Laudanum also known as
Tincture of Opium, is an
alcoholIn chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
ic
herbal preparationHerbalism is a traditional medicinal or folk medicine practice based on the use of plants and plant extracts. Herbalism is also known as botanical medicine, medical herbalism, herbal medicine, herbology, herblore, and phytotherapy...
containing approximately 10%
powdered opiumOpium is the dried latex obtained from the opium poppy . Opium contains up to 12% morphine, an alkaloid, which is frequently processed chemically to produce heroin for the illegal drug trade. The latex also includes codeine and non-narcotic alkaloids such as papaverine, thebaine and noscapine...
by weight (the equivalent of 1%
morphineMorphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
).
It is reddish-brown in colour and extremely bitter to the taste. Laudanum contains almost all of the opium alkaloids, including morphine and
codeineCodeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
. A
potentIn the field of pharmacology, potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. A highly potent drug evokes a larger response at low concentrations, while a drug of lower potency evokes a small response at low concentrations...
narcoticThe term narcotic originally referred medically to any psychoactive compound with any sleep-inducing properties. In the United States of America it has since become associated with opioids, commonly morphine and heroin and their derivatives, such as hydrocodone. The term is, today, imprecisely...
by virtue of its high morphine concentration, laudanum was historically used to
treatThis is a list of types of therapy .* Adventure therapy* Animal-assisted therapy* Aquatic therapy* Aromatherapy* Art and dementia* Art therapy* Authentic Movement* Behavioral therapy* Bibliotherapy* Buteyko Method* Chemotherapy...
a variety of
ailmentsA disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
, but its principal use was as an
analgesicAn analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
and cough suppressant. Until the early 20th century, laudanum was sold without a
prescriptionA prescription is a health-care program implemented by a physician or other medical practitioner in the form of instructions that govern the plan of care for an individual patient. Prescriptions may include orders to be performed by a patient, caretaker, nurse, pharmacist or other therapist....
and was a constituent of many
patent medicinePatent medicine refers to medical compounds of questionable effectiveness sold under a variety of names and labels. The term "patent medicine" is somewhat of a misnomer because, in most cases, although many of the products were trademarked, they were never patented...
s. Nowadays laudanum is strictly regulated and controlled throughout most of the world.
Laudanum is known as a "whole opium" preparation since it historically contained all the opium alkaloids. Today, however, the drug is often processed to remove all or most of the
noscapineNoscapine is a benzylisoquinoline alkaloid from plants of the Papaveraceae family, without significant painkilling properties. This agent is primarily used for its antitussive effects. It has also been shown to have anticancer activity...
(also known as narcotine) present as this is a strong emetic and does not add appreciably to the analgesic or anti-propulsive properties of opium; the resulting solution is called Denarcotized Tincture of Opium or Deodorized Tincture of Opium (DTO).
Laudanum remains available by prescription in the United States and theoretically in the United Kingdom, although today the drug's therapeutic indications are generally confined to controlling
diarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, alleviating pain, and easing
withdrawal symptomsWithdrawal 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...
in infants born to mothers
addictedSubstance use disorders include substance abuse and substance dependence. In DSM-IV, the conditions are formally diagnosed as one or the other, but it has been proposed that DSM-5 combine the two into a single condition called "Substance-use disorder"....
to
heroin or other opioids. Recent enforcement action by the FDA against manufacturers of
paregoricParegoric, or camphorated tincture of opium, also known as tinctura opii camphorata, is a medication known for its antidiarrheal, antitussive, and analgesic properties.-History:...
and opium tincture suggests that opium tincture's availability in the U.S. may be in jeopardy.
The terms
laudanum and
tincture of opium are generally
interchangeableSynonyms are different words with almost identical or similar meanings. Words that are synonyms are said to be synonymous, and the state of being a synonym is called synonymy. The word comes from Ancient Greek syn and onoma . The words car and automobile are synonyms...
, but in contemporary medical practice the latter is used almost exclusively.
History
ParacelsusParacelsus was a German-Swiss Renaissance physician, botanist, alchemist, astrologer, and general occultist....
, born Phillippus Aureolus Theophrastus Bombastus von Hohenheim (1493–1541) in Salzburg, Austria, a 16th-century Swiss-German
alchemistAlchemy is an influential philosophical tradition whose early practitioners’ claims to profound powers were known from antiquity. The defining objectives of alchemy are varied; these include the creation of the fabled philosopher's stone possessing powers including the capability of turning base...
