Stimulant

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Stimulant 

Ritalin sustained-release (SR) 20 mg tablets

Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and invigorating, or drugs that have sympathomimetic effects. Stimulants are widely used throughout the world as prescription medicines as well as without a prescription (either legally or illicitly) as performance-enhancing or recreational drugs. The most frequently prescribed stimulants as of 2013 were lisdexamfetamine, methylphenidate, and amphetamine. It is estimated that the percentage of the population that has used amphetamine-type stimulants (e.g., amphetamine, methamphetamine, MDMA, etc.) and cocaine combined is between 0.8% and 2.1%.

Effects

Acute

Stimulants in therapeutic doses, such as those given to patients with ADHD, increases ability to focus, vigor, sociability, libido and may elevate mood. However, in higher doses stimulants may actually decrease the ability to focus, a principle of the Yerkes-Dodson Law. In higher doses stimulants may also produce euphoria, vigor, and decrease need for sleep. Many, but not all, stimulants have ergogenic effects. Drugs such as ephedrine, pseudoephedrine, amphetamine and methylphenidate have well documented ergogenic effects, while cocaine has the opposite effect. Neurocognitive enhancing effects of stimulants, specifically modafinil, amphetamine and methylphenidate have been documented in healthy adolescents, and is a commonly cited reason among illicit drug users for use, particularly among college students in the context of studying.

In some cases psychiatric phenomenon may emerge such as stimulant psychosis, paranoia, and suicidal ideation. Acute toxicity has been reportedly associated with a homicide, paranoia, aggressive behavior, motor dysfunction, and punding. The violent and aggressive behavior associated with acute stimulant toxicity may partially be driven by paranoia. Most drugs classified as stimulants are sympathomimetics, that is they stimulate the sympathetic branch of the autonomic nervous system. This leads to effects such as mydriasis, increased heart rate, blood pressure, respiratory rate and body temperature. When these changes become pathological, they are called arrhythmia, hypertension, and hyperthermia, and may lead to rhabdomyolysis, stroke, cardiac arrest, or seizures. However, given the complexity of the mechanisms that underlie these potentially fatal outcomes of acute stimulant toxicity, it is impossible to determine what dose may be lethal.

Chronic

Assessment of the effects of stimulants is relevant given the large population currently taking stimulants. A systematic review of cardiovascular effects of prescription stimulants found no association in children, but found a correlation between prescription stimulant use and ischemic heart attacks. A review over a four-year period found that there were few negative effects of stimulant treatment, but stressed the need for longer-term studies. A review of a year long period of prescription stimulant use in those with ADHD found that cardiovascular side effects were limited to transient increases in blood pressure only. Initiation of stimulant treatment in those with ADHD in early childhood appears to carry benefits into adulthood with regard to social and cognitive functioning, and appears to be relatively safe.

Abuse of prescription stimulants (not following physician instruction) or of illicit stimulants carries many negative health risks. Abuse of cocaine, depending upon route of administration, increases risk of cardiorespiratory disease, stroke, and sepsis. Some effects are dependent upon the route of administration, with intravenous use associated with the transmission of many disease such as Hepatitis C, HIV/AIDS and potential medical emergencies such as infection, thrombosis or pseudoaneurysm, while inhalation may be associated with increased lower respiratory tract infection, lung cancer, and pathological restricting of lung tissue. Cocaine may also increase risk for autoimmune disease and damage nasal cartilage. Abuse of methamphetamine produces similar effects as well as marked degeneration of dopaminergic neurons, resulting in an increased risk for Parkinson's disease.

Medical uses

Stimulants have been used in medicine for many conditions including obesity, sleep disorders, mood disorders, impulse control disorders, asthma, nasal congestion and, in case of cocaine, as local anesthetics. Drugs used to treat obesity are called anorectics and generally include drugs that follow the general definition of a stimulant, but other drugs such as cannabinoid receptor antagonists also belong to this group. Eugeroics are used in management of sleep disorders characterized by excessive daytime sleepiness, such as narcolepsy, and include stimulants such as modafinil. Stimulants are used in impulse control disorders such as ADHD and off-label in mood disorders such as major depressive disorder to increase energy, focus and elevate mood. Stimulants such as epinephrine, theophylline and salbutamol orally have been used to treat asthma, but inhaled adrenergic drugs are now preferred due to less systemic side effects. Pseudoephedrine is used to relieve nasal or sinus congestion caused by the common cold, sinusitis, hay fever and other respiratory allergies; it is also used to relieve ear congestion caused by ear inflammation or infection.

Chemistry

A chart comparing the chemical structures of different amphetamine derivatives

Classifying stimulants is difficult, because of the large number of classes the drugs occupy, and the fact that they may belong to multiple classes; for example, ecstasy can be classified as a substituted methylenedioxyphenethylamine, a substituted amphetamine and consequently, a substituted phenethylamine.

When referring to stimulants, the parent drug (e.g., amphetamine) will always be expressed in the singular; with the word "substituted" placed before the parent drug (substituted amphetamines). 

Major stimulant classes include phenethylamines and their daughter class substituted amphetamines.

Amphetamines (class)

Substituted amphetamines are a class of compounds based upon the amphetamine structure; it includes all derivative compounds which are formed by replacing, or substituting, one or more hydrogen atoms in the amphetamine core structure with substituents. Examples of substituted amphetamines are amphetamine (itself), methamphetamine, ephedrine, cathinone, phentermine, mephentermine, bupropion, methoxyphenamine, selegiline, amfepramone, pyrovalerone, MDMA (ecstasy), and DOM (STP). Many drugs in this class work primarily by activating trace amine-associated receptor 1 (TAAR1); in turn, this causes reuptake inhibition and effluxion, or release, of dopamine, norepinephrine, and serotonin. An additional mechanism of some substituted amphetamines is the release of vesicular stores of monoamine neurotransmitters through VMAT2, thereby increasing the concentration of these neurotransmitters in the cytosol, or intracellular fluid, of the presynaptic neuron.

