A placebo-controlled study of the effects of ayahuasca, set and setting on mental health of participants in ayahuasca group retreats
In a placebo-controlled naturalistic study of 30 ayahuasca retreat participants, symptoms of depression, anxiety and stress fell after ceremonies in both ayahuasca (n=14) and placebo (n=16) groups—indicating strong set-and-setting/placebo effects—while ayahuasca specifically increased implicit emotional empathy to negative stimuli. The findings emphasise the need for placebo-controlled designs and investigation of non-pharmacological contributors in psychedelic research.
Authors
- Jordi Riba
- Kim Kuypers
- Johannes Ramaekers
Published
Abstract
Ayahuasca is a plant concoction containing N,N-dimethyltryptamine (DMT) and certain β-carboline alkaloids from South America. Previous research in naturalistic settings has suggested that ingestion of ayahuasca can improve mental health and well-being; however, these studies were not placebo controlled and did not control for the possibility of expectation bias. This naturalistic observational study was designed to assess whether mental health changes were produced by ayahuasca or by set and setting. Assessments were made pre- and post-ayahuasca sessions in 30 experienced participants of ayahuasca retreats hosted in the Netherlands, Spain, and Germany. Participants consumed ayahuasca (N = 14) or placebo (N = 16). Analysis revealed a main effect of time on symptoms of depression, anxiety, and stress. Compared to baseline, symptoms reduced in both groups after the ceremony, independent of treatment. There was a main treatment × time interaction on implicit emotional empathy, indicating that ayahuasca increased emotional empathy to negative stimuli. The current findings suggest that improvements in mental health of participants of ayahuasca ceremonies can be driven by non-pharmacological factors that constitute a placebo response but also by pharmacological factors that are related to the use of ayahuasca. These findings stress the importance of placebo-controlled designs in psychedelic research and the need to further explore the contribution of non-pharmacological factors to the psychedelic experience.
Research Summary of 'A placebo-controlled study of the effects of ayahuasca, set and setting on mental health of participants in ayahuasca group retreats'
Introduction
Ayahuasca is a traditional Amazonian brew prepared from Psychotria viridis (containing the serotonergic 5-HT2A agonist N,N-dimethyltryptamine, DMT) and Banisteriopsis caapi (containing β-carboline MAO inhibitors such as harmine and harmaline). Its use has spread into Western contexts where people attend ayahuasca retreats seeking spiritual, self-developmental, or therapeutic outcomes. Observational field studies have reported acute cognitive and affective benefits and improvements in well-being after ayahuasca use, and clinical trials have reported rapid antidepressant effects in treatment-resistant depression, but many naturalistic studies lack placebo control and therefore cannot rule out expectation or setting effects. Uthaug and colleagues set out to disentangle pharmacological effects of ayahuasca from non-pharmacological influences of set and setting in a naturalistic, placebo-controlled observational study conducted within group retreats. The primary objective was to compare psychological and empathic outcomes before and after ceremonies in participants who received either freeze-dried ayahuasca or a placebo, testing the hypothesis that set and setting would affect both groups while pharmacological effects would be evident only in the ayahuasca group.
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Study Details
- Study Typeindividual
- Journal
- Compounds
- Topics
- Authors
- APA Citation
Uthaug, M. V., Mason, N. L., Toennes, S. W., Reckweg, J. T., de Sousa Fernandes Perna, E. B., Kuypers, K. P. C., van Oorsouw, K., Riba, J., & Ramaekers, J. G. (2021). A placebo-controlled study of the effects of ayahuasca, set and setting on mental health of participants in ayahuasca group retreats. Psychopharmacology, 238(7), 1899-1910. https://doi.org/10.1007/s00213-021-05817-8
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