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Challenging experiences in ayahuasca use, childhood trauma, and posttraumatic growth have not been investigated systematically. This study aimed to explore whether a self-reported history of childhood trauma was associated with challenging experiences during acute ayahuasca effects and whether such challenging experiences were associated with beneficial long-term outcomes measured by posttraumatic growth. For this study, 231 individuals (mean age 40.29, 48% women) completed an online survey about traumatic experiences in childhood, challenges during acute ayahuasca effects, and perceived benefits of those challenges. This study found that people with histories of childhood trauma were not at greater risk of adverse or challenging experiences during acute ayahuasca effects than people without histories of childhood trauma (r = .080, p = .281, 95% CI [–.066, .223]). Additionally, there was no difference in posttraumatic growth among those who had history of childhood trauma versus those who did not (r = –.016, p = .837, 95% CI [–.166, .135]). People who have experienced more challenges during acute ayahuasca effects did not experience more ayahuasca-related posttraumatic growth (r = .137, p = .076, 95% CI [–.014, .281]). These findings are important, as they may indicate that childhood trauma exposure does not pose the same risk for a poor treatment response to ayahuasca, as it predicts in other forms of intervention.