Classic psychedelics and personality: An updated systematic review

Background: The impact of classic psychedelics (5-HT2A receptor agonists) on personality traits has been studied for decades, and it has been hypothesized that the mechanisms underlying these changes are linked to agonism at cortical serotonergic 5-HT 2A receptors. However, research results are contradictory. Therefore, the present paper aims to systematically evaluate the effects of psychedelics on personality, updating (2016–2024) a previous systematic review by Bouso and collaborators (2018). The International Prospective Register of Systematic Reviews ID for this study is CRD42024582704. Method: Systematic review using four databases (PubMed, LILACS, PsycINFO, and SciELO) including randomized controlled trials, open-label, and observational studies. Interventions included the consumption of any classic psychedelic (lysergic acid diethylamide, psilocybin, ayahuasca/dimethyltryptamine, mescaline), and the studies were required to use some instrument for personality assessment. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to conduct the data collection. Results: Out of 6043 references screened, 48 studies were included: 14 experimental and 34 observational. The most consistent findings were increases in Openness and reductions in Neuroticism , especially with psilocybin and ayahuasca. Changes in other traits, such as Extraversion , Agreeableness , and Conscientiousness , were more variable. Microdosing was associated with modest reductions in Neuroticism and higher Absorption . Most studies used instruments based on the Five-Factor Model, reflecting its growing dominance. Conclusions: Classic psychedelics seem to promote lasting personality changes, most consistently increasing Openness and reducing Neuroticism . Future research would benefit from combining experimental and naturalistic designs, using longer follow-up periods and more diverse personality models to better understand the interplay between psychedelics and personality, thus providing a more accurate guide for clinical use.