Over the last two decades, research into psychedelic and cannabinoid-based treatments for mental health disorders has rapidly expanded.
Classical psychedelics (LSD, psilocybin and DMT) are being investigated as treatments for depression and anxiety (Wickham, 2024) and cannabis-based medicines are being increasingly explored for a wide range of indications from insomnia to tic disorders, and autism (De Bode, 2024).
As the scientific community grapples with a rapidly evolving evidence base, contrasting approaches to regulatory approval and government policy have already begun to shape public access. In 2023, Australia became the first country to licence psilocybin as a treatment for depression within psychiatric settings (Henriques, 2023), Meanwhile in the UK, cannabis-based medicinal products are now be prescribed by specialist doctors, although use is largely confined within the private sector.
As these previously prohibited substances become more utilised, familiar questions resurface: what are their long-term effects on the brain and mental health?
A new study by Bouso et al (2026) sought to explore this by investigating if long-term users of cannabis and ayahuasca (a herbal brew containing DMT) differed to non-users with respect to personality, cognition and mental health.
Your brain on drugs? Is long-term use of cannabis and ayahuasca harmful?
Methods
This was a cross-sectional study based in Spain comparing measures of personality, cognition, and mental health between ayahuasca, cannabis, and non-regular substance users.
Ayahuasca users were members of the Spanish Santo Daime Church, a religious group where ayahuasca is consumed ceremonially, whereas cannabis users were members of Catalan cannabis-activist groups.
Participants attended a screening visit, then a study visit where a battery of neuropsychological, personality and mental health scales were completed. To be included participants needed to be abstinent from ayahuasca for 10 days, and cannabis for 30 days prior to the study visit, and have a negative urine drug test on the day.
To identify how personality, cognition and mental health differed across the groups, researchers used multinomial linear regression (MLR). To prevent overloading the model with predictors, only variables that exhibited a near-significant (p<0.1) relationship with user group were included.
Variables were entered into the MLR in stages (stepwise approach). At each stage non-significant predictors were removed. Model fit was assessed using the Akaike Information Criterion (AIC) metric. A lower AIC indicates a better model fit with fewer unnecessary predictors.
Results
The final sample comprised 219 participants: 69 ayahuasca users, 56 cannabis users and 94 non-regular substance users. Lifetime exposure indicated long-term use with ayahuasca users reporting a mean use of nearly 190 times and cannabis users over 33,000 times.
The final model had an adjusted R2 value of 28% meaning that the included predictors explained 28% of the variability in group membership.
Stage 1: sociodemographic, psychiatric history and IQ
Cannabis users were younger, more likely to be male, have lower educational attainment and higher fluid intelligence than non-user controls. Ayahuasca users were more likely to have a previous depression or anxiety diagnosis than non-users. When these variables were added into the MLR, only age, sex and previous depression diagnosis remained statistically significant predictors of group membership. This initial model explained 8% of variability in group membership.
Stage 2: neuropsychological tests
There were no statistically significant differences across user groups on measures of executive functioning, working memory, selective attention, cognitive flexibility or decision making. These measures were therefore not included in the final model.
Stage 3: mental health symptoms
Cannabis users demonstrated statistically significantly lower obsessive-compulsive and psychoticism scores than non-users. However, none of these associations remained significant once entered into the MLR and were therefore not retained, suggesting the presence of mental health symptoms was less important for distinguishing groups.
Stage 4: schizotypal traits
Ayahuasca users reported more unusual experiences than healthy controls, while cannabis users demonstrated greater impulsive non-conformity and introvertive anhedonia. Inclusion of these variables increased the proportion of variance in group membership explained to 14.1%.
Stage 5: temperament and character dimensions
Ayahuasca users demonstrated statistically significantly higher self-transcendence, and lower persistence and harm avoidance to healthy controls. Cannabis users, on the other hand, demonstrated greater novelty seeking than healthy controls. These variables remained significant in the MLR and inclusion increased the explained variance to approximately 28%. This suggests that differences in temperament and character dimensions accounted for the most variation in group membership.
This cross-sectional study compared cognition, personality and mental health in long-term ayahuasca users, cannabis users and non-users, finding that personality traits best distinguished the groups.
Conclusions
Bouso et al. (2026) compared long-term ayahuasca users, cannabis users and non-users on measures of cognition, mental health and personality. While user groups had substantial lifetime substance use, no differences were identified in tests of executive functioning, working memory, attention or decision-making.
Personality measures that assessed temperament and character dimensions explained the largest variation in group membership. Ayahuasca users demonstrated higher self-transcendence and lower persistence and harm-avoidance to non-users, whereas cannabis users demonstrated greater novelty seeking.
Personality, rather than cognition or current mental health symptoms, was most strongly associated with long-term ayahuasca and cannabis use.
Strengths and limitations
Studying the long-term effects of a drug is challenging. Users often consume multiple substances, differ in important sociodemographic characteristics, and may have co-morbid mental health conditions. In an attempt to minimise the influence of these confounding variables, Bouso et al. (2026) adopted a unique naturalistic design, recruiting participants from established social groups where ayahuasca (Santo Daime church) or cannabis (cannabis activist networks) use was an integrated cultural practice.
