LSD

LSD
Chemical Nomenclature
Common names	LSD, LSD-25, Lucy, L, Acid, Cid, Tabs, Blotter
Substitutive name	d-Lysergic acid diethylamide
Systematic name	(6aR,9R)-N,N-Diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo-[4,3-fg]quinoline-9-carboxamide
Class Membership
Psychoactive class	Psychedelic
Chemical class	Lysergamide
Routes of Administration
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section. Sublingual Dosage Bioavailability 71% - 71%[1] Threshold 15 µg Light 25 - 75 µg Common 75 - 150 µg Strong 150 - 300 µg Heavy 300 µg + Duration Total 8 - 12 hours Onset 15 - 30 minutes Come up 45 - 90 minutes Peak 3 - 5 hours Offset 3 - 5 hours After effects 12 - 48 hours DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.
Interactions
Cannabis
Amphetamines
Cocaine
Tramadol
Lithium

Lysergic acid diethylamide (also known as Lysergide, LSD-25, LSD, L, lucy, and acid) is a semisynthetic psychedelic substance of the lysergamide class.^[2] LSD is one of the most potent, well-known and widely used psychedelic substances in history. The pharmacology of LSD is complex, but it produces its primary effects by binding to serotonin receptors in the brain.^{[citation needed]}

The psychoactive effects of LSD were first discovered in 1943 by the Swiss chemist Albert Hofmann. In the 1950s, LSD was marketed under the trade name Delysid and used in psychotherapy and for experimental purposes.^[3] LSD garnered widespread interest from clinicians and researchers and was secretly investigated by the U.S. Central Intelligence Agency (CIA) as a potential mind control agent.^[4] During the mid-1960s, use of LSD spread widely in the emerging counterculture, leading to its prohibition in 1971.^[5][6]

Following a 40 year hiatus, research into LSD's potential therapeutic uses has been revived. LSD is currently under investigation for the treatment of a number of ailments including alcoholism, addiction, cluster headache, and anxiety associated with terminal illness.^[3] LSD remains in widespread illicit use for recreational and spiritual purposes. The lifetime prevalence of LSD use among adults is in the range of 6-8%.^[3]

Characteristic effects of LSD include geometric visual hallucinations, time distortion, enhanced introspection, and ego loss. LSD is commonly described by users to evoke entheogenic and mystical-type experiences that can facilitate self-reflection and personal growth. It is considered by some to be the first modern entheogen, a category which had been limited to traditional plant preparations or extracts.^[7]

Unlike other highly prohibited substances, LSD is not considered to be addictive or physiologically toxic.^[8][9] Nevertheless, adverse psychological reactions such as severe anxiety, paranoia and psychosis are always possible, particularly among those predisposed to mental illness.^[10] It is highly advised to use harm reduction practices if using this substance.

History and culture

LSD was first synthesized on November 16, 1938, by the Swiss chemist Albert Hofmann at the Sandoz Laboratories in Basel, Switzerland. It was part of a large research program searching for medically useful derivatives of ergot, a fungus that grows on rye. The abbreviated form of LSD comes from its early research code name LSD-25 which is an abbreviation for the German spelling "Lysergsäure-diethylamid" followed by a sequential number.^[11] However, its psychoactive properties were not discovered until five years later when Hofmann claimed to have accidentally ingested an unknown quantity of the chemical before proceeding to ride his bike home.^[12]

The first intentional ingestion of LSD occurred on April 19, 1943.^[13] Hofmann ingested 250 micrograms (µg) of LSD, believing it would be a threshold dose based on the doses of other ergot alkaloids. Hofmann found the effects to be much stronger than he anticipated and was impressed by its profound mind-altering effects. In 1947, Sandoz introduced LSD to the medical community under the name Delysid as an experimental tool to induce temporary psychotic-like states in normals (“model-psychosis”) and later to enhance psychotherapeutic treatments (“psycholytic” or “psychedelic” therapy)^[14] LSD had a major impact in the areas of scientific research and psychiatry. Within 15 years of its release, research on LSD and other hallucinogens generated over 1,000 scientific papers and was prescribed to over 40,000 patients.^[15]

In the 1950s, the U.S. Central Intelligence Agency began a research program code named MK-ULTRA that would conduct clandestine research investigating LSD for applications in mind control and chemical warfare. Experiments included administering LSD to CIA employees, military personnel, doctors, prostitutes, mentally ill patients, and members of the general public without their knowledge or consent, which resulted in at least one death.^[16]

In 1963, the Sandoz patents for LSD expired. Several prominent intellectuals, including Aldous Huxley, Timothy Leary, and Al Hubbard, began to advocate for the consumption of LSD. LSD became a central part of the youth-driven counterculture of the 1960s. Along with other hallucinogens, LSD was advocated by new proponents of consciousness expansion such as Leary, Huxley, Alan Watts and Arthur Koestler^[17][18] and according to L. R. Veysey, they profoundly influenced the thinking of the new generation of youth.^[19]

On October 24, 1968, possession of LSD was made illegal in the United States.^[20] 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.^[21]

Chemistry

Binding affinities of LSD for various receptors. The lower the dissociation constant (Ki), the more strongly LSD binds to that receptor (i.e. with higher affinity). The horizontal line represents an approximate value for human plasma concentrations of LSD, and hence, receptor affinities that are above the line are unlikely to be involved in LSD's effect. Data averaged from data from the Ki Database.

