Indoleamine and the phenethylamine hallucinogens: mechanisms of psychotomimetic action

Psychedelic hallucinogens fall into three chemical groups: ergolines (e.g., LSD), simple indoleamines (e.g., DMT and psilocybin), and ring-substituted phenethylamines (e.g., mescaline). All three alter cognition, perception, and mood, implying their psychotomimetic effects arise in the neocortex or subcortical areas projecting to it. Evidence suggests that both indoleamine and phenethylamine hallucinogens bind to the 5-HT2A serotonin receptor, and activation of this receptor mediates their psychotomimetic effects. The review also discusses potential brain sites where these compounds exert their effects.

Study at a glance

Abstract

The psychedelic hallucinogens are comprised of three different groups of compounds according to Ž . Ž . their chemical structure Fig. 1 : 1 the ergolines Ž which contain an indole moiety e.g. lysergic acid . Ž . diethylamide, LSD ; 2 simple indoleamine hallucinoŽ gens e.g. N,N-dimethyltryptamine, DMT and psilocy. bin which share an indoleamine structure with the Ž endogenous neurotransmitter 5-hydroxytryptamine 5. Ž . HT, serotonin ; and 3 the ring-substituted phenethŽ . ylamine hallucinogens e.g. mescaline . One of the outstanding features of ergoline, indoleamine, and phenethylamine hallucinogens is that they alter all cortical functions including cognition, perception, and mood. This implies that the sites mediating the psychotomimetic effects of these hallucinogens are located in the neocortex or in subcortical areas with efferent projections throughout the neocortex. This review will consider evidence suggesting that both the indoleamine and phenethylamine hallucinogens bind to a common neurotransmitter receptor in the brain, Ž . the 5-hydroxytryptamine 5-HT receptor, and 2A 2A that subsequent activation of this serotonin receptor mediates the psychotomimetic effects of these halluciŽ . nogens. We will also discuss potential site s in the brain at which the hallucinogens exert their psychotomimetic effects.