Amphetamines-type stimulants are often used for their therapeutic effects. Physicians sometimes prescribe amphetamine to treat major depression, where subjects do not respond well to traditional SSRI medications,^{[citation needed]} but evidence supporting this use is poor/mixed. Notably, two recent large phase III studies of lisdexamfetamine (a prodrug to amphetamine) as an adjunct to an SSRI or SNRI in the treatment of major depressive disorder showed no further benefit relative to placebo in effectiveness. Numerous studies have demonstrated the effectiveness of drugs such as Adderall (a mixture of salts of amphetamine and dextroamphetamine) in controlling symptoms associated with ADHD. Due to their availability and fast-acting effects, substituted amphetamines are prime candidates for abuse.

Cocaine analogues

Hundreds of cocaine analogues have been created, all of them usually maintaining a benzyloxy connected to the 3 carbon of a tropane. Various modifications include substitutions on the benzene ring, as well as additions or substitutions in place of the normal carboxylate on the tropane 2 carbon. Various compound with similar structure activity relationships to cocaine that aren't technically analogues have been developed as well.

Mechanisms of action

Most stimulants exert their activating effects by enhancing catecholamine neurotranmission. Catecholamine neurotransmitters are employed in regulatory pathways implicated in attention, arousal, motivation, task salience and reward anticipation. Classical stimulants either block the reuptake or stimulate the efflux of these catecholamines, resulting in increased activity of their circuits. Some stimulants, specifically those with empathogenic and hallucinogenic effects, also affect serotonergic transmission. Some stimulants, such as some amphetamine derivatives and, notably, yohimbine, can decrease negative feedback by antagonizing regulatory autoreceptors. Adrenergic agonists, such as, in part, ephedrine, act by directly binding to and activating adrenergic receptors, producing sympathomimetic effects. 

There are also more indirect mechanisms a drug can elicit activating effects. Caffeine is an adenosine receptor antagonist, and only indirectly increases catecholamine transmission in the brain. Pitolisant is an H3-receptor inverse agonist. As H3 receptors mainly act as autoreceptors, pitolisant decreases negative feedback to histaminergic neurons, enhancing histaminergic transmission.

Notable stimulants

Amphetamine

Amphetamine is a potent central nervous system (CNS) stimulant of the phenethylamine class that is approved for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. Amphetamine is also used off-label as a performance and cognitive enhancer, and recreationally as an aphrodisiac and euphoriant. Although it is a prescription medication in many countries, unauthorized possession and distribution of amphetamine is often tightly controlled due to the significant health risks associated with uncontrolled or heavy use. As a consequence, amphetamine is illegally manufactured in clandestine labs to be trafficked and sold to users. Based upon drug and drug precursor seizures worldwide, illicit amphetamine production and trafficking is much less prevalent than that of methamphetamine.

The first pharmaceutical amphetamine was Benzedrine, a brand of inhalers used to treat a variety of conditions. Because the dextrorotary isomer has greater stimulant properties, Benzedrine was gradually discontinued in favor of formulations containing all or mostly dextroamphetamine. Presently, it is typically prescribed as mixed amphetamine salts, dextroamphetamine, and lisdexamfetamine.

Amphetamine is a norepinephrine-dopamine releasing agent (NDRA). It enters neurons through dopamine and norepinephrine transporters and facilitates neurotransmitter efflux by activating TAAR1 and inhibiting VMAT2. At therapeutic doses, this causes emotional and cognitive effects such as euphoria, change in libido, increased arousal, and improved cognitive control. Likewise, it induces physical effects such as decreased reaction time, fatigue resistance, and increased muscle strength. In contrast, supratherapeutic doses of amphetamine are likely to impair cognitive function and induce rapid muscle breakdown. Very high doses can result in psychosis (e.g., delusions and paranoia), which very rarely occurs at therapeutic doses even during long-term use.^[58][59] As recreational doses are generally much larger than prescribed therapeutic doses, recreational use carries a far greater risk of serious side effects, such as dependence, which only rarely arises with therapeutic amphetamine use.

Caffeine

Caffeine is a stimulant compound belonging to the xanthine class of chemicals naturally found in coffee, tea, and (to a lesser degree) cocoa or chocolate. It is included in many soft drinks, as well as a larger amount in energy drinks. Caffeine is the world's most widely used psychoactive drug and by far the most common stimulant. In North America, 90% of adults consume caffeine daily. A few jurisdictions restrict its sale and use. Caffeine is also included in some medications, usually for the purpose of enhancing the effect of the primary ingredient, or reducing one of its side-effects (especially drowsiness). Tablets containing standardized doses of caffeine are also widely available.

Caffeine's mechanism of action differs from many stimulants, as it produces stimulant effects by inhibiting adenosine receptors. Adenosine receptors are thought to be a large driver of drowsiness and sleep, and their action increases with extended wakefulness. Caffeine has been found to increase striatal dopamine in animal models, as well as inhibit the inhibitory effect of adenosine receptors on dopamine receptors, however the implications for humans are unknown. Unlike most stimulants, caffeine has no addictive potential. Caffeine does not appear to be a reinforcing stimulus, and some degree of aversion may actually occur, which people preferring placebo over caffeine in a study on drug abuse liability published in an NIDA research monograph. In large telephone surveys only 11% reported dependence symptoms. However, when people were tested in labs, only half of those who claim dependence actually experienced it, casting doubt on caffeine's ability to produce dependence and putting societal pressures in the spotlight.