, discovered that the alkaloids in opium are far more soluble in alcohol than water. Having experimented with various opium concoctions, Paracelsus came across a specific tincture of
opiumOpium is the dried latex obtained from the opium poppy . Opium contains up to 12% morphine, an alkaloid, which is frequently processed chemically to produce heroin for the illegal drug trade. The latex also includes codeine and non-narcotic alkaloids such as papaverine, thebaine and noscapine...
that was of considerable use in reducing pain. He called this preparation laudanum, derived from the
LatinLatin is an Italic language originally spoken in Latium and Ancient Rome. It, along with most European languages, is a descendant of the ancient Proto-Indo-European language. Although it is considered a dead language, a number of scholars and members of the Christian clergy speak it fluently, and...
verbA verb, from the Latin verbum meaning word, is a word that in syntax conveys an action , or a state of being . In the usual description of English, the basic form, with or without the particle to, is the infinitive...
laudare, to praise. Initially, the term "laudanum" referred to any combination of opium and alcohol. Indeed, Paracelsus' laudanum was strikingly different from the standard laudanum of the 17th century and beyond. His preparation contained opium, crushed pearls,
muskMusk is a class of aromatic substances commonly used as base notes in perfumery. They include glandular secretions from animals such as the musk deer, numerous plants emitting similar fragrances, and artificial substances with similar odors. Musk was a name originally given to a substance with a...
,
amberAmber is fossilized tree resin , which has been appreciated for its color and natural beauty since Neolithic times. Amber is used as an ingredient in perfumes, as a healing agent in folk medicine, and as jewelry. There are five classes of amber, defined on the basis of their chemical constituents...
, and other substances. One researcher has documented that "Laudanum, as listed in the
London Pharmacoepoeia (1618), was a pill made from opium, saffron, castor, ambergris, musk and nutmeg."
Laudanum remained largely unknown until the 1660s when an English physician named
Thomas SydenhamThomas Sydenham was an English physician. He was born at Wynford Eagle in Dorset, where his father was a gentleman of property. His brother was Colonel William Sydenham. Thomas fought for the Parliament throughout the English Civil War, and, at its end, resumed his medical studies at Oxford...
(1624–1689) compounded a proprietary opium tincture that he also named laudanum, although it differed substantially from the laudanum of Paracelsus. In 1676 Sydenham published a seminal work,
Medical Observations Concerning the History and Cure of Acute Diseases, in which he promoted his brand of opium tincture, and advocated its use for a range of medical conditions. By the 18th century, the medicinal properties of opium and laudanum were well-known. Several physicians, including John Jones, John Brown, and George Young, the latter of whom published a comprehensive medical text entitled
Treatise on Opium extolled the virtues of laudanum and recommended the drug for practically every ailment. "Opium, and after 1820, morphine, was mixed with everything imaginable: mercury, hashish, cayenne pepper, ether, chloroform, belladonna, whiskey, wine and brandy."
As one researcher has noted: "To understand the popularity of a medicine that eased—even if only temporarily—coughing, diarrhoea and pain, one only has to consider the living conditions at the time". In the 1850s, "cholera and dysentery regularly ripped through communities, its victims often dying from debilitating diarrhoea," and dropsy,
consumptionTuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
,
agueAgue may refer to:* Fever* MalariaSee also:* Kan Ague, a residential area of Patikul, Sulu, Philippines...
and
rheumatismRheumatism or rheumatic disorder is a non-specific term for medical problems affecting the joints and connective tissue. The study of, and therapeutic interventions in, such disorders is called rheumatology.-Terminology:...
were all too common.
By the 19th century, laudanum was used in many
patent medicinePatent medicine refers to medical compounds of questionable effectiveness sold under a variety of names and labels. The term "patent medicine" is somewhat of a misnomer because, in most cases, although many of the products were trademarked, they were never patented...
s to "relieve
painPain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
... to produce
sleepSleep is a naturally recurring state characterized by reduced or absent consciousness, relatively suspended sensory activity, and inactivity of nearly all voluntary muscles. It is distinguished from quiet wakefulness by a decreased ability to react to stimuli, and is more easily reversible than...
... to allay irritation ... to check excessive secretions ... to support the system ... [and] as a soporific". The limited
pharmacopoeiaPharmacopoeia, pharmacopeia, or pharmacopoea, , in its modern technical sense, is a book containing directions for the identification of samples and the preparation of compound medicines, and published by the authority of a government or a medical or pharmaceutical society.In a broader sense it is...
of the day meant that opium derivatives were among the most efficacious of available treatments, so laudanum was widely prescribed for ailments from
coldsThe common cold is a viral infectious disease of the upper respiratory system, caused primarily by rhinoviruses and coronaviruses. Common symptoms include a cough, sore throat, runny nose, and fever...
to
meningitisMeningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...
to
cardiacThe heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
diseaseA disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
s, in both adults and children. Laudanum was used during the
yellow feverYellow fever is an acute viral hemorrhagic disease. The virus is a 40 to 50 nm enveloped RNA virus with positive sense of the Flaviviridae family....
epidemicIn epidemiology, an epidemic , occurs when new cases of a certain disease, in a given human population, and during a given period, substantially exceed what is expected based on recent experience...
