Lysergic acid diethylamide

Lysergic acid diethylamide

Systematic (IUPAC) name
(6aR,9R)-N,N-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo-[4,3-fg]quinoline-9-carboxamide
Clinical data
Pregnancy cat.	C (US)
Legal status	Prohibited (S9) (AU) Schedule III (CA) CD (UK) Schedule I (US)
Dependence liability	Very low
Routes	Oral, Intravenous, Ocular, Intramuscular
Pharmacokinetic data
Metabolism	Hepatic
Half-life	3–5 hours[1][2]
Excretion	Renal
Identifiers
CAS number	50-37-3 Y
ATC code	?
PubChem	CID 5761
IUPHAR ligand	17
DrugBank	DB04829
ChemSpider	5558 Y
UNII	8NA5SWF92O Y
ChEBI	CHEBI:6605 N
ChEMBL	CHEMBL263881 Y
Synonyms	LSD, LSD-25, lysergide, D-lysergic acid diethyl amide, N,N- diethyl- D- lysergamide
Chemical data
Formula	C20H25N3O
Mol. mass	323.43 g/mol
SMILES CCN(CC)C(=O)[C@H]1CN([C@@H]2Cc3c[nH]c4c3c(ccc4)C2=C1)C
InChI InChI=1S/C20H25N3O/c1-4-23(5-2)20(24)14-9-16-15-7-6-8-17-19(15)13(11-21-17)10-18(16)22(3)12-14/h6-9,11,14,18,21H,4-5,10,12H2,1-3H3/t14-,18-/m1/s1 Y Key:VAYOSLLFUXYJDT-RDTXWAMCSA-N Y
Physical data
Melt. point	80–85 °C (176–185 °F)
N (what is this?)  (verify)

Lysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide (INN) and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed- and open-eye visuals, synesthesia, an altered sense of time and spiritual experiences, as well as for its key role in 1960s counterculture. It is used mainly as an entheogen, recreational drug, and as an agent in psychedelic therapy. LSD is non-addictive, is not known to cause brain damage, and has extremely low toxicity relative to dose.^[3] However, adverse psychiatric reactions such as anxiety, paranoia, and delusions are possible.^[4]

LSD was first synthesized by Albert Hofmann in 1938 from ergotamine, a chemical derived by Arthur Stoll from ergot, a grain fungus that typically grows on rye. The short form "LSD" comes from its early code name LSD-25, which is an abbreviation for the German "Lysergsäure-diethylamid" followed by a sequential number.^[5][6] LSD is sensitive to oxygen, ultraviolet light, and chlorine,^[6] especially in solution, though its potency may last for years if it is stored away from light and moisture at low temperature. In pure form it is a colorless, odorless, tasteless solid.^[7] LSD is typically delivered orally, usually on a substrate such as absorbent blotter paper, a sugar cube, or gelatin. In its liquid form, it can also be administered by intramuscular or intravenous injection. LSD is very potent, with 20–30 µg (micrograms) being the threshold dose.^[8] New clinical LSD experiments in humans started in 2009 for the first time in 35 years.^[9]

Introduced by Sandoz Laboratories, with trade-name Delysid, as a drug with various psychiatric uses in 1947, LSD quickly became a therapeutic agent that appeared to show great promise.^[10] In the 1950s, officials at the U.S. Central Intelligence Agency (CIA) thought the drug might be applicable to mind control and chemical warfare; the agency's MKULTRA research program propagated the drug among young servicemen and students. The subsequent recreational use of the drug by youth culture in the Western world during the 1960s led to a political firestorm that resulted in its prohibition.^[11] Currently, a number of organizations—including the Beckley Foundation, MAPS, Heffter Research Institute and the Albert Hofmann Foundation—exist to fund, encourage and coordinate research into the medicinal and spiritual uses of LSD and related psychedelics.^[12]

Effects

Physical

LSD can cause pupil dilation, reduced or increased appetite, and wakefulness. Other physical reactions to LSD are highly variable and nonspecific, some of which may be secondary to the psychological effects of LSD. Among the reported symptoms are numbness, weakness, nausea, hypothermia or hyperthermia, elevated blood sugar, goose bumps, heart rate increase, jaw clenching, perspiration, saliva production, mucus production, sleeplessness, hyperreflexia, and tremors. Some users, including Albert Hofmann, report a strong metallic taste for the duration of the effects.^[13]

LSD is not considered addictive by the medical community.^[3] Rapid tolerance build-up prevents regular use,^{[citation needed]} and cross-tolerance has been demonstrated between LSD, mescaline^[14] and psilocybin.^[15] This tolerance diminishes after a few days after cessation of use and is probably caused by downregulation of 5-HT_2A receptors in the brain.^[16][17]

Psychological

LSD's psychological effects (colloquially called a "trip") vary greatly from person to person, depending on factors such as previous experiences, state of mind and environment, as well as dose strength. They also vary from one trip to another, and even as time passes during a single trip. An LSD trip can have long-term psychoemotional effects; some users cite the LSD experience as causing significant changes in their personality and life perspective.^{[citation needed]} Widely different effects emerge based on what Timothy Leary called set and setting; the "set" being the general mindset of the user, and the "setting" being the physical and social environment in which the drug's effects are experienced.

Some psychological effects may include an experience of radiant colors, objects and surfaces appearing to ripple or "breathe", colored patterns behind the closed eyelids (eidetic imagery), an altered sense of time (time seems to be stretching, repeating itself, changing speed or stopping), crawling geometric patterns overlaying walls and other objects, morphing objects, a sense that one's thoughts are spiraling into themselves, loss of a sense of identity or the ego (known as "ego death"), and other powerful psycho-physical reactions.^[18] Many users experience a dissolution between themselves and the "outside world".^[19] This unitive quality may play a role in the spiritual and religious aspects of LSD. The drug sometimes leads to disintegration or restructuring of the user's historical personality and creates a mental state that some users report allows them to have more choice regarding the nature of their own personality.

If the user is in a hostile or otherwise unsettling environment, or is not mentally prepared for the powerful distortions in perception and thought that the drug causes, effects are more likely to be unpleasant than if he or she is in a comfortable environment and has a relaxed, balanced and open mindset.^[20]

Sensory

LSD causes an altered sensory experience of senses, emotions, memories, time, and awareness for 6 to 14 hours, depending on dosage and tolerance. Generally beginning within thirty to ninety minutes after ingestion, the user may experience anything from subtle changes in perception to overwhelming cognitive shifts. Changes in auditory and visual perception are typical.^[19][21] Visual effects include the illusion of movement of static surfaces ("walls breathing"), after image-like trails of moving objects ("tracers"), the appearance of moving colored geometric patterns (especially with closed eyes), an intensification of colors and brightness ("sparkling"), new textures on objects, blurred vision, and shape suggestibility. Users commonly report that the inanimate world appears to animate in an unexplainable way; for instance, objects that are static in three dimensions can seem to be moving relative to one or more additional spatial dimensions.^[22] Many of the basic visual effects resemble the phosphenes seen after applying pressure to the eye and have also been studied under the name "form constants". The auditory effects of LSD may include echo-like distortions of sounds, changes in ability to discern concurrent auditory stimuli, and a general intensification of the experience of music. Higher doses often cause intense and fundamental distortions of sensory perception such as synaesthesia, the experience of additional spatial or temporal dimensions, and temporary dissociation.

Potential uses

LSD has been used in psychiatry for its perceived therapeutic value, in the treatment of alcoholism, pain and cluster headache relief, for spiritual purposes, and to enhance creativity. However, government organizations like the United States Drug Enforcement Administration maintain that LSD "produces no aphrodisiac effects, does not increase creativity, has no lasting positive effect in treating alcoholics or criminals, does not produce a 'model psychosis', and does not generate immediate personality change."^[23]

Psychotherapy

In the 1950s and 1960s LSD was used in psychiatry to enhance psychotherapy. Some psychiatrists believed LSD was especially useful at helping patients to "unblock" repressed subconscious material through other psychotherapeutic methods,^[24] and also for treating alcoholism.^[25][26] One study concluded, "The root of the therapeutic value of the LSD experience is its potential for producing self-acceptance and self-surrender,"^[27] presumably by forcing the user to face issues and problems in that individual's psyche.

In December 1968, a survey was made of all 74 UK doctors who had used LSD in humans; 73 replied, 1 had moved overseas and was unavailable. The majority of UK doctors with clinical experience with LSD felt that LSD was effective and had acceptable safety:

• 56% (41) continued with clinical use of LSD
• 15% (11) had stopped because of retirement or other extraneous reasons
• 12% (9) had stopped because they found LSD ineffective
• 10% (7) had stopped for unspecified reasons
• 7% (5) had stopped because they felt LSD was too dangerous^[28]

End-of-life anxiety

Since 2008 there has been ongoing research in Switzerland into using LSD to alleviate anxiety for terminally ill cancer patients coping with their impending deaths. Preliminary results from the study are promising, and no negative effects have been reported.^[29][30][31]

Alcoholism

Some studies in the 1960s that used LSD to treat alcoholism reduced levels of alcohol misuse in almost 60% of those treated, an effect which lasted six months but disappeared after a year.^[32][33] A 1998 review was inconclusive.^[34] However, a 2012 meta-analysis of six randomized controlled trials found evidence that a single dose of LSD in conjunction with various alcoholism treatment programs was associated with a decrease in alcohol abuse, lasting for several months.^[35]

Pain

LSD was studied in the 1960s by Eric Kast as an analgesic for serious and chronic pain caused by cancer or other major trauma.^[36] Even at low (sub-psychedelic) dosages, it was found to be at least as effective as traditional opiates, while being much longer lasting in pain reduction (lasting as long as a week after peak effects had subsided). Kast attributed this effect to a decrease in anxiety; that is to say that patients were not experiencing less pain, but rather were less distressed by the pain they experienced. This reported effect is being tested (though not using LSD) in an ongoing (as of 2006) study of the effects of psilocybin on anxiety in terminal cancer patients.

Cluster headaches

LSD has been used as a treatment for cluster headaches, an uncommon but extremely painful disorder. Researcher Peter Goadsby describes the headaches as "worse than natural childbirth or even amputation without anesthetic."^[37] Although the phenomenon has not been formally investigated, case reports indicate that LSD and psilocybin can reduce cluster pain and also interrupt the cluster-headache cycle, preventing future headaches from occurring. Currently existing treatments include various ergolines, among other chemicals, so LSD's efficacy may not be surprising. A dose-response study testing the effectiveness of both LSD and psilocybin was planned at McLean Hospital, although the current status of this project is unclear. A 2006 study by McLean researchers interviewed 53 cluster-headache sufferers who treated themselves with either LSD or psilocybin, finding that a majority of the users of either drug reported beneficial effects.^[38] Unlike use of LSD or MDMA in psychotherapy, this research involves non-psychological effects and often sub-psychedelic dosages.^[39][40]

Spiritual

LSD is considered an entheogen because it can catalyze intense spiritual experiences, during which users may feel they have come into contact with a greater spiritual or cosmic order. Users claim to experience lucid sensations where they have "out of body" experiences. Some users report insights into the way the mind works, and some experience permanent shifts in their life perspective. LSD also allows users to view their life from an introspective point of view. Some users report using introspection to resolve unresolved or negative feelings towards an individual or incident that occurred in the past. Some users consider LSD a religious sacrament, or a powerful tool for access to the divine. Stanislav Grof has written that religious and mystical experiences observed during LSD sessions appear to be phenomenologically indistinguishable from similar descriptions in the sacred scriptures of the great religions of the world and the secret mystical texts of ancient civilizations.^[41]

Creativity

In the 1950s and 1960s, psychiatrists like Oscar Janiger explored the potential effect of LSD on creativity. Experimental studies attempted to measure the effect of LSD on creative activity and aesthetic appreciation.^{[42][43][44][45]} Seventy professional artists were asked to draw two pictures of a Hopi Indian kachina doll, one before ingesting LSD and one after.^[46]

