LSD

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Summary sheet: LSD
LSD
Molecular structure of Lysergic acid diethylamide
LSD.svg
Chemical Nomenclature
Common names LSD, LSD-25, Lucy, L, Acid, Tabs, Blotter
Substitutive name d-Lysergic acid diethylamide / N,N-diethyllysergamide
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 - 25 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 4 - 6 hours
Offset 3 - 4 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.

Lysergic acid diethylamide (also known as Lysergide, LSD-25, LSD, L, Lucy, and Acid) is an iconic semisynthetic psychedelic substance of the lysergamide chemical class that produces what are now considered to be "classical psychedelic" effects (i.e. those associated with mescaline, psilocybin mushrooms, LSD, and DMT) when administered.[2]

LSD was initially synthesized by the Swiss chemist Albert Hofmann in 1938, but its profound mind altering effects were not discovered until he accidentally exposed himself to it in 1943. In 1947, LSD was introduced to the world as a commercial medication under the trade-name Delysid for various psychiatric applications.[3]

Following its release, LSD had an immediate and profound impact in the areas of scientific research and psychiatry. In the 15 or so year period following its release, research on LSD and other hallucinogens generated over 1,000 scientific papers and was ultimately prescribed to over 40,000 patients.[4] During this time, it was selected for investigation by the U.S. Central Intelligence Agency (CIA) as a potential mind control agent in a clandestine project named MK-ULTRA.[5] Its subsequent proselytization and widespread adoption for recreational and proclaimed spiritual purposes by the Western youth counterculture of the 1960s eventually resulted in its global prohibition in 1971.[6][7]

LSD is commonly 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",[8] and has a long history of being counterfeited by a select few similarly potent psychedelics that are known to be significantly less safe (see below).

Among other things, LSD has been noted for its elusiveness,[9] impact on various youth subcultures and alternative spiritualities,[10] the arbitrariness of the soft prohibition on its research,[11] as well as the relative difficulty of producing it in a clandestine context.[12] It is considered by some to be an example of the world's first modern entheogen, a category which had until that point been limited to traditional plant preparations.[13]

Unlike most highly prohibited substances, LSD is not considered to be addictive or toxic by the scientific community.[14][15] Nevertheless, unpredictable adverse reactions such as uncontrollable anxiety, paranoia, delusions and psychotic breaks can always occur, particularly among those who are predisposed to mental disorders.[16] While these negative reactions or "bad trips" are often attributable to user inexperience or improper preparation of set and setting, they have been known to spontaneously happen among even the most experienced of users as well.

For this reason, it is highly advised to approach this very powerful, long-lasting, and unpredictable hallucinogenic substance with the proper amount of precaution and harm reduction practices if choosing to use it.

History and culture

LSD was first synthesized on November 16, 1938, 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. 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.[17] However, its psychedelic properties were not discovered until five years later when Hofmann purported to accidentally ingest an unknown quantity of the chemical before proceeding on a bike ride home.[18] This event would be come to be known as "Bicycle Day", and is celebrated to this day.[citation needed]

The first intentional ingestion of LSD occurred on April 19, 1943,[19] when Hofmann ingested 250 micrograms (µg) of LSD, believing it would be a threshold dose based on the dosages of other ergot alkaloids. Hofmann found the effects to be much stronger than he anticipated and was impressed and puzzled by its radically mind-altering effects. In 1947, Sandoz Laboratories introduced LSD to the world as a psychiatric drug and made it easily accessible for research and novel therapeutic purposes.[20]

Beginning in the 1950s, the U.S. Central Intelligence Agency began a research program code named MK-ULTRA and investigated the compound for potential applications in mind control, chemical warfare, and the development of a 'truth serum.' 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 subjects' knowledge, and resulted in at least one death. The project was revealed in the U.S. congressional United States President's Commission on CIA activities called Rockefeller Commission report in 1975.[21]

In 1963, the Sandoz patents expired on LSD. Several prominent intellectuals, including Aldous Huxley, Timothy Leary, and Al Hubbard, began to advocate for the consumption of LSD. LSD became central to the counterculture of the 1960s. In the early 1960s, the use of LSD and other hallucinogens was advocated by new proponents of consciousness expansion such as Leary, Huxley, Alan Watts and Arthur Koestler[22][23] and according to L. R. Veysey, they profoundly influenced the thinking of the new generation of youth.[24]

