Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD)
This literature review (2018) of the history of LSD looks back at the research that has been done after its (somewhat) accidental discovery in 1943 by Albert Hofmann.
Abstract
Lysergic acid diethylamide (LSD) is one of the most potent psychoactive agents known, producing dramatic alterations of consciousness after submilligram (≥20 μg) oral doses. Following the accidental discovery of its potent psychoactive effects in 1943, it was supplied by Sandoz Laboratories as an experimental drug that might be useful as an adjunct for psychotherapy, or to give psychiatrists insight into the mental processes in their patients. The finding of serotonin in the mammalian brain in 1953, and its structural resemblance to LSD, quickly led to ideas that serotonin in the brain might be involved in mental disorders, initiating rapid research interest in the neurochemistry of serotonin. LSD proved to be physiologically very safe and nonaddictive, with a very low incidence of adverse events when used in controlled experiments. Widely hailed by psychiatry as a breakthrough in the 1950s and early 1960s, clinical research with LSD ended by about 1970, when it was formally placed into Schedule 1 of the Controlled Substances Act of 1970 following its growing popularity as a recreational drug. Within the past 5 years, clinical research with LSD has begun in Europe, but there has been none in the United States. LSD is proving to be a powerful tool to help understand brain dynamics when combined with modern brain imaging methods. It remains to be seen whether therapeutic value for LSD can be confirmed in controlled clinical trials, but promising results have been obtained in small pilot trials of depression, anxiety, and addictions using psilocybin, a related psychedelic molecule.
Research Summary of 'Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD)'
Introduction
Nichols opens with a historical and scientific portrait of lysergic acid diethylamide (LSD), noting its synthesis by Albert Hofmann in 1938 and the accidental discovery of its powerful psychoactive effects in 1943. Early clinical observations established LSD as unusually potent (active in the submilligram range), with oral human effects beginning around 30 minutes, peaking at roughly 1.5 hours, and often returning to baseline by about 8 hours. The compound was distributed by Sandoz for experimental psychiatric use in the 1950s and 1960s and stimulated rapid interest in serotonin neurochemistry because of structural similarities between LSD and serotonin. This review sets out to summarise what is known about LSD from multiple perspectives: clinical history, therapeutic approaches used in mid-20th-century psychiatry, human experimental studies (including recent work), medicinal chemistry and synthesis, pharmacokinetics and metabolism, receptor pharmacology and structure–activity relationships, and modern neuroimaging studies that probe LSD’s effects on brain dynamics. Nichols stresses both LSD’s scientific importance as a tool for understanding brain function and the unresolved question of whether it will have confirmed therapeutic value in controlled contemporary trials.
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Nichols, D. E. (2018). Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD). ACS Chemical Neuroscience, 9(10), 2331-2343. https://doi.org/10.1021/acschemneuro.8b00043
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