LSD, or d-lysergic acid diethylamide, is a semisynthetic substance of the lysergamide family. LSD's chemical structure consists of a bicyclic hexahydroindole ring fused to a bicyclic quinoline group (lysergic acid). At carbon 8 of the quinoline an N,N-diethyl carboxamide is bound. LSD is additionally substituted at carbon 6 with a methyl group.

LSD is a chiral compound with two stereocenters at R₅ and R₈. LSD, also called (+)-D-LSD, has an absolute configuration of (5R, 8R). The three other stereoisomers of LSD do not have psychoactive properties.^[22]

In its pure form, LSD occurs as a colorless, odorless crystal.^{[citation needed]} LSD is sensitive to oxygen, ultraviolet light, and chlorine (especially in solution).^[23] Its potency may last for years if it is stored away from light and moisture at cold temperatures around 0°C or below, but will slowly degrade at normal room temperature (25°C).^{[citation needed]}

Pharmacology

This image shows how, with eyes-closed, much more of the brain contributes to the visual experience under LSD (right image) than under placebo (left image). The magnitude of this effect correlates with participants’ reports of complex, dreamlike visions.^[24]

LSD is a partial agonist for the 5-HT_1A, 5-HT_2A, 5-HT_2B, 5-HT_2C and 5-H_T6 receptors.^[25][26] LSD binds to most serotonin receptor subtypes except for 5-HT₃ and 5-HT₄. 5-HT_5B receptors, which have not been found in humans, also have a high affinity for LSD.^[27] The psychedelic effects of LSD are thought to be mediated by agonist action 5-HT_2A receptors.^[28]

LSD also shows efficacy at all dopamine and all norepinephrine receptors. Most serotonergic psychedelics are not significantly dopaminergic, so LSD is unique in this respect. LSD's agonism of D2 receptors has been shown to contribute to its psychoactive effects.^[29][30]

Subjective effects

The subjective effects of LSD can be broken down into several components which progressively intensify proportional to dosage in a nonlinear manner. In comparison to other psychedelics such as psilocybin mushrooms, LSA and ayahuasca, LSD is significantly more stimulating and fast-paced in both its physical and cognitive effects and produces a large number of effects that can potentially be attributed to its binding activity at a wide range of CNS receptors other than serotonin, such as dopamine and norepinephrine.

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. These effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances of inducing a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.

Combination effects

• Alcohol - Alcohol's central depressant effects can be used to reduce some of the anxiety and tension produced by LSD. However, alcohol can cause dehydration, nausea and physical fatigue which can negatively impact the direction of the trip. Users are advised to pace themselves and drink a portion of their usual amount.
• Benzodiazepines - Benzodiazepines are highly effective at reducing the intensity of LSD's effects through the general suppression of brain activity.
• Dissociatives - LSD enhances the cognitive, visual and general hallucinatory effects of dissociatives. Dissociative-induced holes, spaces, and voids and internal hallucinations become more vivid and intense on LSD. These effects correspond with an increased risk of confusion, delusions, and psychosis.
• MDMA - LSD and MDMA are highly synergistic and mutually enhance each other's physical, cognitive, and visual effects. The synergy between these substances is unpredictable, and it is advised to start with markedly lower doses than one would take for each individually. There is some evidence that suggests LSD increases the neurotoxicity of MDMA.^[34][35][36]

Experience reports

Anecdotal reports which describe the effects of this compound within our experience index include:

Additional experience reports can be found here:

• Erowid Experience Vaults: LSD

Forms and mimics

LSD is typically distributed in various forms for oral or sublingual administration. It is one of the few psychedelic substances potent enough to fit onto small squares of "blotter paper,"^[37] and has a history of being counterfeited by similarly potent psychedelics that do not have its favorable safety profile.