On October 24, 1968, possession of LSD was made illegal in the United States.[25] 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.[26]

In popular culture, the Grateful Dead became inextricably linked to LSD in the United States, and Grateful Dead concerts provided the primary distribution network for LSD through the mid-1990s.[citation needed]

Chemistry

LSD, or d-lysergic acid diethylamide, is a semisynthetic alkaloid of the lysergamide family. LSD contains a core structure of lysergic acid, with an N,N-diethylamide functional group bound to RN of the chemical structure. This core polycyclic structure of LSD is an indole derivative and has tryptamine and phenethylamine groups embedded within it.

LSD's structure contains a bicyclic hexahydroindole ring fused to a bicyclic quinoline group (lysergic acid). At carbon 8 of the quinoline an N, generally 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.[27]

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.

In terms of its physical properties, LSD is sensitive to oxygen, ultraviolet light, and chlorine (especially in solution)[28]. 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). In one study, there was a 10% loss of potency after LSD was kept at room temperature for one month.[29] However, there are also many anecdotal reports from users who have successfully stored LSD at room temperature for years which contradict the findings of this study.

Pharmacology

Further information: Serotonergic psychedelic
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.[30]

LSD acts as a 5-HT1A, 5-HT1A, 5-HT2A, 5-HT2B, 5-HT2C and 5-HT6 receptor partial agonist.[31][32] LSD binds to most serotonin receptor subtypes except for 5-HT3 and 5-HT4. 5-HT5B receptors, which have not been found in humans, also have a high affinity for LSD.[33] The psychedelic effects are thought to come from LSD's efficacy at the 5-HT2A receptors.[34]

LSD also possesses efficacy at all dopamine and all adrenoreceptors. Most serotonergic psychedelics are not significantly dopaminergic, so LSD is therefore rather unique in this regard. LSD's agonism of D2 receptors has been shown to contribute to its psychoactivity.[35][36]

However, the role of these interactions and how they result in the psychedelic experience continues to remain the subject of ongoing scientific inquiry.

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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 receptors for dopamine and norepinephrine.

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed 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 and are more likely to induce a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include injury or death.

Physical effects
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Visual effects
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Cognitive effects
User.svg

Multi-sensory effects
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Transpersonal effects
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Experience reports

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


Additional experience reports can be found here:

Combinations

  • Cannabis - When used in combination with cannabis, both the sensory and cognitive effects of LSD become intensified and extended with exceptional efficiency. This should be used with extreme caution, particularly if one is not experienced with psychedelics, as this combination has been well-observed to amplify the anxiety, confusion and psychosis inducing aspects of both substances significantly. It is often reported that being under the influence of psychedelics temporarily reduces one's cannabis tolerance to subjectively baseline levels. Those who choose to use this combination are advised to start off with only a fraction of their usual cannabis dose and take at least 20-minute breaks between hits in order to avoid spiralling negative reactions.
  • Dissociatives - When used in combination with dissociatives, the dissociative, cognitive, visuals and general hallucinatory effects become greatly enhanced. Dissociative-induced holes, spaces, and voids while under the influence of LSD have significantly more vivid visuals than dissociatives alone, as well as more intense internal hallucinations, and corresponding confusion which can spontaneously manifest as delusions and psychosis.
  • MDMA - When combined with MDMA, the physical, cognitive, and euphoric effects of MDMA become amplified. The visual, physical and cognitive effects of LSD can also be intensified to the point of overwhelming euphoric pleasure manifested through uniquely pleasurable body highs, headspaces, and uniquely colorful and intricate visuals. The synergy between these substances is unpredictable, and it is advised to start with markedly lower dosages than one would take for both substances individually. Additionally, users should be aware that there are reasons to believe that this combination may result in unforeseen neurotoxic effects, so a strong sense of caution and independent research are highly advised if one decides to experiment with this combination.[citation needed]
  • Alcohol - This interaction is not typically recommended due to alcohol’s ability to cause dehydration and nausea and physical fatigue which can negatively affect a trip if taken in moderate to high dosages. This combination is, however, reasonably safe in low doses and can often "take the edge off" a trip as well as dull its psychedelic effects in a fashion somewhat similar to benzodiazepines, albeit in a more physically draining way.
  • Benzodiazepines - When used in combination with benzodiazepines, benzodiazepines can, depending on the dosage, slightly to completely reduce the intensity of the cognitive, physical and visual effects of an LSD trip. They are very efficient at stopping "bad trips" at the cost of amnesia and reduced trip intensity. Caution is advised when acquiring them for this purpose due to the very high addictive potential that benzodiazepines possess.
  • Psychedelics - When used in combination with other psychedelics, each substance's physical, cognitive and visual effects intensify and synergize strongly. The synergy between those substances is unpredictable, and for this reason generally not advised. If choosing to combine psychedelics, it is recommended to start with significantly lower dosages than one would take for either substance individually.

