Serotonergic psychedelics and personality: A systematic review of contemporary research

The review was conducted according to PRISMA principles. Electronic searches were performed in PubMed, LILACS and SciELO using terms for psychedelics or hallucinogens (including mescaline, psilocybin, LSD, DMT, ayahuasca) combined with "personality". The search covered publications in English from 01 January 1985 to 14 December 2016. Reference lists of retrieved papers were hand-searched for additional citations. The review was restricted to human studies of serotonergic (5-HT2A agonist) psychedelics. Inclusion criteria required peer-reviewed observational or interventional designs that investigated acute or non-acute effects of psychedelics on personality; excluded materials included animal work, reviews, qualitative studies, case reports, letters, abstracts and other non-primary-research items. Two independent reviewers screened titles, abstracts and full texts, with a third reviewer resolving disagreements. Extracted variables comprised authors, year, country, design, sample size, drug and dose, personality measures used, and main findings including statistical thresholds. The literature search yielded 369 unique records; after abstract screening 14 potentially relevant reports were identified and all 14 were included after full-text review, with four further papers added from handsearching, producing a final set of 18 citations. These comprised 10 observational studies and 8 interventional trials. The included work covered studies of ayahuasca, psilocybin, LSD and some broader assessments of hallucinogen users. The authors noted heterogeneity across measures, sample sizes and designs but observed that most interventional trials were placebo-controlled and many observational studies used matched controls.

Overall, the 18 included studies addressed three broad contexts: recreational or polydrug users, long-term ritual/ceremonial users (principally ayahuasca religions), and controlled experimental administrations in healthy volunteers. Despite heterogeneity and generally small samples, a pattern emerged across controlled studies that acute administration of serotonergic hallucinogens can be associated with increases in Openness (a Big Five trait reflecting imagination, aesthetic sensitivity and intellectual curiosity), with effects sometimes persisting for days to months. Interventional findings: Combined analyses of two double-blind controlled psilocybin studies (MacLean et al.) reported significant increases in Openness at 1–2 months after high-dose psilocybin (30 mg/70 kg) compared to baseline (P < 0.023, uncorrected), with changes especially marked in participants who had a "complete mystical experience"; Openness increases correlated with measures of mystical-type and altered-state experiences. By contrast, a 14-month follow-up of an earlier psilocybin trial found no significant personality changes. In a single-blind, placebo-controlled within-subjects study, intravenous LSD (75 μg) produced acute mood improvements and, at two weeks, significant increases in Optimism (LOT-R, P = 0.005, corrected) and Openness (NEO PI-R, P = 0.03, corrected). Neuroimaging from the same LSD cohort showed increased global and regional brain entropy under LSD, and increases in entropy predicted the observed Openness changes (relationships strengthened by music-listening). Observational findings: Studies of long-term ritual ayahuasca users (e.g. União do Vegetal, Santo Daime, Barquinha) commonly found lower Harm Avoidance and higher Self-Transcendence compared with matched nonusers. Specific reports included Grob et al.'s finding of lower Novelty Seeking and Harm Avoidance in UDV members, and Bouso and colleagues' reports of higher reward dependence, self-transcendence and helpfulness, alongside lower harm avoidance and self-directedness in ayahuasca users versus controls; many of these differences remained stable at one-year follow-up. Barbosa et al. conducted a six-month follow-up of naïve participants beginning ceremonial use and reported changes in Harm Avoidance, Reward Dependence, Novelty Seeking and Self-Transcendence associated with participation. A Spanish ayahuasca study found that higher self-transcendence scores correlated inversely with cortical thickness in the posterior cingulate cortex (PCC), linking a personality measure with a neuroanatomical difference. Studies of non-ritual recreational users tended to show higher sensation-seeking, experience-seeking and disinhibition traits; one large occupational sample reported 24% lifetime LSD experimentation among serotonergic hallucinogen users. Other results: Personality predicted aspects of the acute psychedelic response in several studies. Higher Absorption (TAS) and certain baseline emotional states predicted more positive or mystical-type experiences with psilocybin, while higher neuroticism was associated with greater likelihood of unpleasant LSD experiences in some datasets. Across observational studies, long-term ritual use was not associated with increased rates of psychopathology or personality disorder; the authors note associations between ritual use and outcomes described as antidepressant, anxiolytic or antiaddictive, but emphasise these data are observational and do not establish causality.

Bouso and colleagues interpret the evidence as indicating three main types of findings: 1) baseline personality traits influence how individuals respond to psychedelic experiences; 2) consistent personality differences exist between psychedelic users and nonusers, with ritual ayahuasca practitioners showing profiles characterised by higher self-transcendence and lower harm avoidance; and 3) controlled administration of psychedelics can produce measurable changes in some traits, notably Openness, though replication is limited. The authors situate these findings within the renewed scientific interest in psychedelics and note that modern psychometric instruments and neuroimaging techniques allow more precise investigation than earlier work. The review highlights plausible neurobiological mechanisms discussed by the authors: serotonergic psychedelics act as 5-HT2A (and related) receptor agonists in cortical regions, and acute effects on perception, memory and self-awareness may reflect receptor-mediated synaptic changes; longer-term effects might involve psychological reorientation after profound subjective experiences or modulation of gene expression. Neuroimaging findings linking cortical thinning or increased brain entropy to personality measures are offered as preliminary evidence for brain–personality associations. Key limitations are emphasised. The authors point to the small number of studies, small sample sizes, heterogeneity in personality measures and study designs, and the observational nature of many reports that preclude causal inference. They also note potential self-selection bias among ceremonial retreat attendees and the difficulty of distinguishing drug effects from cultural or community factors in ritual contexts. Conflicting results between studies (for example, mixed findings on long-term changes after psilocybin) lead the authors to call for well-controlled, prospective research with standardised measures and larger samples. In terms of implications, the authors suggest this literature could inform debates about personality plasticity and be relevant for therapeutic contexts where personality change might be a meaningful outcome. They recommend further experimental replication, longitudinal designs to disentangle cause and effect, and mechanistic studies linking receptor action, neural dynamics and personality measures.

The authors conclude that contemporary evidence points to three related conclusions: certain personality traits modulate individuals' responses to psychedelics; measurable personality differences are observed between users and nonusers (both recreational and ritual); and controlled psychedelic administration may induce some persistent changes in personality, especially increases in Openness. They emphasise, however, that the evidence for enduring personality change after controlled administration remains weak and limited by methodological constraints. Mechanistically, transient effects may stem from receptor-mediated synaptic changes, while longer-term effects could involve psychological transformation or altered gene expression. Finally, the review notes two practical implications raised by the authors: this research bears on the stability versus malleability debate in personality science, and personality measures may be useful both as outcomes and as process variables in psychotherapeutic applications of psychedelics, pending more definitive evidence.