Do You Know the History of Acid or LSD?

Lysergide (LSD) drug profile

Do You Know the History of Acid or LSD?

Lysergide (LSD) is a semi-synthetic hallucinogen, and is one of the most potent drugs known. Recreational use became popular between the 1960s to 1980s, but is now less common.

It is generally believed that most LSD is produced outside Europe, but secondary preparation of dosage units by dipping or spotting paper squares is more widespread.

These dosage units usually bear coloured designs featuring cartoon characters, geometric and abstract motifs. LSD is related to other substituted tryptamines, and is under international control.


The International Non-proprietary Name (INN) is (+)- lysergide. The abbreviation LSD is derived from its German name LysergSäureDiethylamid (Lysergic acid diethylamide) (CAS-50-37-3).

Lysergide belongs to a family of indole alkylamines that includes numerous substituted tryptamines such as psilocin (found in ‘magic’ mushrooms) and N,N-dimethyltryptamine (DMT). The IUPAC name for LSD is 9,10-didehydro-N,N-diethyl-6-methylergoline-8β-carboxamide.

The (R) stereoisomer is more potent than the (S) form.

Molecular structure

Molecular formula: C20H25N3O
Molecular weight: 323.4

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Physical form

LSD is normally produced as tartrate salt, which is colourless, odourless and water soluble. The common street dose forms are ‘blotters’ or ‘paper squares’ — sheets of absorbent paper printed with distinctive designs and perforated so they may be torn into single small (typically 7 mm) squares each containing a single dose.

Each sheet typically contains 100 or more doses. LSD is less commonly seen as small tablets (‘microdots’) that are 2–3 mm in diameter, as thin gelatine squares (‘window panes’) or in capsules. Solutions of LSD in water or alcohol are occasionally encountered. LSD is light sensitive in solution, but more stable in dosage units.

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LSD was first synthesised by Albert Hoffman while working for Sandoz Laboratories in Basel in 1938. Some years later, during a re-evaluation of the compound, he accidentally ingested a small amount and described the first ‘trip’.

During the 1950s and 1960s, Sandoz evaluated the drug for therapeutic purposes and marketed it under the name Delysid®. It was used for research into the chemical origins of mental illness.

Recreational use started in the 1960s and is associated with the ‘psychedelic period’.

Physical effects (e.g. dilated pupils, mild hypertension and occasionally raised body temperature) appear first. Sensory-perceptual changes are the outstanding features of LSD. Visual disturbances are perceived with eyes closed or open and may consist of geometric shapes or figures in patterns.

Flashes of intense colour are seen and stable objects may appear to move and dissolve. Cross-sensory perception (synaesthesia) such as ‘coloured hearing’ can occur where sounds such as voices or music evoke perception of particular colours or shapes. The perception of time may appear to slow down.

The mode of action of LSD is not well understood.

It is thought to interact with the serotonin system by binding to and activating 5–hydroxytryptamine subtype 2 receptor (5-HT2), which interferes with inhibitory systems resulting in perceptual disturbances.

It is amongst the most potent drugs known, being active at doses from about 20 micrograms. Typical doses are now about 20 to 80 micrograms although in the past, doses as high as 300 micrograms were common. other hallucinogens, dependence does not occur.

When taken orally, the effects become apparent within about 30 minutes and may continue for 8 to 12 hours or more. The duration and intensity of effects are dose-dependant. The plasma half-life is about two-and-a-half hours.

Following a dose of 160 micrograms to 13 subjects, plasma concentrations varied considerably up to 9 micrograms/L. In humans, LSD is extensively transformed in the liver by hydroxylation and glucuronide conjugation to inactive metabolites.

Only about 1 % is excreted unchanged in the urine in 24 hours. A major metabolite found in urine is 2-oxylysergide.

Panic reactions (‘bad trips’) may be sufficiently severe to require medical support. Patients usually recover within a few hours but occasionally hallucinations last up to 48 hours and psychotic states for 3–4 days.

