Substance Use Disorders (SUD)LSDPsilocybinMescaline

Recent advances in the neuropsychopharmacology of serotonergic hallucinogens

This study (2015) reviews the evidence on the neuropsychopharmacology of such substances as LSD, psilocybin, and mescaline.

Authors

  • Adam Halberstadt

Published

Behavioural Brain Research
meta Study

Abstract

Serotonergic hallucinogens, such as (+)-lysergic acid diethylamide, psilocybin, and mescaline, are somewhat enigmatic substances. Although these drugs are derived from multiple chemical families, they all produce remarkably similar effects in animals and humans, and they show cross-tolerance. This article reviews the evidence demonstrating the serotonin 5-HT2A receptor is the primary site of hallucinogen action. The 5-HT2A receptor is responsible for mediating the effects of hallucinogens in human subjects, as well as in animal behavioral paradigms such as drug discrimination, head twitch response, prepulse inhibition of startle, exploratory behavior, and interval timing. Many recent clinical trials have yielded important new findings regarding the psychopharmacology of these substances. Furthermore, the use of modern imaging and electrophysiological techniques is beginning to help unravel how hallucinogens work in the brain. Evidence is also emerging that hallucinogens may possess therapeutic efficacy.

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Research Summary of 'Recent advances in the neuropsychopharmacology of serotonergic hallucinogens'

Introduction

Serotonergic hallucinogens — encompassing two main structural classes, the phenylalkylamines and the indoleamines — produce profound alterations in perception, thought, and mood and have been used by humans for thousands of years, though scientific investigation began only in the late nineteenth century. Defining hallucinogens as a pharmacological class proved contentious: standard definitions based on altered consciousness without delirium or addiction were insufficiently specific, leading to the proposal that, in addition to these properties, hallucinogens should bind to the 5-HT2A receptor and produce full substitution for the prototypical agent DOM in drug discrimination paradigms. Despite their structural heterogeneity, phenylalkylamine and indoleamine hallucinogens produce virtually indistinguishable subjective effects, show cross-tolerance with one another, and share a unifying pharmacological mechanism through 5-HT2A receptor activation. This review aimed to synthesise advances in understanding the neuropsychopharmacology of serotonergic hallucinogens, covering receptor pharmacology, validated animal behavioural models, tolerance and cross-tolerance, evidence from human experimental studies, and the role of the prefrontal cortex and its interactions with subcortical structures as a primary site of hallucinogenic drug action.

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Study Details

References (33)

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