Potential adverse effects

There have been no documented human deaths from an LSD overdose.^[47] It is physiologically well tolerated and there is no evidence for long-lasting physiological effects on the brain or other parts of the human organism.^[48]

LSD may temporarily impair the ability to make sensible judgments and understand common dangers, thus making the user more susceptible to accidents and personal injury. It may cause temporary confusion, difficulty with abstract thinking, or signs of impaired memory and attention span.^[49]

Adverse drug interactions

There is some indication that LSD may trigger a dissociative fugue state in individuals who are taking certain classes of antidepressants such as lithium salts and tricyclics. In such a state, the user has an impulse to wander, and may not be aware of his or her actions, which can lead to physical injury. Anonymous anecdotal reports have attributed seizures and one death to the combination of LSD with lithium.^[50] SSRIs noticeably reduce LSD's subjective effects.^[51] MAOIs are also reported to reduce the effects of LSD.^[50]

Mental disorders

LSD may trigger panic attacks or feelings of extreme anxiety, colloquially referred to as a "bad trip". No real prolonged effects have been proven; however, people with such conditions as schizophrenia and depression can worsen with LSD.^[52]

Suggestibility

While publicly available documents indicate that the CIA and Department Of Defense have discontinued research into the use of LSD as a means of mind control,^[53] research from the 1960s suggests there exists evidence that both mentally ill and healthy people are more suggestible while under its influence.^[54][55]

Psychosis

There are some cases of LSD inducing a psychosis in people who appeared to be healthy before taking LSD.^[56] In most cases, the psychosis-like reaction is of short duration, but in other cases it may be chronic. It is difficult to determine whether LSD itself induces these reactions or if it triggers latent conditions that would have manifested themselves otherwise. The similarities of time course and outcomes between putatively LSD-precipitated and other psychoses suggest that the two types of syndromes are not different and that LSD may have been a nonspecific trigger.^{[citation needed]}

Estimates of the prevalence of LSD-induced prolonged psychosis lasting over 48 hours have been made by surveying researchers and therapists who had administered LSD:

• Cohen (1960) estimated 0.8 per 1,000 volunteers (the single case among approximately 1250 study volunteers was the identical twin of a person with schizophrenia, and he recovered within 5 days) and 1.8 per 1,000 psychiatric patients (7 cases among approximately 3850 patients, of which 2 cases were had schizophrenia, or had previous hallucinatory experience, 1 case had unknown outcome, 1 case had incomplete recovery, and 5 cases recovered within up to 6 months).^[57]
• Malleson (1971) reported no cases of psychosis among experimental subjects (170 volunteers who received a total of 450 LSD sessions) and estimated 9 per 1,000 among psychiatric patients (37 cases among 4300 patients, of which 8 details are unknown, 10 appeared chronic, and 19 recovered completely within up to 3 months).^[28]

However, in neither survey study was it possible to compare the rate of lasting psychosis in these volunteers and patients receiving LSD with the rate of psychosis found in other groups of research volunteers or in other methods of psychiatric treatment (for example, those receiving placebo).

Cohen (1960) noted:^[57]

"The hallucinogenic experience is so striking that many subsequent disturbances may be attributed to it without further justification. The highly suggestible or hysterical individual would tend to focus on his LSD experience to explain subsequent illness. Patients have complained to Abramson that their LSD exposure produced migraine headaches and attacks of influenza up to a year later. One Chinese girl became paraplegic and ascribed that catastrophe to LSD. It so happened that these people were all in the control group and had received nothing but tap water."

According to data from the National Survey on Drug Use and Health, drawing from 130,152 respondents (17,486 of which used LSD), LSD use is associated with a slightly lower risk of psychosis and other mental illness.^[58]

Flashbacks and HPPD

"Flashbacks" are a reported psychological phenomenon in which an individual experiences an episode of some of LSD's subjective effects long after the drug has worn off, usually in the days after typical doses. In some rarer cases, flashbacks have lasted longer, but are generally short-lived and mild compared to the actual LSD "trip". Flashbacks can incorporate both positive and negative aspects of LSD trips, and are typically elicited by triggers such as alcohol or cannabis use, stress, caffeine, or sleepiness. Flashbacks have proven difficult to study and are no longer officially recognized as a psychiatric syndrome. However, colloquial usage of the term persists and usually refers to any drug-free experience reminiscent of psychedelic drug effects, with the typical connotation that the episodes are of short duration.

No definitive explanation is currently available for these experiences. Any attempt at explanation must reflect several observations: first, over 70 percent of LSD users claim never to have "flashed back"; second, the phenomenon does appear linked with LSD use, though a causal connection has not been established; and third, a higher proportion of psychiatric patients report flashbacks than other users.^[59] Several studies have tried to determine how likely a user of LSD, not suffering from known psychiatric conditions, is to experience flashbacks. The larger studies include Blumenfeld's in 1971^[60] and Naditch and Fenwick's in 1977,^[61] which arrived at figures of 20% and 28%, respectively. Interestingly, the experiments by Sidney Cohen in 1960 did not report a single 'flashback' phenomenon.^[62]

Although flashbacks themselves are not recognized as a medical syndrome, there is a recognized syndrome called Hallucinogen Persisting Perception Disorder (HPPD) in which LSD-like visual changes are not temporary and brief, as they are in flashbacks, but instead are persistent, and cause clinically significant impairment or distress. The syndrome is a DSM-IV diagnosis. Several scientific journal articles have described the disorder.^[63]

HPPD differs from flashbacks in that it is persistent and apparently entirely visual (although mood and anxiety disorders are sometimes diagnosed in the same individuals). A recent review suggests that HPPD (as defined in the DSM-IV) is rare and affects only a distinctly vulnerable subpopulation of users.^[64] However, it is possible that the prevalence of HPPD is underestimated because most of the diagnoses are applied to people who are willing to admit to their health care practitioner that they have previously used psychotropics, and presumably many people are reluctant to admit this.^[65]

There is no consensus regarding the nature and causes of HPPD (or flashbacks). A study of 44 HPPD subjects who had previously ingested LSD showed EEG abnormalities.^[66] Given that some symptoms have environmental triggers, it may represent a failure to adjust visual processing to changing environmental conditions. There are no explanations for why only some individuals develop HPPD. Explanations in terms of LSD physically remaining in the body for months or years after consumption have been discounted by experimental evidence.^[59] Some say HPPD is a manifestation of post-traumatic stress disorder, not related to the direct action of LSD on brain chemistry, and varies according to the susceptibility of the individual to the disorder. Many emotionally intense experiences can lead to flashbacks when a person is reminded acutely of the original experience. However, not all published case reports of HPPD appear to describe an anxious hyper-vigilant state reminiscent of post-traumatic stress disorder. Instead, some cases appear to involve only visual symptoms.^[59]

Uterine contractions

Early pharmacological testing by Sandoz in laboratory animals showed that LSD can stimulate uterine contractions, with efficacy comparable to ergobasine, the active uterotonic component of the ergot fungus. (Hofmann's work on ergot derivatives also produced a modified form of ergobasine which became a widely accepted medication used in obstetrics, under the trade name Methergine.) Therefore, LSD use by pregnant women could be dangerous and is contraindicated.^[5] However, the relevance of these animal studies to humans is unclear, and a 2008 medical reference guide to drugs in pregnancy and lactation stated, "It appears unlikely that pure LSD administered in a controlled condition is an abortifacient."^[67]

Genetic

Beginning in 1967, studies raised concerns that LSD might produce genetic damage^[68] or developmental abnormalities in fetuses. However, these initial reports were based on in vitro studies or were poorly controlled and have not been substantiated. In studies of chromosomal changes in human users and in monkeys, the balance of evidence suggests no increase in chromosomal damage. For example, white blood cells of people who had been given LSD in a clinical setting were examined for visible chromosomal abnormalities; overall, there appeared to be no lasting changes.^[68] Several studies have been conducted using illicit LSD users and provide a less clear picture. Interpretation of these data is generally complicated by factors such as the unknown chemical composition of street LSD, concurrent use of other psychoactive drugs, and diseases such as hepatitis in the sampled populations. It seems possible the small number of genetic abnormalities reported in users of street LSD is either coincidental or related to factors other than a toxic effect of pure LSD.^[68] A 2008 medical review concluded, "The available data suggest that pure LSD does not cause chromosomal abnormalities, spontaneous abortions, or congenital malformations. In 1969 Moseley (now Gottschalk) working at the University of California, Riverside, under Edward Crellin Pauling, using e. coli ligase mutant strain obtained results indicating no breakage and that therapeutically high doses actually reduced breakage."^[67]

Treatment of intoxication

Reassurance in a calm, safe environment is beneficial. Agitation can be safely addressed with benzodiazepines such as diazepam. Neuroleptics such as haloperidol reduce hallucinations and paranoid delusions and can be used to terminate the effects of LSD. LSD is rapidly absorbed, so activated charcoal and emptying of the stomach will be of little benefit. Sedation or physical restraint is rarely required, and excessive restraint may cause complications such as hyperthermia (over-heating) or rhabdomyolysis.^[69]

Massive doses require supportive care, which may include endotracheal intubation or respiratory support. High blood pressure, tachycardia (rapid heart-beat) and hyperthermia, if present, should be treated symptomatically. Treat low blood pressure initially with fluids and then with pressors if necessary. Intravenous administration of anticoagulants, vasodilators, and sympatholytics may be useful with massive doses.

Chemistry and structure

LSD is a chiral compound with two stereocenters at the carbon atoms C-5 and C-8, so that theoretically four different optical isomers of LSD could exist. LSD, also called (+)-D-LSD, has the absolute configuration (5R,8R). The C-5 isomers of lysergamides do not exist in nature and are not formed during the synthesis from D-lysergic acid. Retrosynthetically, the C-5 stereocenter could be analysed as having the same configuration of the alpha carbon of the naturally occurring amino acid L-tryptophan, the precursor to all biosynthetic ergoline compounds.

However, LSD and iso-LSD, the two C-8 isomers, rapidly interconvert in the presence of bases, as the alpha proton is acidic and can be deprotonated and reprotonated. Non-psychoactive iso-LSD which has formed during the synthesis can be separated by chromatography and can be isomerized to LSD.

A totally pure salt of LSD will emit small flashes of white light when shaken in the dark.^[6] LSD is strongly fluorescent and will glow bluish-white under UV light.

Synthesis

LSD is an ergoline derivative. It is commonly synthesised by reacting diethylamine with an activated form of lysergic acid. Activating reagents include phosphoryl chloride^[70] and peptide coupling reagents.^[71] Lysergic acid is made by alkaline hydrolysis of lysergamides like ergotamine, a substance usually derived from the ergot fungus on agar plate, or theoretically possible, but impractical and uncommon from ergine (lysergic acid amide, LSA) extracted from morning glory seeds.^[72]

Reactivity and degradation

"LSD," writes the chemist Alexander Shulgin, "is an unusually fragile molecule...As a salt, in water, cold, and free from air and light exposure, it is stable indefinitely."^[6]

LSD has two labile protons at the tertiary stereogenic C5 and C8 positions, rendering these centres prone to epimerisation. The C8 proton is more labile due to the electron-withdrawing carboxamide attachment, but removal of the chiral proton at the C5 position (which was once also an alpha proton of the parent molecule tryptophan) is assisted by the inductively withdrawing nitrogen and pi electron delocalisation with the indole ring.^{[citation needed]}

LSD also has enamine-type reactivity because of the electron-donating effects of the indole ring. Because of this, chlorine destroys LSD molecules on contact; even though chlorinated tap water contains only a slight amount of chlorine, the small quantity of compound typical to an LSD solution will likely be eliminated when dissolved in tap water.^[6] The double bond between the 8-position and the aromatic ring, being conjugated with the indole ring, is susceptible to nucleophilic attacks by water or alcohol, especially in the presence of light. LSD often converts to "lumi-LSD", which is inactive in human beings.^[6]

A controlled study was undertaken to determine the stability of LSD in pooled urine samples.^[73] The concentrations of LSD in urine samples were followed over time at various temperatures, in different types of storage containers, at various exposures to different wavelengths of light, and at varying pH values. These studies demonstrated no significant loss in LSD concentration at 25°C for up to four weeks. After four weeks of incubation, a 30% loss in LSD concentration at 37°C and up to a 40% at 45°C were observed. Urine fortified with LSD and stored in amber glass or nontransparent polyethylene containers showed no change in concentration under any light conditions. Stability of LSD in transparent containers under light was dependent on the distance between the light source and the samples, the wavelength of light, exposure time, and the intensity of light. After prolonged exposure to heat in alkaline pH conditions, 10 to 15% of the parent LSD epimerized to iso-LSD. Under acidic conditions, less than 5% of the LSD was converted to iso-LSD. It was also demonstrated that trace amounts of metal ions in buffer or urine could catalyze the decomposition of LSD and that this process can be avoided by the addition of EDTA.

