Medicinal Chemistry & Drug DevelopmentMDMAPsilocybinDMTLSD

The behavioral pharmacology of hallucinogens

This review (2007) discusses the behavioural pharmacology of phenethylamine (MDMA), tryptamine (psilocybin, DMT), and ergoline (LSD) hallucinogens.

Authors

  • Fantegrossi, W. E.
  • Murnane, K. S.
  • Reissig, C. J.

Published

Biochemical Pharmacology
meta Study

Abstract

Until very recently, comparatively few scientists were studying hallucinogenic drugs. Nevertheless, selective antagonists are available for relevant serotonergic receptors, the majority of which have now been cloned, allowing for reasonably thorough pharmacological investigation. Animal models sensitive to the behavioral effects of the hallucinogens have been established and exploited. Sophisticated genetic techniques have enabled the development of mutant mice, which have proven useful in the study of hallucinogens. The capacity to study post-receptor signaling events has lead to the proposal of a plausible mechanism of action for these compounds. The tools currently available to study the hallucinogens are thus more plentiful and scientifically advanced than were those accessible to earlier researchers studying the opioids, benzodiazepines, cholinergics, or other centrally active compounds. The behavioral pharmacology of phenethylamine, tryptamine, and ergoline hallucinogens are described in this review, paying particular attention to important structure activity relationships which have emerged, receptors involved in their various actions, effects on conditioned and unconditioned behaviors, and in some cases, human psychopharmacology. As clinical interest in the therapeutic potential of these compounds is once again beginning to emerge, it is important to recognize the wealth of data derived from controlled preclinical studies on these compounds.

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Research Summary of 'The behavioral pharmacology of hallucinogens'

Introduction

Fantegrossi and colleagues frame this review by noting that although substances that alter perception have long histories of human use, modern scientific study of classic hallucinogens contracted after the 1960s and has only recently begun to revive. The authors restrict their focus to three prototypical classes — phenethylamines (mescaline-like), tryptamines (psilocybin-like) and ergolines (LSD-like) — and emphasise that a convergent body of preclinical and some clinical work now implicates 5-HT2A receptor agonism as a central molecular initiation point for the characteristic effects of these drugs. They also acknowledge conceptual and terminological controversies (for example over the label "hallucinogen") and stress that a range of pharmacologies exist under that rubric, so their review concentrates on compounds sharing 5-HT2A-mediated actions. The paper sets out to synthesise behavioural pharmacology, structure–activity relationships, receptor pharmacology, results from animal models (conditioned and unconditioned behaviours), and selected human findings to chart recent advances and remaining uncertainties. Fantegrossi and colleagues highlight new experimental tools — selective receptor antagonists, cloned receptor subtypes, genetic mouse models and signalling studies — that have permitted more mechanistic investigations than were possible in earlier eras of research, and they aim to show how these tools have clarified (and complicated) understanding of hallucinogen action.

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Study Details

References (9)

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