Ruffell SGD, Netrband N, Tsang W, et al. Ceremonial ayahuasca in Amazonian retreats—mental health and epigenetic outcomes from a six-month naturalistic study. Front Psychiatry. June 9, 2021;12:687615. doi: 10.3389/fpsyt.2021.687615.
Ayahuasca, a psychoactive plant brew, is used in traditional ceremonies by indigenous people in the Western Amazon basin. The brew is prepared by boiling stems of the caapi (yage; Banisteriopsis caapi, Malpighiaceae) vine with chacruna (Psychotria viridis, Rubiaceae) or chaliponga (Diplopterys cabrerana, Malpighiaceae) leaves. The effects of ayahuasca have been linked to transcendental and mystical experiences characterized by alterations in an individual's sense of self and reality, emotional and cognitive processing, and spatiotemporal orientation. In this prospective, observational, naturalistic study, the authors sought to determine whether ceremonial ayahuasca use is associated with positive effects on mental health.
The study was conducted at the Ayahuasca Foundation, a retreat and research center in the Amazon rainforest near Iquitos, Peru. Ayahuasca was given to participants who signed up for a retreat in a traditional Shipibo setting adapted for tourists. The retreats were offered in 8-day (4 ayahuasca ceremonies) 2-week (6 ceremonies), 3-week (9 ceremonies), and 1-month (11 ceremonies) sessions.
The ceremonies lasted about five hours and were led by a local curandero with help from trained Ayahuasca Foundation facilitators. The participants consumed about 150 mL of the ayahuasca brew at the beginning of a ceremony. Each participant was instructed to determine what he or she hoped to achieve before the ceremonies.
Standardized questionnaires were given to the participants before their first ceremony (baseline), the day after their last ceremony (post-retreat), and six months after their final ceremony. Saliva samples were gathered for epigenetic analyses. The following assessments were used: the Beck Depression Inventory-Second Edition (BDI-II), State-Trait Anxiety Inventory (STAI), Self-Compassion Scale, Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM), Childhood Trauma Questionnaire, Mystical Experience Questionnaire, Sentence Completion for Events from the Past Test (SCEPT), and SCEPT Inter-rater Reliability.
Sixty-three self-selected participants aged 19-63 years were included in the study. Of those, 48 reported no physical health problems; 3 reported hypertension, 1 reported irritable bowel syndrome, 1 reported seizures, and 11 reported other conditions. Forty-two participants had not been diagnosed with any psychiatric disorders, 15 reported depression, 15 reported anxiety, 5 reported attention deficit-hyperactivity disorder, and 5 had post-traumatic stress disorder. Twenty-seven participants had experienced problems with substance use. Thirty-seven participants had not used ayahuasca. The participants took part in the following retreat durations: 18 in the 8-day, 12 in the 2-week, 12 in the 3-week, and 19 in the 1-month retreats.
Significant decreases occurred in BDI-II, STAI-T, and CORE-OM scores at post-retreat compared with baseline (P < 0.001 for all). At the six-month follow-up, those scores were lower compared with baseline scores (P < 0.001) but not compared with post-retreat scores. Compared with baseline scores, the self-compassion scores were higher at post-retreat (P < 0.001) but not at the six-month follow-up. Memory specificity scores on the SCEPT did not change; however, significant reductions in negative valance memory scores from baseline to the six-month follow-up were observed (P = 0.004).
At baseline, 31 participants were depressed as indicated by BDI-II scores. Of those participants, 24 were no longer depressed at post-retreat and at the six-month follow-up. At post-retreat, depression was mild in four participants, moderate in one, and severe in two. After six months, two of those participants had mild depression, and one was severely depressed. The changes in depression severity were significant (P < 0.001).
In the epigenetic analysis, an error prevented the brain-derived neurotrophic factor gene analysis. Sigma non-opoid intracellular receptor 1 (SIGMAR-1) DNA methylation increased across the five analyzed CpG sites within the gene (P = 0.001); FK506-binding protein 5 DNA methylation did not change significantly (P = 0.13).
This study has some limitations, including the absence of a control group and the possibility of self-selection bias. Factors other than the ayahuasca, such as being in a retreat setting in the Amazon, with a group, and without internet access, could have affected the results and caused a significant placebo effect. Controlling the effects of maturation and life events between the post-retreat and follow-up assessments was difficult. Some patients had used ayahuasca before. The medical histories of the participants could not be adequately confirmed, and the amounts of ayahuasca given to the participants were not standardized. Because the epigenetic analyses were conducted using samples from peripheral cells (that is, saliva samples), the results may not represent epigenetic changes in the central nervous system.
"The findings of this study suggest ayahuasca use in a traditional Amazonia setting is associated with significant improvements in a number of mental health outcomes" and "support hypotheses that SIGMAR-1 may be involved mechanistically in the positive outcomes of ayahuasca use," conclude the authors.
This study was funded by the Medical Research Council, United Kingdom, and by King's College London and GCRF: Trauma and Adverse Childhood Experiences Springboard; the National Institute for Health Research Biomedical Research Centre in South London: and Maudsley NHS Foundation Trust.