Dosage

A single dose of LSD may be between 40 and 500 micrograms—an amount roughly equal to one-tenth the mass of a grain of sand. Threshold effects can be felt with as little as 25 micrograms of LSD.^[8][74] Dosages of LSD are measured in micrograms (µg), or millionths of a gram. By comparison, dosages of most drugs, both recreational and medicinal, are measured in milligrams (mg), or thousandths of a gram. For example, an active dose of mescaline, roughly 0.2 to 0.5 g, has effects comparable to 100 µg or less of LSD.^[5]

In the mid-1960s, the most important black market LSD manufacturer (Owsley Stanley) distributed acid at a standard concentration of 270 µg.^[75] While street samples of the 1970s contained 30 to 300 µg. By the 1980s, the amount had reduced to between 100 and 125 µg, lowering more in the 1990s to the 20–80 µg range,^[76] and even more in the 2000s (decade).^{[75] [77]}

Estimates for the median lethal dose (LD₅₀) of LSD range from 200 µg/kg to more than 1 mg/kg of human body mass, though most sources report that there are no known human cases of such an overdose. Other sources note one report of a suspected fatal overdose of LSD occurring in November 1975 in Kentucky in which there were indications that ~1/3 of a gram (320 mg or 320,000 µg) had been injected intravenously. (This is a very extraordinary amount, equivalent to over 3,000 times the average LSD dosage of ~100 µg).^[78][79] Experiments with LSD have also been done on animals; in 1962, an elephant named Tusko died shortly after being injected with 297 mg, but whether the LSD was the cause of his death is controversial (due, in part, to a plethora of other chemical substances administered simultaneously).^[80]

Pharmacokinetics

LSD's effects normally last from 6–12 hours depending on dosage, tolerance, body weight and age.^[6] The Sandoz prospectus for "Delysid" warned: "intermittent disturbances of affect may occasionally persist for several days."^[5] Contrary to early reports and common belief, LSD effects do not last longer than the amount of time significant levels of the drug are present in the blood. Aghajanian and Bing (1964) found LSD had an elimination half-life of only 175 minutes.^[1] However, using more accurate techniques, Papac and Foltz (1990) reported that 1 µg/kg oral LSD given to a single male volunteer had an apparent plasma half-life of 5.1 hours, with a peak plasma concentration of 5 ng/mL at 3 hours post-dose.^[2]

Detection in biological fluids

LSD may be quantified in urine as part of a drug abuse testing program, in plasma or serum to confirm a diagnosis of poisoning in hospitalized victims or in whole blood to assist in a forensic investigation of a traffic or other criminal violation or a case of sudden death. Both the parent drug and its major metabolite are unstable in biofluids when exposed to light, heat or alkaline conditions and therefore specimens are protected from light, stored at the lowest possible temperature and analyzed quickly to minimize losses.^[81]

Pharmacodynamics

LSD affects a large number of the G protein-coupled receptors, including all dopamine receptor subtypes, and all adrenoreceptor subtypes, as well as many others.^{[citation needed]} Most serotonergic psychedelics are not significantly dopaminergic, and LSD is therefore rather unique in this regard. LSD's agonism of D₂ receptors contributes to its psychoactive effects.^[82][83] LSD binds to most serotonin receptor subtypes except for 5-HT₃ and 5-HT₄. However, most of these receptors are affected at too low affinity to be sufficiently activated by the brain concentration of approximately 10–20 nM.^[84] In humans, recreational doses of LSD can affect 5-HT_1A (K_i=1.1nM), 5-HT_2A (K_i=2.9nM), 5-HT_2B (K_i=4.9nM), 5-HT_2C (K_i=23nM), 5-HT_5A (K_i=9nM [in cloned rat tissues]), and 5-HT₆ receptors (K_i=2.3nM).^[1][85] 5-HT_5B receptors, which are not present in humans, also have a high affinity for LSD.^[86] The psychedelic effects of LSD are attributed to its strong partial agonist effects at 5-HT_2A receptors as specific 5-HT_2A agonists are psychedelics and largely 5-HT_2A specific antagonists block the psychedelic activity of LSD. LSD exhibits functional selectivity at the 5-HT_2A and 5HT_2C receptors in that it activates the signal transduction enzyme phospholipase A2 instead of activating the enzyme phospholipase C as the endogenous ligand serotonin does.^[87] Exactly how LSD produces its effects is unknown, but it is thought that it works by increasing glutamate release in the cerebral cortex^[84] and therefore excitation in this area, specifically in layers IV and V.^[88] LSD, like many other drugs, has been shown to activate DARPP-32-related pathways.^[89]

History

LSD was first synthesized on November 16, 1938^[91] by Swiss chemist Albert Hofmann at the Sandoz Laboratories in Basel, Switzerland as part of a large research program searching for medically useful ergot alkaloid derivatives. LSD's psychedelic properties were discovered 5 years later when Hofmann himself accidentally ingested an unknown quantity of the chemical.^[92] The first intentional ingestion of LSD occurred on April 19, 1943,^[93] when Hofmann ingested 250 µg of LSD. He said this would be a threshold dose based on the dosages of other ergot alkaloids. Hofmann found the effects to be much stronger than he anticipated.^[94] Sandoz Laboratories introduced LSD as a psychiatric drug in 1947.^[95]

Beginning in the 1950s the US Central Intelligence Agency began a research program code named Project MKULTRA. Experiments included administering LSD to CIA employees, military personnel, doctors, other government agents, prostitutes, mentally ill patients, and members of the general public in order to study their reactions, usually without the subject's knowledge. The project was revealed in the US congressional Rockefeller Commission report in 1975.

In 1963 the Sandoz patents expired on LSD.^[76] Also in 1963, the US Food and Drug Administration classified LSD as an Investigational New Drug, which meant new restrictions on medical and scientific use.^[76] Several figures, including Aldous Huxley, Timothy Leary, and Al Hubbard, began to advocate the consumption of LSD. LSD became central to the counterculture of the 1960s.^[96] On October 24, 1968, possession of LSD was made illegal in the United States.^[97] The last FDA approved study of LSD in patients ended in 1980, while a study in healthy volunteers was made in the late 1980s. Legally approved and regulated psychiatric use of LSD continued in Switzerland until 1993.^[98] Today, medical research is resuming around the world.^[9]

Production

An active dose of LSD is very minute, allowing a large number of doses to be synthesized from a comparatively small amount of raw material. Twenty five kilograms of precursor ergotamine tartrate can produce 5–6 kg of pure crystalline LSD; this corresponds to 100 million doses. Because the masses involved are so small, concealing and transporting illicit LSD is much easier than smuggling other illegal drugs like cocaine or cannabis.^[99]

Manufacturing LSD requires laboratory equipment and experience in the field of organic chemistry. It takes two to three days to produce 30 to 100 grams of pure compound. It is believed that LSD is not usually produced in large quantities, but rather in a series of small batches. This technique minimizes the loss of precursor chemicals in case a step does not work as expected.^[99]

Forms

LSD is produced in crystalline form and then mixed with excipients or redissolved for production in ingestible forms. Liquid solution is either distributed in small vials or, more commonly, sprayed onto or soaked into a distribution medium. Historically, LSD solutions were first sold on sugar cubes, but practical considerations forced a change to tablet form. Appearing in 1968 as an orange tablet measuring about 6 mm across, "Orange Sunshine" acid was the first largely available form of LSD after its possession was made illegal. Tim Scully, a prominent chemist, made some of it, but said that most "Sunshine" in the USA came by way of Ronald Stark, who imported approximately thirty-five million doses from Europe.^[100]

Over a period of time, tablet dimensions, weight, shape and concentration of LSD evolved from large (4.5–8.1 mm diameter), heavyweight (≥150 mg), round, high concentration (90–350 µg/tab) dosage units to small (2.0–3.5 mm diameter) lightweight (as low as 4.7 mg/tab), variously shaped, lower concentration (12–85 µg/tab, average range 30–40 µg/tab) dosage units. LSD tablet shapes have included cylinders, cones, stars, spacecraft, and heart shapes. The smallest tablets became known as "Microdots".^[101]

After tablets came "computer acid" or "blotter paper LSD", typically made by dipping a preprinted sheet of blotting paper into an LSD/water/alcohol solution.^[100][101] More than 200 types of LSD tablets have been encountered since 1969 and more than 350 blotter paper designs have been observed since 1975.^[101] About the same time as blotter paper LSD came "Windowpane" (AKA "Clearlight"), which contained LSD inside a thin gelatin square a quarter of an inch (6 mm) across.^[100] LSD has been sold under a wide variety of often short-lived and regionally restricted street names including Acid, Trips, Uncle Sid, Blotter, Lucy, Alice and doses, as well as names that reflect the designs on the sheets of blotter paper.^[102][103] Authorities have encountered the drug in other forms—including powder or crystal, and capsule.^[104]

Modern distribution

LSD manufacturers and traffickers in the United States can be categorized into two groups: A few large-scale producers, and an equally limited number of small, clandestine chemists, consisting of independent producers who, operating on a comparatively limited scale, can be found throughout the country.^[105] As a group, independent producers are of less concern to the Drug Enforcement Administration than the larger groups, as their product reaches only local markets.^[106]

Mimics

Since 2005, law enforcement in the United States and elsewhere has seized several chemicals and combinations of chemicals in blotter paper which were sold as LSD mimics, including DOB,^[107][108] 2C-I,^[109][110] DOC,^[110] a mixture of DOC and DOI,^[111] and a mixture of DOC and DOB.^[112] Street users of LSD are often under the impression that blotter paper which is actively hallucinogenic can only be LSD because that is the only chemical with low enough doses to fit on a small square of blotter paper. While it is true that LSD requires lower doses than most other hallucinogens, blotter paper is capable of absorbing a much larger amount of material. The DEA performed a chromatographic analysis of blotter paper containing 2C-C which showed that the paper contained a much greater concentration of the active chemical than typical LSD doses, although the exact quantity was not determined.^[113] Blotter LSD mimics can have relatively small dose squares; a sample of blotter paper containing DOC seized by Concord, California police had dose markings approximately 6 mm apart.^[110]

Legal status

The United Nations Convention on Psychotropic Substances (adopted in 1971) requires its parties to prohibit LSD. Hence, it is illegal in all parties to the convention, which includes the United States, Australia, New Zealand, and most of Europe. However, enforcement of extant laws varies from country to country. Medical and scientific research with LSD in humans is permitted under the 1971 UN Convention.^[114]

Canada

In Canada, LSD is a controlled substance under Schedule III of the Controlled Drugs and Substances Act.^[115] Every person who seeks to obtain the substance, without disclosing authorization to obtain such substances 30 days before obtaining another prescription from a practitioner, is guilty of an indictable offense and liable to imprisonment for a term not exceeding 3 years. Possession for purpose of trafficking is an indictable offense punishable by imprisonment for 10 years.

