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

This open-label (naturalistic) study (n=63) found that participants in ayahuasca retreats improved in scores of mental health (depression, anxiety, self-compassion), these effects lasted and were even somewhat improved at the 6-month follow-up. A study of participant’s epigenetic data didn’t yield conclusive results.

Abstract

“Ayahuasca is a natural psychoactive brew, used in traditional ceremonies in the Amazon basin. Recent research has indicated that ayahuasca is pharmacologically safe and its use may be positively associated with improvements in psychiatric symptoms. The mechanistic effects of ayahuasca are yet to be fully established. In this prospective naturalistic study, 63 self-selected participants took part in ayahuasca ceremonies at a retreat centre in the Peruvian Amazon. Participants undertook the Beck Depression Inventory (BDI-II), State-Trait Anxiety Inventory (STAI), Self-compassion Scale (SCS), Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM), as well as secondary measures, pre- and post-retreat and at 6-months. Participants also provided saliva samples for pre/post epigenetic analysis. Overall, a statistically significant decrease in BDI-II (13.9 vs. 6.1, p < 0.001), STAI (44.4 vs. 34.3 p < 0.001) scores, and CORE-OM scores were observed (37.3 vs. 22.3 p < 0.001) at post-retreat, as well as a concurrent increase in SCS (3.1 vs. 3.6, p < 0.001). Psychometric improvements were sustained, and on some measures values further decreased at 6-month follow-up, suggesting a potential for lasting therapeutic effects. Changes in memory valence were linked to the observed psychometric improvements. Epigenetic findings were equivocal, but indicated that further research in candidate genes, such as sigma non-opioid intracellular receptor 1 (SIGMAR1), is warranted. This data adds to the literature supporting ayahuasca’s possible positive impact on mental health when conducted in a ceremonial context. Further investigation into clinical samples, as well as greater analyses into the mechanistic action of ayahuasca is advised.“

Authors: Simon G. D. Ruffell, Nige Netzband, WaiFung Tsang, Merlin Davies, Matthew Butler, James J. H. Rucker, Luís F. Tófoli, Emma L. Dempster, Allan H. Young & Celia J. A. Morgan

Notes

Many studies have been pointing out that the mental health of people can be improved after going to an ayahuasca retreat. There is an ongoing debate surrounding the different factors leading to this positive change. As people go in with many expectations, could it be that most of the positive outcomes are placebo effects? Or could it be that people who participate in a retreat are at their worst in terms of mental health? And thus a ‘regression to the mean’ takes place, where people become better but that this would have happened regardless of the retreat.

The current paper isn’t able to address these issues head-on. The participants in the study were self-selected and there was no placebo being used. That all being said, the study did confirm some findings that other studies have previously found. Significant improvements in mental health, and these effects being sustained six months later.

The outcomes of the study

• Of those who were depressed before the retreat, 77% were no longer qualified as such after the retreat and at the 6-month follow-up
• Scores on all the measures (depression, anxiety, lack of self-compassion) were significantly lower after the retreat and this effect held up at the follow-up (i.e. stayed low)
• Genetic analysis of the participants didn’t show any noteworthy results, partly because the analysis of BDNF was not done due to an error

If we put aside all the reasons why mental health improves after an ayahuasca retreat, we can still wonder at the impressive effect size. A single retreat led to 77% of participants who were depressed no longer qualifying for depression.

The researchers propose that a reduction in the valence, or strength, of negative emotions is a possible explanation for the reduction in depression scores. If negative memories are recalled less, and less intensively, one might break free of the thought loops that we spoke about last week.

Summary

INTRODUCTION

Ayahuasca is a natural psychoactive plant brew used for medicinal and spiritual purposes by indigenous populations throughout the Western Amazon basin. It was first introduced to religious settings in small Brazilian urban centres in the 1930s, and has since spread to larger cities internationally.

Ayahuasca brew is prepared by boiling the broken stems of the Banisteriopsis caapi vine, alongside leaves from the Psychotria viridis shrub or leaves of the Diplopterys cabrerana. It contains powerful psychedelic effects due to the interaction of MAOIs and DMT.