The effects are greatly affected by the set (an individual’s mental state) and the setting (surroundings) in which the drug is taken. Sensory disturbances known as ‘flashbacks’ sometimes occur.

Serious side effects often attributed to LSD such as irrational acts leading to suicide or accidental deaths, are extremely rare. Deaths attributed to LSD overdose are virtually unknown.

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Synthesis and precursors

Methods for producing LSD are complex and require an experienced chemist. Several methods are known, but the majority use lysergic acid as the precursor. Lysergic acid itself is also often produced in clandestine laboratories using ergometrine or ergotamine tartrate as the starting material.

Ergotamine occurs naturally in the ergot fungus (Claviceps purpurea), a common parasite on rye. Depending on the method used, other essential reagents include N,N-carbonyldi-imidazole, diethylamine or hydrazine.

Absorbent paper doses (blotters) are prepared by dipping the paper in an aqueous alcoholic solution of the tartrate salt, or by dropping the solution onto individual squares.

Ergometrine (also known as ergonovine), ergotamine and lysergic acid are listed in Table I in the Annex to the United Nations 1988 Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances. The corresponding EU legislation is set out in Council Regulation (EEC) No 3677/90 and its amendments,  which governs trade between the EU and third countries.

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Mode of use

LSD is taken orally. Paper doses are placed on the tongue, where the drug is rapidly absorbed. Tablets or capsules are swallowed. LSD is not absorbed through dry skin.

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Other names

Synonyms include N,N-diethyl-lysergamide, lysergic acid diethylamide,  LSD, and LSD-25. There are many street names including acid, blotter, dots, tabs, tickets, trips and many others related to the particular designs on the paper dosage forms.

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LSD may be detected in paper doses after extracting the drug into methanol. The extract is spotted onto filter paper, dried and examined under ultraviolet light (360 nm); LSD gives a strong blue fluorescence.

Ehrlich’s reagent (p-dimethyl-aminobenzaldehyde) gives a blue/purple colour and may be applied after thin layer chromatography. HPLC with fluorescence detection or gas chromatography/mass spectrometry are used for confirmation or quantification. The major ions in the mass spectrum are m/z = 323, 221, 181, 222, 207, 72, 223 and 324.

Commercial immunoassays are available for the detection of LSD in urine at concentrations at or above 0.5 micrograms/L.

Many ergot alkaloids can interfere with LSD analysis, e.g. ergometrine, methylergometrine, dihydroergotamine, ergocornine, ergocristine, methysergide, and ergotamine.

LSD degrades readily, particularly in biological specimens, unless protected from light and elevated temperatures; it may also bind to glass containers in acidic solutions.

The only analogue of LSD to have received widespread interest is the N-methylpropylamide of lysergic acid (LAMPA), and any analytical technique should be capable of separating LAMPA from LSD.

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Typical purities

Because LSD is so potent, there is no need for it to be adulterated. Laboratories rarely encounter the drug as a powder so rarely measure purity. As mentioned earlier, the drug decomposes in light and at high temperatures.

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Control status

LSD is listed in Schedule I of the United Nations 1971 Convention on Psychotropic Substances.

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Medical use

Although once used in psychotherapy, LSD has no current medical use.

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Clark, C. C. (1989), ‘The differentiation of lysergic acid diethylamide (LSD) from N-methyl-N-propyl and N-butyl amides of lysergic acid’, Journal of Forensic Science, 34(3).

Freedman, D.X. (1968), ‘On the use and abuse of LSD’, Archives of General Psychiatry, 18(3), pp. 330–347.

Klette, K.L., Horn, C.K., Stout, P.R., Anderson, C.J. (2002), ‘LC–MS Analysis of human urine specimens for 2-Oxo-3-Hydroxy LSD: method validation for potential interferants and stability study of 2-Oxo-3-Hydroxy LSD under various storage conditions’, Journal of Analytical Toxicology, Volume 26, Number 4, pp. 193–200.

