A Brief Historical Overview of Psychedelic Research

Classical serotonergic psychedelics such as lysergic acid diethylamide or the naturally occurring compounds psilocybin and mescaline produce profound changes in mood, thought, intuition, sensory perception, the experience of time and space, and even the experience of self. Research examining psychedelic compounds has had a complex and turbulent evolution. Many cultures throughout the world have used psychedelic plants not only for mystical, ritualistic, or divinatory purposes but also for curing illnesses. Much of the genesis and progress of modern investigations into the effects and underlying mechanisms of action of psychedelics have been intertwined with studies of the neurotransmitter serotonin. Early hypotheses that serotonergic systems mediate psychedelic effects were supported initially by preclinical animal studies and subsequently confirmed by pharmacological studies in healthy humans. The use of psychedelic compounds as putative psychotomimetics that reproduce some features of naturally occurring psychotic disorders met with some limited success. More recent studies are exploring psychedelics as potential psychotherapeutic agents. Recent indications that even 1 or 2 psychedelic treatments produce robust and sustained reductions in clinical symptoms in a variety of psychiatric disorders have prompted an enormous resurgence of interest in the nature and mechanisms contributing to their effects.