Spontaneous and deliberate creative cognition during and after psilocybin exposure

Creativity is described as a dynamic cognitive capacity involving shifts between idea generation (divergent thinking, DT) and idea evaluation (convergent thinking, CT). Previous anecdotal and historical reports have linked serotonin 5-HT2A agonist psychedelics such as psilocybin to enhanced creativity, but prior scientific evidence is limited, methodologically heterogeneous, and inconclusive. Contemporary work has suggested psychedelics can produce hyper-associative cognition and persistent changes in DT or CT in naturalistic or pseudo-experimental settings, while neuroimaging studies indicate acute changes in large-scale resting-state networks (RSNs) — notably disintegration of the default mode network (DMN), widened dynamic repertoire of connectivity, and increased coupling of normally anticorrelated networks — that can persist beyond the acute drug phase. Mason and colleagues aimed to provide a controlled experimental test of whether psilocybin affects both the acute and persisting (7-day) components of creative cognition, and whether drug-induced brain changes predict those effects. The study measured task-based DT and CT using the Alternate Uses Test (AUT) and Picture Concept Test (PCT), subjective spontaneous creative experiences via the insightfulness subscale of the 5D-ASC, resting-state functional connectivity (rsfMRI) of the DMN, frontoparietal control network (FPN) and salience network (SN), and local glutamate (via 7T MRS) in the medial prefrontal cortex (mPFC) and hippocampus. The primary hypotheses were that psilocybin would acutely and persistently increase DT (predicted by DMN within-network FC) and acutely decrease CT (predicted by DMN–FPN between-network FC).

This was a double-blind, placebo-controlled, parallel-group randomised trial conducted at Maastricht University between July 2017 and June 2018. Sixty healthy adults with prior psychedelic experience (but none within the prior 3 months) were randomised 1:1 to receive 0.17 mg/kg oral psilocybin or placebo. Groups were matched on age, sex and education. Participants attended three visits: baseline familiarisation and cognitive testing; an acute testing day with drug administration, multimodal neuroimaging and acute cognitive testing; and a follow-up testing day 7 days later. The protocol and ethics approvals followed standard human research guidelines. Creativity assessment used parallel versions of two tasks at baseline, acute and follow-up to reduce learning effects. The PCT was given at ~120 minutes post-dose to index CT (number correct) and DT via alternative associations scored for fluency, originality and an originality/fluency ratio. The AUT (~130 minutes post-dose) required listing uses for two household objects (3 minutes per item) and yielded fluency, originality, ratio and a novelty count based on participant-reported ideas that were entirely new to them. Subjective spontaneous creative cognition was assessed with the insightfulness subscale of the 5D-ASC, administered 360 minutes after treatment. Neuroimaging took place at ultrahigh field (7T). Structural MRI, single‑voxel proton MRS (mPFC and right hippocampus; glutamate/tCr ratios reported) and resting-state fMRI (258 volumes; TR 1400 ms) were acquired during peak effects. Resting‑state preprocessing and independent component analysis (ICA) were performed in the CONN toolbox with 20 components to identify RSNs of interest (DMN anterior/posterior, FPN subcomponents, anterior SN). MRS spectra were analysed with LCModel. Venous blood was sampled at 80, 150 and 360 minutes to measure psilocin concentrations. Statistical analyses included mixed-model ANOVAs with treatment (psilocybin/placebo) as between-subject factor and time (acute, follow-up) and construct as within-subject factors, nonparametric tests for non-normal measures (insightfulness, glutamate), and canonical correlation analysis to relate multivariate biological predictors (within- and between-network FC, glutamate) to multivariate creativity outcomes. Imaging between-network FC used bivariate correlations of ICA-derived time series and FDR correction; within-network contrasts used voxel thresholds and cluster FDR correction. An iterative imputation approach was applied for missing data when needed.