. Innumerable Victorian women were prescribed the drug for relief of menstrual cramps and vague aches. Nurses also spoon-fed laudanum to infants. The
RomanticRomanticism was an artistic, literary and intellectual movement that originated in the second half of the 18th century in Europe, and gained strength in reaction to the Industrial Revolution...
and
Victorian eraThe Victorian era of British history was the period of Queen Victoria's reign from 20 June 1837 until her death on 22 January 1901. It was a long period of peace, prosperity, refined sensibilities and national self-confidence...
s were marked by the widespread use of laudanum in Europe and the
United StatesThe United States of America is a federal constitutional republic comprising fifty states and a federal district...
.
Mary Todd LincolnMary Ann Lincoln was the wife of the 16th President of the United States, Abraham Lincoln, and was First Lady of the United States from 1861 to 1865.-Life before the White House:...
, for example, the wife of President
Abraham LincolnAbraham Lincoln was the 16th President of the United States, serving from March 1861 until his assassination in April 1865. He successfully led his country through a great constitutional, military and moral crisis – the American Civil War – preserving the Union, while ending slavery, and...
, was a laudanum addict, as was the English poet
Samuel Taylor ColeridgeSamuel Taylor Coleridge was an English poet, Romantic, literary critic and philosopher who, with his friend William Wordsworth, was a founder of the Romantic Movement in England and a member of the Lake Poets. He is probably best known for his poems The Rime of the Ancient Mariner and Kubla...
, who was famously interrupted in the middle of an opium-induced writing session of
Kubla KhanKubla Khan is a poem by Samuel Taylor Coleridge, completed in 1797 and published in Christabel, Kubla Khan, and the Pains of Sleep in 1816...
by a "
person from PorlockThe Person from Porlock was an unwelcome visitor to Samuel Taylor Coleridge during his composition of the poem Kubla Khan. Coleridge claimed to have perceived the entire course of the poem in a dream , but was interrupted by this visitor from Porlock while in the process of writing it...
." Initially a working class drug, laudanum was cheaper than a bottle of
ginGin is a spirit which derives its predominant flavour from juniper berries . Although several different styles of gin have existed since its origins, it is broadly differentiated into two basic legal categories...
or
wineWine is an alcoholic beverage, made of fermented fruit juice, usually from grapes. The natural chemical balance of grapes lets them ferment without the addition of sugars, acids, enzymes, or other nutrients. Grape wine is produced by fermenting crushed grapes using various types of yeast. Yeast...
, because it was treated as a medication for legal purposes and not taxed as an
alcoholic beverageAn alcoholic beverage is a drink containing ethanol, commonly known as alcohol. Alcoholic beverages are divided into three general classes: beers, wines, and spirits. They are legally consumed in most countries, and over 100 countries have laws regulating their production, sale, and consumption...
.
Laudanum was used in home remedies and prescriptions, as well as a single medication. For example, a 1901 medical book published for home health use gave the following two "Simple Remedy Formulas" for
DYSENTERRY [sic]: (1) Thin boiled starch, 2 ounces; Laudanum, 20 drops; "Use as an
injectionAn enema is the procedure of introducing liquids into the rectum and colon via the anus. The increasing volume of the liquid causes rapid expansion of the lower intestinal tract, often resulting in very uncomfortable bloating, cramping, powerful peristalsis, a feeling of extreme urgency and...
every six to twelve hours"; (2) Tincture rhubarb, 1 ounce; Laudanum 4 drachms; "Dose: One teaspoonful every three hours." In a section entitled "Professional Prescriptions" is a formula for
DIARRHOEA (ACUTE): Tincture opium, deodorized, 15 drops; Subnitrate of bismuth, 2 drachms; Simple syrup, 1/2 ounce; Chalk mixture, 1½ ounces, "A teaspoonful every two or three hours to a child one year old."
DIARRHOEA (CHRONIC): Aqueous extract of ergot, 20 grains; Extract of nux vomica, 5 grains; Extract of Opium, 10 grains, "Make 20 pills. Take one pill every three or four hours."
The early 20th century brought increased regulation of all manner of narcotics, including laudanum, as the addictive properties of opium became more widely understood, and "patent medicines came under fire largely because of their mysterious compositions." In the United States, the Pure Food and Drug Act of 1906 required that certain specified drugs, including alcohol, cocaine, heroin, morphine, and cannabis, be accurately labeled with contents and dosage. Previously many drugs had been sold as patent medicines with secret ingredients or misleading labels. Cocaine, heroin, cannabis, and other such drugs continued to be legally available without prescription as long as they were labeled. It is estimated that sale of patent medicines containing opiates decreased by 33% after labeling was mandated. In 1906 in Britain and in 1908 in Canada "laws requiring disclosure of ingredients and limitation of narcotic content were instituted."
The
Harrison Narcotics Tax ActThe Harrison Narcotics Tax Act was a United States federal law that regulated and taxed the production, importation, and distribution of opiates...
of 1914 restricted the manufacture and distribution of opiates, including laudanum, and coca derivatives in the United States; this was followed by France's
Loi des stupefiants in 1916, and Britain's Dangerous Drugs Act in 1920.
