potent synthetic hallucinogenic (hallucinogen) drug that can be derived from the ergot alkaloids (as ergotamine and ergonovine, principal constituents of ergot, the grain deformity and toxic infectant of flour caused by the fungus Claviceps purpurea). LSD usually is prepared by chemical synthesis in a laboratory. Its basic chemical structure is similar to that of the ergot alkaloids, and it is structurally related to several other drugs (e.g., bufotenine, psilocybin, harmine, and ibogaine), which can all block the action of serotonin (the indole amine transmitter of nerve impulses) in brain tissue.

LSD produces marked deviations from normal behaviour, probably the consequence of its ability to inhibit the action of serotonin, though the mechanism of the drug remains uncertain. LSD was used experimentally in medicine as a psychotomimetic agent to induce mental states that were believed to resemble those of actual psychotic diseases (primarily the schizophrenias (schizophrenia)). After administration, LSD can be absorbed readily from any mucosal surface—even the ear—and acts within 30 to 60 minutes. Its effects usually last for 8 to 10 hours, and occasionally some effects persist for several days. Two serious side effects are the prolongation and transient reappearance of the psychotic reaction.

Since LSD is not an approved drug, its therapeutic applications are regarded as experimental. In the 1960s LSD was proposed for use in the treatment of neuroses, especially for patients who were recalcitrant to more conventional psychotherapeutic procedures. LSD also was tried as a treatment for alcoholism and to reduce the suffering of terminally ill cancer patients. It was studied as an adjunct in the treatment of narcotic addiction, of children with autism, and of the so-called psychopathic personality. None of these uses were successful by the early 1990s, and most researchers concluded that there was no clinical value in the use of LSD. In the early 21st century, however, research into the treatment of alcoholism with LSD was revived, some researchers concluding that it might provide benefits.

The use of LSD outside a clinical setting can be dangerous. Mood shifts, time and space distortions, and impulsive behaviour are especially hazardous complications to an individual who takes the drug. The individual may become increasingly suspicious of the intentions and motives of those around him and may act aggressively against them.

Legitimate use of LSD declined markedly in the mid-1960s. In the United States, manufacture, possession, sale, transfer, and use of LSD came under the restrictions of the drug abuse Control Amendment of 1965. The following year the only authorized manufacturer of LSD in the United States withdrew the drug from the market and transferred its supplies to the federal government. Research projects have continued under the supervision of the National Institute of Mental Health, a governmental agency.

During the 1960s LSD was popular within the hippie subculture that emerged in the United States and western Europe. One critical pioneer in this movement was Augustus Owsley Stanley III, a California-based underground chemist who manufactured several million doses of the drug. Owsley's efforts supplied the drug to several figures who would become advocates for LSD, including novelist Ken Kesey (Kesey, Ken) and Harvard psychologist Timothy Leary (Leary, Timothy) (Owsley also was a personal supplier of LSD to the Grateful Dead (Grateful Dead, the)). During the mid-1960s, LSD (“acid”) spread widely in the emerging counterculture, and the shapes and colours characteristic of LSD-induced trips appear frequently in the visual art of the period. The drug also powerfully shaped the popular music of the 1960s and encouraged the mystical experimentation of these years. LSD retained a youth following into the mid-1970s, when publicity about the drug's psychiatric ill effects slowed usage. Nevertheless, a revival of LSD use occurred in the United States and elsewhere in the 1990s.