LSD can be found in a number of forms, with blotter paper being the most common:

• Blotters are typically small squares pulled off sheets of perforated blotting paper that are dipped into an LSD/alcohol solution which are then either swallowed or chewed, or held sublingually. There should not be a bitter metallic taste which numbs the mouth when chewing the blotters as this likely indicates the presence of a 25x-NBOMe compound.
• Liquid solutions are often found in vials with a pipette. It is often dropped directly into the mouth or tongue. It may also be dropped onto individual sugar cubes or candy before consumption.^[38]
• Tablets & Microdots are very small tablets which can be chewed or swallowed.
• Powder can, in theory, be administered orally, sublingually, or via insufflation or injection. However, LSD is rarely encountered or taken in this way in practice due to its incredible potency. It is almost always diluted into a liquid solution or 'laid' onto blotter paper to allow for more accurate and consistent dosing.
• Gel tabs can be taken orally and are small pieces of gelatin which contain LSD. These are less common now than in the past, but are still occasionally present in some areas of the world.

• 

  Blotters

• 

  Liquid solution

• 

  Microdots

• 

  Gel tabs

Mimics ("Fake acid")

LSD is unusually potent among psychedelic substances, active at just 15-30 micrograms (µg).^[39] It has a long history of being counterfeited by a few other psychedelics potent enough to be laid onto blotter paper (colloquially known as "fake acid" or "bunk acid"). This can be attributed to major differences in cost and ease of synthesis as well as the general inability of inexperienced users to tell the difference.

While pure LSD is almost completely tasteless,^{[citation needed]} the blotter paper it is absorbed onto can impart a mildly bitter taste if it contains any ink. Mimics are usually described as having an obvious "metallic", "numbing", "chemical-like" or "extremely bitter or sour" taste. It is commonly advised to immediately spit out any blotters of acid that are found to have a strong, persisting taste. However, the taste test can only partially ensure user safety. Users should always test each tab of purported LSD that they plan to take using a reagent test kit. Testing kits are considered important because mimics (such as 25x-NBOMe and DOx) have considerably worse safety profiles than LSD and includes the possibility of death.^{[citation needed]}

25I-NBOMe, which has been attributed to several deaths,^{[40][41][42][43]} may commonly be mistaken for LSD by sellers and users.^[44]

Research

Alcoholism

Some studies in the 1960s that used LSD to treat alcoholism found reduced levels of alcohol misuse in almost 60% of those treated, an effect which lasted six months but disappeared after a year.^{[33][45][46][47][48]} 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.^[33]

Trauma-related pain

LSD was studied in the 1960s by Eric Kast as an analgesic for acute and chronic pain caused by cancer or other major trauma.^[49] Even at low (i.e. 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 purported effect is being tested using a similar psychedelic substance, in an ongoing (as of 2006) study of the effects of psilocin on anxiety in terminal cancer patients.^{[citation needed]}

Cluster headaches

LSD has been used as a treatment for cluster headaches, an uncommon but extremely painful disorder. Although the phenomenon has not been formally investigated, case reports indicate that LSD and psilocin can reduce cluster pain and also interrupt the cluster-headache cycle, preventing future headaches from occurring. Currently existing treatments include various tryptamines among other chemicals, so LSD's efficacy in this regard may not be surprising. A dose-response study testing the effectiveness of both LSD and psilocin 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 psilocin, finding that a majority of users of either drug reported beneficial effects.^[50]

Unlike the use of LSD or MDMA in psychotherapy, this research involves non-psychological effects and often sub-psychedelic dosages.^[51][52]

End-of-life anxiety

From 2008 to 2011 there was ongoing research in Switzerland into using LSD to alleviate anxiety for terminally ill cancer patients coping with their impending deaths. Preliminary results of the study are promising, and no negative effects have been reported.^[53][54]

Toxicity and harm potential

Radar plot showing relative physical harm, social harm, and dependence of LSD^[55]

LSD is physiologically well-tolerated and has an extremely low toxicity relative to dose. There is no evidence for long-lasting effects on the brain or other parts of the human organism. There are no documented deaths attributed to the direct effects of LSD toxicity.^[56]

Although classical psychedelics like LSD have not directly caused any deaths, they are capable of impairing the judgment of users. In extreme cases, users may believe that they are invincible or in a dream and may do things they would not normally consider, such as believing they can fly and jumping off of buildings.^[57] This is particularly a concern in non-supervised settings or with excessive doses. While an overdose of LSD is incapable of causing direct bodily harm to the user it can still have serious negative consequences in the form of dangerous, erratic behaviors or psychologically traumatic experiences.

Additionally, LSD may trigger symptoms in those who have or are predisposed to mental illness such as bipolar disorder or schizophrenia.^[56] Those with a personal or family history of mental illness should not use LSD without the advice of a qualified medical practitioner.

It is strongly recommended to apply harm reduction practices when using this substance.

Overdose

LSD has no known toxic dose. However, higher doses increase the risk of adverse psychological reactions. These reactions include anxiety, delusions, panic attacks and, more rarely, seizures. Medical attention is usually not needed except in the case of severe psychotic episodes or the ingestion of fake acid (such as 25i-NBOMe or DOB). Administration of benzodiazepines or antipsychotics can help to relieve the acute negative cognitive effects of LSD.

