Anxiety DisordersTreatment-Resistant Depression (TRD)Depressive DisordersSubstance Use Disorders (SUD)LSDPsilocybin

Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety, and substance-use disorders: a systematic review of systematic reviews

This expert review (2018) of systematic reviews concludes that the research into psychedelics is promising but needs bigger samples and longer duration studies.

Authors

  • Jamie Hallak
  • Rafael dos Santos
  • José Carlos Bouso

Published

Expert Review of Clinical Pharmacology
meta Study

Abstract

Introduction: Mood, anxiety, and substance-use disorders are among the most prevalent psychiatric disorders in the population. Although several pharmacological treatments are available, they are not effective for a significant proportion of patients and are associated with several adverse reactions. Therefore, new treatments should be explored. Recent studies suggest that serotonergic hallucinogens/psychedelics including ayahuasca, psilocybin, and lysergic acid diethylamide (LSD) have anxiolytic, antidepressive, and antiaddictive effects.Areas Covered: A systematic review of systematic reviews assessing the efficacy, safety, and tolerability of serotonergic hallucinogens/psychedelic was performed using the PubMed data base until 11 April 2018. Systematic reviews with or without meta-analysis were analyzed, but only reviews that described at least one randomized controlled trial (RCT) were included.Expert Commentary: Psilocybin and LSD reduced anxiety and depression in cancer patients and symptoms of alcohol and tobacco dependence, and ayahuasca reduced depression symptoms in treatment-resistant depression. Although the results are promising, several studies were open-label, and only few were RCTs, and most had small sample sizes and short duration. Single or few doses of these drugs seem to be well-tolerated, but long-term studies are lacking. New RCTs with bigger samples and longer duration are needed to replicate these findings.

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Research Summary of 'Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety, and substance-use disorders: a systematic review of systematic reviews'

Introduction

Mood, anxiety, and substance-use disorders contribute substantially to the global burden of disease and remain inadequately treated for many patients. Dos Santos and colleagues note that existing pharmacotherapies often produce incomplete responses and problematic adverse effects, while few novel agents have emerged in recent decades. Against this backdrop there has been renewed interest in serotonergic (classical) psychedelics — including LSD, psilocybin, DMT/ayahuasca and mescaline — which act primarily as 5-HT2A receptor agonists and are hypothesised to increase cortical glutamate release, neuroplasticity (for example via BDNF expression), and large-scale changes in functional connectivity (reduced default mode network activity, altered amygdala responses) that may underlie anxiolytic, antidepressant and antiaddictive effects. This paper reports a systematic review of systematic reviews that sought to summarise the clinical evidence available up to 11 April 2018 for the efficacy, tolerability, and safety of serotonergic psychedelics in mood, anxiety and substance-use disorders. The stated aim was to collate and appraise prior systematic reviews (with or without meta-analysis) that included at least one randomised controlled trial (RCT), and to describe therapeutic findings alongside safety and methodological quality of those reviews.

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