Ayahuasca is safe when used with due caution, and has been shown to have rapid and sustained antidepressant and anxiolytic effects in both animals and humans. It has also been linked to transcendental and mystical experiences, and has been associated with improved psychosocial well-being, quality of life, and positive traits.

Ayahuasca experiences have been likened to intense psychotherapy, with some reports suggesting that ayahuasca can help reprocess trauma-related memories. However, the evidence for ayahuasca’s efficacy in treating trauma-related conditions is still limited.

Ayahuasca may have direct effects on trauma-related neurobiology via the sigma non-opioid intracellular receptor 1 (SIGMAR1), which is a stress-responsive neuro-receptor found primarily on the surface of the endoplasmic reticulum.

Most empirical human studies on ayahuasca have been carried out amongst Brazilian syncretic church members, with a few studies investigating its use in retreat centres following a traditional framework.

In this study, we attempted to ascertain whether ceremonial ayahuasca use may be associated with positive effects on mental health. We also explored possible mechanistic hypotheses for potential benefits of ayahuasca, including epigenetic changes via DNA methylation of three candidate genes with stress-induced psychopathology.

Participants and Design

The study was conducted at the Ayahuasca Foundation, an ayahuasca retreat and research centre, located in the Amazon rainforest near Iquitos, Peru. Participants were self-selected and provided with information about the research before each retreat.

Participants had to complete an online screening questionnaire about their mental, physical health conditions and medications before being accepted onto the retreats.

Preparation for Retreat—“Washout Period”

Each participant was given instructions to engage in a 2 week washout period, abstaining from any substances with possible interactions with the constituents of ayahuasca, and to reduce serum tyramine levels.

Procedure

Ayahuasca was administered in traditional Shipibo settings to participants in 8-day, 2-week, 3-week, and 1-month retreats.

Ayahuasca ceremonies generally commenced around 20:00, lasted 5 h, and were led by the local curandero (shaman) with assistance from four to five specially trained facilitators employed by AF. Participants consumed 150 ml of the prepared ayahuasca brew, presented by the curandero at the beginning of the ceremony.

Standardised questionnaires were administered to participants prior to, the day after, and 6 months after their final ceremony. Qualitative data was collected throughout the retreat and is included in a separate article.

Measures

The 21 item Beck Depression Inventory – Second Edition is one of the most widely used psychometric tests for measuring depression severity.

State-Trait Anxiety Inventory

The STAI measures two types of anxiety – State Anxiety and Trait Anxiety. The STAI-T score was used to analyze long-term change.

Childhood Trauma Questionnaire

The CTQ is a 28-item measure that inquires about five types of maltreatment in childhood.

Mystical Experience Questionnaire

The 30 item MEQ measures psychedelic-occasioned spiritual/peak experiences and was administered at post-retreat only to capture participants’ perceptions of their ayahuasca experiences.

Data Analysis

Ayahuasca administration caused a change in DNA methylation at two candidate genes, which was assessed using ANOVA, Greenhouse-Geisser correction, and Pearson bivariate correlation analysis.

Bisulfite Conversion

DNA samples were diluted to 25 ng/ml and bisulfite converted using the EZ Methylation – Gold Kit D5005 & 5005.

Bisulfite Pyrosequencing

The SIGMAR1 and FKBP5 assays were designed to span 5 CpGs located in the promoter of the genes, and were optimised using fully methylated DNA (positive control) and a negative control.

Pyrosequencing was used to obtain individual gene DNA methylation data per DNA sample. The process was carried out as per manufacturer’s instructions, using a Qiagen Pyromark Q48 Autoprep Pyrosequencer.

Sample Demographics

63 participants were interviewed, 35 males and 25 females, aged between 19 and 63. Most participants were White and earned between $10 and 50K and $50 to 100K annually.

Forty-eight participants reported no diagnosed physical health problems, 15 reported depression, 15 anxiety, five ADHD (two comorbid. 4.8%), and five PTSD, and 27 reported having experienced problem substance use, including alcohol, tobacco, or caffeine.

Outcome Measures

Mean outcome scores differed statistically between time points for the BDI-II, STAI-T, SCS, and CORE-OM. Six-month follow-up scores for the BDI-II, STAI-T, and CORE-OM further decreased, but not for the post-retreat score, suggesting sustained improvement.

