Albert Hofmann, a Swiss chemist, first synthesized LSD in 1938 but set it aside. In 1943, he accidentally ingested a small amount and experienced an extremely stimulated imagination. Three days later, on April 19, 1943, he intentionally took 250 micrograms of LSD to verify the effects, then rode his bicycle home—a ride now known as Bicycle Day. LSD was initially hailed as a tool for psychoanalysis and understanding schizophrenia, but in the 1960s figures like Timothy Leary promoted it as a path to spiritual enlightenment.
Lysergic acid diethylamide (LSD) reduces local brain activity and connectivity in sensory and association regions, with effects linked to specific neurotransmitter receptors. In 15 healthy adults, fMRI scans under LSD versus placebo showed decreased amplitude of low-frequency fluctuations (ALFF) in somatosensory, visual, default mode, and frontoparietal networks, and decreased regional homogeneity (ReHo) in sensory and subcortical areas. Test-retest reliability was high for ALFF and moderate for ReHo. LSD-induced changes correlated negatively with densities of D2 and 5-HT1A receptors, suggesting the drug engages neurochemical processes beyond its primary 5-HT2A target. These preliminary results indicate complex, dynamic mechanisms underlying LSD's neural effects.