Anxiety DisordersDepressive DisordersSubstance Use Disorders (SUD)Ayahuasca

Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies

This review (2016) examines studies on the mental health effects of ayahuasca, harmine, and harmaline within humans and animals, and shows consistent evidence for its antidepressant and anxiolytic (anxiety) effects.

Authors

  • Jamie Hallak
  • Rafael dos Santos
  • Jaime Crippa

Published

brazilian Journal of Psychiatry
meta Study

Abstract

Objective

To conduct a systematic literature review of animal and human studies reporting anxiolytic or antidepressive effects of ayahuasca or some of its isolated alkaloids (dimethyltryptamine, harmine, tetrahydroharmine, and harmaline).

Methods

Papers published until 3 April 2015 were retrieved from the PubMed, LILACS and SciELO databases following a comprehensive search strategy and using a predetermined set of criteria for article selection.

Results

Five hundred and fourteen studies were identified, of which 21 met the established criteria. Studies in animals have shown anxiolytic and antidepressive effects of ayahuasca, harmine, and harmaline, and experimental studies in humans and mental health assessments of experienced ayahuasca consumers also suggest that ayahuasca is associated with reductions in anxiety and depressive symptoms. A pilot study reported rapid antidepressive effects of a single ayahuasca dose in six patients with recurrent depression.

Conclusion

Considering the need for new drugs that produce fewer adverse effects and are more effective in reducing anxiety and depression symptomatology, the described effects of ayahuasca and its alkaloids should be further investigated.

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Research Summary of 'Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies'

Introduction

Ayahuasca is a traditional Amazonian botanical brew made from Banisteriopsis caapi (rich in b‑carbolines such as harmine, tetrahydroharmine and harmaline) and Psychotria viridis (which contains N,N‑dimethyltryptamine, DMT). The b‑carbolines inhibit monoamine oxidase A (MAO‑A), permitting orally administered DMT to reach the systemic circulation and activate 5‑HT1A/2A/2C receptors in frontal and paralimbic brain regions. Apart from ritual and spiritual uses, anecdotal reports and preliminary studies in consumers and patients have suggested potential therapeutic effects of ayahuasca for substance dependence, anxiety and mood disorders, and safety data from acute administration and long‑term consumer assessments have been broadly reassuring. Dos Santos and colleagues therefore conducted a systematic literature review to collate animal and human studies that evaluated anxiolytic or antidepressive effects of ayahuasca and its main alkaloids (DMT, harmine, THH and harmaline). The review aimed to summarise preclinical and clinical evidence up to 3 April 2015 and to identify gaps that warrant further research, particularly given the need for new treatments that are faster‑acting and have favourable adverse‑effect profiles.

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Study Details

References (32)

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Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance

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