Laudanum was supplied to druggists and physicians in regular and concentrated versions. For example, in 1915, Frank S. Betz Co., a medical supply company in Hammond, Indiana, advertised Tincture of Opium, U.S.P., for $2.90 per lb., Tincture of Opium Camphorated, U.S.P, for 85 cents per lb., and Tincture of Opium Deodorized, for $2.85 per lb. Four versions of opium as a fluid extract were also offered: (1) Opium, Concentrated (assayed) "For making Tincture Opii (Laudanum) U.S.P. Four times the strength of the regular U.S.P." tincture, for $9.35 per pint; (2) Opium, Camphorated Conc. "1 oz. making 8 ozs. Tr. Opii Camphorated U.S.P (Paregoric)" for $2.00 per pint; (3) Opium, Concentrated (Deodorized and Denarcotized) "Four times the strength of tincture, Used when Tinct. Opii U.S.P. is contraindicated" for $9.50 per pint, and (4) Opium (Aqueous), U.S.P., 1890, "Tr. (assayed) Papayer Somniferum" for $2.25 per pint.
In 1929–30, Parke, Davis & Co., a major United States drug manufacturer based in Detroit, Michigan, sold "Opium, U.S.P. (Laudanum)" as Tincture No. 23 for $10.80 per pint (16 fluid ounces), and "Opium Camphorated, U.S.P. (Paregoric)" as Tincture No. 20, for $2.20 per pint. Concentrated versions were available. "Opium Camphorated, for U.S.P. Tincture: Liquid No. 338" was "exactly 8
times the strength of Tincture Opium Camphorated (Paregoric) [italics in original], U.S.P., "designed for preparing the tincture by direct dilution," and cost $7 per pint. Similarly, at a cost of $36 per pint, "Opium Concentrated, for U.S.P. Tincture: Liquid No. 336," was "four times the strength of the official tincture," and "designed for the extemporaneous preparation of the tincture." The catalog also noted: "For quarter-pint bottles add 80c. per pint to the price given for pints."
Toward the middle 20th century, the use of opiates was generally limited to the treatment of pain, and opium was no longer a medically-accepted "cure-all". Further, the pharmaceutical industry began synthesizing various
opioidAn opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
s, such as propoxyphene,
oxymorphoneOxymorphone or 14-Hydroxydihydromorphinone is a powerful semi-synthetic opioid analgesic first developed in Germany circa 1914, patented in the USA by Endo Pharmaceuticals in 1955 and introduced to the United States market in January 1959 and other countries around the same time...
and
oxycodoneOxycodone is an opioid analgesic medication synthesized from opium-derived thebaine. It was developed in 1916 in Germany, as one of several new semi-synthetic opioids in an attempt to improve on the existing opioids: morphine, diacetylmorphine , and codeine.Oxycodone oral medications are generally...
. These synthetic opioids, along with
codeineCodeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
and
morphineMorphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
were preferable to laudanum since a single opioid could be prescribed for different types of pain rather than the "cocktail" of laudanum, which contains nearly all of the opium alkaloids. Consequently, laudanum became mostly obsolete as an
analgesicAn analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
, since its principal ingredient is
morphineMorphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
, which can be prescribed by itself to treat pain. There is no medical evidence that laudanum is superior to treating pain over morphine alone.
In 1970, the U.S. adopted the
Uniform Controlled Substances ActThe Uniform Controlled Substances Act was drafted by the United States Department of Justice in 1969 and promulgated by the National Conference of Commissioners on Uniform State Laws while the federal Controlled Substances Act was being drafted. Modeled after the federal Act, the uniform act...
, which regulated opium tincture (Laudanum) as a Schedule II substance (currently DEA #9630), placing even tighter controls on the drug.
By the late 20th century, laudanum's use was almost exclusively confined to treating severe
diarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
. The current prescribing information for laudanum in the U.S. states that opium tincture's sole indication is as an antidiarrheal, although the drug is occasionally prescribed off-label for treating pain and neonatal withdrawal syndrome.
Historical varieties
Several historical varieties of laudanum exist, including
ParacelsusParacelsus was a German-Swiss Renaissance physician, botanist, alchemist, astrologer, and general occultist....
' laudanum,
Sydenham's LaudanumThomas Sydenham was an English physician. He was born at Wynford Eagle in Dorset, where his father was a gentleman of property. His brother was Colonel William Sydenham. Thomas fought for the Parliament throughout the English Civil War, and, at its end, resumed his medical studies at Oxford...
(also known as
tinctura opii crocata), benzoic laudanum (
tinctura opii benzoica), and deodorized tincture of opium (the most common contemporary formulation), among others. Depending on the version, additional amounts of the substances and additional active ingredients (e.g.
saffronSaffron is a spice derived from the flower of Crocus sativus, commonly known as the saffron crocus. Crocus is a genus in the family Iridaceae. Each saffron crocus grows to and bears up to four flowers, each with three vivid crimson stigmas, which are each the distal end of a carpel...