Dependence and abuse potential

Like other serotonergic psychedelics, LSD is considered to be non-addictive with a low abuse potential.^[56] There are no literature reports of successful attempts to train animals to self-administer LSD — an animal model predictive of abuse liability — indicating that it does not have the necessary pharmacology to either initiate or maintain dependence.^[56] Likewise, there is virtually no withdrawal syndrome when chronic use of LSD is stopped.^{[citation needed]}

Tolerance to the effects of LSD forms almost immediately after ingestion. After that, it takes about 7 days for the tolerance to return to baseline (in the absence of further consumption). LSD produces cross-tolerance with all psychedelics, meaning that after the use of LSD all psychedelics will have a reduced effect.

Some anecdotal reports suggest that extremely high doses of LSD can produce a tolerance which can last subsequently longer anywhere from weeks to months. High doses of LSD, along with high tolerances, can produce variations in intensity, duration, and effects.

Dangerous interactions

Although many psychoactive substances are safe to use on their own, they can quickly become dangerous or even life-threatening when combined with other substances. The following lists some known dangerous combinations, but may not include all of them. A combination that appears to be safe in low doses can still increase the risk of injury or death. Independent research should always be conducted to ensure that a combination of two or more substances is safe to consume. Some interactions listed have been sourced from Tripsit.

• Lithium - Individuals who take lithium for bipolar disorder or other psychiatric conditions should not take LSD. There are numerous anecdotal reports of individuals experiencing seizures and/or psychosis from this combination.^{[58][59][60][61]}
• Cannabis - Cannabis has an unexpectedly strong and somewhat unpredictable synergy with psychedelics. It strongly intensifies the sensory and cognitive effects of LSD. Extreme caution is advised when using this combination as it can significantly increase the chances of negative psychological effects like anxiety, paranoia, confusion, and psychosis. Users are advised to start off with only a fraction of their usual cannabis dose and take long breaks between hits to avoid accidental over intake.
• Amphetamines & Cocaine - Stimulants elevate anxiety levels and increase the risk of paranoia and thought loops which can lead to negative experiences.
• Tramadol - Tramadol is well known to lower the seizure threshold and psychedelics also have the potential to induce seizures in susceptible individuals.^{[citation needed]}

Legal status

Internationally, the UN 1971 Convention on Psychotropic Substances 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. Medical and scientific research with LSD in humans is permitted under the 1971 UN Convention, although has been reported to be difficult to actually carry out in practice.^[62]

• Austria: LSD is illegal to possess, produce and sell under the SMG (Suchtmittelgesetz Österreich).^{[citation needed]}
• Canada: LSD is a Schedule III drug in Canada.^[63]
• Latvia: LSD is a Schedule I drug in Latvia.^[64]
• United Kingdom: LSD is a Class A drug in the United Kingdom.^[65]
• United States: LSD is a Schedule I drug under the Controlled Substances Act of 1970. This means it is illegal to manufacture, buy, possess, process, or distribute without a license from the Drug Enforcement Administration (DEA).^[66]

See also

• Responsible use (Hallucinogens)
• Reagent test kits
• Psychedelics
• Lysergamide
• Psilocybin mushrooms
• Mescaline
• DMT

External links

• LSD (Wikipedia)
• LSD (Erowid Vault)
• LSD (TiHKAL / Isomer Design)

Literature

• Nichols, D. E. (2016). Psychedelics. Pharmacological Reviews, 68(2), 264-355. http://dx.doi.org/10.1124/pr.115.011478
• Passie, T., Halpern, J. H., Stichtenoth, D. O., Emrich, H. M., & Hintzen, A. (2008). The Pharmacology of Lysergic Acid Diethylamide: A Review, 14, 295–314. https://doi.org/10.1111/j.1755-5949.2008.00059.x
• Carhart-Harris, R. L., Muthukumaraswamy, S., Roseman, L., Kaelen, M., Droog, W., Murphy, K., … Nutt, D. J. (2016). Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1518377113
• Schmid, Y., Enzler, F., Gasser, P., Grouzmann, E., Preller, K.H., Vollenweider, F.X., Brenneisen, R., Mueller, F., Borgwardt, S.J., & Liechti, M.E. (2015). Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects. Biological psychiatry, 78 8, 544-53. https://doi.org/10.1016/j.biopsych.2014.11.015
• Carhart-Harris, R.L., Kaelen, M., Bolstridge, M., Williams, T.M., Williams, L.T., Underwood, R., Feilding, A., & Nutt, D.J. (2016). The paradoxical psychological effects of lysergic acid diethylamide (LSD). Psychological medicine, 46 7, 1379-90. https://doi.org/10.1017/S0033291715002901

Further reading

• Hoffman, A. (1980). LSD - My Problem Child. New York: McGraw-Hill.

References