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    ayahuasca endocannabinoid system

    Effects of Ayahuasca on the Endocannabinoid System


    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 L. Osório, Genís Oña, José Carlos Bouso, Gabriela de Oliveira Silveira, Mauricio Yonamine, Camila Marchioni, Eduardo José Crevelin, Maria Eugênia Queiroz, José Alexandre Crippa, and Jaime E. C. Hallak

    Human Psychopharmacology: Clinical and Experimental



    About the study

    Although agonism of cortical 5‐HT2A receptors is probably one of the main mechanisms of action of ayahuasca and other hallucinogens, other non‐serotonergic targets like the endocannabinoid system could also be involved.

    In order to test this hypothesis in humans, the authors administered a single oral ayahuasca dose to a healthy 34‐year‐old man and evaluated AEA and 2‐AG plasma levels in two randomized, placebo‐controlled trials.

    The results suggest that ayahuasca modulates the endocannabinoids differently in healthy individuals and in social anxiety disorder patients.



    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 (Χ2(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.


    Link to the study


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    Photo by Austin Schmid on Unsplash.


    Categories: Studies & papers , Ayahuasca , Cannabis
    Tags: ayahuasca , scientific research , study , psychedelics , endocannabinoid system