or after effects from MDMA. Tolerance and after effects ("withdrawal
Withdrawal
Withdrawal can refer to any sort of separation, but is most commonly used to describe the group of symptoms that occurs upon the abrupt discontinuation/separation or a decrease in dosage of the intake of medications, recreational drugs, and alcohol...
" effects) are symptoms of dependence for many drugs, but seem to occur in some MDMA users who are actually not dependent. For example, studies in Switzerland
Switzerland
Switzerland name of one of the Swiss cantons. ; ; ; or ), in its full name the Swiss Confederation , is a federal republic consisting of 26 cantons, with Bern as the seat of the federal authorities. The country is situated in Western Europe,Or Central Europe depending on the definition....
in which MDMA was given to people who had never used it before documented after effects. When people are classified as addicted to MDMA, it is not clear if that indicates a difficulty in quitting the drug. In a prospective study in Germany
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
, many who were initially categorized as addicted, spontaneously 'improved' without any treatment for the alleged addiction. Given the complexities in classifying MDMA users as addicted, conclusions about the addictive potential of MDMA are less reliable than those about nicotine addiction. Cases have been reported of addictive personality
Addictive personality
An addictive personality refers to a particular set of personality traits that make an individual predisposed to addictions. People who are substance dependent are characterized by: a physical or psychological dependency that negatively impacts the quality of life...
types abusing MDMA as they would with alcohol, tobacco, or other drugs, taking excessively high doses against the natural recommendations, and taking it too frequently and even daily, against recommendations. However they typically end up abandoning MDMA for drugs more suitable to addictive behavior after a period of time, and the tolerance issues of MDMA make it naturally antagonistic to long term daily addiction.
Retracted article on MDMA-induced dopamine neurotoxicity in primates
In a retracted article on toxicity of MDMA on dopamine cells, a research team led by Dr. George A. RicaurteGeorge 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...
at Johns Hopkins University
Johns Hopkins University
The Johns Hopkins University, commonly referred to as Johns Hopkins, JHU, or simply Hopkins, is a private research university based in Baltimore, Maryland, United States...
implicated MDMA as a cause of Parkinson's-like brain abnormalities in monkeys, suggesting that a single use of MDMA caused permanent and serious damage to dopamine neurons. This controversial finding was subsequently retracted with the researchers stating that they had inadvertently injected their experimental animals with methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...
instead of MDMA.
External links
- Erowid Vaults: MDMA
- WWW Psychedelic Bibliography - A searchable database with full text of many scientific articles on psychedelics
- Kobie Whetstone - "The Brain Damage of MDMA ("Ecstasy"): Causes and Prevention for the Recreational User" (2009)
- Kobie Whetstone - "An Analysis of MDMA-induced Neurotoxicity." (2009).