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

This double-blind placebo-controlled study (n=30) controlled for expectation bias in a naturalistic ayahuasca ceremony. The use of ayahuasca led to more emotional empathy, but both groups improved as much on symptoms of depression, anxiety, and stress. Noted should be that the dosage of ayahuasca was relatively low (14-21mg DMT, 2-4x lower than usual).


“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.”

Authors: Malin V. Uthaug, Natasha L. Mason, Stefan W. Toennes, Johannes T. Reckweg, Elizabeth B. de Sousa Fernandes Perna, Kim P. C. Kuypers, Kim van Oorsouw, Jordi Riba & Johannes G. Ramaekers


A double-blind, placebo-controlled study (n=30) by Malin Uthaug and colleagues adds even more evidence to the power of set and setting. The expectation of participants, and the ceremonial environment of ayahuasca retreats (in Spain, The Netherlands, and Germany) led to lower scores on scales of depression, anxiety, and stress.

And you may have guessed it already, this reduction in scores was the same for the group that received ayahuasca or placebos. Both groups received pills, and those for the placebo group contained cacao and other substances to still taste the same when someone burbs. A clever study that once again shows the power of the environment when studying psychedelics.

What was found in this study?

  • Ayahausca, versus placebo, did have a significant effect on implicit arousal to negative stimuli, a measure that indicates increased empathy. Still, this effect was relatively small (not going higher than the baseline for the placebo group).
  • The placebo group came into this study with much higher depression and stress scores, and improved more than the ayahuasca group.
  • Of the participants, 57% and 69% guessed correctly that they were in the ayahuasca or placebo group (with 50% being chance). But, the dosage of ayahuasca was relatively low, coming in at 2 to 4 times lower than a (very) high dose.

Doing this type of analysis can provide information on what factors contribute to the beneficial effects of psychedelics. They don’t only show the power of psychedelics, but also highlight the need for a set and setting that is beneficial for participants.

Study details

Topics studied
Anxiety Depression

Study characteristics
Placebo-Controlled Double-Blind Randomized


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