Schneider, S. et al. (1998), ‘Methods for the determination of lysergide in body fluids’, Journal of Chromatography B: Biomedical Sciences and Applications 13, pp.189–200.

Shulgin, A. and A. (1997), Tryptamines I have known and loved: the chemistry continues, Transform Press

Sklerov, J. S., Kalasinsky, K. S., and Ehorn, C. A. (1999), ‘Detection of Lysergic Acid Diethylamide (LSD) in urine by gas chromatography-ion trap tandem mass spectrometry’, Journal of Analytical Toxicology, Volume 23, Number 6, pp. 474–478.

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Therapeutic Use of LSD in Psychiatry: A Systematic Review of Randomized-Controlled Clinical Trials

Do You Know the History of Acid or LSD?

Since its discovery in 1938 by Swiss chemist Albert Hofmann (1), lysergic acid diethylamide (lysergide, LSD) has maintained an unstable relationship with psychiatry. Hofmann synthesized LSD in an effort to develop ergot derivatives with the goal of reducing postpartum hemorrhage.

Some years later, after accidentally getting into contact with a small dose, he was the first subject in history to experience its effects (2).

At the end of the 1940s, there was great interest among psychiatrist in the potential use of LSD as a therapeutic agent (3), which was actually marketed by Sandoz laboratories under the brand name “Delysid” in the 1950s (4) and used in several psychiatric departments in Europe and America.

Even the US Army and CIA experimented with this substance as a truth serum, and LSD was further investigated by the US Army as a potential incapacitating agent, however without success (5). After its prohibition in USA in 1967, due to an increase in popularity and its association with counter-cultural movements, it has taken several decades for a resurgence of interest in its therapeutic potential for psychiatry (6–9).

LSD is part of the pharmacological group known as “classical hallucinogens” or “psychedelics” (term coined by Osmond in 1957) (4), sharing its chemical structure with psilocybin and dimethyltryptamine (DMT) as a variant of indolamine (chemical structure similar to the neurotransmitter serotonin) (10).

The term “classical hallucinogen” is a widely accepted synonym in the literature, with a greater emphasis on the alteration of the perception that these substances cause (11), although its use has been controversial as it does not specify the effect of these agents in consciousness and the self, as indicated by recent psychological and biological studies (12–14). LSD could also be defined, from an anthropological perspective, as an “entheogen”, which implies that users experience (mainly in a religious, shamanic or spiritual context) an altered state of consciousness: “as if the eyes had been cleansed and the person could see the world as new in all respects” (15).

Classical hallucinogens are psychoactive substances that are believed to mediate their effects mainly through an agonist activity in the serotonin 2A receptor (5-HT2A) (16). Experimental studies have previously shown that the use of 5-HT2A antagonists attenuate the main effects of these substances, both in rats (17, 18) and human subjects (19–22).

Other receptors which may contribute to the effects of these agents are the serotonin 2C and 1A receptors, as well as other effects in the dopaminergic and noradrenergic system (16). wise, these are potent regulators of transcription factors, which could mediate a potential mechanism of action in the synaptic structure with greater persistence of their effects over time (23, 24).

LSD is one of the most potent classical hallucinogens available, with active doses between 0.5 and 2 mcg/kg (100–150 mcg per dose).

Its half-life is approximately 3 h, varying between 2 and 5 h, and its psychoactive effects are prolonged over time (up to 12 h depending on the dose, tolerance, weight and age of the subject) (25, 26).

Recently LSD has been used in microdoses as low as 10 mcg to enhance performance (27).

The usual mental effects of LSD are distortion of sense of time and identity, alteration in depth and time perception, visual hallucinations, sense of euphoria or certainty, distorted perception of the size and shape of objects, movements, color, sounds, touch and body image and delusions (28).

