Classic psychedelics and personality: An updated systematic review

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.

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.

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.

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.