United Kingdom

In the United Kingdom, LSD is a Schedule 1 Class 'A' drug. This means it has no recognised legitimate uses and possession of the drug without a license is punishable with 7 years imprisonment and/or an unlimited fine, and trafficking is punishable with life imprisonment and an unlimited fine (see main article on drug punishments Misuse of Drugs Act 1971).

In 2000, after consultation with members of the Royal College of Psychiatrists' Faculty of Substance Misuse, the UK Police Foundation issued the Runciman Report which recommended "the transfer of LSD from Class A to Class B".^[116]

In November 2009, the UK Transform Drug Policy Foundation released in the House of Commons a guidebooks to the legal regulation of drugs, After the War on Drugs: Blueprint for Regulation, which details options for regulated distribution and sale of LSD and other psychedelics.^[117]

United States

LSD is Schedule I in the United States, according to the Controlled Substances Act of 1970.^[118] This means LSD is illegal to manufacture, buy, possess, process, or distribute without a DEA license. By classifying LSD as a Schedule I substance, the Drug Enforcement Administration holds that LSD meets the following three criteria: it is deemed to have a high potential for abuse; it has no legitimate medical use in treatment; and there is a lack of accepted safety for its use under medical supervision. There are no documented deaths from chemical toxicity; most LSD deaths are a result of behavioral toxicity.^[119]

There can also be substantial discrepancies between the amount of chemical LSD that one possesses and the amount of possession with which one can be charged in the U.S. This is because LSD is almost always present in a medium (e.g. blotter or neutral liquid), and the amount that can be considered with respect to sentencing is the total mass of the drug and its medium. This discrepancy was the subject of 1995 United States Supreme Court case, Neal v. U.S.^[120]

Lysergic acid and lysergic acid amide, LSD precursors, are both classified in Schedule III of the Controlled Substances Act. Ergotamine tartrate, a precursor to lysergic acid, is regulated under the Chemical Diversion and Trafficking Act.

Notable individuals

Some notable individuals have commented publicly on their experiences with LSD.^[121][122] Some of these comments date from the era when it was legally available in the US and Europe for non-medical uses, and others pertain to psychiatric treatment in the 1950s and 1960s. Still others describe experiences with illegal LSD, obtained for philosophic, artistic, therapeutic, spiritual, or recreational purposes.

• Dock Ellis, pitching for the Pittsburgh Pirates, threw a no-hitter against the San Diego Padres on June 12, 1970 while under the influence of LSD.
• Italian film director Federico Fellini experimented with LSD under the supervision of his psychoanalyst Emilio Servadio in 1964.
• Richard Feynman, a notable physicist at California Institute of Technology, tried LSD during his professorship at Caltech. Feynman largely sidestepped the issue when dictating his anecdotes; he mentions it in passing in the "O Americano, Outra Vez" section.^[123][124]
• Jerry Garcia stated in a July 3, 1989 interview for Relix Magazine, in response to the question "Have your feelings about LSD changed over the years?", "They haven’t changed much. My feelings about LSD are mixed. It’s something that I both fear and that I love at the same time. I never take any psychedelic, have a psychedelic experience, without having that feeling of, “I don’t know what’s going to happen.” In that sense, it’s still fundamentally an enigma and a mystery."^[125]
• Bill Gates implied in an interview with Playboy that he tried LSD during his youth.^[126]
• Aldous Huxley, author of Brave New World, became a user of psychedelics after moving to Hollywood. He was at the forefront of the counterculture's experimentation with psychedelic drugs, which led to his 1954 work The Doors of Perception. Dying from cancer, he asked his wife on 22 November 1963 to inject him with 100 µg of LSD. He died later that day.^[127]
• Steve Jobs, co-founder and former CEO of Apple Inc., said, "Taking LSD was a profound experience, one of the most important things in my life."^[128]
• In a 2004 interview, Paul McCartney said that The Beatles' songs "Day Tripper" and "Lucy in the Sky with Diamonds" are about LSD, although John Lennon explicitly declared that "Lucy" was never about LSD but rather inspired by a picture drawn by his son Julian.^[129][130] John Lennon, George Harrison, and Ringo Starr also experimented with the drug, although McCartney cautioned that "it's easy to overestimate the influence of drugs on the Beatles' music."^[131]
• Kary Mullis is reported to credit LSD with helping him develop DNA amplification technology, for which he received the Nobel Prize in Chemistry in 1993.^[132]

See also

References

Further reading

External links

Wikiquote has a collection of quotations related to: LSD

Wikimedia Commons has media related to LSD.

Wikinews has related news: Drug website surveys LSD users and culture

• Drug Profiles: LSD European Monitoring Centre for Drugs and Drug Addiction
• LSD-25 at Erowid
• The Lycaeum Archive: LSD
• LSD entry in TiHKAL • info
• InfoFacts - Hallucinogens NIDA
• Scholarly bibliography on the histories of LSD use
• LSD Returns-For Psychotherapeutics (Scientific American Magazine article)
• U.S. National Library of Medicine: Drug Information Portal - Lysergic acid diethylamide
• My LSD Trip: a non-cop, non-hippie report of the unvarnished facts, by Robert Gannon, Popular Science Magazine, December 1967.
• WWW Psychedelic Bibliography, MAPS - large database of scientific publications on LSD and other psychedelics, fulltext PDFs

Documentaries

• Hofmann's Potion a documentary on the origins of LSD
• Power & Control LSD in The Sixties on YouTube, documentary film directed by Aron Ranen, 2006
• Inside LSD National Geographic Channel, 2009

v t e Recreational drug use Major recreational drugs Opioids Buprenorphine (Suboxone · Subutex) Codeine Dextropropoxyphene (Darvocet · Darvon) Diamorphine (heroin) \ Morphine (Opium) Hydrocodone Hydromorphone (Dilaudid) Methadone Mitragyna speciosa (Kratom) Oxycodone Depressants Barbiturates Benzodiazepines Ethanol (Alcoholic beverages) GHB Kava Nonbenzodiazepines Stimulants Amphetamine Arecoline (Areca) Betel Caffeine (Coffee Tea) Cathinone (Khat) Cocaine (Coca) Ephedrine (Ephedra) MDPV Mephedrone Methamphetamine Methylone Methylphenidate Nicotine (Tobacco) Theobromine (Cocoa) Entactogens MDA MDMA (Ecstasy) 2C-B alpha-Methyltryptamine 2C-I 6-APB (Benzofury) Hallucinogens Psychedelics Bufotenin Psychoactive toads Vilca Yopo DMT (Ayahuasca) LSA LSD-25 Mescaline Peruvian Torch Peyote San Pedro Psilocybin \ Psilocin (Psilocybin mushrooms) Dissociatives DXM Inhalants Nitrous oxide alkyl nitrites – poppers, such as amyl nitrite Ketamine MXE Muscimol (Amanita muscaria) PCP Salvinorin A (Salvia divinorum) Deliriants Atropine and Scopolamine Datura Deadly Nightshade Henbane Mandrake Dimenhydrinate Diphenhydramine Cannabinoids JWH-018 THC (Cannabis Hashish Hash oil) Oneirogens Calea zacatechichi Silene capensis Drug culture Cannabis (Marijuana) 420 Cannabis cultivation Cannabis smoking Legal history of cannabis in the United States Legality of cannabis Marijuana Policy Project Medical cannabis NORML Religious and spiritual use of cannabis Stoner film Psychedelic Art Drug Experience Literature Music Other Club drug Counterculture of the 1960s Dance party Drug paraphernalia Drug tourism Entheogen Hippie Mary Joy Party and play Poly drug use Rave Self-medication Sex and drugs Whoonga Drug production and trade Drug production Coca production in Colombia Drug precursors Opium production in Afghanistan Rolling meth lab Drug trade Illegal drug trade in Colombia Issues with drug use Abuse Date rape drug Effects of cannabis Dependence Prevention Opioid replacement therapy Rehabilitation Responsible use Drug-related crime Fetal alcohol spectrum disorder Illegal drug trade Long-term effects of cannabis Neurotoxicity Overdose Passive smoking (of tobacco or other substances) Legality of drug use International 1961 Narcotic Drugs 1971 Psychotropic Substances 1988 Drug Trafficking Council of the European Union decisions on designer drugs State level Drug policy Decriminalization Prohibition Supply reduction Policy reform Demand reduction Drug Policy Alliance Harm reduction Law Enforcement Against Prohibition Liberalization (Latin America) Students for Sensible Drug Policy Transform Drug Policy Foundation Drug policy by country Australia Canada Germany India Netherlands Portugal Sweden Switzerland Soviet Union United States Just Say No Office of National Drug Control Policy School district drug policies California Colorado Maryland Virginia Other Arguments for and against drug prohibition Capital punishment for drug trafficking Designer drug Drug court Drug harmfulness Drug possession Drug test Mexican Drug War Narc Politics of drug abuse War on Drugs Zero tolerance Lists of countries by... Alcohol legality Alcohol consumption Anabolic steroid legality Cannabis legality Annual use Lifetime use Cigarette consumption Cocaine legality Cocaine use Methamphetamine legality Opiates use Psilocybin mushrooms legality Salvia legality

