Personality, not cognition, distinguishes chronic ayahuasca and cannabis users from non-users.

The increasing interest in the therapeutic potential of psychedelics and cannabis underscores the need to understand their long-term neuropsychological and personality effects. This cross-sectional study compared regular users of ayahuasca (n = 69), cannabis (n = 56), and non-substance users (n = 94) on a battery of neuropsychological tasks and psychological questionnaires. Participants were matched by age, education, and IQ and abstained from drug use for at least 10-30 days before assessment. No significant group differences were observed in neuropsychological performance. However, multinomial regression analyses revealed that personality traits best distinguished the user groups. Ayahuasca users exhibited significantly higher self-transcendence and lower harm avoidance and persistence, while cannabis users were associated with higher novelty seeking and impulsive nonconformity, as well as lower introvertive anhedonia. These results persisted after controlling for demographics and psychiatric history. Contrary to previous findings associating cannabis with neurocognitive impairments and psychopathology, no significant deficits were found in the abstinent cannabis users. Similarly, ayahuasca users, despite a higher lifetime prevalence of mood and anxiety disorders, showed no current psychopathological symptoms. Our findings suggest that chronic use of ayahuasca or cannabis is not associated with detectable lasting neuropsychological impairments in the executive and working memory tasks assessed in this study, and that personality characteristics-rather than cognition or psychopathology-most clearly distinguish chronic users from non-users. However, these results are based on a cross-sectional, self-selected, non-treatment-seeking sample and may therefore not be representative of all ayahuasca and cannabis users. These insights may inform future clinical applications and safety evaluations of these substances.