Coffee consumption is associated with a lower overall risk of cancer. This is primarily due to a decrease in the risks of hepatocellular and endometrial cancer, but it may also have a modest effect on colorectal cancer. There does not appear to be a significant protective effect against other types of cancers, and heavy coffee consumption may increase the risk of bladder cancer. A protective effect of caffeine against Alzheimer's disease is possible, but the evidence is inconclusive. Moderate coffee consumption may decrease the risk of cardiovascular disease, and it may somewhat reduce the risk of type 2 diabetes. Drinking 1-3 cups of coffee per day does not affect the risk of hypertension compared to drinking little or no coffee. However those who drink 2–4 cups per day may be at a slightly increased risk. Caffeine increases intraocular pressure in those with glaucoma but does not appear to affect normal individuals. It may protect people from liver cirrhosis. There is no evidence that coffee stunts a child's growth. Caffeine may increase the effectiveness of some medications including ones used to treat headaches. Caffeine may lessen the severity of acute mountain sickness if taken a few hours prior to attaining a high altitude.

Ephedrine

Ephedrine is a sympathomimetic amine similar in molecular structure to the well-known drugs phenylpropanolamine and methamphetamine, as well as to the important neurotransmitter epinephrine (adrenaline). Ephedrine is commonly used as a stimulant, appetite suppressant, concentration aid, and decongestant, and to treat hypotension associated with anaesthesia.

In chemical terms, it is an alkaloid with a phenethylamine skeleton found in various plants in the genus Ephedra (family Ephedraceae). It works mainly by increasing the activity of norepinephrine (noradrenaline) on adrenergic receptors. It is most usually marketed as the hydrochloride or sulfate salt. 

The herb má huáng (Ephedra sinica), used in traditional Chinese medicine (TCM), contains ephedrine and pseudoephedrine as its principal active constituents. The same may be true of other herbal products containing extracts from other Ephedra species.

MDMA

Tablets containing MDMA

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy, or molly) is a euphoriant, empathogen, and stimulant of the amphetamine class. Briefly used by some psychotherapists as an adjunct to therapy, the drug became popular recreationally and the DEA listed MDMA as a Schedule I controlled substance, prohibiting most medical studies and applications. MDMA is known for its entactogenic properties. The stimulant effects of MDMA include hypertension, anorexia (appetite loss), euphoria, social disinhibition, insomnia (enhanced wakefulness/inability to sleep), improved energy, increased arousal, and increased perspiration, among others. Relative to catecholaminergic transmission, MDMA enhances serotonergic transmission significantly more, when compared to classical stimulants like amphetamine. MDMA does not appear to be significantly addictive or dependence forming.

Due to the relative safety of MDMA, some researchers such as David Nutt have criticized the scheduling level, writing a satirical article finding MDMA to be 28 times less dangerous than horseriding, a condition he termed "equasy" or "Equine Addiction Syndrome".

MDPV

Methylenedioxypyrovalerone (MDPV) is a psychoactive drug with stimulant properties that acts as a norepinephrine-dopamine reuptake inhibitor (NDRI). It was first developed in the 1960s by a team at Boehringer Ingelheim. MDPV remained an obscure stimulant until around 2004, when it was reported to be sold as a designer drug. Products labeled as bath salts containing MDPV were previously sold as recreational drugs in gas stations and convenience stores in the United States, similar to the marketing for Spice and K2 as incense.

Incidents of psychological and physical harm have been attributed to MDPV use.

Mephedrone

Mephedrone is a synthetic stimulant drug of the amphetamine and cathinone classes. Slang names include drone and MCAT. It is reported to be manufactured in China and is chemically similar to the cathinone compounds found in the khat plant of eastern Africa. It comes in the form of tablets or a powder, which users can swallow, snort, or inject, producing similar effects to MDMA, amphetamines, and cocaine.

Mephedrone was first synthesized in 1929, but did not become widely known until it was rediscovered in 2003. By 2007, mephedrone was reported to be available for sale on the Internet; by 2008 law enforcement agencies had become aware of the compound; and, by 2010, it had been reported in most of Europe, becoming particularly prevalent in the United Kingdom. Mephedrone was first made illegal in Israel in 2008, followed by Sweden later that year. In 2010, it was made illegal in many European countries, and, in December 2010, the EU ruled it illegal. In Australia, New Zealand, and the US, it is considered an analog of other illegal drugs and can be controlled by laws similar to the Federal Analog Act. In September 2011, the USA temporarily classified mephedrone as illegal, in effect from October 2011.

Methamphetamine

Methamphetamine (contracted from N-methyl-alpha-methylphenethylamine) is a potent psychostimulant of the phenethylamine and amphetamine classes that is used to treat attention deficit hyperactivity disorder (ADHD) and obesity. Methamphetamine exists as two enantiomers, dextrorotary and levorotary. Dextromethamphetamine is a stronger CNS stimulant than levomethamphetamine; however, both are addictive and produce the same toxicity symptoms at high doses. Although rarely prescribed due to the potential risks, methamphetamine hydrochloride is approved by the United States Food and Drug Administration (USFDA) under the trade name Desoxyn. Recreationally, methamphetamine is used to increase sexual desire, lift the mood, and increase energy, allowing some users to engage in sexual activity continuously for several days straight.

Methamphetamine may be sold illicitly, either as pure dextromethamphetamine or in an equal parts mixture of the right- and left-handed molecules (i.e., 50% levomethamphetamine and 50% dextromethamphetamine). Both dextromethamphetamine and racemic methamphetamine are schedule II controlled substances in the United States. Also, the production, distribution, sale, and possession of methamphetamine is restricted or illegal in many other countries due to its placement in schedule II of the United Nations Convention on Psychotropic Substances treaty. In contrast, levomethamphetamine is an over-the-counter drug in the United States.