v t e Hallucinogens Psychedelics 5-HT2AR agonists Lysergamides AL-LAD ALD-52 BU-LAD CYP-LAD IP-LAD Diallyllysergamide Dimethyllysergamide Ergometrine ETH-LAD LAE-32 LPD-824 LSA LSD LSD-Pip LSH LSM-775 Lysergic acid 2-butyl amide LSZ Lysergic acid 3-pentyl amide Methylergometrine Methylisopropyllysergamide Methysergide N1-Methyl-lysergic acid diethylamide PARGY-LAD PRO-LAD Phenethylamines Aleph 2-Methyl-MDA 2C-B 2C-B-Dragonfly 2C-B-FLY βk-2C-B 2C-C 2C-C-FLY 25C-NBOMe 25CN-NBOH 25CN-NBOMe 25D-NBOMe 2C-D 2C-D-FLY 2C-E 2C-E-FLY 2C-E-NBOMe 2C-EF 2C-F 2C-F-NBOMe 2C-G 2C-G-NBOMe 2C-H-NBOMe 2C-I 2C-I-FLY 2C-N 25N-NBOMe 2C-O 2C-O-4 2C-P 2C-T 2C-T-2 2C-T-4 2C-T-4-NBOMe 2C-T-7 2C-T-7-FLY 2C-T-7-NBOH 2C-T-8 2C-T-13 2C-T-15 2C-T-17 2C-T-19 2C-T-21 2C-TFM 25TFM-NBOMe 2C-YN 2CBCB-NBOMe 2CBFly-NBOMe 2CD-5EtO 25B-NBOMe 25C-NBOH 25I-NBMD 25I-NBOH 25I-NBOMe 2C-P-NBOMe 3C-AL 3C-E 3C-P 5-APB 5-APDB 5-APDI 5-Methyl-MDA 6-APB 6-APDB 6-Methyl-MDA Br-DFLY DESOXY DMMDA DMMDA-2 DOB DOB-FLY DOC DOEF DOET DOF DOI DOM DOM-FLY DON DOPR DOTFM Escaline Ganesha HOT-2 HOT-7 HOT-17 Isoproscaline Jimscaline Juncosamine Lophophine Macromerine MDA MDEA MDMA Mescaline Methallylescaline MMA MMDA MMDA-2 MMDA-3a MMDMA NBOMe-mescaline Proscaline TCB-2 TFMFly TMA Piperazines pFPP TMFPP mCPP Tryptamines 1-Methyl-5-methoxy-diisopropyltryptamine 2,N,N-TMT 4,5-DHP-AMT 4,5-DHP-DMT 4-Acetoxy-DALT 4-Acetoxy-DET 4-Acetoxy-DiPT 4-Acetoxy-DMT 4-Acetoxy-DPT 4-Acetoxy-MiPT 4-HO-5-MeO-DMT 4-HO-DBT 4-HO-DPT 4-HO-MET 4-HO-MPMI 4-HO-MPT 4,N,N-TMT 4-Propionyloxy-DMT 5,6-diBr-DMT 5-AcO-DMT 5-Bromo-DMT 5-Me-MIPT 5-MeO-2,N,N-TMT 5-MeO-4,N,N-TMT 5-MeO-α,N,N-TMT 5-MeO-α-ET 5-MeO-α-MT 5-MeO-DALT 5-MeO-DET 5-MeO-DiPT 5-MeO-DMT 5-MeO-DPT 5-MeO-EiPT 5-MeO-MET 5-MeO-MiPT 5-MeO-MPMI 5-N,N-TMT 7,N,N-TMT α-ET α-MT α,N,N-TMT Aeruginascin Baeocystin Bufotenin DALT DBT DCPT DET DIPT DMT DPT EiPT Ethocin Ethocybin Iprocin MET Miprocin MiPT Norbaeocystin PiPT Psilocin Psilocybin Others AL-38022A Elemicin Ibogaine Myristicin Noribogaine Voacangine Dissociatives NMDAR antagonists Adamantanes Amantadine Memantine Rimantadine Arylcyclohexylamines 3-MeO-PCP 4-MeO-PCP Dieticyclidine Diphenidine Esketamine Ethketamine Eticyclidine Gacyclidine Ketamine Methoxetamine Methoxyketamine Neramexane PCPr Phencyclidine Rolicyclidine Tenocyclidine Tiletamine Morphinans Dextrallorphan Dextromethorphan Dextrorphan Racemethorphan Racemorphan Others 2-MDP 8A-PDHQ Aptiganel Dexoxadrol Dizocilpine Etoxadrol Ibogaine Midafotel NEFA Nitrous oxide Noribogaine Perzinfotel Remacemide Selfotel Xenon Deliriants mAChR antagonists 3-Quinuclidinyl benzilate Atropine Benactyzine Benzatropine Benzydamine Biperiden BRN-1484501 Brompheniramine CAR-226,086 CAR-301,060 CAR-302,196 CAR-302,282 CAR-302,368 CAR-302,537 CAR-302,668 Chloropyramine Chlorphenamine Clemastine CS-27349 Cyclizine Cyproheptadine Dicycloverine Dimenhydrinate Diphenhydramine Ditran Doxylamine EA-3167 EA-3443 EA-3580 EA-3834 Flavoxate Hyoscyamine Meclozine Mepyramine N-Ethyl-3-piperidyl benzilate N-Methyl-3-piperidyl benzilate Orphenadrine Oxybutynin Pheniramine Phenyltoloxamine Procyclidine Promethazine Scopolamine Tolterodine Trihexyphenidyl Tripelennamine Triprolidine WIN-2299 Miscellaneous Cannabinoids CB1R agonists Phytocannabinoids Cannabinol THC (Dronabinol) THCV (Cannabidiol has different mechanism of action) Synthetic CP 47,497 CP 55,244 CP 55,940 DMHP HU-210 JWH-018 JWH-030 JWH-073 JWH-081 JWH-200 JWH-250 Levonantradol Nabilone Nabitan Parahexyl WIN 55,212-2 D2R agonists Aporphine Bromocriptine Cabergoline Lisuride Memantine Nuciferine Pergolide Piribedil Pramipexole Ropinirole Rotigotine Also indirect D2 agonists, such as dopamine reuptake inhibitors (cocaine, methylphenidate), releasing agents (amphetamine, methamphetamine), and precursors (levodopa). GABAAR agonists Eszopiclone Gaboxadol Ibotenic acid Muscimol Zaleplon Zolpidem Zopiclone Inhalants Mixed MOA Aliphatic hydrocarbons Butane Gasoline Kerosene Propane Aromatic hydrocarbons Toluene Ethers Diethyl ether Enflurane Haloalkanes Chlorofluorocarbons Chloroform κOR agonists 2-EMSB 2-MMSB Alazocine Bremazocine Butorphanol Cyclazocine Cyprenorphine Dextrallorphan Dezocine Enadoline Herkinorin HZ-2 Ibogaine Ketazocine LPK-26 Metazocine Nalbuphine Nalorphine Noribogaine Pentazocine Phenazocine Salvinorin A Spiradoline Tifluadom U-50488 U-69,593 MAO inhibitors Harmaline Harmine Tetrahydroharmine Yohimbine σR agonists DMT Dextrallorphan Dextromethorphan Dextrorphan Noscapine Others Efavirenz Glaucine Isoaminile Pukateine

v t e Adrenergics   Receptor ligands α1 Agonists: 5-FNE 6-FNE Amidephrine Anisodamine Anisodine Cirazoline Dipivefrine Dopamine Ephedrine Epinephrine Etilefrine Ethylnorepinephrine Indanidine Levonordefrin Metaraminol Methoxamine Methyldopa Midodrine Naphazoline Norepinephrine Octopamine Oxymetazoline Phenylephrine Phenylpropanolamine Pseudoephedrine Synephrine Tetrahydrozoline Antagonists: Abanoquil Adimolol Ajmalicine Alfuzosin Amosulalol Arotinolol Atiprosin Benoxathian Buflomedil Bunazosin Carvedilol CI-926 Corynanthine Dapiprazole DL-017 Domesticine Doxazosin Eugenodilol Fenspiride GYKI-12,743 GYKI-16,084 Hydroxyzine Indoramin Ketanserin L-765,314 Labetalol Mephendioxan Metazosin Monatepil Moxisylyte Naftopidil Nantenine Neldazosin Nicergoline Niguldipine Pelanserin Phendioxan Phenoxybenzamine Phentolamine Piperoxan Prazosin Quinazosin Ritanserin RS-97,078 SGB-1,534 Silodosin SL-89.0591 Spiperone Talipexole Tamsulosin Terazosin Tibalosin Tiodazosin Tipentosin Tolazoline Trimazosin Upidosin Urapidil Zolertine * Note that many TCAs, TeCAs, antipsychotics, ergolines, and some piperazines like buspirone and trazodone all antagonize α1-adrenergic receptors as well, which contributes to their side effects such as orthostatic hypotension. α2 Agonists: (R)-3-Nitrobiphenyline 4-NEMD 6-FNE Amitraz Apraclonidine Brimonidine Cannabivarin Clonidine Detomidine Dexmedetomidine Dihydroergotamine Dipivefrine Dopamine Ephedrine Ergotamine Epinephrine Esproquin Etilefrine Ethylnorepinephrine Guanabenz Guanfacine Guanoxabenz Levonordefrin Lofexidine Medetomidine Methyldopa Mivazerol Naphazoline Norepinephrine Oxymetazoline Phenylpropanolamine Piperoxan Pseudoephedrine Rilmenidine Romifidine Talipexole Tetrahydrozoline Tizanidine Tolonidine Urapidil Xylazine Xylometazoline Antagonists: 1-PP Adimolol Aptazapine Atipamezole BRL-44408 Buflomedil Cirazoline Efaroxan Esmirtazapine Fenmetozole Fluparoxan GYKI-12,743 GYKI-16,084 Idazoxan Mianserin Mirtazapine MK-912 NAN-190 Olanzapine Phentolamine Phenoxybenzamine Piperoxan Piribedil Rauwolscine Rotigotine SB-269,970 Setiptiline Spiroxatrine Sunepitron Tolazoline Yohimbine * Note that many atypical antipsychotics and azapirones like buspirone (via metabolite 1-PP) antagonize α2-adrenergic receptors as well. β Agonists: 2-FNE 5-FNE Amibegron Arbutamine Arformoterol Arotinolol BAAM Bambuterol Befunolol Bitolterol Broxaterol Buphenine Carbuterol Cimaterol Clenbuterol Denopamine Deterenol Dipivefrine Dobutamine Dopamine Dopexamine Ephedrine Epinephrine Etafedrine Etilefrine Ethylnorepinephrine Fenoterol Formoterol Hexoprenaline Higenamine Indacaterol Isoetarine Isoprenaline Isoxsuprine Levonordefrin Levosalbutamol Mabuterol Methoxyphenamine Methyldopa Mirabegron N-Isopropyloctopamine Norepinephrine Orciprenaline Oxyfedrine Phenylpropanolamine Pirbuterol Prenalterol Ractopamine Procaterol Pseudoephedrine Reproterol Rimiterol Ritodrine Salbutamol Salmeterol Solabegron Terbutaline Tretoquinol Tulobuterol Xamoterol Zilpaterol Zinterol Antagonists: Acebutolol Adaprolol Adimolol Afurolol Alprenolol Alprenoxime Amosulalol Ancarolol Arnolol Arotinolol Atenolol Befunolol Betaxolol Bevantolol Bisoprolol Bopindolol Bormetolol Bornaprolol Brefonalol Bucindolol Bucumolol Bufetolol Buftiralol Bufuralol Bunitrolol Bunolol Bupranolol Burocrolol Butaxamine Butidrine Butofilolol Capsinolol Carazolol Carpindolol Carteolol Carvedilol Celiprolol Cetamolol Cicloprolol Cinamolol Cloranolol Cyanopindolol Dalbraminol Dexpropranolol Diacetolol Dichloroisoprenaline Dihydroalprenolol Dilevalol Diprafenone Draquinolol Dropranolol Ecastolol Epanolol Ericolol Ersentilide Esatenolol Esmolol Esprolol Eugenodilol Exaprolol Falintolol Flestolol Flusoxolol Hydroxycarteolol Hydroxytertatolol ICI-118,551 Idropranolol Indenolol Indopanolol Iodocyanopindolol Iprocrolol Isoxaprolol Isamoltane Labetalol Landiolol Levobetaxolol Levobunolol Levocicloprolol Levomoprolol Medroxalol Mepindolol Metalol Metipranolol Metoprolol Moprolol Nadolol Nadoxolol Nafetolol Nebivolol Neraminol Nifenalol Nipradilol Oberadilol Oxprenolol Pacrinolol Pafenolol Pamatolol Pargolol Parodilol Penbutolol Penirolol PhQA-33 Pindolol Pirepolol Practolol Primidolol Procinolol Pronethalol Propafenone Propranolol Ridazolol Ronactolol Soquinolol Sotalol Spirendolol SR 59230A Sulfinalol TA-2005 Talinolol Tazolol Teoprolol Tertatolol Terthianolol Tienoxolol Tilisolol Timolol Tiprenolol Tolamolol Toliprolol Tribendilol Trigevolol Xibenolol Xipranolol   Reuptake inhibitors NET Selective norepinephrine reuptake inhibitors: Amedalin Atomoxetine (Tomoxetine) Ciclazindol Daledalin Edivoxetine Esreboxetine Lortalamine Mazindol Nisoxetine Reboxetine Talopram Talsupram Tandamine Viloxazine; Norepinephrine-dopamine reuptake inhibitors: Amineptine Bupropion (Amfebutamone) Fencamine Fencamfamine Lefetamine Levophacetoperane LR-5182 Manifaxine Methylphenidate Nomifensine O-2172 Radafaxine; Serotonin-norepinephrine reuptake inhibitors: Bicifadine Desvenlafaxine Duloxetine Eclanamine Levomilnacipran Milnacipran Sibutramine Venlafaxine; Serotonin-norepinephrine-dopamine reuptake inhibitors: Brasofensine Diclofensine DOV-102,677 DOV-21,947 DOV-216,303 JNJ-7925476 JZ-IV-10 Methylnaphthidate Naphyrone NS-2359 PRC200-SS SEP-225,289 SEP-227,162 Tesofensine; Tricyclic antidepressants: Amitriptyline Butriptyline Cianopramine Clomipramine Desipramine Dosulepin Doxepin Imipramine Lofepramine melitracen Nortriptyline Protriptyline Trimipramine; Tetracyclic antidepressants: Amoxapine Maprotiline Mianserin Oxaprotiline Setiptiline; Others: Cocaine CP-39,332 Ethanol EXP-561 Fezolamine Ginkgo biloba Indeloxazine Nefazodone Nefopam Pridefrine Tapentadol Tedatioxetine Teniloxazine Tofenacin Tramadol Ziprasidone VMAT Ibogaine Reserpine Tetrabenazine   Releasing agents Morpholines: Fenbutrazate Fenmetramide Morazone Phendimetrazine Phenmetrazine Pseudophenmetrazine; Oxazolines: 4-MAR Aminorex Clominorex Cyclazodone Fenozolone Fluminorex Pemoline Thozalinone; Phenethylamines (also amphetamines, cathinones, etc): 2-OH-PEA 4-CAB 4-FA 4-FMA 4-MA 4-MMA Alfetamine Amfecloral Amfepentorex Amfepramone Amphetamine (Dextroamphetamine Levoamphetamine) Amphetaminil β-Me-PEA BDB Benzphetamine BOH Buphedrone Butylone Cathine Cathinone Clobenzorex Clortermine Dimethylamphetamine Dimethylcathinone DMA DMMA EBDB Ephedrine Ethcathinone Ethylone Etilamfetamine Famprofazone Fenethylline Fenproporex Flephedrone Fludorex Furfenorex Hordenine Hydroxyamphetamine IAP IMP Iofetamine Lisdexamfetamine Lophophine MBDB MDA MDEA MDMA MDMPEA MDOH MDPEA Mefenorex Mephedrone Mephentermine Methamphetamine (Dextromethamphetamine Levomethamphetamine) Methcathinone Methedrone Methylone Naphthylisopropylamine Ortetamine pBA pCA Pentorex Phenethylamine Pholedrine Phenpromethamine Phentermine Phenylpropanolamine pIA Prenylamine Propylamphetamine Pseudoephedrine Selegiline (also D-Deprenyl) Tiflorex Tyramine Xylopropamine Zylofuramine; Piperazines: 2C-B-BZP BZP MBZP mCPP MDBZP MeOPP pFPP; Others: 2-ADN 2-AI 2-AT 2-BP 4-BP 5-IAI Clofenciclan Cyclopentamine Cypenamine Cyprodenate Feprosidnine Gilutensin Heptaminol Hexacyclonate Indanorex Isometheptene Methylhexanamine Octodrine Phthalimidopropiophenone Propylhexedrine (Levopropylhexedrine) Tuaminoheptane   Enzyme inhibitors Anabolism PAH 3,4-Dihydroxystyrene TH 3-Iodotyrosine Aquayamycin Bulbocapnine Metirosine Oudenone AAAD Benserazide Carbidopa DFMD Genistein Methyldopa DBH Bupicomide Disulfiram Dopastin Fusaric acid Nepicastat Phenopicolinic acid Tropolone PNMT CGS-19281A SKF-64139 SKF-7698 Catabolism MAO Nonselective: Benmoxin Caroxazone Echinopsidine Furazolidone Hydralazine Indantadol Iproclozide Iproniazid Isocarboxazid Isoniazid Linezolid Mebanazine Metfendrazine Nialamide Octamoxin Paraxazone Phenelzine Pheniprazine Phenoxypropazine Pivalylbenzhydrazine Procarbazine Safrazine Tranylcypromine; MAO-A selective: Amiflamine Bazinaprine Befloxatone Brofaromine Cimoxatone Clorgiline Eprobemide Esuprone Harmala alkaloids (Harmine, Harmaline Tetrahydroharmine Harman Norharman, etc) Methylene blue Metralindole Minaprine Moclobemide Pirlindole Sercloremine Tetrindole Toloxatone Tyrima; MAO-B selective: Ladostigil Lazabemide Milacemide Mofegiline Pargyline Rasagiline Safinamide Selegiline (also D-Deprenyl) * Note that MAO-B inhibitors also influence norepinephrine/epinephrine levels since they inhibit the breakdown of their precursor dopamine. COMT Entacapone Nitecapone Tolcapone   Others Precursors L-Phenylalanine → L-Tyrosine → L-DOPA (Levodopa) → Dopamine L-DOPS (Droxidopa) Cofactors Ferrous Iron (Fe2+) S-Adenosyl-L-Methionine Vitamin B3 (Niacin Nicotinamide → NADPH) Vitamin B6 (Pyridoxine Pyridoxamine Pyridoxal → Pyridoxal Phosphate) Vitamin B9 (Folic acid → Tetrahydrofolic acid) Vitamin C (Ascorbic acid) Zinc (Zn2+) Others Activity enhancers: BPAP PPAP; Release blockers: Bethanidine Bretylium Guanadrel Guanazodine Guanclofine Guanethidine Guanoxan; Toxins: 6-OHDA List of adrenergic drugs

