A placebo-controlled study of the effects of ayahuasca, set and setting on mental health of participants in ayahuasca group retreats

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.

Ceremonial Ayahuasca in Amazonian Retreats—Mental Health and Epigenetic Outcomes From a Six-Month Naturalistic Study

“…In our study, ayahuasca use was associated with reductions in trait anxiety and improvements in general well-being. These findings are consistent with recent research in traditional frameworks in the Amazon basin (33,48), neoshamanic settings (49,50), and church settings previously (70,71). In one study, ceremonial ayahuasca was found to be associated with reductions in levels of neuroticism, a personality trait underlying anxiety disorders (33).…”

“…Thus far, most empirical human studies on ayahuasca have been carried out amongst Brazilian syncretic church members (46), with a small number of studies investigating the use of the brew in retreat centres following a traditional framework (33,47,48) and neoshamanic settings (49,50). While it is important for researchers to investigate ayahuasca use in its varied contexts and traditions, this has been limited by the brew's illicit status in most countries.…”

The Potential Role of Serotonergic Hallucinogens in Depression Treatment

“…In our study, we decided not to, mainly because the ayahuasca solution contains other than DMT components, such as harmine, harmaline, and tetrahydroharmine. In addition, in studies with ayahuasca, the dose of DMT was often not stable [ 53 , 54 , 55 ]. On the other hand, neither of those two studies included MDMA, while we decided otherwise, considering the positive outcomes in reducing depressive symptoms among patients with PTSD [ 33 , 34 ].…”

Moral Psychopharmacology Needs Moral Inquiry: The Case of Psychedelics

“…Another challenge involves observing how psychedelics are used beyond the laboratory and the clinic, turning psychopharmacology into a field science by adopting practices from ethnopharmacology, ecology, and other areas of field biology. For instance, battery-powered EEG equipment already allows one to study in naturalistic settings how ayahuasca, an Amazonian jungle environment, guidance by experienced ayahuasceros, and other variables concur in their effect on brain waves, and placebo-controlled field experiments seek to tease apart the impact of pharmacological and extra-pharmacological factors in such an ayahuasca ceremony ( 53 , 54 ). Other field sciences such as cultural primatology that use recent advances in statistics to explain how complex interactions between large numbers of ecological factors shape animal behavior might provide further methodological inspiration for how to study the interplay between pharmacological and extrapharmacological factors [e.g., ( 29 , 55 ), p.180–90; ( 56 )].…”