,
sugarSugar is a class of edible crystalline carbohydrates, mainly sucrose, lactose, and fructose, characterized by a sweet flavor.Sucrose in its refined form primarily comes from sugar cane and sugar beet...
,
eugenolEugenol is a phenylpropene, an allyl chain-substituted guaiacol. Eugenol is a member of the phenylpropanoids class of chemical compounds. It is a clear to pale yellow oily liquid extracted from certain essential oils especially from clove oil, nutmeg, cinnamon, basil and bay leaf. It is slightly...
) are added, modifying its effects (e.g., amount of
sedationSedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure...
, or anti-tussive properties).
There is probably no single reference that lists all the pharmaceutical variations of laudanum that were created and used in different countries during centuries since it was initially formulated. The reasons are that in addition to official variations described in pharmacoepias, pharmacists and drug manufacturers were free to alter such formulas. The alcohol content of Laudanum probably varied substantially; on the labels of turn-of-the-century bottles of Laudanum, alcoholic content is stated as 48%. In contrast, the current version of Laudanum contains about 18% alcohol.
The four variations of Laudanum listed here were used in the United States during the late 19th century. The first, from an 1870 publication, is "Best Turkey opium 1 oz., slice, and pour upon it boiling water 1 gill, and work it in a bowl or mortar until it is dissolved; then pour it into the bottle, and with alcohol of 70 percent proof 1/2 pt., rinse the dish, adding the alcohol to the preparation, shaking well, and in 24 hours it will be ready for us. Dose—From 10 to 30 drops for adults, according to the strength of the patient, or severity of the pain. Thirty drops of this laudanum will be equal to one grain of opium. And this is a much better way to prepare it than putting the opium into alcohol, or any other spirits alone, for in that case much of the opium does not dissolve." The remaining three formulas are copied from an 1890 publication of the day: (1)
Sydenham's Laudanum: "According to the
Paris Codex this is prepared as follows: opium, 2 ounces; saffron, 1 ounce; bruised cinnamon and bruised cloves, each 1 drachm; sherry wine, 1 pint. Mix and macerate for 15 days and filter. Twenty drops are equal to one grain of opium." (2)
Rousseau's Laudanum: "Dissolve 12 ounces white honey in 3 pounds warm water, and set it aside in a warm place. When fermentation begins add to it a solution of 4 ounces selected opium in 12 ounces water. Let the mixture stand for a month at a temperature of 86° Fahr.; then strain, filter, and evaporate to 10 ounces; finally strain and add 4½ ounces proof alcohol. Seven drops of this preparation contain about 1 grain of opium." (3)
Tincture of Opium (Laudanum), U.S.P., attributed to the
United States Pharmacoepia of 1863: "Macerate 2½ ounces opium, in moderately fine powder in 1 pint water for 3 days, with frequent agitation. Add 1 pint alcohol, and macerate for 3 days longer. Percolate, and displace 2 pints tincture by adding dilute alcohol in the percolator."
United States
Tincture of Opium is available by
prescriptionA prescription is a health-care program implemented by a physician or other medical practitioner in the form of instructions that govern the plan of care for an individual patient. Prescriptions may include orders to be performed by a patient, caretaker, nurse, pharmacist or other therapist....
in the
United StatesThe United States of America is a federal constitutional republic comprising fifty states and a federal district...
. It is regulated as a
Schedule II drug (No. 9639) under the
Controlled Substances ActThe Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...
.
In the United States opium tincture is marketed and distributed by several pharmaceutical firms, each producing a single formulation of the drug, which is deodorized. Each mL contains 10 mg of anhydrous morphine (the equivalent of 100 mg of
powdered opium), other opium alkaloids (except
noscapineNoscapine is a benzylisoquinoline alkaloid from plants of the Papaveraceae family, without significant painkilling properties. This agent is primarily used for its antitussive effects. It has also been shown to have anticancer activity...
), and ethanol, 19%. It is available prepackaged in bottles of four ounces (118 mL) and 16 ounces (1 pint or 473 mL).
Tincture of Opium is what is known as an "unapproved drug" by the U.S. Food and Drug Administration (FDA); the marketing and distribution of opium tincture are permitted today because opium tincture was sold prior to the Federal Food, Drug & Cosmetic Act of 1938. Given its "grandfathered" status, opium tincture has never been required to undergo the strict FDA drug review and approval process. Nevertheless, the FDA has closely monitored the labeling of opium tincture.
Bottles of opium tincture are required by the FDA to bear a bright red "
POISONIn the context of biology, poisons are substances that can cause disturbances to organisms, usually by chemical reaction or other activity on the molecular scale, when a sufficient quantity is absorbed by an organism....
" label given the potency of the drug and the potential for overdose (see discussion about confusion with Paregoric below). Despite opium tincture being an "unapproved drug" as discussed above, a search of FDA's website does not reveal any efforts at this time to ban opium tincture or restrict its use; in fact, the FDA has a
web page devoted to patient and practitioner education about opium tincture.