In low doses, methamphetamine can cause an elevated mood and increase alertness, concentration, and energy in fatigued individuals. At higher doses, it can induce psychosis, rhabdomyolysis, and cerebral hemorrhage. Methamphetamine is known to have a high potential for abuse and addiction. Recreational use of methamphetamine may result in psychosis or lead to post-withdrawal syndrome, a withdrawal syndrome that can persist for months beyond the typical withdrawal period. Unlike amphetamine and cocaine, methamphetamine is neurotoxic to humans, damaging both dopamine and serotonin neurons in the central nervous system (CNS). Entirely opposite to the long-term use of amphetamine, there is evidence that methamphetamine causes brain damage from long-term use in humans; this damage includes adverse changes in brain structure and function, such as reductions in gray matter volume in several brain regions and adverse changes in markers of metabolic integrity.

Methylphenidate

Methylphenidate is a stimulant drug that is often used in the treatment of ADHD and narcolepsy and occasionally to treat obesity in combination with diet restraints and exercise. Its effects at therapeutic doses include increased focus, increased alertness, decreased appetite, decreased need for sleep and decreased impulsivity. Methylphenidate is not usually used recreationally, but when it is used, its effects are very similar to those of amphetamines. 

Methylphenidate acts a norepinephrine-dopamine reuptake inhibitor, by blocking the norepinephrine transporter (NET) and the dopamine transporter (DAT). Methylphenidate has a higher affinity for the dopamine transporter than for the norepinephrine transporter, and so its effects are mainly due to elevated dopamine levels caused by the inhibited reuptake of dopamine, however increased norepinephrine levels also contribute to various of the effects caused by the drug.

Methylphenidate is sold under a number of brand names including Ritalin. Other versions include the long lasting tablet Concerta and the long lasting transdermal patch Daytrana. 

A 2018 Cochrane review found tentative evidence that methylphenidate may result in serious side effects such as heart problems, psychosis, and death.

Cocaine

Lines of illicit cocaine, used as a recreational stimulant

Cocaine is an SNDRI. Cocaine is made from the leaves of the coca shrub, which grows in the mountain regions of South American countries such as Bolivia, Colombia, and Peru. In Europe, North America, and some parts of Asia, the most common form of cocaine is a white crystalline powder. Cocaine is a stimulant but is not normally prescribed therapeutically for its stimulant properties, although it sees clinical use as a local anesthetic, in particular in ophthalmology. Most cocaine use is recreational and its abuse potential is high (higher than amphetamine), and so its sale and possession are strictly controlled in most jurisdictions. Other tropane derivative drugs related to cocaine are also known such as troparil and lometopane but have not been widely sold or used recreationally.

Nicotine

Nicotine is the active chemical constituent in tobacco, which is available in many forms, including cigarettes, cigars, chewing tobacco, and smoking cessation aids such as nicotine patches, nicotine gum, and electronic cigarettes. Nicotine is used widely throughout the world for its stimulating and relaxing effects. Nicotine exerts its effects through the agonism of nicotinic acetylcholine receptor, resulting in multiple downstream effects such as increase in activity of dopaminergic neurons in the midbrain reward system, and acetaldehyde one of the tobacco constituent decreased the expression of monoamine oxidase in the brain. Nicotine is addictive and dependence forming. Tobacco, the most common source of nicotine, has an overall harm to user and self score 3 percent below cocaine, and 13 percent above amphetamines, ranking 6th most harmful of the 20 drugs assessed, as determined by a multi-criteria decision analysis.

Phenylpropanolamine

Phenylpropanolamine (PPA; Accutrim; β-hydroxyamphetamine), also known as the stereoisomers norephedrine and norpseudoephedrine, is a psychoactive drug of the phenethylamine and amphetamine chemical classes that is used as a stimulant, decongestant, and anorectic agent. It is commonly used in prescription and over-the-counter cough and cold preparations. In veterinary medicine, it is used to control urinary incontinence in dogs under trade names Propalin and Proin.

In the United States, PPA is no longer sold without a prescription due to a proposed increased risk of stroke in younger women. In a few countries in Europe, however, it is still available either by prescription or sometimes over-the-counter. In Canada, it was withdrawn from the market on 31 May 2001. In India, human use of PPA and its formulations were banned on 10 February 2011.

Propylhexedrine

Propylhexedrine (Hexahydromethamphetamine, Obesin) is a stimulant medication, sold over-the-counter in the United States as the cold medication Benzedrex. The drug has also been used as an appetite suppressant in Europe. Propylhexedrine is not an amphetamine, though it is structurally similar; it is instead a cycloalkylamine, and thus has stimulant effects that are less potent than similarly structured amphetamines, such as methamphetamine. 

The abuse potential of propylhexedrine is fairly limited, due its limited routes of administration: in the United States, Benzedrex is only available as an inhalant, mixed with lavender oil and menthol. These ingredients cause unpleasant tastes, and abusers of the drug have reported unpleasant "menthol burps". Injection of the drug has been found to cause transient diplopia and brain stem dysfunction.

Pseudoephedrine

Pseudoephedrine is a sympathomimetic drug of the phenethylamine and amphetamine chemical classes. It may be used as a nasal/sinus decongestant, as a stimulant, or as a wakefulness-promoting agent.

The salts pseudoephedrine hydrochloride and pseudoephedrine sulfate are found in many over-the-counter preparations, either as a single ingredient or (more commonly) in combination with antihistamines, guaifenesin, dextromethorphan, and/or paracetamol (acetaminophen) or another NSAID (such as aspirin or ibuprofen). It is also used as a precursor chemical in the illegal production of methamphetamine.

