Lysergic Acid Diethylamide Toxicity

D-lysergic acid diethylamide (LSD) is an indolamine compound of the lysergamide class known for having 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, reports suggested Hofmann ingested around 250 μg of the drug, marking the first intentional “LSD trip.” Hofmann and numerous subsequent individuals, having consumed the drug at different dosages, describe a diverse range of effects. However, a shared element is the profound nature of the experience elicited by the drug in users. A substance of significant pharmacological and clinical interest, LSD was historically the most researched hallucinogen. In the 1950s, the Central Intelligence Agency famously studied LSD through the research program MK-ULTRA to investigate potential methods and pharmacological agents for developing “truth serums.” Researchers conducted additional studies on the substance’s mechanism of action, ultimately confirming the early belief that it possessed serotonergic properties. 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 at 15 μg. A relatively heavy dose at the opposite end of the accepted spectrum is around 300 μg. As the dosage increases beyond this arbitrary setpoint, reports suggest an increase in the intensity of the drug’s effects. This dosing brings an all-important question that applies to any substance under scrutiny: pharmacologically speaking, what is the drug’s toxicity? No deaths have been attributed to LSD’s direct effects. Researchers in the last century conducted studies on the therapeutic use of LSD under experimental conditions that today’s standards consider insufficient.