Interactive Effects of Ayahuasca and Cannabidiol in Social Cognition in Healthy Volunteers: A Pilot, Proof-of-Concept, Feasibility, Randomized-Controlled Trial
In a small randomised, placebo-controlled pilot trial in healthy volunteers, 600 mg oral cannabidiol given before ayahuasca produced no detectable interaction on facial emotion recognition, empathy tasks or subjective effects — both groups showed reduced reaction times and decreases in anxiety/sedation with no between-group differences. Ayahuasca with or without CBD was generally well tolerated, supporting feasibility of further, larger trials to confirm these null-interaction findings.
Authors
- Jamie Hallak
- Rafael dos Santos
- Gonzalo Ona
Published
Abstract
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.
Research Summary of 'Interactive Effects of Ayahuasca and Cannabidiol in Social Cognition in Healthy Volunteers: A Pilot, Proof-of-Concept, Feasibility, Randomized-Controlled Trial'
Introduction
Earlier research indicates that serotonergic hallucinogens and the endocannabinoid system can alter recognition of emotions in facial expressions (REFE) and empathy, but the role of cannabidiol (CBD) in moderating such effects is unclear. CBD is a negative allosteric modulator at CB1 and has activity at serotonergic receptors, while ayahuasca is a dimethyltryptamine (DMT)‑containing decoction whose effects on endocannabinoids have been sparsely described. The clinical relevance of cannabinoid–psychedelic interactions for social cognition and for therapeutic outcomes in conditions such as depression and anxiety therefore remains uncertain. Rossi and colleagues designed this pilot, proof‑of‑concept randomised controlled trial to evaluate whether oral CBD (600 mg) alters the acute and short‑term effects of a single oral dose of ayahuasca (1 mL/kg) on social cognition in healthy volunteers. Primary outcomes were performance on REFE and an empathy task; secondary outcomes included subjective effects, tolerability, plasma ayahuasca alkaloids, brain‑derived neurotrophic factor (BDNF), and cardiovascular and liver safety measures. The investigators hypothesised that ayahuasca would reduce recognition of negative emotions and produce anxiolysis, that CBD could moderate REFE effects, and that combined CBD–ayahuasca would yield greater anxiolysis and attenuated psychedelic effects compared with placebo plus ayahuasca.
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Study Details
- Study Typeindividual
- Journal
- Compounds
- Topics
- Authors
- APA Citation
Rossi, G. N., Rocha, J. M., Osório, F. L., Bouso, J. C., Ona, G., Silveira, G. D. O., Yonamine, M., Bertozi, G., Crevelin, E. J., Queiroz, M. E., Crippa, J. A. S., Hallak, J. E. C., & dos Santos, R. G. (2023). Interactive Effects of Ayahuasca and Cannabidiol in Social Cognition in Healthy Volunteers: A Pilot, Proof-of-Concept, Feasibility, Randomized-Controlled Trial. Journal of Clinical Psychopharmacology, 43(4), 339-349. https://doi.org/10.1097/JCP.0000000000001691
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