Catha edulis (Khat)

Catha edulis

Khat is a flowering plant native to the Horn of Africa and the Arabian Peninsula.

Khat contains a monoamine alkaloid called cathinone, a "keto-amphetamine", that is said to cause excitement, loss of appetite, and euphoria. In 1980, the World Health Organization (WHO) classified it as a drug of abuse that can produce mild to moderate psychological dependence (less than tobacco or alcohol), although the WHO does not consider khat to be seriously addictive. It is banned in some countries, such as the United States, Canada, and Germany, while its production, sale, and consumption are legal in other nations, including Djibouti, Ethiopia, Somalia, and Yemen.

Recreational use and issues of abuse

Stimulants enhance the activity of the central and peripheral nervous systems. Common effects may include increased alertness, awareness, wakefulness, endurance, productivity, and motivation, arousal, locomotion, heart rate, and blood pressure, and a diminished desire for food and sleep. Use of stimulants may cause the body to reduce significantly its production of natural body chemicals that fulfill similar functions. Until the body reestablishes its normal state, once the effect of the ingested stimulant has worn off the user may feel depressed, lethargic, confused, and miserable. This is referred to as a "crash", and may provoke reuse of the stimulant.

Abuse of central nervous system (CNS) stimulants is common. Addiction to some CNS stimulants can quickly lead to medical, psychiatric, and psychosocial deterioration. Drug tolerance, dependence, and sensitization as well as a withdrawal syndrome can occur. Stimulants may be screened for in animal discrimination and self-administration models which have high sensitivity albeit low specificity. Research on a progressive ratio Self-administration protocol has found amphetamine, methylphenidate, modafinil, cocaine, and nicotine to all have a higher break point than placebo that scales with dose indicating reinforcing effects.

Drug	Mean	Pleasure	Psychological dependence	Physical dependence.
Methamphetamine	5.53	6.0	7.0	3.0
Cocaine	2.39	3.0	2.8	1.3
Tobacco	2.21	2.3	2.6	1.8
Amphetamine	1.67	2.0	1.9	1.1
Ecstasy	1.13	1.5	1.2	0.7

Testing

The presence of stimulants in the body may be tested by a variety of procedures. Serum and urine are the common sources of testing material although saliva is sometimes used. Commonly used tests include chromatography, immunologic assay, and mass spectrometry.

Eugeroic

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Eugeroic 

 

Eugeroic
Drug class
The chemical structure of modafinil, the prototypical drug of this class.
Class identifiers
Synonyms	wakefulness-promoting agent wakefulness-promoting drug
Use	Promote wakefulness and alertness
ATC code	N06B

Eugeroics (originally, "eugrégorique" or "eugregoric"), also known as wakefulness-promoting agents and wakefulness-promoting drugs, are a class of drugs that promote wakefulness and alertness. They are medically indicated for the treatment of certain sleep disorders including excessive daytime sleepiness (EDS) in narcolepsy or obstructive sleep apnea (OSA). They generally have a very low addictive potential. Eugeroics are also often prescribed off-label for the treatment of EDS in idiopathic hypersomnia, a rare and often debilitating sleep disorder which currently has no official treatments approved by the Food and Drug Administration (FDA).

Modafinil and armodafinil each act as a selective, weak, atypical dopamine reuptake inhibitor (DRI) whereas adrafinil acts as a prodrug for modafinil. Other eugeroics include solriamfetol, which acts as a norepinephrine–dopamine reuptake inhibitor (NDRI), and pitolisant, which acts as a histamine 3 (H₃) receptor antagonist/inverse agonist.

Examples

Marketed

• Armodafinil (Nuvigil)
• Modafinil (Provigil)
• Solriamfetol (Sunosi)
• Pitolisant (Wakix)

Discontinued

• Adrafinil

Never marketed

• Flmodafinil (CRL-40,940)
• Fluorafinil (CRL-40,941)
• Fluorenol

In development

• Selective H₃ receptor antagonists/inverse agonists
• Selective orexin receptor agonists (two are currently under development)^[7]

Confessions of an English Opium-Eater

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Confessions_of_an_English_Opium-Eater 

 

Confessions of an English Opium-Eater

Front cover of the second edition of the Confessions of an English Opium-Eater (London, 1823)
Author	Thomas De Quincey
Country	England
Language	English
Genre	Autobiography
Published	1821 (London Magazine)
Media type	Print

Confessions of an English Opium-Eater (1821) is an autobiographical account written by Thomas De Quincey, about his laudanum addiction and its effect on his life. The Confessions was "the first major work De Quincey published and the one which won him fame almost overnight..."

First published anonymously in September and October 1821 in the London Magazine, the Confessions was released in book form in 1822, and again in 1856, in an edition revised by De Quincey.

Synopsis

As originally published, De Quincey's account was organized into two parts:

• Part I begins with a notice "To the Reader", to establish the narrative frame: "I here present you, courteous reader, with the record of a remarkable period in my life...." It is followed by the substance of Part I,
  • Preliminary Confessions, devoted to the author's childhood and youth, and concentrated upon the emotional and psychological factors that underlay the later opium experiences — especially the period in his late teens that De Quincey spent as a homeless runaway in Oxford Street in London in 1802 and 1803.
• Part II is split into several sections:
  • A relatively brief introduction and connecting passage, followed by
  • The Pleasures of Opium, which discusses the early and largely positive phase of the author's experience with the drug, from 1804 until 1812;
  • Introduction to the Pains of Opium, which delivers a second installment of autobiography, taking De Quincey from youth to maturity; and
  • The Pains of Opium, which recounts the extreme of the author's opium experience (up to that time), with insomnia, nightmares, frightening visions, and difficult physical symptoms.
• Another "Notice to the Reader" attempts to clarify the chronology of the whole.

