StatPearls
D-lysergic acid diethylamide, or LSD, is a compound of the lysergamide class known for its powerful psychedelic effects on humans. Although first synthesized in 1938 by Albert Hofmann in an attempt to create a central nervous system stimulant, it was not until 1943 when Hofmann discovered the molecule’s subjective effects on the human body after accidental absorption through the skin. Only a few days later, on the 19 of April 1943, reports suggest Hofmann ingested around 250 micrograms of the drug, marking the very first intentional “LSD trip.” While Hofmann, and countless others afterward, who report ingesting the drug at various dosages, indicate a wide variety of effects, a common denominator of sorts is the absolute profundity of the experience that the drug seems to elicit in users. A substance of significant pharmacological and clinical interest, LSD remains the most researched hallucinogen. It was famously examined by the CIA in the 1950s when the research program MK-ULTRA was implemented to investigate potential methods and pharmacological agents to aid in the development of “truth serums.” Further research centered on the substance’s mechanism of action in the body was conducted, and the early belief that it had serotonergic properties were eventually confirmed. Specifically, the drug acts as a partial agonist at the 5-HT1A, 5-HT2A, 5-HT2B, 5-HT2C, and 5-HT6 receptors. The threshold dose of LSD is commonly accepted to be 15 micrograms, while a relatively heavy dose at the opposite end of the accepted spectrum is around 300 micrograms. As the dosage increases beyond this arbitrary setpoint, reports suggest an increase in the intensity of the drug’s effects. This dosing brings up an all-important question that applies to any substance under scrutiny pharmacologically speaking, what is the drug’s toxicity Interestingly, in the case of LSD, no deaths can be attributed to its direct effects.