(See FDA Patient Education Webcast on Confusion between Opium Tincture and Paregoric) However, in a warning letter to a manufacturer of opium tincture in late 2009, the FDA noted that "In regard to your unapproved drugs, we found that your firm is manufacturing and distributing the prescription drug Opium Tincture USP (Deodorized—10 mg/mL). Based on our information, there are no FDA-approved applications on file for this drug product." This warning may indicate a shift in FDA policy toward banning opium tincture or at least requiring the product to be brought within the FDA's regulatory framework.
United Kingdom
Opium tincture remains in the British Pharmacoepia, where it is referred to as Tincture of Opium, B.P., Laudanum, Thebaic Tincture, or Tinctura Thebaica, and "adjusted to contain 1% w/v of anhydrous morphine." It is a
Class A substance under the Misuse of Drugs Act of 1971. At least one manufacturer (Macfarlan Smith) still produces opium tincture in the U.K. . However, it is unclear whether opium tincture is prescribed by itself or whether it is incorporated into weaker solutions, such as Gee's Linctus.
Pharmacology
Opium tincture is useful as an
analgesicAn analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
and antidiarrheal. Opium enhances the
toneIn physiology, medicine, and anatomy, muscle tone is the continuous and passive partial contraction of the muscles, or the muscle’s resistance to passive stretch during resting state. It helps maintain posture, and it declines during REM sleep.-Purpose:Unconscious nerve impulses maintain the...
in the long segments of the longitudinal muscle and inhibits propulsive contraction of circular and longitudinal muscles. The pharmacological effects of opium tincture are due principally to its morphine content. The quantity of the
papaverinePapaverine is an opium alkaloid antispasmodic drug, used primarily in the treatment of visceral spasm, vasospasm , and occasionally in the treatment of erectile dysfunction...
and
codeineCodeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
alkaloids in opium tincture is too small to have any demonstrable central nervous system effect.
Most modern formulations of opium tincture do not contain the alkaloid narcotine (also known as
noscapineNoscapine is a benzylisoquinoline alkaloid from plants of the Papaveraceae family, without significant painkilling properties. This agent is primarily used for its antitussive effects. It has also been shown to have anticancer activity...
), which has antitussive properties. Even modest doses of narcotine can induce profound
nauseaNausea , 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
vomitingVomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
. Since opium tincture is usually prescribed for its antidiarrheal and analgesic properties (rather than as an antitussive), opium tincture without narcotine is generally preferred. This "de-narcotized" or "deodorized" opium tincture is formulated using a
petroleumPetroleum or crude oil is a naturally occurring, flammable liquid consisting of a complex mixture of hydrocarbons of various molecular weights and other liquid organic compounds, that are found in geologic formations beneath the Earth's surface. Petroleum is recovered mostly through oil drilling...
distillate to remove the narcotine.
Oral doses of opium tincture are rapidly absorbed in the
gastrointestinal tractThe human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
and metabolized in the
liverThe liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
. Peak plasma concentrations of the morphine content are reached in about one hour, and nearly 75% of the morphine content of the opium tincture is excreted in the urine within 48 hours after oral administration.
Diarrhea
Opium tincture is indicated for the treatment of severe
fulminantFulminant is any event or process that occurs suddenly and quickly, and is intense and severe to the point of lethality, i.e., it has an explosive character. The word comes from Latin fulmināre, to strike with lightning...
diarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
that does not respond to mainline therapy or .
The recommended dose is 0.6 mL (6 mg or 10
minimsThe minim is a unit of volume in both the imperial and US customary systems of measurement. Specifically it is of a fluidram or of a fluid ounce....
) by mouth four times a day. Refractory cases (such as diarrhea resulting from the complications of
AIDSAcquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
) may require higher than normal dosing. In terminal diseases, there is no ceiling dose for opium tincture; the dose is increased slowly until diarrhea is controlled.
Neonatal Abstinence Syndrome (NAS)
Opium tincture is used to treat
neonatal abstinence syndromeNeonatal withdrawal or neonatal abstinence syndrome is a withdrawal syndrome of infants, caused by administration of drugs. Tolerance, dependence and withdrawal may occur as a result of repeated administration of drugs, or even after short-term high dose use for example during mechanical...
(NAS) when diluted 1:25 (one part opium tincture to 25 parts water). The recommended dose is 0.2 mL of the diluted solution under the tongue every three hours, which may be increased by 0.05 mL every three hours until no objective signs of withdrawal are observed. In no event, however, should the dose exceed 0.7 mL every three hours. The opium tincture is gradually tapered over a 3–5 week period, at which point the newborn should be completely free of withdrawal symptoms.
