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

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.

Changes in mental health, wellbeing and personality following ayahuasca consumption: Results of a naturalistic longitudinal study

“…Following encouraging initial data from human and animal studies with ayahuasca, there is growing interest in the potential medical use of this substance for the treatment of mental health conditions. Our findings relating to mental health effects for individuals with and without a lifetime mental health diagnosis are in-line with reports of depression, anxiety, and stress reductions in placebocontrolled studies (Palhano-Fontes et al, 2018), observational studies with follow-up periods up to 6 months (Barbosa et al, 2005;Barbosa et al, 2009;Jiménez-Garrido et al, 2020;Ruffell et al, 2021), and cross-sectional studies comparing ayahuasca users to nonusers (Kaasik and Kreegipuu, 2020;Sarris et al, 2021). Participants also reported less problematic alcohol and cannabis use 1-month post-ceremony, corroborated by decreased frequency of alcohol use and a trend toward decreased alcohol binges.…”

“…Long-term follow-up is also necessary to assess the durability of treatment effects identified. Sustained improvements have been reported 6-month posttreatment in one study, and a large cross-sectional study identified little diminishing of reported improvements in mental health or reductions in drug and alcohol use over time (Jiménez-Garrido et al, 2020;Ruffell et al, 2021). However, another study found that at a 4-7-year follow-up, treatment gains from ayahuasca were lost after a single administration, suggesting repeated administration may be necessary (dos Santos et al, 2016).…”

Psychedelic Therapy's Transdiagnostic Effects: A Research Domain Criteria (RDoC) Perspective

“…A recent study in male mice using the relatively selective 5-HT2A/2C receptor agonist DOI (1-(2,5-Dimethoxy-4iodophenyl)-2-aminopropane) showed that it accelerated fear extinction, reduced immobility time in the FST, increased the density of transitional dendritic spines in the frontal cortex, and for the first time showed epigenetic changes in enhancer regions of genes involved in synaptic assembly which lasted for 7 days, in conjunction with more transient transcriptomic changes (128). The clinical relevance of putative epigenetic changes in humans are not yet clear (129).…”

Ayahuasca as a Decoction Applied to Human: Analytical Methods, Pharmacology and Potential Toxic Effects

“…No physiological toxicity or psychological, neuropsychological or psychiatric harm has been observed [67]. Later, the long-term effects of ayahuasca in naive and chronic users were also examined, and it was found that both groups had better scores for depression after half a year [68] or psychometric improvements were sustained [69]. Approximately four weeks after the ayahuasca ritual, participants were found to have improved cognitive thinking style and mindfulness [70].…”