Sample description (n = 5,400).

Ayahuasca is a decoction native to the Amazon, where it plays a central role in the traditional medicine of many local cultures and has expanded internationally over the last decades. Ayahuasca has also attracted the interest of scientists for its potential benefits on mental health, but its adverse effects are under-researched. We analyzed data from the Global Ayahuasca Survey, including 10,836 participants who rated predetermined adverse effects. Data were collected from March 1st, 2017, to December 31st, 2019, and accessed for analysis on November 30th, 2021. Only DP and JJS had access to identifiable participant data. Machine learning and statistical methods were used to examine the relationship between sample characteristics, post-ayahuasca adverse mental states, and mental health outcomes measured by the 12-Item Short Form Survey (SF-12). Among participants, 14.2% (767) had a prior anxiety disorder and 19.7% (1,064) a depressive disorder. Despite this, the median SF-12 score was 50.16, comparable to the general population. A history of anxiety or depression was associated with more adverse mental states after ayahuasca use. However, increased experiences of “visual distortions” and higher ayahuasca use correlated with better mental health. Women reported more adverse states but did not show worsened mental health. The classification of adverse mental states in psychedelic research should be reconsidered, as certain experiences traditionally labeled as negative may contribute to long-term psychological benefits. The context in which these experiences occur, along with individual factors, plays a crucial role in determining whether these states lead to positive or negative outcomes. Understanding these dynamics is essential for improving harm reduction strategies and maximizing therapeutic potential. Individuals with a history of depression require special attention, as they are more prone to experiencing post-ayahuasca adverse mental states and may benefit from additional psychological support.