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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 via OpenAlex

Summary

AI-generated from the abstract

A post-hoc analysis of two small randomized placebo-controlled trials measured 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. In the SAD group, ayahuasca intake was associated with a significant difference in AEA concentrations over time, and near-significant increases in AEA were observed at 90 and 240 minutes after intake. No definitive conclusions could be drawn due to high interindividual variability and small sample sizes. Larger studies are needed to clarify ayahuasca's effects on the endocannabinoid system.

Study at a glance

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
Citations 20
Key finding 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.

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