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Effects of ayahuasca on the endocannabinoid system of healthy volunteers and in volunteers with social anxiety disorder: Results from two pilot, proof‐of‐concept, randomized, placebo‐controlled trials

Rafael G. Dos Santos, Juliana Mendes Rocha, Giordano Novak Rossi, Flávia de Lima Osório, Genís Ona, José Carlos Bouso, Gabriela de Oliveira Silveira, Maurı́cio Yonamine, Camila Marchioni, Eduardo José Crevelin, Maria Eugênia Costa Queiroz, José Alexandre S. Crippa, Jaime E. C. Hallak

Human Psychopharmacology Clinical and Experimental February 2, 2022 DOI: 10.1002/hup.2834 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Post-hoc analysis of two parallel-group, randomized, placebo-controlled trials Peer reviewed
Sample size 37
Population Healthy volunteers and volunteers with social anxiety disorder (SAD)
Intervention Ayahuasca
Dose average 1.58 mg/ml dimethyltryptamine (DMT) in Study 1, average 0.680 mg/ml DMT in Study 2
Duration Single dose, measured at baseline, 90 and 240 minutes after intake
Topics Anxiety Ayahuasca
Keywords Placebo Endocannabinoid system Post-hoc analysis Randomized controlled trial Pharmacology Anesthesia
Citations 20
Key findings Ayahuasca intake was associated with a significant difference in anandamide (AEA) concentrations over time in volunteers with social anxiety disorder, with near-significant increases at 90 and 240 minutes after intake.

Abstract

Abstract Objective To assess endocannabinoid (anandamide, AEA; 2‐arachidonoylglycerol, 2‐AG) plasma levels in healthy volunteers and in volunteers with social anxiety disorder (SAD) after a single oral dose of ayahuasca or placebo.

Methods: Post hoc analysis of endocannabinoid plasma levels (baseline, 90 and 240 min after drug intake) from two parallel‐group, randomized, placebo‐controlled trials. In Study 1, 20 healthy volunteers ingested ayahuasca (average 1.58 mg/ml dimethyltryptamine (DMT)) or placebo, and in Study 2, 17 volunteers with SAD received ayahuasca (average 0.680 mg/ml DMT) or placebo.

Results: A significant difference was observed in AEA concentrations in Study 2 after ayahuasca intake (Χ 2 (2) = 6.5, p = 0.03, Friedman test), and near significant differences (increases) were observed between baseline and 90 (Z = 0, p = 0.06, Wilcoxon test) and 240 (Z = 10, p = 0.06) minutes after ayahuasca intake.

Conclusions: Although our findings suggest that ayahuasca could modulate AEA levels in SAD patients, the high interindividual variability in both trials and the small samples preclude definitive conclusions. More research with larger samples is needed to better understand the effects of ayahuasca and other hallucinogens in the endocannabinoid system.

Comparable studies

Other randomized controlled trials on ayahuasca for anxiety, most cited first.

Study Year Design Participants
Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial Patients with treatment-resistant depression 2018 Randomized controlled trial n = 29
Subjective effects and tolerability of the South American psychoactive beverage Ayahuasca in healthy volunteers Healthy male volunteers with prior experience using ayahuasca 2001 Single-blind crossover placebo-controlled clinical trial n = 6
Effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in Santo Daime members Members of the Santo Daime religion who ingested ayahuasca for at least 10 consecutive... 2007 Double-blind, placebo-controlled study
Ayahuasca Improves Self-perception of Speech Performance in Subjects With Social Anxiety Disorder Volunteers with social anxiety disorder 2021 Randomized controlled trial n = 17
Effects of Ayahuasca on the Recognition of Facial Expressions of Emotions in Naive Healthy Volunteers Healthy volunteers 2021 Randomized controlled trial n = 22

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