Interactive Effects of Ayahuasca and Cannabidiol in Social Cognition in Healthy Volunteers: A Pilot, Proof-of-Concept, Feasibility, Randomized-Controlled Trial
Giordano Novak Rossi 1, Juliana Mendes Rocha 1, Flávia L Osório, José Carlos Bouso, Genis Ona, Gabriela de Oliveira Silveira 2, Mauricio Yonamine 2, Giuliana Bertozi 3, Eduardo José Crevelin 4, Maria Eugênia Queiroz, José Alexandre S Crippa 1, Jaime E Cecílio Hallak, Rafael G Dos Santos
- 1From the Department of Neurosciences and Behavior, Ribeirão Preto Medical School, University of São Paulo.
- 2School of Pharmaceutical Sciences, University of Sao Paulo, São Paulo.
- 3Department of Pharmacology, Ribeirão Preto Medical School.
- 4Departamento of Chemistry.
Affiliationer
Background: Serotonergic hallucinogens and cannabinoids may alter the recognition of emotions in facial expressions (REFE). Cannabidiol (CBD) attenuates the psychoactive effects of the cannabinoid-1 agonist tetrahydrocannabinol. Ayahuasca is a dimethyltryptamine-containing hallucinogenic decoction. It is unknown if CBD may moderate and attenuate the effects of ayahuasca on REFE.
Procedures: Seventeen healthy volunteers participated in a 1-week preliminary parallel-arm, randomized controlled trial for 18 months. Volunteers received a placebo or 600 mg of oral CBD followed by oral ayahuasca (1 mL/kg) 90 minutes later. Primary outcomes included REFE and empathy tasks (coprimary outcome). Tasks were performed at baseline and 6.5 hours, 1 and 7 days after the interventions. Secondary outcome measures included subjective effects, tolerability, and biochemical assessments.
Results: Significant reductions (all P values <0.05) only in reaction times were observed in the 2 tasks in both groups, without between-group differences. Furthermore, significant reductions in anxiety, sedation, cognitive deterioration, and discomfort were observed in both groups, without between-group differences. Ayahuasca, with or without CBD, was well tolerated, producing mainly nausea and gastrointestinal discomfort. No clinically significant effects were observed on cardiovascular measurements and liver enzymes. Conclusions: There was no evidence of interactive effects between ayahuasca and CBD. The safety of separate and concomitant drug intake suggests that both drugs could be applied to clinical populations with anxiety disorders and in further trials with larger samples to confirm findings.