No significant changes in memory specificity were found on the SCEPT, but there were trend levels of reduction in negatively valanced memories from pre to post-retreat, and post retreat to follow-up.

Subsample Meeting Screening Cut-Off for Depression

At post-retreat, 24 participants were no longer depressed, four had mild depression, one moderate, and two severe, and at 6-month, 24 participants were remained not depressed, two mild, and one severe. There was no difference in total CTQ scores between the depressed and non-depressed subsamples.

Predictors of Change in Psychopathology

Pearson’s correlations were conducted with CTQ and MEQ total scores and subscales and BDI-II change scores to minimise the risk of type 1 errors. The mystical experience subscale of the MEQ was negatively correlated with change in BDI-II post-retreat in the depressed subsample.

SIGMAR1 Methylation Correlation Analyses

Methylation change scores were calculated for SIGMAR1 and correlated with CTQ total scores. Those with higher childhood trauma had increased methylation changes in SIGMAR1 post retreat.

DISCUSSION

In this naturalistic study, ayahuasca use was associated with reductions in depression, anxiety, and global distress, and a change in DNA methylation at loci on the SIGMAR1 receptor gene.

Depression

Results suggest that ayahuasca use in ceremonial settings may be associated with improvements in well-being, particularly depression and its related conditions. Although no correlation was found between change in BDI-II score and memory specificity, a reduction in negatively valanced memories was observed in the overall sample.

We found that participants who reported a greater degree of mystical experience improved more at follow-up, and that the ritualistic element of the ceremonies amplified their perceived mystical states.

Ayahuasca improves depressive outcomes in patients with treatment-resistant depression, and attenuates the default mode network (DMN), a neural network known to be hyperactive in patients with major depressive disorder.

Anxiety and Well-Being

Ayahuasca use was associated with reductions in trait anxiety and improvements in general well-being in our study, which supports previous evidence suggesting improvements in general well-being and quality of life.

Contextual Factors

Although individual ayahuasca sessions may be beneficial, our study did not show a direct correlation between the number of ceremonies and outcome measures.

Ayahuasca is typically given at night in a ceremonial setting with minimal contact between participants. However, the results of the current study are in line with those based in both syncretic church settings and controlled studies in laboratories.

Ayahuasca rituals can be beneficial, but only if the participant feels safe and supported. This can be achieved in a laboratory setting, but for some participants the Amazon rainforest may be the best setting.

Epigenetics

Ayahuasca exposure affects the epigenetic regulation of SIGMAR1, however, the mean increase in DNA methylation is small and it remains unclear if this change in DNA methylation has biological impacts.

The modest changes in methylation in our sample may be due in part to the minimal trauma history of many of our participants, and the improvement in mental health outcomes observed in our present sample.

STRENGTHS AND LIMITATIONS

This study is the first to investigate the effects of ayahuasca on epigenetics, but it has several limitations. It is also difficult to control for the impact of maturation and life events between post-retreat and 6-month follow up.

Researchers could not confirm medical histories of participants and the quantity of ayahuasca given to participants was not standardised.

Limitations of Epigenetic Analyses

The approach taken here is arguably open to bias, as biological samples were taken from peripheral cells (i.e., saliva samples). Future research should consider other methods of analysis, including microRNAs, and alternative splicing as a result of ayahuasca consumption.

AYAHUASCA TOURISM

Researchers highlight issues surrounding ayahuasca tourism, including safety and cultural appropriation. Furthermore, many retreat centres in the Amazon are owned by Westerners, and the use of ayahuasca for financial gain has been called into question.

CONCLUSIONS

This study suggests that ayahuasca use in a traditional Amazonian setting is associated with significant improvements in a number of mental health outcomes. These effects were sustained at 6-month follow-up without further dosing, suggesting lasting therapeutic potential.

AUTHOR CONTRIBUTIONS

SR, NN, WT, CM, LT, AY, and CM contributed to the conceptualisation, data collection, analysis, writing, and supervision of the study.

FUNDING

Professor Young receives funding from the Medical Research Council, UK, and King’s College London, UK. His independent research is funded by the National Institute for Health Research.