Concerning safety, the administration of classical hallucinogens carries some risks. One of them is the so-called “bad trip” or “challenging experience”, described as an acute state of anxiety, dysphoria and confusion, which can lead to unpredictable behavior in uncontrolled or unsupervised environments (29).

Another possible risk is the exacerbation of psychotic disorders or the generation of prolonged psychotic reactions, which could be related to the subject's previous predisposition (30).

Although no contemporary study has reported psychosis after the administration of classical hallucinogens, an adequate screening of previous psychotic episodes and the patient's vulnerability is necessary for the use of these substances (31).

Another possible adverse effect is a modest increase in blood pressure and heart rate; therefore, patients with severe cardiovascular disease should be excluded from the administration of this agent. Other usual absolute contraindications are pregnancy, epilepsy or paranoid personality traits (32). The remaining adverse effects should not limit its therapeutic use (31, 33).

As a recreational drug, LSD does not entail physical dependence as withdrawal syndrome, as do most of these substances (opioids, cocaine, cannabis and methamphetamine) (34). Its frequent or long-term use can lead to tolerance, and after a single dose, emotional, physical and mental stability is quickly recovered (35, 36).

wise, classical hallucinogens in general, and LSD in particular, exhibit very low physiological toxicity, even at very high doses, without any evidence of organic damage or neuropsychological deficits (36, 37) associated with their use.

Their safety has recently led to considering LSD as one of the safest psychoactive recreational substances (38–42).

However, LSD remains one of the most stigmatized and legally restricted agents among psychoactive substances.

It is still included in Schedule I of the United Nations classification of drugs, restricting its use in research and making it difficult to potentially use it as a therapeutic tool in medicine. This classification has recently been questioned by various authors (8, 43).

A few decades ago, anecdotal reports of suicidal acts in recreational users were published, and intensely emphasized by the media (44, 45).

These attempts are in contrast with some recent population studies, which show significant associations between the use of a single dose of classical hallucinogens and a decrease in the lihood of psychological distress and suicide (46–48).

Other recent studies also established a clear link between life-time use of classical hallucinogens and a lower probability of developing mental problems, as well as a positive association, although non-significant, regarding several variables related to mental health (49, 50). Nevertheless, the unpredictability of subject behavior makes it necessary to adequately control the environment and monitor the reaction of each individual.

Regarding its therapeutic potential, LSD was used from the 1950s to the 1970s to achieve behavioral and personality changes, as well as remission of psychiatric symptoms in various disorders (30, 51). LSD was used in the treatment of anxiety, depression, psychosomatic diseases and addiction (52).

During that time, it was also observed that LSD together with suitable accompaniment during its administration, could reduce pain, anxiety and depression in patients with advanced cancer (53–55) Other studies involving larger patient samples also established its safety and promising results in patients with terminal cancer (56, 57).

Studies in schizophrenic patients, however, reached less response to the same dose (58) and worse clinical outcomes (59) compared with non-schizophrenics patients, and negative effects on these patients have been described, both in LSD experience itself and later benefits (60, 61).

The data indicate that the responsivity of schizophrenic patients to the administration of lysergic acid is less than that of normal subjects.

Prediction of individual responses to LSD depends on several variables, some of which were already discussed at the international LSD therapy conference in 1965 (52).

LSD reaction involves a series of complex interactions between doses, “set” (thoughts, mood and expectations of the subject prior to treatment) and “setting” (the physical and interpersonal environment in which the subject undergoes treatment) (30).

Three different major approaches to LSD use as a treatment were then applied to clinical research: “psycholytic therapy”, “psychedelic-chemotherapy” and “psychedelic-peak therapy” (62). In psycholytic therapy, mainly practiced in Europe, low-moderate doses (25-200 mcg) of this drug were used in more than one therapeutic session of psychodynamic orientation.

In psychedelic-chemotherapy, drug use itself was emphasized at relatively high doses (200 mcg or more), with a very limited or absent psychotherapeutic approach.