Pain
Given its high concentration of morphine, opium tincture is useful for treating moderate to severe
painPain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
. (The amount of codeine in the tincture is negligible and does not have any appreciable analgesic effect.) The dose of tincture is generally the same as that of morphine in opioid-
naïveDrug-naïve is the term used to describe patients or animals who are not under the influence of any psychotropic substances . This term usually refers to patients or animals undergoing drug-related testing, such as the effect of a certain drug on behaviour or cognitive ability.More specifically, it...
patients, titrated upward as needed. The usual starting dose in adults is 1.5 mL by mouth every 3 to 4 hours, representing the equivalent of 15 mg (approximately 1/4 grain) of morphine per dose. Opioid-tolerant patients may require higher than normal dosing. There is a danger of overdose in treating pain with opium tincture; see below. Today morphine and codeine are available in various forms as single formulation products, which are easier to dose and are much cheaper than opium tincture. Thus, opium is rarely prescribed to treat pain in contemporary medicine. Further, opium tincture contains 17% to 19% alcohol, by volume, which may complicate its use as an analgesic in patients for whom alcohol is contraindicated.
A brief uptick in the use of laudanum occurred in the middle of the current decade when a crop failure and other problems caused the shortage of multi-purpose soluble tablets of morphine, used at highest volume in recent times as an oral, sublingual, or buccally-administered analgesic.
Dosage
Extreme caution should be employed in administering doses of Tincture of Opium. Doses should be carefully measured using an oral syringe or calibrated dropper. Apothecary measurements should be avoided in contemporary medical prescriptions, and the prescriber should dose opium tincture in mL or fractions thereof. If in the prescriber's judgment dosing in
dropThe drop is a unit of measure of volume, the amount dispensed as one drop from a dropper. It is often used in giving quantities of liquid drugs to patients, and occasionally in cooking....
s would be appropriate, it should be borne in mind that in contemporary medicine, there are 20 drops per mL.
The differences between Tincture of Opium (Laudanum) and Camphorated Tincture of Opium (Paregoric) are important and should be kept in mind when administering either of these drugs. Care and caution should always be taken in administering doses of Tincture of Opium, such as the use of a dosage syringe or other suitable measurement device, and by pharmacists in preparing Paregoric from Laudanum, and to note that the dosages in this article refer to Apothecaries weight and fluid measure. In particular, "the difference between a minim and a drop should be borne in mind when figuring doses. A minim is always a sixtieth part of a fuidrachm regardless of the character of the substance, while a drop varies from a forty-fifth to a two-hundred-and-fiftieth part, according to the surface tension of the fluid." Tincture of Opium (Laudanum) and Camphorated Tincture of Opium (Paregoric) each have 50.9 drops per gram; 50.0 drops per cc; 185.0 drops per fluid drachm; and 3.10 drops per minim." The importance of these distinctions is evident in view of the dangers of erroneously relying upon more general descriptions of Apothecaries' fluid measures, which typically list 60 minims per fluid dram, and 8 fluid drams per fluid ounce (480 minims).
Potency of laudanum
Opium tincture is one of the most
potentIn the field of pharmacology, potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. A highly potent drug evokes a larger response at low concentrations, while a drug of lower potency evokes a small response at low concentrations...
oral formulations of morphine available by prescription. Accidental or deliberate overdose is common with opium tincture given the highly-concentrated nature of the solution. Overdose and
deathDeath is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....
may occur with a single oral dose of between 100 – 150 mg of morphine in a healthy adult who is not habituated to opiates. This represents the equivalent of between two to three
teaspoonA teaspoon, an item of cutlery, is a small spoon, commonly part of a silverware place setting, suitable for stirring and sipping the contents of a cup of tea or coffee...
s of opium tincture.
SuicideSuicide is the act of intentionally causing one's own death. Suicide is often committed out of despair or attributed to some underlying mental disorder, such as depression, bipolar disorder, schizophrenia, alcoholism, or drug abuse...
by laudanum was not uncommon in the mid-19th century. Prudent medical judgment necessitates toward dispensing very small quantities of opium tincture in small dropper bottles or in pre-filled syringes to reduce the risk of intentional or accidental overdose.
Danger of confusion with paregoric
In the United States, opium tincture contains 10 mg per mL of
anhydrousAs a general term, a substance is said to be anhydrous if it contains no water. The way of achieving the anhydrous form differs from one substance to another...
morphineMorphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
. By contrast, opium tincture's weaker cousin,
paregoricParegoric, or camphorated tincture of opium, also known as tinctura opii camphorata, is a medication known for its antidiarrheal, antitussive, and analgesic properties.-History:...
, also confusingly known as "camphorated tincture of opium", is 1/25th the strength of opium tincture, containing only 0.4 mg of morphine per mL. A 25-fold morphine overdose may occur if opium tincture is used where paregoric is indicated. Opium tincture is almost always dosed in drops, or fractions of a mL, or less commonly, in
minimsThe minim is a unit of volume in both the imperial and US customary systems of measurement. Specifically it is of a fluidram or of a fluid ounce....
, while paregoric is dosed in teaspoons or tablespoons. Thus, an order for opium tincture containing directions in teaspoons is almost certainly in error. To avoid this potentially fatal outcome, the term "camphorated tincture of opium" is avoided in place of paregoric since the former can easily be mistaken for opium tincture.
