Trial PaperBipolar DisorderDepressive DisordersMajor Depressive Disorder (MDD)Healthy VolunteersAyahuasca

Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression a SPECT study

This open-label study (n=17) found that a single dose of ayahuasca (100-200ml) had significant antidepressant effects up to 21 days later (MADRS-scale and others).

Authors

  • Jordi Riba
  • Jamie Hallak
  • Rafael dos Santos

Published

Journal of Clinical Psychopharmacology
individual Study

Abstract

Ayahuasca is an Amazonian botanical hallucinogenic brew which contains dimethyltryptamine, a 5-HT2A receptor agonist, and harmine, a monoamine-oxidase A inhibitor. Our group recently reported that ayahuasca administration was associated with fast-acting antidepressive effects in 6 depressive patients. The objective of the present work was to assess the antidepressive potentials of ayahuasca in a bigger sample and to investigate its effects on regional cerebral blood flow. In an open-label trial conducted in an inpatient psychiatric unit, 17 patients with recurrent depression received an oral dose of ayahuasca (2.2 mL/kg) and were evaluated with the Hamilton Rating Scale for Depression, the Montgomery-Åsberg Depression Rating Scale, the Brief Psychiatric Rating Scale, the Young Mania Rating Scale, and the Clinician Administered Dissociative States Scale during acute ayahuasca effects and 1, 7, 14, and 21 days after drug intake. Blood perfusion was assessed eight hours after drug administration by means of single photon emission tomography. Ayahuasca administration was associated with increased psychoactivity (Clinician Administered Dissociative States Scale) and significant score decreases in depression-related scales (Hamilton Rating Scale for Depression, Montgomery-Åsberg Depression Rating Scale, Brief Psychiatric Rating Scale) from 80 minutes to day 21. Increased blood perfusion in the left nucleus accumbens, right insula and left subgenual area, brain regions implicated in the regulation of mood and emotions, were observed after ayahuasca intake. Ayahuasca was well tolerated. Vomiting was the only adverse effect recorded, being reported by 47% of the volunteers. Our results suggest that ayahuasca may have fast-acting and sustained antidepressive properties. These results should be replicated in randomized, double-blind, placebo-controlled trials.

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Research Summary of 'Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression a SPECT study'

Introduction

Ayahuasca is an Amazonian botanical brew combining Banisteriopsis caapi, which provides reversible monoamine oxidase A (MAO-A) inhibitors (β-carbolines such as harmine), and Psychotria viridis, a source of N,N-dimethyltryptamine (DMT), a 5-HT1A/2A/2C receptor agonist. Because DMT is normally metabolised by MAO-A in the gut and liver, co‑administration with β-carbolines allows DMT to reach the systemic circulation and the brain. Earlier preclinical, observational and experimental studies in healthy volunteers suggested potential antidepressant effects of ayahuasca, and the authors previously reported rapid and lasting antidepressant effects in six patients with recurrent major depressive disorder (MDD).

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Study Details

Related Clinical Trial

Completed

Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: An Open-Label SPECT Neuroimaging Study

Open-label inpatient pilot study (Brazil; collaborating institutions include Universidade de São Paulo–Ribeirão Preto and Universidade Federal do Rio Grande do Norte) of a single oral dose of ayahuasca in 17 adults with recurrent MDD (14 women; mean age 42.7 ± 12.11 years) who had an inadequate response to their current antidepressant and were undergoing a planned medication change. Three participants had a mild current episode, 13 moderate, and one severe. After a 2-week washout, participants underwent medical screening (clinical examination, laboratory tests, ECG) and a structured diagnostic interview (SCID-IV). Exclusion criteria: bipolar or psychotic disorder, active psychotic symptoms, pregnancy, history of antidepressant- or substance-induced mania/hypomania. Primary objective: characterise changes in regional cerebral blood flow using single-photon emission computed tomography (SPECT) neuroimaging. Secondary outcomes: Hamilton Depression Rating Scale (HDRS) and Montgomery-Åsberg Depression Rating Scale (MADRS) assessed at baseline and multiple post-dosing time points including 80 minutes, 24 hours, 48 hours, 72 hours, and 21 days. Study preceded the randomized placebo-controlled RCT by the same group (NCT02914769, UFRN, n=35, started 2014), which cites this open-label pilot as background. Approved by a local ethics committee. No trial registration number reported; study pre-dates routine REBEC registration requirements for open-label pilot work and was classified as a single-arm neuroimaging study.

Started
Type
interventional
Randomized
No
Registry ID
SANCHES-2016-JCP-AYAHUASCA-SPECT

References (11)

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The current state of research on ayahuasca: A systematic review of human studies assessing psychiatric symptoms, neuropsychological functioning, and neuroimaging

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Effects of Ayahuasca and its Alkaloids on Drug Dependence: A Systematic Literature Review of Quantitative Studies in Animals and Humans

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Exploring the therapeutic potential of Ayahuasca: acute intake increases mindfulness-related capacities

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Antidepressant effects of a single dose of... — Research Summary & Context | Blossom