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.

Highlights

  • Ayahuasca, meaning “vine of the soul” in the Quechua language [1], is a natural psychoactive plant brew traditionally used for medicinal and spiritual purposes by indigenous populations throughout the Western Amazon basin [2]

  • We found that ayahuasca was associated with reductions in depression, anxiety, and global distress from baseline to postretreat which were sustained at 6-month follow-up

  • Coupled with previous evidence for the marker’s role in trauma [42, 43], the correlation between childhood trauma and changes in sigma non-opioid intracellular receptor 1 (SIGMAR1) methylation, alongside the improvements in mental health outcomes observed in our present sample, we propose that future research should investigate SIGMAR1 as a potential mechanism of action underlying ayahuasca

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Summary

Introduction

Ayahuasca, meaning “vine of the soul” in the Quechua language [1], is a natural psychoactive plant brew traditionally used for medicinal and spiritual purposes by indigenous populations throughout the Western Amazon basin [2]. Scientists first became aware of the Amazonian use of ayahuasca. The ayahuasca brew is usually prepared by boiling the broken stems of the Banisteriopsis caapi vine, alongside leaves from the Psychotria viridis shrub or leaves of the Diplopterys cabrerana [8]. P. viridis and D. cabrerana contain the psychedelic tryptamine N,N-dimethyltryptamine (DMT), an agonist of the serotonin 2A receptor (5HT2AR) and sigma non-opioid intracellular receptor 1 (SIGMAR1). Agonism of these receptors have been associated with antidepressive and anxiolytic effects [11, 12]

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