In 2004 the FDA issued a "Patient Safety" news bulletin stating that "To help resolve the confusion [between opium tincture and paregoric], FDA will be working with the manufacturers of these two drugs to clarify the labeling on the containers and in the package inserts." Indeed, in 2005, labels for opium tincture began to include the concentration of morphine (10 mg/mL) in large text beneath the words "Opium Tincture". The FDA has also alerted pharmacists and other medical practitioners about the dangers of confusing these drugs, and has recommended that opium tincture not be stocked as a standard item (i.e., that it should not be "on the shelf"), that opium tincture be dispensed in oral syringes, and that pharmacy software alert the dispenser if unusually large doses of opium tincture appear to be indicated.
Despite the FDA's efforts over the past few years, the confusion persists, sometimes with deadly results. The Institute for Safe Medication Practices recommends that opium tincture not be stocked at all in a pharmacy's inventory, and that "It may be time to relegate opium tincture and paregoric to the museum of outmoded opioid therapy." Despite the risk of confusion, opium tincture, like many end-stage medications, is indispensable for intractable diarrhea for terminally ill patients, such as those suffering from AIDS and cancer.
Misinterpretation of "DTO"
"DTO" is an abbreviation for
Deodorized
Tincture of
Opium. However, DTO is sometimes also erroneously employed to abbreviate "
diluted tincture of opium", a 1:25 mixture of opium tincture to water prescribed to treat withdrawal symptoms in newborns whose mothers were using opiates while pregnant. The
United States PharmacopeiaThe United States Pharmacopeia is the official pharmacopeia of the United States, published dually with the National Formulary as the USP-NF. The United States Pharmacopeial Convention is the nonprofit organization that owns the trademark and copyright to the USP-NF and publishes it every year...
and FDA recommend that practitioners refrain from using DTO in prescriptions given this potential for confusion. In cases where pharmacists have misinterpreted DTO to mean "deodorized tincture of opium" when "diluted tincture of opium" was meant, infants have received a massive 25-fold overdose of morphine, sometimes resulting in fatalities.
Side effects
Adverse effects of laudanum are generally the same as with
morphineMorphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
, and include
euphoriaEuphoria 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...
,
dysphoriaDysphoria is medically recognized as a mental and emotional condition in which a person experiences intense feelings of depression, discontent and indifference to the world around them.Mood disorders can induce dysphoria, often with a heightened risk of suicide, especially in...
, pruritis,
sedationSedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure...
,
constipationConstipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
, reduced
tidal volumeTidal volume is the lung volume representing the normal volume of air displaced between normal inspiration and expiration when extra effort is not applied.Typical values are around 500ml or 7ml/kg bodyweight.-Mechanical Ventilation:...
, respiratory depression, as well as
psychological dependenceThe section about substance dependence in the Diagnostic and Statistical Manual of Mental Disorders does not use the word addiction at all. It explains:...
, physical dependence,
miosisMiosis is the constriction of the pupil of the eye to two millimeters or less...
, and
xerostomiaXerostomia is the medical term for the subjective complaint of dry mouth due to a lack of saliva. Xerostomia is sometimes colloquially called pasties, cottonmouth, drooth, or doughmouth. Several diseases, treatments, and medications can cause xerostomia. It can also be exacerbated by smoking or...
. Overdose can result in severe respiratory depression or collapse and death. The ethanol component can also induce adverse effects at higher doses; the side effects are the same as with alcohol.
Long-term use of laudanum in nonterminal diseases is discouraged due to the possibility of drug tolerance and addiction. Long-term use can also lead to abnormal liver function tests; specifically, prolonged morphine use can increase ALT and AST blood serum levels.
Treatment for overdose
NaloxoneNaloxone is an opioid antagonist drug developed by Sankyo in the 1960s. Naloxone is a drug used to counter the effects of opiate overdose, for example heroin or morphine overdose. Naloxone is specifically used to counteract life-threatening depression of the central nervous system and respiratory...
, a quick-acting opioid antagonist, is the first-line treatment to reverse respiratory depression caused by an opioid overdose.
See also
- Confessions of an English Opium-Eater
Confessions of an English Opium-Eater is an autobiographical account written by Thomas De Quincey, about his laudanum addiction and its effect on his life...
- Paregoric
Paregoric, or camphorated tincture of opium, also known as tinctura opii camphorata, is a medication known for its antidiarrheal, antitussive, and analgesic properties.-History:...
- Poppy tea
Poppy tea is an infusion brewed from poppy straw or seeds of several species of poppy. The species most commonly used for this purpose is Papaver somniferum, which contains opium....
- Thomas Sydenham
Thomas Sydenham was an English physician. He was born at Wynford Eagle in Dorset, where his father was a gentleman of property. His brother was Colonel William Sydenham. Thomas fought for the Parliament throughout the English Civil War, and, at its end, resumed his medical studies at Oxford...
External links