As for psychedelic-peak therapy (or “psychedelic therapy”), it involves administering a single and relatively high dose with the aim of triggering a mystical-type experience (“peak experience” or “ego dissolution” as synonyms).

This approach should include the proper prior preparation of the patient (set) and a comfortable environment during the session (setting), as well as a discussion on it during subsequent follow-up sessions with the subject (after-care related to LSD session) (63). Mystical experiences are referred to as those in which a sense of unity with the environment is experienced achieving a vivid transcendental experience at an emotional, cognitive and ego-structural level, after a previous and personal therapeutic preparation (64). The aim is to catalyze rapid and fundamental changes in the value system and self-image of the subject (65).

Despite the foregoing, most clinical studies involving the use of LSD were published between the 1960s and 1970s, up to the strict prohibition of its use in research. Obviously, most of these studies were not performed under contemporary standards.

The purpose of this systematic review is to identify controlled and randomized clinical trials that assess the potential use of LSD in psychiatry and identify variables controlled by the researcher as potentially related to therapeutic outcomes.

This is with the aim of informing a discussion on the benefits and challenges of integrating contemporary classic hallucinogens research into modern clinical trial designs and providing a guide for further research involving LSD as a therapeutic agent.

Data Acquisition and Search Strategy

This study was conducted according to the requirements established in the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocols (66).


LSD Fast Facts

Do You Know the History of Acid or LSD?

LSD (lysergic acid diethylamide) is a synthetic (man-made) drug that has been abused for its hallucinogenic properties since the 1960s. If consumed in a sufficiently large dose, LSD produces delusions and visual hallucinations that distort the user's sense of time and identity.

What does it look ?

LSD typically is sold as a liquid (often packaged in small bottles designed to hold breath freshening drops) or applied to blotter paper, sugar cubes, gelatin squares, and tablets.

LSD blotter paper. 


    Bottle containing liquid LSD.

PA Bureau of Narcotics Investigation

How is LSD abused?

LSD generally is taken by mouth. The drug is colorless and odorless but has a slightly bitter taste.

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Who uses LSD?   

Individuals of all ages use LSD. Data reported in the National Household Survey on Drug Abuse indicate that an estimated 20.2 million U.S. residents aged 12 and older used LSD at least once in their lifetime. The survey also revealed that many teenagers and young adults use LSD—742,000 individuals aged 12 to 17 and 4.5 million individuals aged 18 to 25 used the drug at least once.

LSD use among high school students is a particular concern. More than 8 percent of high school seniors in the United States used the drug at least once in their lifetime, and nearly 4 percent used the drug in the past year, according to the University of Michigan's Monitoring the Future Survey.

What are the risks?

The effects associated with LSD use are unpredictable and depend upon the amount taken, the surroundings in which the drug is used, and the user's personality, mood, and expectations.

Some LSD users experience a feeling of despair, while others report terrifying fears—of losing control, going insane, or dying.

Some users have suffered fatal accidents while under the influence of LSD.

LSD users often have flashbacks, during which certain aspects of their LSD experience recur even though they have stopped taking the drug. In addition, LSD users may develop long-lasting psychoses, such as schizophrenia or severe depression.

LSD is not considered an addictive drug—that is, it does not produce compulsive drug-seeking behavior as cocaine, heroin, and methamphetamine do. However, LSD users may develop tolerance to the drug, meaning that they must consume progressively larger doses of the drug in order to continue to experience the hallucinogenic effects that they seek.

What is it called?

The most common names for LSD are acid, boomers, and yellow sunshine. (Please see the Street Terms text box below for additional names.)

Street Terms for LSD

Back breaker

Battery acid




Loony toons

Lucy in the sky with diamonds



Window pane


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Is LSD illegal?

Yes,  LSD is illegal. LSD is a Schedule I substance under the Controlled Substances Act. Schedule I drugs, which include heroin and MDMA, have a high potential for abuse and serve no legitimate medical purpose.

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