v t e Dopaminergics   Receptor ligands Agonists Adamantanes: Amantadine Memantine Rimantadine; Aminotetralins: 7-OH-DPAT 8-OH-PBZI Rotigotine UH-232; Benzazepines: 6-Br-APB Fenoldopam SKF-38,393 SKF-77,434 SKF-81,297 SKF-82,958 SKF-83,959; Ergolines: Bromocriptine Cabergoline Dihydroergocryptine Epicriptine Lisuride LSD Pergolide; Dihydrexidine derivatives: 2-OH-NPA A-86,929 Ciladopa Dihydrexidine Dinapsoline Dinoxyline Doxanthrine; Others: A-68,930 A-77636 A-412,997 ABT-670 ABT-724 Aplindore Apomorphine Aripiprazole Bifeprunox BP-897 CY-208,243 Dizocilpine Etilevodopa Flibanserin Ketamine Melevodopa Modafinil Pardoprunox Phencyclidine PD-128,907 PD-168,077 PF-219,061 Piribedil Pramipexole Propylnorapomorphine Pukateine Quinagolide Quinelorane Quinpirole RDS-127 Ro10-5824 Ropinirole Rotigotine Roxindole Salvinorin A SKF-89,145 Sumanirole Terguride Umespirone WAY-100,635 Antagonists Typical antipsychotics: Acepromazine Azaperone Benperidol Bromperidol Clopenthixol Chlorpromazine Chlorprothixene Droperidol Flupentixol Fluphenazine Fluspirilene Haloperidol Levosulpiride Loxapine Mesoridazine Methotrimeprazine Nemonapride Penfluridol Perazine Periciazine Perphenazine Pimozide Prochlorperazine Promazine Sulforidazine Sulpiride Sultopride Thioridazine Thiothixene Trifluoperazine Triflupromazine Trifluperidol Zuclopenthixol; Atypical antipsychotics: Amisulpride Asenapine Blonanserin Cariprazine Carpipramine Clocapramine Clorotepine Clozapine Gevotroline Iloperidone Lurasidone Melperone Molindone Mosapramine Olanzapine Paliperidone Perospirone Piquindone Quetiapine Remoxipride Risperidone Sertindole Tiospirone Zicronapine Ziprasidone Zotepine; Antiemetics: AS-8112 Alizapride Bromopride Clebopride Domperidone Metoclopramide Thiethylperazine; Others: Amoxapine Buspirone Butaclamol Ecopipam EEDQ Eticlopride Fananserin Hydroxyzine L-745,870 Nafadotride Nuciferine PNU-99,194 Raclopride Sarizotan SB-277,011-A SCH-23,390 SKF-83,959 Sonepiprazole Spiperone Spiroxatrine Stepholidine Tetrahydropalmatine Tiapride UH-232 Yohimbine   Reuptake inhibitors Plasmalemmal DAT inhibitors Piperazines: DBL-583 GBR-12,935 Nefazodone Vanoxerine; Piperidines: BTCP Desoxypipradrol Dextromethylphenidate Difemetorex Ethylphenidate Methylnaphthidate Methylphenidate Phencyclidine Pipradrol; Pyrrolidines: Diphenylprolinol MDPV Naphyrone Prolintane Pyrovalerone; Tropanes: Altropane Brasofensine CFT Cocaine Dichloropane Difluoropine FE-β-CPPIT FP-β-CPPIT Ioflupane (123I) Iometopane RTI-112 RTI-113 RTI-121 RTI-126 RTI-150 RTI-177 RTI-229 RTI-336 Tenocyclidine Tesofensine Troparil Tropoxane WF-11 WF-23 WF-31 WF-33; Others: Adrafinil Armodafinil Amfonelic acid Amphetamine Amineptine Benzatropine Bromantane BTQ BTS-74,398 Bupropion Ciclazindol Diclofensine Dimethocaine Diphenylpyraline Dizocilpine DOV-102,677 DOV-21,947 DOV-216,303 Etybenzatropine EXP-561 Fencamine Fencamfamine Fezolamine Fluorenol GYKI-52,895 Indatraline Ketamine Lefetamine Levophacetoperane LR-5182 Manifaxine Mazindol Medifoxamine Mesocarb Modafinil Nefopam Nomifensine NS-2359 O-2172 Pridefrine Propylamphetamine Radafaxine SEP-225,289 SEP-227,162 Sertraline Sibutramine Tametraline Tedatioxetine Tripelennamine Vesicular VMAT inhibitors Deserpidine Ibogaine Reserpine Tetrabenazine   Releasing agents Morpholines: Fenbutrazate Fenmetramide Morazone Phendimetrazine Phenmetrazine Pseudophenmetrazine; Oxazolines: 4-MAR Aminorex Clominorex Cyclazodone Fenozolone Fluminorex Pemoline Thozalinone; Phenethylamines (also amphetamines, cathinones, etc): 2-OH-PEA 4-CAB 4-FA 4-FMA 4-MA 4-MMA Alfetamine Amfecloral Amfepentorex Amfepramone Amphetamine (Dextroamphetamine Levoamphetamine) Amphetaminil β-Me-PEA BDB BOH Benzphetamine Buphedrone Butylone Cathine Cathinone Clobenzorex Clortermine D-Deprenyl DMA DMMA Dimethylamphetamine Dimethylcathinone Ephedrine Ethcathinone EBDB Ethylone Etilamfetamine Famprofazone Fenethylline Fenproporex Flephedrone Fludorex Furfenorex Hordenine Hydroxyamphetamine Iofetamine Lophophine Mefenorex Mephedrone Methamphetamine (Dextromethamphetamine, Levomethamphetamine) Methcathinone Methedrone MMDA MMDMA MBDB MDA MDEA MDMA MDMPEA MDOH MDPEA Methylone Ortetamine pBA pCA pIA Pholedrine Phenethylamine Pholedrine Phenpromethamine Prenylamine Propylamphetamine Pseudoephedrine Tiflorex Tyramine Xylopropamine Zylofuramine; Piperazines: 2C-B-BZP BZP MBZP MDBZP MeOPP; Others: 2-ADN 2-AI 2-AT 4-BP 5-IAI Clofenciclan Cyclopentamine Cypenamine Cyprodenate Feprosidnine Gilutensin Heptaminol Hexacyclonate IAP Indanorex Isometheptene Methylhexanamine Naphthylisopropylamine Octodrine Phthalimidopropiophenone Propylhexedrine (Levopropylhexedrine) Tuaminoheptane   Allosteric modulators Quinazolinamines: SoRI-9804 SoRI-20040 SoRI-20041   Enzyme inhibitors Anabolism PAH inhibitors 3,4-Dihydroxystyrene TH inhibitors 3-Iodotyrosine Aquayamycin Bulbocapnine Metirosine Oudenone AAAD/DDC inhibitors Benserazide Carbidopa DFMD Genistein Methyldopa Catabolism MAO inhibitors Nonselective: Benmoxin Caroxazone Echinopsidine Furazolidone Hydralazine Indantadol Iproclozide Iproniazid Isocarboxazid Isoniazid Linezolid Mebanazine Metfendrazine Nialamide Octamoxin Paraxazone Phenelzine Pheniprazine Phenoxypropazine Pivalylbenzhydrazine Procarbazine Safrazine Tranylcypromine; MAO-A selective: Amiflamine Bazinaprine Befloxatone Brofaromine Cimoxatone Clorgiline Eprobemide Esuprone Harmala alkaloids Methylene Blue Metralindole Minaprine Moclobemide Pirlindole Sercloremine Tetrindole Toloxatone Tyrima; MAO-B selective: D-Deprenyl Ethanol L-Deprenyl (Selegiline) Ladostigil Lazabemide Milacemide Nicotine Pargyline Rasagiline Safinamide COMT inhibitors Entacapone Nitecapone Tolcapone DBH inhibitors Disulfiram Dopastin Fusaric acid Nepicastat Tropolone   Others Precursors L-Phenylalanine → L-Tyrosine → L-DOPA (Levodopa) Cofactors Ferrous iron (Fe2+) Tetrahydrobiopterin Vitamin B3 (Niacin Nicotinamide → NADPH) Vitamin B6 (Pyridoxine Pyridoxamine Pyridoxal → Pyridoxal phosphate) Vitamin B9 (Folic acid → Tetrahydrofolic acid) Vitamin C (Ascorbic acid) Zinc (Zn2+) Others Activity enhancers: BPAP * PPAP; Toxins: 6-OHDA; Steroids: Anabolic-androgenic steroids List of dopaminergic drugs

