Anxiety DisordersDepressive DisordersPTSDDMT

Effects of N, N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression

This rat study with DMT found that it reduced anxiety by extinguishing of cued fear memory and reduces immobility in the forced swim test (a proxy for depression).

Authors

  • Lindsay Cameron
  • Lee Edmunds Dunlap

Published

ACS Chemical Neuroscience
individual Study

Abstract

Depression and anxiety disorders are debilitating diseases resulting in substantial economic costs to society. Traditional antidepressants often take weeks to months to positively affect mood and are ineffective for about 30% of the population. Alternatives, such as ketamine, a dissociative anesthetic capable of producing hallucinations, and the psychoactive tisane ayahuasca, have shown great promise due to their fast-acting nature and effectiveness in treatment-resistant populations. Here, we investigate the effects of N,N-dimethyltryptamine (DMT), the principle hallucinogenic component of ayahuasca, in rodent behavioral assays relevant to anxiety and depression using adult, male, Sprague-Dawley rats. We find that while DMT elicits initial anxiogenic responses in several of these paradigms, its long-lasting effects tend to reduce anxiety by facilitating the extinction of cued fear memory. Furthermore, DMT reduces immobility in the forced swim test, which is a characteristic behavioral response induced by many antidepressants. Our results demonstrate that DMT produces antidepressant and anxiolytic behavioral effects in rodents, warranting further investigation of ayahuasca and classical psychedelics as treatments for depression and post-traumatic stress disorder.

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Research Summary of 'Effects of N, N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression'

Introduction

Mood and anxiety disorders cause large amounts of disability worldwide and current antidepressant medications often take weeks to become effective, with about 30% of patients failing to respond. This therapeutic gap has prompted interest in fast-acting alternatives such as ketamine and classical serotonergic psychedelics. Ayahuasca, a traditional Amazonian tisane that combines DMT-containing Psychotria viridis with MAO-inhibiting Banisteriopsis caapi, has shown antidepressant and anxiolytic effects in humans and in some animal paradigms, but the contribution of individual constituents—particularly N,N-dimethyltryptamine (DMT), the principal hallucinogenic component—remains unclear. Cameron and colleagues set out to characterise the behavioural effects of a hallucinogenic dose of DMT in adult male Sprague-Dawley rats using standard assays relevant to anxiety, post-traumatic stress disorder (PTSD), and depression. The study aimed to determine both acute and longer-lasting behavioural consequences of DMT administration in paradigms including novelty-induced locomotion (NIL), the elevated plus maze (EPM), fear conditioning and extinction (cued and contextual), and the forced swim test (FST). This work seeks to clarify whether DMT alone can account for the anxiogenic, anxiolytic, or antidepressant effects attributed to ayahuasca and whether its profile resembles that of other fast-acting agents such as ketamine.

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Study Details

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