Hallucinogenic drug research--if so, so what? Symposium summary and commentary.

Abstract

The conference brought a critical focus both on older findings and new strategies in hallucinogenic drug research as well as on behavioral and electrophysiologic tools that correlate with neurobehavioral and neurochemical events. A number of unsolved problems to be investigated were noted. The sensitizing effects of both mescaline and LSD on other inputs at motor nuclei or at limbic sites, and effects on afferent processes were examples of important new directions as were drug discrimination tests that can determine the relative roles of aminergic systems in drug effect. Fixed ratio operant schedules can differentiate serotonin blocking agents, detect active indole psychotomimetics and demonstrate temporal and tolerance parameters relevant to drug induced neurochemical changes. Data and critique as well as pharmacokinetics no longer support the presynaptic-disinhibition model of LSD effects, nor is LSD induced "slowed turnover" of serotonin seen as an accurate description of neurochemical changes. The distinct nerve ending biochemical changes after LSD are reviewed. Subcellular compartmental analyses require a radical revision of the picture of the ratio in the nerve ending of cytoplasmic and vesicular amine as well as factors normally regulating accessibility of amine to intraneuronal MAO.