Forms and mimics

Forms

Blotters of LSD

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 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.[39]
  • 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.

Mimics ("Fake acid")

LSD has been noted for being unusually potent among psychedelic substances, displaying activity starting from just 15-30 micrograms (µg).[40] 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 may be attributed to the major differences in cost, ease of synthesis, and black-market connections required to produce these compounds as well as the general inability of inexperienced users to tell the difference.

It should be noted that while pure LSD is theoretically almost completely tasteless,[citation needed] the blotter paper it is laid on can impart a mildly bitter taste if it contains any ink. Mimics are often described as having a marked "metallic", "numbing", "chemical-like" or "extremely bitter or sour" taste. It is advised to immediately spit out any blotters of "acid" if they are found to have a distinct, persisting taste.

However, the taste test alone is not enough to maximize user safety. One should always test each tab of purported LSD that they plan to take using a reagent test kit. This is vital as mimics are considerably less predictable and can pose severe health risks (including possible death) that LSD does not.[citation needed]

Common mimics

25I-NBOMe, which has been attributed to several deaths,[41][42][43][44] may commonly be mistaken for LSD by sellers and users.[45]

Research

Alcoholism

Some studies in the 1960s that used LSD to treat alcoholism resulted in reduced levels of alcohol misuse in almost 60% of those treated, an effect which lasted six months but disappeared after a year.[38][46][47][48][49] 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.[38]

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.[50]

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 reported 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. Researcher Peter Goadsby describes the headaches as "worse than natural childbirth or even amputation without anesthetic."[citation needed]

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 ergolines 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.[51]

Unlike the use of LSD or MDMA in psychotherapy, this research involves non-psychological effects and often sub-psychedelic dosages.[52][53]

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.[54][55]

Toxicity and harm potential

Radar plot showing relative physical harm, social harm, and dependence of LSD[56]

LSD is considered to be non-addictive, is not known to cause brain damage, and has an extremely low toxicity relative to dose.[57]

As with most other psychedelic substances, there are very few physical side effects associated with acute LSD exposure. Various studies have shown that in reasonable doses in a sufficiently prepared context, it is very unlike to present negative physical, cognitive, psychiatric or other toxic consequences.

However, it has been postulated that it can act as a potential trigger for those with underlying psychiatric conditions, so those with a family history of mental illness are generally advised not to use this substance.

Lethal dosage

The median lethal dose or dosage at which 50% of participants die (LD50) for human beings has never been reached in any setting and is predicted to be roughly 12,000 micrograms, based on studies involving rats whereas the active dosage is between 100 and 500 micrograms.[citation needed]

This means that assuming a person has unusually potent tabs, each of which is 200 micrograms in strength, they would have to consume at least 60 of them to reach a potentially lethal dosage. Today, the average tab of LSD found through street dealers is perhaps 75 micrograms or less in strength.[citation needed]

Nevertheless, despite its lack of physical toxicity, it is strongly recommended that one uses harm reduction practices when using this substance.

Tolerance and addiction potential

LSD is not habit-forming and the desire to use it can actually decrease with use. As with most psychedelics, it is generally considered to have a built-in, self-regulating aspect to it, though cases of dependence and addiction have been documented in the scientific literature.[citation needed] Notably, there is virtually no withdrawal syndrome when the chronic use of this substance is ceased.[58]

Tolerance to the effects of LSD is built almost immediately after ingestion. After that, it takes about 5-7 days for the tolerance to be reduced to half and 14 days to be back at baseline (in the absence of further consumption). LSD presents cross-tolerance with all psychedelics, meaning that after the use of LSD all psychedelics will have a reduced effect.

