A recent systematic review Journal of Psychopharmacology Classical psychedelic use has been suggested to be associated with lasting changes in personality traits, particularly increased openness and decreased neuroticism. A comprehensive analysis of nearly 50 recent studies provides evidence that substances like psilocybin, LSD, and ayahuasca can shape human personality in lasting ways.
Psychologists often understand human personality through the five-factor model. This framework divides personality into five broad categories. These are openness to experience, conscientiousness, extraversion, agreeableness, and neuroticism.
Openness reflects curiosity, imagination, and a willingness to accept new ideas. Integrity includes self-discipline, organization, and goal-directed behavior. Extraversion captures a person’s sociability, aggressiveness, and energy level.
Agreeableness refers to a tendency to empathize with, cooperate with, and consider others. Neuroticism refers to how people deal with negative emotions, and high levels indicate vulnerability to anxiety, mood swings, or depression.
Although personality tends to be stable over the lifespan, evidence shows that life experiences and biology can change these enduring traits. Biology and environmental influences interact to constantly adjust how personality traits are expressed. In recent years, scientists have focused on how classic psychedelics affect these psychological categories.
Classic psychedelics include substances such as psilocybin, LSD, mescaline, and ayahuasca. These drugs primarily interact with serotonin receptors in the brain and help regulate mood, cognition, and perception. A previous review in 2018 examined early evidence of personality changes associated with these substances.
Since then, the field of psychedelic science has grown significantly. The authors of the current paper aimed to update that old literature review. Rafael Guimarães dos Santos, a professor in the Department of Neuroscience and Behavior at the Ribeirão Preto School of Medicine at the University of São Paulo in Brazil, helped lead the new analysis.
“The effects of classic psychedelic drugs (5-HT2A receptor agonists, LSD, DMT, psilocybin) on personality traits have been studied for decades, and it has been hypothesized that the mechanisms underlying these changes are related to agonism of cortical serotonergic 5-HT2A receptors,” said Dos Santos, who is also a member of the Fantastica Institute.
Agonism refers to a chemical binding to a receptor and activating it. In this case, the drug activates specific serotonin receptors in the outer layer of the brain. “For example, some studies have found that openness increases and neuroticism decreases,” Dos Santos added. “However, research results are contradictory.”
To resolve these discrepancies, the researchers wanted to capture the recent surge in data. They were particularly interested in studies that investigated naturalistic drug use and microdosing. Naturalistic use refers to people taking psychedelics in real-world settings rather than in a laboratory. Microdosing involves taking very small amounts of a sub-hallucinogenic drug on a regular schedule.
The scientists searched four major academic databases for papers published between January 2016 and early 2025. They screened more than 6,000 scientific abstracts to find studies that specifically focused on classic psychedelics and personality assessment. This process yielded 48 relevant studies.
The final collection included 14 experimental trials and 34 observational studies. Experimental trials are conducted in controlled laboratory or clinical settings and often use a placebo comparison to test specific drug doses. Observational studies follow people who are already using these substances themselves.
Across the 48 papers, sample sizes varied widely. Some clinical trials had fewer than 20 participants, while some online surveys collected data from thousands of recreational users. Most of the included studies relied on questionnaires based on the five-factor model to measure personality traits, although some used alternative psychological frameworks.
When the data were combined, the researchers found some consistent patterns. People who use psychedelics long-term share similar personality profiles, and the substances themselves appear to promote these changes.
“In fact, the most consistent results were an increase in openness and a decrease in neuroticism, especially in the case of psilocybin and ayahuasca,” dos Santos told Cypost. “Changes in other traits, such as extraversion, agreeableness, and conscientiousness, were more variable. However, controlled studies were few and the number of doses administered was limited, making comparisons with real-world usage scenarios difficult.”
Observational data shows that experienced users tend to have unusually high openness scores and low neuroticism scores. In some groups, such as those that use ayahuasca in traditional religious ceremonies, individuals also exhibit higher levels of attunement and self-transcendence. Self-transcendence is a psychological concept related to connection with the wider universe, spiritual acceptance, and oneness with nature.
A person’s basic personality tends to predict how they will react to hallucinogens. Participants with higher innate openness scores are more likely to have positive, deep and meaningful experiences during their psychedelic trips. People with high levels of neuroticism or impulsivity are prone to psychological reactions of defiance, anxiety, or fear. This finding highlights how a person’s initial mindset can shape their response to powerful psychoactive compounds.
This review presents evidence that consuming psychedelics under controlled conditions can cause lasting personality changes. In clinical trials involving psilocybin, the active compound in “magic mushrooms,” participants consistently showed reduced neuroticism and increased openness. These psychological changes often remained stable for several months after drug administration. In some clinical studies, patients treated with psilocybin also showed a slight increase in extraversion.
Similar long-term effects were found in controlled trials testing LSD. Healthy volunteers and patients who received LSD in an experimental setting showed a sustained reduction in neuroticism. Evaluations up to a year after LSD sessions also showed that these people had increased extraversion and conscientiousness.
The findings regarding ayahuasca were a little more complicated in experimental settings. Although observational studies have shown that ayahuasca use is significantly associated with increased openness and reduced neuroticism, controlled clinical trials have not always been able to precisely reproduce these results. One controlled trial found that openness increased after ayahuasca administration, but other trials found no significant changes in personality traits. Scientists suggest that differences in the chemical composition of various ayahuasca brews may contribute to these inconsistent results.
This review also focused on the practice of microdosing psychedelic drugs, which has been studied primarily through observational studies. The authors found that people who microdosed on a daily basis reported moderate reductions in neuroticism and higher levels of absorption. Absorption is a characteristic that describes how easily a person becomes fully immersed in a sensory or imaginative experience. Changes in other traits, such as extraversion and conscientiousness, were less consistent across the microdosing literature.
Although the data collected shows that psychedelics shape personality, the authors point out some potential misconceptions and limitations. Because the majority of reviews rely on observational studies, scientists cannot conclusively prove cause and effect in these specific cases.
“The data are difficult to interpret because there were several study designs and some people may already have different personality traits at baseline that may be associated with psychedelic drug use,” Dos Santos said. “For example, people with high baseline traits such as tolerance for experience and neuroticism may be more likely to take psychedelic drugs.”
Observational studies often rely on self-reported data and can be influenced by personal biases and expectations. If a person expects a drug to make them more empathetic or open-minded, they are likely to rate themselves more highly on those traits after taking the drug. Experimental tests provide more rigorous evidence to counter this issue. However, clinical trials often have small sample sizes and carefully selected participants, making it difficult to communicate the results to the general public.
Future studies would benefit from combining controlled experimental procedures with long-term naturalistic tracking. The authors suggest using a longer follow-up period to see if changes in personality really persist over many years. We also recommend the use of more diverse personality questionnaires to capture individual differences that may be missed by standard models.
Expanding these research methods will help scientists understand exactly how psychedelics alter human personality, allowing them to provide more precise guides for clinical applications. To build on this systematic review, the research team is actively expanding its focus. “Most studies have been conducted in healthy volunteers, so we are currently investigating these variables in clinical populations,” Dos Santos said.
The study, “Classical Psychedelics and Personality: An Updated Systematic Review,” was authored by Anna Beatriz Visentini, Caio César de Paula, José Augusto Silva Reis, José Carlos Buso, Jaime EC Hallac, and Rafael G. dos Santos.
