Ayahuasca is a traditional Amazonian decoction containing N, N-dimethyltryptamine (DMT) and monoamine oxidase inhibitors (MAOIs), which has gained global attention for its religious use and mental health benefits. Scientists have shown significant interest in ayahuasca mainly due to its potential therapeutic effects in treating depression. However, the possible risks have been less studied. Research suggests that ayahuasca alters brain function, enhances specific subjective experiences, and may improve the overall well-being of people. However, it is also frequently associated with adverse mental health effects. A prior study found that 55.4% of ayahuasca users experienced adverse mental effects, which were often linked to previous mental health issues or using it in non-traditional settings.
A new analysis published in PLOS Mental Health explores how various factors (Clinical, sociodemographic, acute experience, extreme fear, spiritual significance, and ayahuasca use history) influence post-ayahuasca adverse effects and current mental health using a mediational model analyzed through combined classical statistical and machine learning methods.
In this study, participants were recruited from >50 countries between March 1, 2017, and December 31, 2019, through a global ayahuasca survey. Data on various factors were collected using validated tools like the persisting effects questionnaire (PEQ) and the short form health survey–12 items (SF-12). Acute adverse effects were assessed using the modified patient health questionnaire–4 items (PHQ-4). All statistical analysis was conducted through R version 4.2.3.
A total of 10,836 participants (mean age = 40.9±12.01 years, female = 47.1%) who reported adverse effects after using ayahuasca were included in this analysis. Individuals first used ayahuasca at an average age of 31.5±12.34 years. While 16% had not used it in the previous year, 59.9% had consumed it >31 times, and 20% had used it >397 times in their whole lives. Additionally, 19.7% of participants had depression, and 14.2% had anxiety. The average SF-12 score was found to be 50.16±9.11. Out of 24 variables, 20 were selected for optimal model performance (R² = 0.256, root mean square error [RMSE] = 7.92). Gender was not found to be a significant factor in the random forest regression analysis with R² = 0.282.
The mediational model showed excellent fit with χ² = 1.295, p = 0.523, comparative fit index (CFI) = 1.00, Tucker-Lewis index (TLI) = 1.00, root mean square error of approximation (RMSEA) <0.001, and standardized root mean square residual (SRMR) = 0.001. The model also explained 30% of the variance in current mental health, as well as the variance of adverse effects, ranging from R² = 0.060 to R² = 0.206.
Variables related to participants’ ayahuasca use history were not significantly associated with increased reports of half the adverse mental states examined. However, an older age of first use and greater lifetime use were significantly correlated with higher reports of specific adverse mental effects such as feeling down, depressed/hopeless (β = 0.091–0.097 and p < 0.037), hearing/seeing things others do not (β = 0.178–0.103 and p < 0.006), visual distortions (β = 0.113–0.146 and p < 0.001), and feeling energetically attacked/connected to a harmful spirit world (β = 0.116–0.226 and p ≤ 0.001).
Anxiety and depression predicted greater post-ayahuasca adverse effects, especially in non-traditional settings (β ≥ 0.108 and p ≤ 0.007). Non-traditional country participants showed mixed effects. Extreme fear increased all adverse states (β ≥ -0.155 and p-values [ps] < 0.001) while spiritual significance had both protective (β = -0.051 and p ≤0.002) and amplifying (β ≥ 0.063; ps ≤ 0.002) association. Ayahuasca use history was associated with better current mental health (β ≥ 0.088 and ps ≤ 0.001) while a history of anxiety and depression (β ≤ -0.220 and ps < 0.001), extreme fear (β = -0.151 and p < 0.001) and lower spiritual significance (β = 0.130 and p < 0.001) were associated with worse current mental health.
This study’s limitations include recall and selective reporting bias, self-selection bias, and cultural/contextual variations.
In conclusion, this analysis highlights that ayahuasca use can lead to both beneficial and harmful effects on mental health, depending on a person’s history and context. Individuals with anxiety and depression are more likely to have negative effects, whereas some effects, like visual changes, can lead to better mental health. Recognizing these dynamics is key to enhancing harm reduction and therapeutic effectiveness.
Reference: Andión Ó, Bouso JC, Sarris JJ, Tófoli LF, Opaleye ES, Perkins D. A new insight into ayahuasca’s adverse effects: Reanalysis and perspectives on its mediating role in mental health from the Global Ayahuasca Survey (GAS). PLOS Ment Health. 2025;2(4):e0000097. doi:10.1371/journal.pmen.0000097