While this approach strengthens the study through improved ecological validity by capturing functioning individuals with real-world exposure rather than skewed treatment-seeking populations, it likely introduced selection bias. Religious organisations and activist networks may attract individuals with distinct beliefs, values and attitudes independent of substance use. Consequently, although the observed personality profiles were consistent with previous research (higher self-transcendence in ayahuasca users and novelty seeking in cannabis users), it is unclear whether these differences reflect community membership or the long-term effects of the drug. Without prospective assessment, the direction of causality cannot be inferred. The distinctive recruitment strategy may also limit the generalisability of the findings to people who use these substances outside these communities.
While the distinct recruitment strategy aimed to reduce the occurrence of polysubstance use, participants also reported using other substances. This is not an unusual finding in drug research. Here, more than 40% of cannabis users reported MDMA or cocaine use in the previous month and 42% of ayahuasca users reporting cannabis use in the last month. Although the frequency of use of these substances was not reported, these levels of polysubstance use are not insignificant and may have contributed to the findings. Additionally, while the recruitment approach was intended to improve matching groups on age, sex, education and mental health history, differences between groups remained, with age, sex and previous depression being retained in the final model.
Despite these limitations, the authors should be commended for their efforts to minimise acute drug effects by requiring both an abstinence period and a negative drug test before participation. This is particularly important when investigating cognition, as previous meta-analyses suggest that many cognitive deficits associated with cannabis use diminish following prolonged abstinence (Schreiner & Dunn, 2012). That said, the 10-day abstinence period for ayahuasca users was intended to reduce acute effects, however it remains unclear whether subacute changes in neuroplasticity could still have influenced cognition or mental health outcomes (De Vos et al., 2021).
Additionally, the authors used a comprehensive assessment battery incorporating several validated tests assessing a variety of cognitive domains, alongside questionnaires measuring psychopathology and personality. This allowed the authors to compare multiple competing explanations for group differences within a single analytical framework.
Recruiting ayahuasca users from religious communities and cannabis users from activist networks improved ecological validity, but limits the extent to which these findings can be generalised to other users.
Implications for practice
In 1987, anti-drug campaigners in the United States ran an advertisement comparing the effects of drugs on the brain to frying an egg.
While Bouso et al.’s study challenges this simplistic message, finding no significant differences across a range of neuropsychological tests, the results require careful interpretation. Yes, ayahuasca and cannabis users in this study did not differ from controls on measures of working memory, executive functioning, selective attention or cognitive flexibility. However, this does not necessarily mean these substances have no long-term cognitive effects.
On the one hand, Bouso et al.’s cognitive findings align with previous cannabis research suggesting that cognitive deficits may diminish following prolonged abstinence (Schreiner & Dunn, 2012). However, previous reviews indicate that cannabis-related cognitive outcomes may be affected by age of onset, frequency of use, THC dose and co-occurring mental health difficulties (Kroon et al., 2021). As this was a cross-sectional study recruiting socially integrated users, it is possible that individuals who experienced harmful cognitive or mental health consequences arising from cannabis were less likely to be recruited because they had already stopped using cannabis or were no longer part of these socially integrated communities. Therefore, the study’s sample may represent a subgroup of users who can tolerate these substances or who had higher baseline cognitive functioning, perhaps reflected by the high fluid intelligence observed among cannabis users.
While the limitations of the personality findings have already been discussed, the differences observed between ayahuasca and cannabis users are particularly interesting given that individual differences may influence one’s response to psychoactive substances. This is a central assumption in psychedelic research, where “set” (an individual’s mindset, expectations and personality) and “setting” (the social, cultural and physical environment in which a substance is taken) have been hypothesised to influence the acute drug experiences – although this has largely lacked empirical testing (Carhart-Harris et al., 2018). Therefore, when character dimensions such as self-transcendence are higher in ayahuasca users this may not simply represent an effect of the drug or the type of person drawn to ayahuasca. Instead, it may reflect an interaction between personality, the cultural context of use, and the drug’s pharmacological effects. This interaction may have important clinical implications as psychedelic- or cannabis-based treatments enter clinical practice, with certain individuals potentially being more likely to seek particular substances and to experience both desired therapeutic and adverse outcomes.
To disentangle these possibilities, long-term prospective research is needed to determine if personality traits predict subsequent substance use, and whether repeated exposure can itself produce lasting psychological changes. Understanding who takes these substances, the context in which they are consumed, and how individuals make meaning from these experiences may be just as important as understanding the pharmacological effects of the substances themselves.
These findings suggest that selecting the right patients for psychedelic and cannabis-based therapies may require consideration of personality and context, not just the pharmacology of the drug.
Statement of interests
Matthew Cohen does not know the researchers involved in this study. He has been a study medic in psychedelic trials and has received payment for that work. AI was used to help polish the text of this article to improve clarity.
Editor
Edited by Éimear Foley. ChatGPT assisted with language refinement and formatting during the editorial phase.
Links
Primary paper
José Carlos Bouso, Jordi Riba et al (2026) Personality, not cognition, distinguishes chronic ayahuasca and cannabis users from non-users. European Neuropsychopharmacology 106, 112782. https://doi.org/10.1016/j.euroneuro.2026.112782
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