Depressive DisordersPTSDNeuroimaging & Brain MeasuresInterpersonal Functioning & Social ConnectednessLSDMDMAKetamineMescalinePsilocybin

Hallucinogens in Mental Health: Preclinical and Clinical Studies on LSD, Psilocybin, MDMA, and Ketamine

This review summarises preclinical and clinical evidence that ketamine, psilocybin, LSD and MDMA have therapeutic potential for psychiatric disorders — with robust support for ketamine in depression, emerging evidence for psilocybin and LSD in treating depression and modulating functional brain connectivity, and MDMA showing efficacy in PTSD. It also delineates the pharmacology and behavioural effects of psychedelic versus non‑psychedelic hallucinogens and entactogens.

Authors

  • Katrin Preller
  • Boris Heifets
  • Gabriella Gobbi

Published

Journal of Neuroscience
meta Study

Abstract

A revamped interest in the study of hallucinogens has recently emerged, especially with regard to their potential application in the treatment of psychiatric disorders. In the last decade, a plethora of preclinical and clinical studies have confirmed the efficacy of ketamine in the treatment of depression. More recently, emerging evidence has pointed out the potential therapeutic properties of psilocybin and LSD, as well as their ability to modulate functional brain connectivity. Moreover, MDMA, a compound belonging to the family of entactogens, has been demonstrated to be useful to treat post-traumatic stress disorders. In this review, the pharmacology of hallucinogenic compounds is summarized by underscoring the differences between psychedelic and nonpsychedelic hallucinogens as well as entactogens, and their behavioral effects in both animals and humans are described. Together, these data substantiate the potentials of these compounds in treating mental diseases.

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Research Summary of 'Hallucinogens in Mental Health: Preclinical and Clinical Studies on LSD, Psilocybin, MDMA, and Ketamine'

Introduction

Psychiatric disorders impose a heavy global burden, and progress in new therapeutic approaches has been slowed by regulatory restrictions that curtailed research on hallucinogens for decades. Since the 2000s there has been a renewed research interest, with two broad pharmacological groupings commonly distinguished: classic serotonergic hallucinogens (psychedelics), which primarily act at 5-HT2A receptors, and dissociative anesthetics such as ketamine, which act principally on glutamatergic systems. Compounds that produce prosocial or entactogenic effects, most notably MDMA, are typically classed separately because their mechanisms and behavioural profiles differ from classic psychedelics. This review by Hibicke and colleagues sets out to summarise preclinical and clinical evidence for LSD, psilocybin, MDMA and ketamine, emphasising pharmacology, behavioural effects in animals and humans, and neuroimaging findings. The authors focus particularly on three domains: (1) effects of psychedelics in rodents and their impact on human brain functional connectivity; (2) preclinical and clinical data on ketamine's antidepressant effects; and (3) the prosocial actions of MDMA and its therapeutic applications, notably in PTSD.

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Study Details

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