v t e Serotonergics   5-HT1 receptor ligands 5-HT1A Agonists: Azapirones: Alnespirone Binospirone Buspirone Enilospirone Eptapirone Gepirone Ipsapirone Perospirone Revospirone Tandospirone Tiospirone Umespirone Zalospirone; Antidepressants: Etoperidone Nefazodone Trazodone Vortioxetine; Antipsychotics: Aripiprazole Asenapine Clozapine Quetiapine Ziprasidone; Ergolines: Dihydroergotamine Bromocriptine Ergotamine Lisuride Methysergide LSD; Tryptamines: 5-CT 5-MeO-DMT 5-MT Bufotenin DMT Indorenate Psilocin Psilocybin; Others: 8-OH-DPAT Adatanserin Bay R 1531 Befiradol BMY-14802 Cannabidiol Dimemebfe Ebalzotan Eltoprazine F-11,461 F-12,826 F-13,714 F-14,679 F-15,063 F-15,599 Flesinoxan Flibanserin Lesopitron LY-293,284 LY-301,317 MKC-242 Naluzotan NBUMP Osemozotan Oxaflozane Pardoprunox Piclozotan Rauwolscine Repinotan Roxindole RU-24,969 S 14,506 S-14,671 S-15,535 Sarizotan SSR-181,507 Sunepitron U-92,016-A Urapidil Vilazodone Xaliproden Yohimbine Antagonists: Antipsychotics: Iloperidone Risperidone Sertindole; Beta blockers: Alprenolol Cyanopindolol Iodocyanopindolol Oxprenolol Pindobind Pindolol Propranolol Tertatolol; Others: AV965 BMY-7,378 CSP-2503 Dotarizine Flopropione GR-46611 Isamoltane Lecozotan Mefway Metitepine/Methiothepin MPPF NAN-190 Robalzotan S-15535 SB-649,915 SDZ 216-525 Spiperone Spiramide Spiroxatrine UH-301 WAY-100,135 WAY-100,635 Xylamidine 5-HT1B Agonists: Lysergamides: Dihydroergotamine Ergotamine Methysergide; Piperazines: Eltoprazine TFMPP; Triptans: Avitriptan Eletriptan Sumatriptan Zolmitriptan; Tryptamines: 5-CT 5-MT; Others: CGS-12066A Bromocriptine CP-93,129 CP-94,253 CP-135,807 RU-24,969 Vortioxetine Antagonists: Lysergamides: Metergoline; Others: AR-A000002 Elzasonan GR-127,935 Isamoltane Metitepine/Methiothepin SB-216,641 SB-224,289 SB-236,057 Yohimbine 5-HT1D Agonists: Lysergamides: Dihydroergotamine Methysergide; Triptans: Almotriptan Avitriptan Eletriptan Frovatriptan Naratriptan Rizatriptan Sumatriptan Zolmitriptan; Tryptamines: 5-CT 5-Ethyl-DMT 5-MT 5-(Nonyloxy)tryptamine; Others: CP-135,807 Bromocriptine CP-286,601 GR-46611 L-694,247 L-772,405 PNU-109,291 PNU-142633 Antagonists: Lysergamides: Metergoline; Others: Alniditan BRL-15,572 Elzasonan GR-127,935 Ketanserin LY-310,762 LY-367,642 LY-456,219 LY-456,220 Metitepine/Methiothepin Ritanserin Yohimbine Ziprasidone 5-HT1E Agonists: Lysergamides: Methysergide; Triptans: Eletriptan; Tryptamines: BRL-54443 Tryptamine Antagonists: Metitepine/Methiothepin 5-HT1F Agonists: Triptans: Eletriptan Naratriptan Sumatriptan; Tryptamines: 5-MT; Others: BRL-54443 Bromocriptine Lasmiditan LY-334,370 Antagonists: Metitepine/Methiothepin   5-HT2 receptor ligands 5-HT2A Agonists: Lysergamides: ALD-52 Ergometrine Lisuride LA-SS-Az LSD LSD-Pip Lysergic acid 2-butyl amide Lysergic acid 3-pentyl amide Methysergide; Phenethylamines: 25I-NBF 25I-NBMD 25I-NBOH 25I-NBOMe 2C-B 2C-B-FLY 2CB-Ind 25B-NBOMe 25C-NBOMe 2C-E 2C-I 25TFM-NBOMe 2C-T-2 2C-T-7 2C-T-21 2CBCB-NBOMe 2CBFly-NBOMe Juncosamine Bromo-DragonFLY DOB DOC DOI DOM MDA MDMA Mescaline 25CN-NBOH TCB-2 TFMFly; Piperazines: BZP Quipazine TFMPP; Tryptamines: 5-CT 5-MeO-α-ET 5-MeO-α-MT 5-MeO-DET 5-MeO-DiPT 5-MeO-DMT 5-MeO-DPT 5-MT α-ET α-Methyl-5-HT α-MT Bufotenin DET DiPT DMT DPT Psilocin Psilocybin; Others: AL-34662 AL-37350A Bromocriptine Dimemebfe Medifoxamine O-4310 Oxaflozane PHA-57378 PNU-22394 PNU-181731 RH-34 Antagonists: Atypical antipsychotics: Amperozide Aripiprazole Blonanserin Carpipramine Clocapramine Clorotepine Clozapine Gevotroline Iloperidone Melperone Mosapramine Olanzapine Paliperidone Quetiapine Risperidone Sertindole Zicronapine Ziprasidone Zotepine; Typical antipsychotics: Loxapine Pipamperone; Antidepressants: Amitriptyline Amoxapine Aptazapine Etoperidone Mianserin Mirtazapine Nefazodone Pimozide Teniloxazine Trazodone; Others: 5-I-R91150 5-MeO-NBpBrT AC-90179 Adatanserin Altanserin AMDA APD-215 Cinanserin CSP-2503 Cyproheptadine Deramciclane Dotarizine Eplivanserin Esmirtazapine Fananserin Flibanserin Glemanserin Ketanserin KML-010 Lubazodone Mepiprazole Metitepine/Methiothepin Nantenine Pimavanserin Pizotifen Pruvanserin Rauwolscine Ritanserin S-14,671 Sarpogrelate Setoperone Spiperone Spiramide SR-46349B Volinanserin Xylamidine Yohimbine 5-HT2B Agonists: Oxazolines: 4-Methylaminorex Aminorex; Phenethylamines: Chlorphentermine Cloforex DOB DOC DOI DOM Fenfluramine (Dexfenfluramine, Levofenfluramine) MDA MDMA Norfenfluramine; Tryptamines: 5-CT 5-MT α-Methyl-5-HT; Others: BW-723C86 Bromocriptine Cabergoline mCPP Pergolide PNU-22394 Ro60-0175 Antagonists: Agomelatine Asenapine EGIS-7625 Ketanserin Lisuride LY-272,015 Metitepine/Methiothepin PRX-08066 Rauwolscine Ritanserin RS-127,445 Sarpogrelate SB-200,646 SB-204,741 SB-206,553 SB-215,505 SB-221,284 SB-228,357 SDZ SER-082 Tegaserod Yohimbine 5-HT2C Agonists: Phenethylamines: 2C-B 2C-E 2C-I 2C-T-2 2C-T-7 2C-T-21 DOB DOC DOI DOM MDA MDMA Mescaline; Piperazines: Aripiprazole mCPP TFMPP; Tryptamines: 5-CT 5-MeO-α-ET 5-MeO-α-MT 5-MeO-DET 5-MeO-DiPT 5-MeO-DMT 5-MeO-DPT 5-MT α-ET α-Methyl-5-HT α-MT Bufotenin DET DiPT DMT DPT Psilocin Psilocybin; Others: A-372,159 AL-38022A Alstonine Bromocriptine CP-809,101 Dimemebfe Lorcaserin Medifoxamine MK-212 Org 12,962 ORG-37,684 Oxaflozane PHA-57378 PNU-22394 PNU-181731 Ro60-0175 Ro60-0213 Vabicaserin WAY-629 WAY-161,503 YM-348 Antagonists: Atypical antipsychotics: Clorotepine Clozapine Iloperidone Melperone Olanzapine Paliperidone Quetiapine Risperidone Sertindole Ziprasidone Zotepine; Typical antipsychotics: Chlorpromazine Loxapine Pimozide Pipamperone; Antidepressants: Agomelatine Amitriptyline Amoxapine Aptazapine Etoperidone Fluoxetine Mianserin Mirtazapine Nefazodone Nortriptyline Tedatioxetine Trazodone; Others: Adatanserin CEPC Cinanserin Cyproheptadine Deramciclane Dotarizine Eltoprazine Esmirtazapine FR-260,010 Ketanserin Ketotifen Latrepirdine Metitepine/Methiothepin Methysergide Pizotifen Ritanserin RS-102,221 S-14,671 SB-200,646 SB-206,553 SB-221,284 SB-228,357 SB-242,084 SB-243,213 SDZ SER-082 Xylamidine   5-HT3 5-HT4 5-HT5 5-HT6 5-HT7 ligands 5-HT3 Agonists: Piperazines: BZP Quipazine; Tryptamines: 2-Methyl-5-HT 5-CT; Others: Chlorophenylbiguanide Butanol Ethanol Halothane Isoflurane RS-56812 SR-57,227 SR-57,227-A Toluene Trichloroethane Trichloroethanol Trichloroethylene YM-31636 Antagonists: Antiemetics: AS-8112 Alosetron Azasetron Batanopride Bemesetron Cilansetron Dazopride Dolasetron Galanolactone Granisetron Lerisetron Ondansetron Palonosetron Ramosetron Renzapride Tropisetron Zacopride Zatosetron; Atypical antipsychotics: Clozapine Olanzapine Quetiapine; Tetracyclic antidepressants: Amoxapine Mianserin Mirtazapine; Others: CSP-2503 ICS-205,930 MDL-72,222 Memantine Nitrous Oxide Ricasetron Sevoflurane Tedatioxetine Thujone Tropanserin Vortioxetine Xenon 5-HT4 Agonists: Gastroprokinetic Agents: Cinitapride Cisapride Dazopride Metoclopramide Mosapride Prucalopride Renzapride Tegaserod Velusetrag Zacopride; Others: 5-MT BIMU8 CJ-033,466 PRX-03140 RS-67333 RS-67506 SL65.0155 Antagonists: GR-113,808 GR-125,487 L-Lysine Piboserod RS-39604 RS-67532 SB-203,186 SB-204,070 5-HT5A Agonists: Lysergamides: Ergotamine LSD; Tryptamines: 5-CT; Others: Valerenic Acid Antagonists: Asenapine Latrepirdine Metitepine/Methiothepin Ritanserin SB-699,551 * Note that the 5-HT5B receptor is not functional in humans. 5-HT6 Agonists: Lysergamides: Dihydroergotamine Ergotamine Lisuride LSD Mesulergine Metergoline Methysergide; Tryptamines: 2-Methyl-5-HT 5-BT 5-CT 5-MT Bufotenin E-6801 E-6837 EMD-386,088 EMDT LY-586,713 N-Methyl-5-HT Tryptamine; Others: WAY-181,187 WAY-208,466 Antagonists: Antidepressants: Amitriptyline Amoxapine Clomipramine Doxepin Mianserin Nortriptyline; Atypical antipsychotics: Aripiprazole Asenapine Clorotepine Clozapine Fluperlapine Iloperidone Olanzapine Tiospirone; Typical antipsychotics: Chlorpromazine Loxapine; Others: BGC20-760 BVT-5182 BVT-74316 Cerlapirdine EGIS-12,233 GW-742,457 Ketanserin Latrepirdine Lu AE58054 Metitepine/Methiothepin MS-245 PRX-07034 Ritanserin Ro04-6790 Ro 63-0563 SB-258,585 SB-271,046 SB-357,134 SB-399,885 SB-742,457 5-HT7 Agonists: Lysergamides: LSD; Tryptamines: 5-CT 5-MT Bufotenin; Others: 8-OH-DPAT AS-19 Bifeprunox E-55888 LP-12 LP-44 RU-24,969 Sarizotan Antagonists: Lysergamides: 2-Bromo-LSD Bromocriptine Dihydroergotamine Ergotamine Mesulergine Metergoline Methysergide; Antidepressants: Amitriptyline Amoxapine Clomipramine Imipramine Maprotiline Mianserin; Atypical antipsychotics: Amisulpride Aripiprazole Asenapine Clorotepine Clozapine Olanzapine Risperidone Sertindole Tiospirone Ziprasidone Zotepine; Typical antipsychotics: Chlorpromazine Loxapine; Pimozide; Others: Butaclamol EGIS-12,233 Ketanserin LY-215,840 Metitepine/Methiothepin Ritanserin SB-258,719 SB-258,741 SB-269,970 SB-656,104 SB-656,104-A SB-691,673 SLV-313 SLV-314 Spiperone SSR-181,507 Vortioxetine   Reuptake inhibitors SERT Selective serotonin reuptake inhibitors (SSRIs): Alaproclate Citalopram Dapoxetine Desmethylcitalopram Desmethylsertraline Escitalopram Femoxetine Fluoxetine Fluvoxamine Indalpine Ifoxetine Litoxetine Lubazodone Omiloxetine Panuramine Paroxetine Pirandamine RTI-353 Seproxetine Sertraline Vilazodone Vortioxetine Zimelidine; Serotonin-norepinephrine reuptake inhibitors (SNRIs): Bicifadine Desvenlafaxine Duloxetine Eclanamine Levomilnacipran Milnacipran Sibutramine Venlafaxine; Serotonin-norepinephrine-dopamine reuptake inhibitors (SNDRIs): Brasofensine Diclofensine DOV-102,677 DOV-21,947 DOV-216,303 NS-2359 SEP-225289 SEP-227,162 Tedatioxetine Tesofensine; Tricyclic antidepressants (TCAs): Amitriptyline Butriptyline Cianopramine Clomipramine Desipramine Dosulepin Doxepin Imipramine Lofepramine Nortriptyline Pipofezine Protriptyline Trimipramine; Tetracyclic antidepressants (TeCAs): Amoxapine; Piperazines: Nefazodone Trazodone; Antihistamines: Brompheniramine Chlorphenamine Diphenhydramine Mepyramine/Pyrilamine Pheniramine Tripelennamine; Opioids: Pethidine Methadone Propoxyphene; Others: Cocaine CP-39,332 Cyclobenzaprine Dextromethorphan Dextrorphan EXP-561 Fezolamine Mesembrine Nefopam PIM-35 Pridefine Roxindole SB-649,915 Tofenacin Ziprasidone VMAT Ibogaine Reserpine Tetrabenazine   Releasing agents Aminoindanes: 5-IAI AMMI ETAI MDAI MDMAI MMAI TAI; Aminotetralins: 6-CAT 8-OH-DPAT MDAT MDMAT; Oxazolines: 4-Methylaminorex Aminorex Clominorex Fluminorex; Phenethylamines (also Amphetamines, Cathinones, Phentermines, etc): 2-Methyl-MDA 4-CAB 4-FA 4-FMA 4-HA 4-MTA 5-APDB 5-Methyl-MDA 6-APDB 6-Methyl-MDA AEMMA Amiflamine BDB BOH Brephedrone Butylone Chlorphentermine Cloforex Amfepramone Metamfepramone DCA DFMDA DMA DMMA EBDB EDMA Ethylone Etolorex Fenfluramine (Dexfenfluramine, Levofenfluramine) Flephedrone IAP IMP Iofetamine Lophophine MBDB MDA MDEA MDHMA MDMA MDMPEA MDOH MDPEA Mephedrone Methedrone Methylone MMA MMDA MMDMA MMMA NAP Norfenfluramine 4-TFMA pBA pCA pIA PMA PMEA PMMA TAP; Piperazines: 2C-B-BZP 3-MeOPP BZP DCPP MBZP mCPP MDBZP MeOPP Mepiprazole pCPP pFPP pTFMPP TFMPP; Tryptamines: 4-Methyl-αET 4-Methyl-αMT 5-CT 5-MeO-αET 5-MeO-αMT 5-MT αET αMT DMT Tryptamine (itself); Others: Indeloxazine Tramadol Viqualine   Enzyme inhibitors Anabolism TPH AGN-2979 Fenclonine AAAD Benserazide Carbidopa Genistein Methyldopa Catabolism MAO Nonselective: Benmoxin Caroxazone Echinopsidine Furazolidone Hydralazine Indantadol Iproclozide Iproniazid Isocarboxazid Isoniazid Linezolid Mebanazine Metfendrazine Nialamide Octamoxin Paraxazone Phenelzine Pheniprazine Phenoxypropazine Pivalylbenzhydrazine Procarbazine Safrazine Tranylcypromine; MAO-A Selective: Amiflamine Bazinaprine Befloxatone Brofaromine Cimoxatone Clorgiline Eprobemide Esuprone Harmala alkaloids (Harmine Harmaline Tetrahydroharmine Harman Norharman, etc) Methylene Blue Metralindole Minaprine Moclobemide Pirlindole Sercloremine Tetrindole Toloxatone Tyrima   Others Precursors L-Tryptophan → 5-HTP Cofactors Ferrous iron (Fe2+) Magnesium (Mg2+) Tetrahydrobiopterin Vitamin B3 (Niacin Nicotinamide → NADPH) Vitamin B6 (Pyridoxine Pyridoxamine Pyridoxal → Pyridoxal phosphate) Vitamin B9 (Folic Acid → Tetrahydrofolic acid) Vitamin C (Ascorbic acid) Zinc (Zn2+) Others Activity enhancers: BPAP * PPAP; Reuptake enhancers: Tianeptine; Steroids: Anabolic-androgenic steroids

