Journal of Psychopharmacology
January 17, 2018
Taylor Lyons, Robin Carhart‐Harris
176 citations
In patients with moderate to severe treatment-resistant depression, psilocybin given in two oral doses (10 mg and 25 mg one week apart) was associated with increased nature relatedness and decreased authoritarianism one week after dosing. Nature relatedness remained significantly higher 7–12 months later, while the reduction in authoritarianism persisted only at a trend level. No changes occurred in healthy control subjects. The findings suggest that psilocybin combined with psychological support may produce lasting shifts in attitudes and beliefs, though the small sample size precludes causal conclusions.
Frontiers in Psychology
October 12, 2018
Taylor Lyons, Robin Carhart‐Harris
78 citations
Patients with treatment-resistant depression showed a significant pessimism bias when predicting future life events, which was linked to the severity of their depressive symptoms. One week after receiving two doses of psilocybin (10 and 25 mg) with psychological support, this pessimism bias decreased significantly, depressive symptoms greatly improved, and patients became more accurate at predicting future events. No such change occurred in non-depressed controls. The findings suggest that psilocybin with psychological support might correct pessimism biases in treatment-resistant depression, enabling a more positive and accurate outlook.
Scientific reports
January 29, 2025
Richard J Zeifman, Meg J Spriggs, Hannes Kettner et al.
26 citations
A preliminary test of the REBUS model found that a high dose of psilocybin (25 mg) reduced confidence in negative self-beliefs in 11 healthy individuals, both during the acute experience and four weeks later. Greater brain signal entropy and stronger subjective effects under psilocybin correlated with larger decreases in negative self-belief confidence. Decreases in negative self-belief confidence were linked to increases in well-being. The findings provide initial evidence that relaxing and revising negative self-beliefs may underlie psilocybin's positive psychological effects, with increased neuronal entropy as a possible mechanism. Replication in larger clinical samples is needed.
Journal of Psychopharmacology
November 14, 2022
Meg J Spriggs, Bruna Giribaldi, Taylor Lyons et al.
15 citations
A fixed 25 mg dose of psilocybin produces similar acute psychedelic effects and improvements in well-being regardless of body mass index (BMI). Pooling data from three therapeutic studies, results support the null hypothesis that BMI does not predict overall intensity of the altered state, mystical experiences, perceptual changes, or emotional breakthroughs. There was weak evidence that lower BMI participants reported greater 'dread of ego dissolution,' but BMI did not meaningfully add to predictions beyond age, sex, and study. Mystical-type experiences and emotional breakthroughs strongly predicted well-being improvements, but BMI did not. These findings suggest body weight-adjusted dosing may be unnecessary, supporting fixed dosing to reduce practical and financial burdens on psychedelic therapy scalability.
July 7, 2022
Richard J. Zeifman, Meg J. Spriggs, Hannes Kettner et al.
13 citations
preprint
The Relaxed Beliefs Under pSychedelics (REBUS) model suggests that psychedelics reduce the strength of deeply held beliefs. In a preliminary test of this idea, 11 healthy adults received a low (1 mg) and a high (25 mg) dose of psilocybin four weeks apart. Confidence in negative self-beliefs decreased after the high dose but not after the low dose. Greater brain signal entropy and stronger subjective effects during the high dose correlated with larger decreases in negative belief confidence, both during the session and four weeks later. Reduced confidence in negative beliefs was strongly linked to improved well-being at the four-week follow-up. These findings provide initial psychological support for the REBUS model, though replication in larger and clinical samples is needed.
Frontiers in Psychology
June 6, 2025
William Roseby, Hannes Kettner, Leor Roseman et al.
6 citations
Psychedelics like psilocybin strongly increase the sense that life has meaning, based on three different studies: a clinical trial for depression, a healthy volunteer study, and naturalistic retreats. The 'presence of meaning' rose substantially after a psychedelic experience, while the 'search for meaning' dropped only slightly. These meaning enhancements were moderately linked to improvements in mental health, such as greater wellbeing and reduced depression. Mystical, ego dissolution, and emotional breakthrough experiences were associated with increased meaning, though the strength varied by context. The evidence converges to show a robust, lasting positive effect of psychedelics on meaning in life, with context influencing outcomes.
Neuroscience Applied
December 2, 2024
Kate Godfrey, Brandon Weiss, Joseph Peill et al.
5 citations
A single high dose of psilocybin (25 mg) given to healthy volunteers who had never used psychedelics reduced neuroticism one month later, consistent with prior research. The reduction was linked to how meaningful the experience felt and to the dread of ego dissolution during the drug's acute effects. Personality was measured with the Big Five Inventory and Big Five Aspect Scale; acute effects were tracked with the Altered States of Consciousness questionnaire and Psychological Insight Scale. Electroencephalography measured alpha power and Lempel-Ziv complexity. The findings suggest that acute psychedelic states can catalyze lasting personality changes in a beneficial direction, with implications for therapy and understanding personality.
bioRxiv (Cold Spring Harbor Laboratory)
November 7, 2024
Lorenzo Pasquini, Jakub Vohryzek, Anira Escrichs et al.
4 citations
preprint
Psilocybin induces fast and sustained improvements in mental well-being, yet its long-term mechanisms are not fully understood. Four weeks after a full dose, fronto-striatal-thalamic (FST) circuitry—involved in goal-directed behavior and motivation—shows increased dynamic activity and flexibility in healthy volunteers. Computational modeling indicates that reduced structural constraints on functional dynamics cause this increased flexibility. Long-term changes include increased bottom-up and reduced top-down information flow, mediated by serotonergic (5-HT2A) and dopaminergic (D2) receptor systems. This functional re-organization of FST circuits may represent a common mechanism underlying clinical improvements across neuropsychiatric disorders such as substance abuse, major depression, and anorexia.
medRxiv
March 21, 2025
Jessica S. Henry, Bruna Giribaldi, David Nutt et al.
2 citations
preprint
In a randomized controlled trial of 59 patients with major depressive disorder, two high-dose psilocybin therapy sessions produced large increases in optimism and improvements in dysfunctional attitudes related to achievement, dependency, and self-control after six weeks. By contrast, a six-week daily course of escitalopram produced no change in optimism and only improved dysfunctional attitudes in the achievement domain. Psilocybin therapy was superior to escitalopram in remediating negative cognitive biases in depression.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
June 23, 2025
Jessica Henry, Bruna Giribaldi, David J Nutt et al.
1 citation
In patients with major depressive disorder, two high-dose psilocybin therapy sessions produced large increases in optimism and improvements in all three domains of dysfunctional attitudes (achievement, dependency, self-control) at six weeks, while a six-week daily course of escitalopram improved only the achievement domain and did not change optimism. Psilocybin also made patients more optimistic about desirable life events, whereas escitalopram reduced pessimism about negative life events. The findings suggest psilocybin therapy is superior to escitalopram for remediating negative cognitive biases in depression.
Journal of psychopharmacology (Oxford, England)
May 1, 2026
Otto Simonsson, Taylor Lyons, Joseph Marks et al.
Across three studies—a naturalistic observation, a single-arm psilocybin trial with healthy volunteers, and a randomized controlled trial comparing psilocybin to escitalopram in depressed patients—psychedelic use did not produce significant changes in authoritarian attitudes. Contrary to earlier suggestions, the evidence does not reliably show that psychedelics decrease authoritarian attitudes. Future work should use larger, more diverse samples and examine other political outcomes.