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Jacobs BI, Heym J, Rasmussen K.
“Action of Hallucinogenic Drugs at Postsynaptic Serotonergic Receptors”.
Psychopharmacology Bulletin. 1982;18(3):168-172.
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Abstract
Hallucinogenic drugs such as LSD, psilocin, 2,5-dimethoxy-4-methylamphetamine (DOM), mescaline, and N,N-dimethyltryptamine (DMT) appear to constitute a distinct drug class based on their similar phenomenological effects in humans and the fact that cross-tolerance can be demonstrated between many of them. Theories regarding the mechanism of action of these drugs have gone through several distinct phases, all of them focusing on the role of serotonin. In the initial phase, in the mid-1950s, LSD was hypothesized to exert its psychological actions by blocking serotonin's synaptic effect. These conclusions, however, were based exclusively on pharmacological studies of LSD's action in the periphery, and were soon criticized. Following this, in the early 1960s, the emphasis shifted to an effect upon serotonin in the central nervous system (CNS), but without regard to the precise site of action, i.e. presynaptic or postsynaptic. In the mid-1960s, studies employing fluorescence histochemistry delineated the localization of serotonin-containing neurons within the CNS, their projection pathways, and their axon terminal distribution. This information provided the foundation for theories inthe 1970s which proposed that the effects of LSD and related hallucinogens were mediated specifically by an action upon the cell bodies of serotonergic neurons (hereafter referred to as the "presynaptic" effect). Finally, in the fourth phase, emphasis has switched to the action of the hallucinogenic drugs directly upon the target neurons of serotonergic projections (hereafter referred to as the "postsynaptic" effect). The data supporting this latest concept, which have been gathered primarily within the last few years, will be the subject of this brief review.
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