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Lysergic acid diethylamide (LSD),[a] also known colloquially as acid, is a psychedelic drug.[11] Effects typically include intensified thoughts, emotions, and sensory perception.[12] At sufficiently high dosages LSD manifests primarily visual, as well as auditory, hallucinations.[13][14] Dilated pupils, increased blood pressure, and increased body temperature are typical.[15] Since LSD binds to dopamine receptors in addition to serotonin receptors its effects are also more energetic and fast paced compared to psychedelics such as psilocybin, which is not a dopamine agonist.[16] Effects typically begin within half an hour and can last for up to 20 hours.[15][17] LSD is also capable of occasioning mystical experiences and ego disillusion, albeit less frequently than compounds such as psilocybin.[18][14] It is used mainly as a recreational drug or for spiritual reasons.[15][19] LSD is both the prototypical psychedelic and one of the ‘classical’ psychedelics, being the psychedelics with the greatest scientific and cultural significance.[11]

LSD is considered to be non-addictive with low potential for abuse.[20][21] There are no recorded successful attempts to train animals to self-administer LSD in laboratory settings.[21] Frequent use rapidly builds tolerance, requiring exponentially larger doses to feel an effect. Adverse psychological reactions are possible, such as anxiety, paranoia, and delusions.[7] It is possible for LSD to induce either intermittent or chronic visual hallucinations, in spite of no further use, in some individuals, typically in the absence of the psychological effects associated with LSD. Common effects include visual snow and palinopsia. In cases where this causes distress or impairment it is diagnosed as hallucinogen persisting perception disorder (HPPD).[22][23] While overdose from LSD is unknown, despite there being various case studies of individuals taking extremely high dosages,[11] LSD can cause injury and death as a result of accidents stemming from psychological impairment.[15][11] The effects of LSD are thought to stem primarily from it being an agonist at the 5-HT2A receptor.[21][7][11] While the exact nature of how LSD exerts its effects via this receptor is still unknown, reduced default mode network activity causing a corresponding increase in global functional connectivity,[24][25][26] as well as increased glutamatergic transmission,[11] are likely primary underlying mechanisms. LSD is exceptionally potent, with as little as 20 μg capable of producing a noticeable effect.[15] In pure form, LSD is clear or white in color, has no smell, and is crystalline.[12] It breaks down with exposure to ultraviolet light.[15]

As of 2017, about 10% of people in the United States have used LSD at some point in their lives, while 0.7% have used it in the last year.[27] It was most popular in the 1960s to 1980s.[15] The use of LSD among US adults increased 56.4% from 2015 to 2018.[28] LSD is typically either swallowed or held under the tongue.[12] It is most often sold on blotter paper and less commonly as tablets or in gelatin squares.[15]

LSD was first synthesized by Swiss chemist Albert Hofmann in 1938 from lysergic acid, a chemical derived from the hydrolysis of ergotamine, an alkaloid found in ergot, a fungus that infects primarily rye among other grains.[15][22] LSD was one of various lysergamides Hofmann synthesized from lysergic acid while working for Sandoz in Basel, Switzerland while trying to develop a new respiratory stimulant. Hofmann discovered its effects in humans in 1943, after somehow unintentionally ingesting the substance, possibly absorbing it through his skin.[29][30][31] LSD was subject to exceptional interest within the field of psychiatry in the 1950s and early 1960s, with Sandoz distributing LSD to researchers under the trademark name Delysid in an attempt to find a marketable use for it.[30] LSD was initially believed to mimic schizophrenia, being classified as a ‘psychotomimetic’, and as a result was viewed as a tool to better understand how schizophrenia changes cognition subjectively. The fact that dopamine and mescaline are chemically similar – since they are both phenethylamines – combined with the high potency of LSD also gave rise to the theory that schizophrenia was caused by an endogenously produced hallucinogenic substance in small enough quantities to remain undetected.[30] However, the psychotomimetic model was eventually abandoned due to its reported ability to induce transcendental experiences with lasting psychological benefit – in contrast to schizophrenia. A medical use for this property was pioneered in the form of LSD-assisted psychotherapy by psychiatrists such as Humphry Osmond, with promising results in areas such as alcoholism,[32][30][33][34] resulting in Osmond coining the term ‘psychedelic’ (lit. mind manifesting) as a term for LSD and mescaline to replace ‘psychotomimetic’. During this time, the Central Intelligence Agency (CIA) was interested in LSD as an addition to its preexisting research into using psychoactive substances to aid interrogation under Project MKUltra, although the CIA eventually ceased research into this in favor of the possibility of giving LSD to world leaders so that they would discredit themselves under its influence, resulting in the CIA administering LSD to unwitting test subjects in order to observe how they would react, one of the most well known examples of this being Operation Midnight Climax.[30] LSD was one of several psychoactive substances evaluated by the U.S. Army Chemical Corps as possible non-lethal incapacitants at the Edgewood Arsenal in Maryland; some of these tests were also conducted on humans.[30]

In the 1960s LSD and other psychedelics were adopted by, and became synonymous with, the counterculture movement due to their perceived ability to ‘expand consciousness’, resulting in LSD being viewed as a cultural threat to American values and the Vietnam war effort and being designated as a Schedule I substance in 1968.[35] It was listed as a schedule 1 controlled substance by the United Nations in 1971[15] and currently has no approved medical uses.[15] In November 2020, a referendum determined that it would be decriminalized in the US state of Oregon.[36]

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