Sample and biosamples: The behavioural sample remained 60 (psilocybin n = 30, placebo n = 30). Psilocin peaked at 80 minutes (15.61 ± 1.66 ng/mL) and measured 12.86 ± 1.13 ng/mL at 150 minutes. Psilocybin increased scores across 5D-ASC subscales, with the insightfulness subscale showing a large effect versus placebo (U = 44.5; p ≤ 0.001; d = 1.78). Relative glutamate concentrations were reported as significantly higher in the mPFC in the psilocybin group, but the extracted text truncates the placebo value and full details are not clearly reported here. Task reliability and behavioural outcomes: Interrater reliability for originality was excellent (ICC = 0.95 for the PCT; ICC = 0.91 for the AUT). On the PCT (acute testing sample: psilocybin n = 25, placebo n = 26) a significant treatment × time × construct interaction was found (F3,47 = 4.53, p = 0.007). Acutely, psilocybin decreased CT (effect size d = 0.85) and DT measures including fluency (d = 0.84) and originality (d = 0.65) relative to placebo. At 7-day follow-up CT remained significantly reduced in the psilocybin group compared to placebo (d = 0.60). On the AUT (psilocybin n = 28, placebo n = 29), there was a parallel treatment × time × construct interaction (F3,53 = 4.50, p = 0.007). Acutely, fluency decreased under psilocybin (d = 0.80). Conversely, at the 7-day follow-up psilocybin increased the number of novel ideas (self-reported novelty) compared to placebo (d = 0.52). No consistent increase in overall fluency or originality at follow-up was reported. Imaging: After quality control the rsfMRI/MRS sample comprised 22 psilocybin and 26 placebo participants. Within-network FC analyses showed significantly reduced coactivation in both anterior and posterior DMN subcomponents under psilocybin versus placebo; within-network FC of the FPN and SN did not differ. Between-network analyses revealed widespread increases in FC under psilocybin, notably between anterior/posterior DMN and FPN subcomponents and between anterior DMN and the SN. Multivariate brain–behaviour relationships: A canonical correlation relating eight biological predictors to eight creativity outcomes produced seven functions; the full model was significant (F(56,193.79) = 1.48, p = 0.027) and explained 85.3% of variance. The first three functions were highlighted. Function 1 (Rc2 = 0.553) implicated higher subjective insight and longer-term increases in novelty as the dominant outcome contributors, with lower within-network anterior and posterior DMN FC as dominant predictors and hippocampal glutamate as a secondary predictor; lower DMN integrity acutely predicted greater insight and later novelty. Function 2 (Rc2 = 0.483) linked acute decreases in originality to lower posterior DMN FC. Function 3 (Rc2 = 0.165) associated acute and long-term decreases in CT with higher between-network FC between DMN components and the FPN. The mPFC glutamate measures did not emerge as strong predictors in the canonical model according to the extracted text. Other notes: The authors acknowledge potential learning effects on the PCT despite using parallel versions and withholding feedback; patterns of within-group change suggested learning in the placebo group that was attenuated by psilocybin. Some imaging–behaviour inferences are qualified by correlating resting-state metrics with tasks performed outside the scanner.

Mason and colleagues interpret their findings as evidence for a time- and construct-dependent effect of psilocybin on creative cognition. Acutely, psilocybin reduced objective task-based measures of both idea generation (DT fluency and some originality measures) and idea evaluation (CT), while increasing subjective reports resembling spontaneous creative insight. Subacutely, at 7 days, the drug increased the number of novel ideas on the AUT without reliably increasing overall fluency or originality. The authors emphasise a dissociation between subjective experience and objective task performance during the acute psychedelic state: individuals felt more insightful even though they produced fewer task-directed ideas. Neurobiologically, acute disintegration (reduced within‑network FC) of the DMN predicted higher subjective insight and later increases in novel idea generation, suggesting a role for DMN integrity in permitting spontaneous, unconstrained cognition. Conversely, increased resting-state coupling between DMN and FPN subcomponents predicted larger decreases in CT both acutely and at follow-up; the authors propose that elevated DMN–FPN coupling at rest may reflect intrusion of internally-focused processes during task contexts, impairing goal-directed evaluation and executive aspects of creativity. Hippocampal glutamate appeared as a secondary predictor linked to insight ratings, potentially implicating medial temporal contributions to DMN desynchronisation and spontaneous associative processes. The mPFC glutamate measures did not show a prominent role in the canonical model, which the authors suggest may reflect the mPFC’s network integrative function rather than local glutamatergic activity per se. Key limitations acknowledged include possible residual learning effects on the PCT despite countermeasures, a reduced imaging sample after quality control that limits power for some neuroimaging analyses, and the inferential gap created by correlating resting-state measures with behavioural tasks performed outside the scanner. The extracted text also lacked full reporting of some glutamate values. The authors therefore present the results as preliminary and call for replication studies that administer creativity tasks during neuroimaging, examine clinical populations, and further probe the temporal dynamics of network and neurochemical changes. Finally, the investigators situate their findings within broader implications: rather than uniformly enhancing creativity, psilocybin appears to shift the balance between spontaneous and deliberate modes of creative cognition in a time-dependent way. They suggest this shift could be relevant to therapeutic strategies for disorders characterised by rigid thought patterns, by temporarily reducing convergent, fixed thinking while increasing spontaneous ideation that may later be integrated in therapy. The authors emphasise the need for targeted clinical studies to evaluate such translational applications.

The study concludes that psilocybin produces a differentiated effect on creative cognition: it acutely reduces performance on task-based convergent and some divergent measures while increasing subjective spontaneous insight, and it increases self-reported novelty of ideas one week later. These effects were associated with acute alterations in DMN integrity and DMN–FPN interactions, supporting the idea that psychedelics can serve as tools to probe neural mechanisms underlying different modes of creative thought. The authors suggest potential therapeutic relevance for conditions with inflexible thinking, but recommend further clinical and mechanistic research before clinical applications are claimed.