A Dose of Creativity: An Integrative Review of the Effects of Serotonergic Psychedelics on Creativity

The paper is presented as an integrative literature review carried out according to PRISMA guidelines. Electronic searches were performed in multiple databases; the results section reports 401 initial records comprising 272 from MEDLINE, 69 from Web of Science, and 60 from PsycINFO, supplemented by hand‑searching references of relevant articles. After deduplication and screening by title and abstract, studies were selected for full‑text review and final inclusion. The selection and screening process was performed by a single reviewer. Data extraction logged study characteristics including authors, year, study design, sample and size, drug and dosage, phase assessed (acute, sub‑acute, long‑term), creativity measures used, task approach (process, person, product, press), and outcomes. The authors conducted a critical appraisal of included studies using the Joanna Briggs Institute tools for systematic reviews. Given the heterogeneity of designs (randomised trial, quasi‑experiments, naturalistic observational studies) and outcome measures, the synthesis is qualitative rather than meta‑analytic. The review emphasises measures of divergent and convergent thinking as the principal outcome domains across studies, with relatively scarce use of product or person approaches.

From 401 initial records, the review identified 10 studies for qualitative synthesis (publication years 1964–2019). Study designs included one randomised controlled trial, five quasi‑experimental studies, and four observational naturalistic studies. Sample sizes ranged roughly from the high teens to 72 participants; most studies enrolled healthy volunteers. Creativity assessment predominantly targeted process measures—divergent thinking and convergent thinking—with only a single instance of product assessment. Early experimental work: McGlothlin et al. (1964) used a quasi‑experimental design with 15 LSD subjects (200 μg) and 14 non‑placebo controls; after accounting for practice effects the study found no significant sub‑acute (one week) changes in divergent or convergent thinking. Harman et al. (1966) administered mescaline (200 mg) in a setting designed to promote expectancy and task focus; among 18 participants who completed a creativity task, fluency of ideas increased in 13 subjects, while flexibility did not change significantly. McGlothlin et al. (1967) ran a larger study of 72 male graduate students across three matched groups (200 μg LSD, 25 μg LSD, and 20 mg amphetamine); 25% of the 200 μg LSD group self‑reported enhanced creativity at six months versus 9% and 0% in control groups, but objective measures of creativity showed no significant changes at two weeks or six months. Zegans et al. (1967) randomised 20 subjects to LSD and 11 to control and stratified participants by projective test predictions of responsiveness. The LSD group showed some acute mean improvements on several creativity tests (except the Remote Associates Test), outperforming controls on one task (WAT) but performing worse on another (MDT); effects varied by individual predisposition, suggesting that LSD may enhance access to remote associations in suitably predisposed subjects while impairing aspects of product development. Naturalistic and modern studies: Frecska et al. (2012) compared 40 ceremony participants ingesting repeated doses of ayahuasca over two weeks with 21 controls and used the Torrance Tests of Creative Thinking. Repeated ayahuasca ingestion did not change fluency, relative flexibility, or relative originality, but significantly increased the number of highly original solutions. Kuypers et al. (2016) assessed two groups (total N = 26) during ayahuasca ceremonies with controlled sampling of DMT concentrations; on the Picture Concept Task (PCT) ayahuasca increased originality but decreased convergent thinking acutely, with group differences and dose‑related patterns suggesting a possible inverted‑U dose response for fluency. Uthaug et al. (2018), an observational study of 57 ayahuasca participants assessed at baseline, 24 hours and 4 weeks, reported that convergent thinking increased at 24 hours (approaching significance) and reached significance at 4 weeks, while divergent thinking parameters were unchanged; ego‑dissolution did not correlate with convergent thinking changes. Procházková et al. (2018) evaluated microdosing of psilocybin‑containing truffles in 38 participants and reported significant improvements in both convergent and divergent thinking (fluency, flexibility, originality) the morning after ingestion, with no change in fluid intelligence; dose, weight, and prior experience did not interact with the time effect in their analyses. A separate naturalistic psilocybin study reported increased fluency and originality the morning after and increased convergent thinking seven days later, but high attrition and incomplete extraction details limit clarity of that result in the extracted text. Uthaug et al. (2019) studied inhalation of dried toad secretion containing 5‑MeO‑DMT in 42 participants and observed significant increases in convergent thinking at 24 hours and at 4 weeks compared with baseline; divergent thinking measures were unchanged. Convergent thinking increases were negatively correlated with measures of ego‑dissolution, and country‑level differences were reported. Across studies, adverse event reporting was limited in the extracted text; methodological concerns noted by the authors included variable dosing, lack of placebo controls, absence of blinding in many studies, self‑selection and attrition biases, and heterogeneous outcome measures.

Abi‑Dargham and colleagues interpret the assembled evidence as indicating a pattern in which classic serotonergic psychedelics tend to enhance aspects of divergent thinking during the acute psychedelic state—particularly originality and fluency—while convergent thinking may be impaired acutely but can improve during sub‑acute or longer‑term periods. The authors link acute increases in divergent thinking to drug‑induced changes in brain dynamics: 5‑HT2A receptor activation may produce neural hyperconnectivity and reduced segregation between the default mode network and task‑positive networks, potentially increasing access to remote associations and internal imagery. Indirect modulation of mesolimbic dopamine is offered as another pathway by which psychedelics might alter flexibility and latent inhibition, remembering the proposed inverted‑U relationship between dopamine and cognitive performance. The review highlights dose‑dependence as a plausible moderator: microdoses or sub‑perceptual doses of psilocybin were associated with improved convergent thinking in one study, suggesting that low doses that do not induce a full altered state might benefit persistence‑based cognitive processes, whereas higher, hallucinogenic doses may disrupt them. Individual differences also emerged as important: predisposition, cognitive capacity, and personality traits such as openness may determine who benefits creatively. The authors stress that the majority of studies assessed only process measures (divergent/convergent thinking) and that product‑ and person‑level outcomes (actual creative achievement or domain‑specific creative production) are under‑studied. Key limitations acknowledged by the authors include generally small sample sizes, paucity of randomised controlled trials (only one early RCT), frequent lack of placebo or double‑blind conditions, uncontrolled or unreported dosing in naturalistic studies, potential self‑selection and expectancy effects, and substantial heterogeneity in creativity measures. The authors call for future research using randomised, placebo‑controlled designs, standardised dosing and measurement, investigations of dose‑response (including microdosing), domain‑specific product assessments, and exploration of how ego‑dissolution and positive versus negative subjective experiences interact with creative outcomes. They also recommend studies that examine individual moderators such as IQ, executive function, and personality.

The authors conclude that current evidence, though limited and methodologically heterogeneous, suggests psychedelics can affect creative thinking: enhancing divergent thinking acutely and potentially improving convergent thinking in post‑acute or longer‑term phases. They emphasise the tentative nature of these findings given small samples, methodological shortcomings, and the scarcity of randomised controlled trials. The review identifies substantial gaps—particularly in product‑level and person‑level assessment and in controlled dose‑response studies—and recommends that future rigorous trials and diversified measurement approaches are needed to clarify whether and how psychedelics could be used strategically to boost creative production.