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Cited by 112Psychedelics and Drug StudiesPain Management and Placebo EffectReligion, Spirituality, and Psychology

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

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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. +1 more·2021·Psychopharmacology
DOI 10.1007/s00213-021-05817-8PMC PMC8233273
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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.

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  • The subjective experience shared phenomenological similarities with ayahuasca and other serotonergic psychedelics such as psilocybin, including alterations of consciousness captured by the 11 subscales of the 5D-ASC.

    “Overall, the subjective experience shared phenomenological similarities with ayahuasca and other serotonergic psychedelics such as psilocybin (19, 49), including alterations of consciousness captured by the 11 subscales of the widely used 5D-ASC scale (63, 75).”

    From Potential therapeutic effects of an ayahuasca-inspired N,N-DMT and harmine formulation: a controlled trial in healthy subjects (2024) · cites this paper as [75]

    The Methods section (‘The psychedelic experience’; page unavailable) says the 5D-ASC assesses alterations from normal waking consciousness across 11 subscales, and the Results report its use in the ayahuasca retreat study. The paper does not establish that the reported experience was phenomenologically similar to psilocybin experiences. (LLM, conf=0.84)

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  • A blinded, placebo-controlled study found comparable reductions in depression, anxiety, and stress in participants in group-based ceremonies whether they received ayahuasca or placebo.

    “These findings are consistent with results from a blinded, placebo-controlled study (N = 30) demonstrating that participants in group-based ceremonies showed comparable reductions in depression, anxiety, and stress whether they received ayahuasca or placebo, indicating a potential therapeutic effect of the groupbased ceremony in itself.13”

    From Innovations in group-based psilocybin-assisted therapy of major depression in patients with cancer (2024) · cites this paper as [13]

  • The group-based ceremony itself may have a therapeutic effect.

    “indicating a potential therapeutic effect of the groupbased ceremony in itself.13”

    From Innovations in group-based psilocybin-assisted therapy of major depression in patients with cancer (2024) · cites this paper as [13]

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Research works printed but not linked: 1

  1. Kuypers KPC Dolder PC Ramaekers JG Liechti ME Multifaceted empathy of healthy volunteers after single doses of MDMA: a pooled sample of placebo-controlled studies J Psychopharmacol 2017 31 589 598 28372480 PMC5418931

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Authors
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.
Affiliations
  • Maastricht University (NL)
  • Goethe University Frankfurt (DE)
Corresponding author
  • Uthaug, M. V.
  • Ramaekers, J. G.
ORCID
Venue
Psychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2021-03-10
Volume
238
Issue
7
Pages
1899-1910
ISSN
  • 0033-3158 (ISSN-L)
  • 1432-2072
DOI
10.1007/s00213-021-05817-8
PMC
PMC8233273
OpenAlex
W3133906491
Cited by
112
References
78
Citations by year
2026: 11 · 2025: 26 · 2024: 23 · 2023: 25 · 2022: 14 · 2021: 13
FWCI
12.79
Type
journal article
Language
en
Open access
Licence
Locations
  • Psychopharmacology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (publishedVersion, cc-by)
  • Research Publications (Maastricht University) (submittedVersion, other-oa)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
  • Social Sciences › Health › Religion, Spirituality, and Psychology
Keywords
ayahuasca, set and setting, placebo response, mental health, depression, anxiety, stress, affective empathy, N,N-dimethyltryptamine
MeSH terms
Adult, Alkaloids, Mental Disorders, Ceremonial Behavior, Double-Blind Method, Female, Germany, Hallucinogens, Humans, Male, Mental Health, Middle Aged, Netherlands, Plant Extracts, Spain, Banisteriopsis

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