The cover of Thomas De Quincey's book Confessions of an Opium-Eater. This version was published by the Mershon Company in 1898.

 

Though De Quincey was later criticized for giving too much attention to the pleasure of opium and not enough to the harsh negatives of addiction, The Pains of Opium is in fact significantly longer than The Pleasures. However, even when trying to convey darker truths, De Quincey's language can seem seduced by the compelling nature of the opium experience:

"The sense of space, and in the end, the sense of time, were both powerfully affected. Buildings, landscapes, &c. were exhibited in proportions so vast as the bodily eye is not fitted to conceive. Space swelled, and was amplified to an extent of unutterable infinity. This, however, did not disturb me so much as the vast expansion of time; I sometimes seemed to have lived for 70 or 100 years in one night; nay, sometimes had feelings representative of a millennium passed in that time, or, however, of a duration far beyond the limits of any human experience."

Style

From its first appearance, the literary style of the Confessions attracted attention and comment. De Quincey was well-read in the English literature of the sixteenth and seventeenth centuries, and assimilated influences and models from Sir Thomas Browne and other writers. Arguably the most famous and often-quoted passage in the Confessions is the apostrophe to opium in the final paragraph of The Pleasures:

"Oh! just, subtle, and mighty opium! that to the hearts of poor and rich alike, for the wounds that will never heal, and for 'the pangs that tempt the spirit to rebel,' bringest an assuaging balm; eloquent opium! that with thy potent rhetoric stealest away the purposes of wrath; and to the guilty man, for one night givest back the hopes of his youth, and hands washed pure of blood...."

De Quincey modelled this passage on the apostrophe "O eloquent, just and mightie Death!" in Sir Walter Raleigh's History of the World.

Earlier in The Pleasures of Opium, De Quincey describes the long walks he took through the London streets under the drug's influence:

"Some of these rambles led me to great distances; for an opium-eater is too happy to observe the motions of time. And sometimes in my attempts to steer homewards, upon nautical principles, by fixing my eye on the pole-star, and seeking ambitiously for a north-west passage, instead of circumnavigating all the capes and headlands I had doubled in my outward voyage, I came suddenly upon such knotty problems of alleys, such enigmatical entries, and such sphinx's riddles of streets without thoroughfares, as must, I conceive, baffle the audacity of porters, and confound the intellects of hackney-coachmen."

The Confessions represents De Quincey's initial effort to write what he called "impassioned prose", an effort that he would later resume in Suspiria de Profundis (1845) and The English Mail-Coach (1849).

The 1856 revision

In the early 1850s, De Quincey prepared the first collected edition of his works for publisher James Hogg. For that edition, he undertook a large-scale revision of the Confessions, more than doubling the work's length. Most notably, he expanded the opening section on his personal background, until it consumed more than two-thirds of the whole. Yet he gave the book "a much weaker beginning" and detracted from the impact of the original with digressions and inconsistencies; "the verdict of most critics is that the earlier version is artistically superior".

"De Quincey undoubtedly spoiled his masterpiece by revising it... anyone who compares the two will prefer the unflagging vigour and tension of the original version to the tired prosiness of much of the revised one".

Influence

36 Tavistock Street in London's Covent Garden, where De Quincey wrote Confessions - photographed in 2019

The Confessions maintained a place of primacy in De Quincey's literary output, and his literary reputation, from its first publication; "it went through countless editions, with only occasional intervals of a few years, and was often translated. Since there was little systematic study of narcotics until long after his death, De Quincey's account assumed an authoritative status and actually dominated the scientific and public views of the effects of opium for several generations."

Yet from the time of its publication, De Quincey's Confessions was criticized for presenting a picture of the opium experience that was too positive and too enticing to readers. As early as 1823, an anonymous response, Advice to Opium Eaters, was published "to warn others from copying De Quincey." The fear of reckless imitation was not groundless: several English writers — Francis Thompson, James Thomson, William Blair, and perhaps Branwell Brontë — were led to opium use and addiction by De Quincey's literary example. Charles Baudelaire's 1860 translation and adaptation, Les paradis artificiels, spread the work's influence further. One of the characters of the Sherlock Holmes story, The Man with the Twisted Lip (1891), is an opium addict who began experimenting with the drug as a student after reading the Confessions. De Quincey attempted to address this type of criticism. When the 1821 original was printed in book form the following year, he added an Appendix on the withdrawal process; and he inserted significant material on the medical aspects of opium into his 1856 revision.

More generally, De Quincey's Confessions influenced psychology and abnormal psychology, and attitudes towards dreams and imaginative literature.

Confessions of an English Opium-Eater also served as inspiration to one of Hector Berlioz's most famous pieces, Symphonie fantastique. The play The Opium Eater by Andrew Dallmeyer was also based on Confessions of an English Opium-Eater, and has been published by Capercaillie Books. In 1962, Vincent Price starred in the full-length film Confessions of an Opium Eater which was a reimagining of De Quincey's Confessions by Hollywood producer Albert Zugsmith.

In the 1999 documentary Tripping, recounting Ken Kesey's Further bus and its influence, Malcolm McLaren refers to De Quincey's book as the influence for the beatnik generation before Jack Kerouac's popular On the Road was written.

