Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents.

The hallucinogenic potency of psychoactive agents, including LSD and related compounds, is closely linked to their ability to bind to 5-HT2 receptors in the brain. Binding affinities for 5-HT2 sites strongly correlated with both behavioral effects in animals (r = 0.938) and hallucinogenic potency in humans (r = 0.924). These findings indicate that activation of 5-HT2 receptors is a key mechanism underlying the hallucinogenic effects of these substances.

Study at a glance

Abstract

The affinities (Ki values) of twenty two psycho-active agents, including LSD, 5-OMe DMT and a series of phenalkylamine derivatives, for cortical 5-HT1 and 5-HT2 binding sites were compared with two measures of behavioral activity. It was found that a significant correlation (r = 0.938) exists between the 5-HT2 binding affinities of these agents and their ED50 values as determined in tests of stimulus generalization using 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) as the training drug. Furthermore, for fifteen of these agents where human data were available, a significant correlation (r = 0.924) also exists between 5-HT2 binding affinities and their human hallucinogenic potencies. The results of this study suggest that the mechanism of action of these agents involves 5-HT2-related events.