v t e Trace amine-associated receptor (TAAR) ligands TAAR1 Agonists Selective: O-Phenyl-3-iodotyramine RO5166017 Non-selective: 3-Iodothyronamine 3-Methoxytyramine 5-MeO-DMT Amphetamine Bromocriptine DMT DOI Dopamine LSD m-Octopamine m-Tyramine MDMA Methamphetamine N-Methylphenethylamine N-Methyltryptamine N-Methyltyramine Norepinephrine p-Octopamine p-Tyramine Phenethylamine Serotonin Synephrine Tryptamine; Unknown: RG7351 Antagonists Selective EPPTB (RO5212773) *Note that other phenethylamines, tryptamines, ergolines, and thyronamines are either known to or are likely to act as non-selective TAAR1 agonists as well.

v t e Ergolines Lysergic acid derivatives 2-Bromo-LSD (BOL-148) Bromocriptine Cabergoline Dihydroergocornine Dihydroergocristine Dihydroergocryptine Dihydroergometrine (Dihydroergonovine, Dihydroergobasine) Dihydroergotamine Epicriptine Ergine (LSA; LA-111; Lysergamide) Ergocornine Ergocristine Ergocryptine Ergoloid (Dihydroergotoxine) Ergometrine (Ergonovine, Ergobasine) Ergometrinine Ergotamine Ergotoxine Ergovaline Lisuride LSD LSH Lysergic Acid Lysergic acid cyclobutylamide Lysergic acid cyclopentylamide Lysergic Acid Methyl Ester Lysergol Mesulergine Metergoline Methergine (Methylergometrine, Methylergonovine, Methylergobasine) Methysergide Pergolide Syntometrine Psychedelic lysergamides AL-LAD ALD-52 BU-LAD CYP-LAD DAL DAM-57 Ergonovine ETH-LAD IP-LAD LAE-32 LSD LPD-824 LSM-775 LSH LSD-Pip Lysergic Acid 2-Butylamide Lysergic Acid 2,4-Dimethylazetidide Lysergic Acid 3-Pentylamide Methylergonovine Methylisopropyllysergamide MLD-41 PARGY-LAD PRO-LAD Other ergolines Ergoline Natural sources Achnatherum robustum (Sleepy Grass) Claviceps spp. (Ergot) Morning glory: Argyreia nervosa (Hawaiian Baby Woodrose), Ipomoea spp.(Morning Glory, Tlitliltzin, Badoh Negro), Rivea corymbosa (Coaxihuitl, Ololiúqui)

v t e Drugs mentioned in TiHKAL AL-LAD DBT DET DiPT 5-MeO-α-MT DMT 2,α-DMT α,N-DMT DPT EiPT α-ET ETH-LAD Harmaline Harmine 4-HO-DBT 4-HO-DSBT 4-HO-DET 4-HO-DiPT 4-HO-DMT 5-HO-DMT 4-HO-DPT 4-HO-MET 4-HO-MiPT 4-HO-MPT 4-HO-pyr-T Ibogaine LSD MBT 4,5-MDO-DiPT 5,6-MDO-DiPT 4,5-MDO-DMT 5,6-MDO-DMT 5,6-MDO-MiPT 2-Me-DET 2-Me-DMT Melatonin 5-MeO-DET 5-MeO-DiPT 5-MeO-DMT 4-MeO-MiPT 5-MeO-MiPT 5,6-MeO-MiPT 5-MeO-NMT 5-MeO-pyr-T 6-MeO-THH 5-MeO-TMT 5-MeS-DMT MiPT α-MT NET NMT PRO-LAD pyr-T Tryptamine Tetrahydroharmine α,N,O-TMS

International Chemical Identifier
InChI=	1/C20H25N3O/c1-4-23(5-2)20(24)14-9-16-15-7-6-8-17-19(15)13(11-21-17)10-18(16)22(3)12-14/h6-9,11,14,18,21H,4-5,10,12H2,1-3H3/t14-,18-/m1/s1
InChIKey=	VAYOSLLFUXYJDT-RDTXWAMCBY
CASRN=	50-37-3
PIN=	Lysergic acid diethylamide