Laudanum

From Wikipedia, the free encyclopedia

Laudanum

Combination of
opium	analgesic
ethanol	tincture
Clinical data
Pronunciation	/ˈlɔːdnəm, -dənəm/
Pregnancy category	US: C (Risk not ruled out)
Routes of administration	Oral, buccal, sublingual
ATC code	A07DA02 (WHO)
Legal status
Legal status	UK: Class A US: Schedule II UN: Narcotic Schedule I

Laudanum is a tincture of opium containing approximately 10% powdered opium by weight (the equivalent of 1% morphine).

Reddish-brown and extremely bitter, laudanum contains almost all of the opium alkaloids, including morphine and codeine. Laudanum was historically used to treat a variety of conditions, but its principal use was as a pain medication and cough suppressant. Until the early 20th century, laudanum was sold without a prescription and was a constituent of many patent medicines. Today, laudanum is recognized as addictive and is strictly regulated and controlled as such throughout most of the world. The United States Uniform Controlled Substances Act, for one example, lists it on Schedule II.

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 noscapine (also called narcotine) present as this is a strong emetic and does not add appreciably to the analgesic or antipropulsive 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 diarrhea, alleviating pain, and easing withdrawal symptoms in infants born to mothers addicted to heroin or other opioids. Recent enforcement action by the U.S. Food and Drug Administration (FDA) against manufacturers of paregoric 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 interchangeable, but in contemporary medical practice the latter is used almost exclusively.

History

Paracelsus von Hohenheim, a 16th-century Swiss-German alchemist, experimented with various opium concoctions, and recommended opium for reducing pain. One of his preparations, a pill which he extolled as his "archanum" or "laudanum", may have contained opium. Paracelsus' laudanum was strikingly different from the standard laudanum of the 17th century and beyond, containing crushed pearls, musk, amber, and other substances. One researcher has documented that "Laudanum, as listed in the London Pharmacopoeia (1618), was a pill made from opium, saffron, castor, ambergris, musk and nutmeg".

Laudanum remained largely unknown until the 1660s when English physician Thomas Sydenham (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, and the term "laudanum" came to refer to any combination of opium and alcohol. 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."

Confessions of a laudanum drinker, The Lancet, 1866.

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, consumption, ague and rheumatism were all too common.

By the 19th century, laudanum was used in many patent medicines to "relieve pain ... to produce sleep ... to allay irritation ... to check excessive secretions ... to support the system ... [and] as a soporific". The limited pharmacopoeia of the day meant that opium derivatives were among the most effective of available treatments, so laudanum was widely prescribed for ailments from colds to meningitis to cardiac diseases, in both adults and children. Laudanum was used during the yellow fever epidemic.

Innumerable Victorian women were prescribed the drug for relief of menstrual cramps and vague aches. Nurses also spoon-fed laudanum to infants. The Romantic and Victorian eras were marked by the widespread use of laudanum in Europe and the United States. Mary Todd Lincoln, for example, the wife of the US president Abraham Lincoln, was a laudanum addict, as was the English poet Samuel Taylor Coleridge, who was famously interrupted in the middle of an opium-induced writing session of Kubla Khan by a "person from Porlock". Initially a working class drug, laudanum was cheaper than a bottle of gin or wine, because it was treated as a medication for legal purposes and not taxed as an alcoholic beverage.

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 injection [meaning as an enema] 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, 1​¹⁄₂ 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 US, the 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 Act of 1914 restricted the manufacture and distribution of opiates, including laudanum, and coca derivatives in the US. This was followed by France's Loi des stupéfiants 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 US 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 opioids, such as propoxyphene, oxymorphone and oxycodone. These synthetic opioids, along with codeine and morphine 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 analgesic, since its principal ingredient is morphine, which can be prescribed by itself to treat pain. Until now, there has been no medical consensus on which of the two (laudanum or morphine alone) is the better choice for treating pain.

In 1970, the US adopted the Uniform Controlled Substances 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 diarrhea. The current prescribing information for laudanum in the US states that opium tincture's sole indication is as an anti-diarrheal, although the drug is occasionally prescribed off-label for treating pain and neonatal withdrawal syndrome.

Historical varieties

Italian Sydenham laudanum tincture from the 1950s

Several historical varieties of laudanum exist, including Paracelsus' laudanum, Sydenham's Laudanum (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. saffron, sugar, eugenol) are added, modifying its effects (e.g., amount of sedation, or antitussive 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 pharmacopeias, 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 use. 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 4​¹⁄₂ 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 2​¹⁄₂ 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."

Modern status

United States

Tincture of Opium is available by prescription in the United States. It is regulated as a Schedule II drug (No. 9639) under the Controlled Substances Act.

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 noscapine), and ethanol, 19%. It is available packaged in bottles of four US fluid ounces (118 mL) and 16 US fluid ounces (1 US pt; 473 mL).

Tincture of Opium is known as one of many "unapproved drugs" regulated by the U.S. Food and Drug Administration (FDA); the marketing and distribution of opium tincture prevails today only because opium tincture was sold prior to the Federal Food, Drug & Cosmetic Act of 1938. Its "grandfathered" status protects opium tincture from being required to undergo strict FDA drug reviews and subsequent approval processes. However, the FDA closely monitors the labeling of opium tincture. Bottles of opium tincture are required by the FDA to bear a bright red "POISON" label given the potency of the drug and the potential for overdose (see discussion about confusion with Paregoric below). Additionally, in a warning letter to a manufacturer of opium tincture in late 2009, the FDA noted that "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."

United Kingdom

Opium tincture remains in the British Pharmacopoeia, 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 UK as of 2011. "Gee's Linctus" is also available from most UK pharmacies, especially independent stores. This contains "Opium Tincture", at 0.083 mL, per 5 mL.