Dangerous interactions

Although many substances are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be relatively harmless in low doses of each but can still increase the risk of unpredictable injury or death. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.

  • Lithium - Individuals who take lithium for bipolar disorder or other psychiatric conditions should not take LSD. There are numerous anecdotal reports of seizures and or psychosis from this combination.[59][60][61][62]
  • Stimulants - Combining stimulants with psychedelics may induce states of uncontrollable anxiety, over-stimulation, thought loops, and increase the risk of psychosis.[63]
  • Tramadol - Tramadol is known to lower the seizure threshold[64] and psychedelics are believed to be potential triggers for seizures, particularly in those who are predisposed to them.[65][66][67]

Legal status

  • International - 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 do in practice.[68]
  • Canada - LSD is a Schedule III drug.[69]
  • United Kingdom - LSD is a Class A drug.[70]
  • United States - LSD is a Schedule I drug.[71]
  • Latvia - LSD is a Schedule I drug.[72]

See also

External links

Psychedelic Research Institutions

Literature

References

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  2. Nichols, D. E. (2016). Psychedelics, (April), 264–355. https://doi.org/10.1124/pr.115.011478
  3. Hofmann, A., & Ott, J. (1980). LSD: My Problem Child. McGraw-Hill.
  4. Henderson and Glass, “Introduction,” p. 3; Goodman and Gilman, p. 554.8 Joseph L. Zentner, “The Recreational Use of LSD-25 and Drug Prohibition,” Journal of Psychedelic Drugs, Vol. 8 (No. 4), Oct.-Dec. 1976, p. 301.
  5. Project MK-ULTRA - The CIA's Program of Research in Behavioral Modification, Washington, DC, Government Printing Office, August 31, 1977. http://publicintelligence.net/ssci-mkultra-1977
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  7. UN General Assembly, 1971 Convention on Psychotropic Substances, 9 December 1975, A/RES/3443
  8. Greiner T, Burch NR, Edelberg R (1958). "Psychopathology and psychophysiology of minimal LSD-25 dosage; a preliminary dosage-response spectrum". AMA Arch Neurol Psychiatry. 79 (2): 208–10. PMID 13497365. https://doi.org/10.1001/archneurpsyc.1958.02340020088016
  9. Thompson, H. S. (2012). Fear and Loathing: On the Campaign Trail '72. New York: Simon & Schuster Paperbacks. “Jesus man! You don't look for acid! Acid finds you when *it* thinks you're ready.”
  10. 09) Henderson and Glass, Introduction, p. 4; Goodman and Gilman, p. 554; Daniel X. Freedman, A Psychiatrist Looks at LSD, Federal Probation, June 1968, pp. 20, 22.
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  19. Hofmann, A., & Ott, J. (1980). LSD: My Problem Child. McGraw-Hill.
  20. Hofmann, A., & Ott, J. (1980). LSD: My Problem Child. McGraw-Hill.
  21. Project MK-ULTRA - The CIA's Program of Research in Behavioral Modification, Washington, DC, Government Printing Office, August 31, 1977. http://publicintelligence.net/ssci-mkultra-1977
  22. "LSD: cultural revolution and medical advances". Royal Society of Chemistry. Retrieved September 27, 2007.
  23. https://web.archive.org/web/20100201234435/http://pages.cthome.net/tobelman/The_Out-Of-Sight_SMiLE_Site.html |Out-Of-Sight! SMiLE Timeline
  24. L. R. Veysey, The Communal Experience: Anarchist and Mystical Communities in Twentieth-Century America (Chicago IL, University of Chicago Press, 1978), ISBN 0-226-85458-2, p. 437.
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  28. Entry #26 LSD-25 from TiHKAL by Alexander & Ann Shulgin | http://www.erowid.org/library/books_online/tihkal/tihkal26.shtml
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  39. Long LSD Prison Terms--It's All in the Packaging | http://articles.latimes.com/1992-07-27/news/mn-4335_1_prison-term
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