Pharmacology

Opium tincture is useful as an analgesic and antidiarrheal. Opium enhances the tone 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 papaverine and codeine 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 noscapine), which has antitussive properties. Even modest doses of narcotine can induce profound nausea and vomiting. 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 petroleum distillate to remove the narcotine.

Oral doses of opium tincture are rapidly absorbed in the gastrointestinal tract and metabolized in the liver. 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.

Medical uses

Diarrhea

Opium tincture is indicated for the treatment of severe fulminant (intense, prolific) diarrhea that does not respond to standard therapy (e.g., Imodium or Lomotil). The usual starting dose is 0.3 mL to 0.6 mL (about six to 12 drops) in a glass of water or juice four times a day. Refractory cases (such as diarrhea resulting from the complications of HIV/AIDS) may require higher than normal dosing, for example, 1 to 2 mL every 3 hours, for a total daily dose of up to 16mL a day. In terminal diseases, there is no ceiling dose for opium tincture; the dose is increased slowly until diarrhea is controlled.

Neonatal abstinence syndrome

Opium tincture is used to treat neonatal abstinence syndrome (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- to 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 pain. 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-naïve 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. For the opioid tolerant patient, doses in the range of 3–6 mL every 3–4 hours would be usual. This would represent an equivalent daily dose of between 180 mg and 480 mg of morphine.

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 17–19% alcohol, by volume, which may complicate its use as an analgesic in patients for whom alcohol is contraindicated.

Dosage

Extreme caution is advised when 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 drops 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 fluidrachm 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).

Hazards

Potency of laudanum

Opium tincture is one of the most potent 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 death may occur with a single oral dose of between 100 and 150 mg of morphine in a healthy adult who has no tolerance to opiates. This represents the equivalent of between two to three teaspoons (10–15 mL) of opium tincture. Suicide 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 anhydrous morphine. By contrast, opium tincture's weaker cousin, paregoric, 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 minims, 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"

The abbreviation "DTO," traditionally used to refer to Deodorized Tincture of Opium, is sometimes also erroneously employed to abbreviate "diluted tincture of opium." Diluted tincture of opium, also known as Camphorated Tincture of Opium (Paregoric) is a 1:25 mixture of opium tincture to water prescribed to treat withdrawal symptoms in newborns whose mothers were using opioids while pregnant. The United States Pharmacopeia and FDA recommend that practitioners refrain from using DTO in prescriptions, given this potential for confusion. In cases where pharmacists have misinterpreted DTO, and given "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

Side effects of laudanum are generally the same as with morphine, and include euphoria, dysphoria, pruritus, sedation, constipation, reduced tidal volume, respiratory depression, as well as psychological dependence, physical dependence, miosis, and xerostomia. 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

Life-threatening overdose of opium tincture owes to the preparation's morphine content. Morphine produces a dose-dependent depressive effect on the respiratory system, which can lead to profound respiratory depression, hypoxia, coma and finally respiratory arrest and death. If overdose of opium tincture is suspected, rapid professional intervention is required. The primary concern is re-establishing a viable airway and institution of assisted or controlled ventilation if the patient is unable to breathe on his own. Other supportive measures such as the use of vasopressors and oxygen may be indicated to treat cardiac and/or pulmonary failure. Cardiac arrhythmias or arrest will require advanced life-saving measures.

Intravenous naloxone or nalmefene, quick-acting opioid antagonists, are the first-line treatment to reverse respiratory depression caused by an overdose of opium tincture. Gastric lavage may be of some use in certain cases.

In fiction

• In Mary Shelley's novel Frankenstein (1818), Victor Frankenstein takes laudanum as his only means of sleeping and thus preserving his life while in recovery from months of fever and a series of horrible events.
• In Uncle Tom's Cabin (1852), an anti-slavery novel by Harriet Beecher Stowe, a slave named Cassy talks about how she killed her newborn by laudanum overdose to spare him from experiencing the horrors of slavery.
• Wilkie Collins' novel The Moonstone (1868) features laudanum "as an essential ingredient of the plot." Collins based his description of the drug's effects on his own experiences with it.
• A laudanum-addicted character also appeared in Wilkie Collins' novel Armadale (1864–66).
• Laudanum appears in Charles Baudelaire's prose poem The Double Room, published in his collection Le Spleen de Paris in 1869.
• Laudanum is portrayed as the surgical drug of choice for fifteenth-century physicians in Lawrence Schoonover's novel The Burnished Blade (1948), the plot of which deals in part with the smuggling of expensive raw opium into France from the Empire of Trebizond.
• In William Faulkner's novel Requiem for a Nun (1951), Compson, Doctor Peabody, and Ratcliffe give whiskey tainted with laudanum to a group of rowdy lynchers and a militia band that had joined together. Upon their falling asleep, they were gathered up and locked in jail while still unconscious.
• Dr Stephen Maturin, one of the main characters in Patrick O'Brian's Aubrey–Maturin series of novels (1969-2004) about the Napoleonic wars, is a sometime laudanum addict.
• Laudanum is prescribed in Glendon Swarthout's novel The Shootist (1975) to the character J.B. Books, played by John Wayne in Don Siegel's movie adaptation (1976).
• In Philippa Gregory's novel Wideacre (1987), the main character Beatrice Lacey nearly becomes addicted to laudanum when her eventual husband Dr. John MacAndrew prescribes it to her after her mother's death.
• In Dan Simmons’s novel Drood (2009) the narrator Wilkie Collins takes laudanum daily to alleviate a wide variety of pains as well as to induce sleep.
• In the horror video-game Amnesia: The Dark Descent (2010), laudanum can be found at several places in the castle, and can be used to regain health.
• In Sara Collins' novel The Confessions of Frannie Langton (2019) the titular character becomes addicted to laudanum.