ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2023
Acute psilocybin enhances cognitive flexibility in rats.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 2 syntheses or guidelines pooled it, 62 citations in OpenAlex.
- Multilevel Mechanisms and Clinical Efficacy of Psilocybin in Depression Treatment: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Cognitive functioning associated with acute and subacute effects of classic psychedelics and MDMA - a systematic review and meta-analysis.Scientific reports · 2024Pooled it
- Effects of psilocybin on personality, psychiatric symptoms, and values: Exploring mediating effects of the acute psychedelic experience.Journal of psychopharmacology (Oxford, England) · 2026Trial
- Psilocybin therapy for mood dysfunction in Parkinson's disease: an open-label pilot trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Trial
- Serotonin biology as a basis for explaining psychedelic drug action.Current biology : CB · 2026Review
- Single ayahuasca administration mitigates long-term behavioral and neurochemical effects of early-life stress in rats.Journal of neural transmission (Vienna, Austria : 1996) · 2026Article
- Psychedelics do not always enhance cognitive flexibility: The potential role of time-varying effects on reward learning processes.Neuroscience and biobehavioral reviews · 2026Review
- Psychedelics produce enduring enhancement of reward responsiveness in male rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Psilocybin selectively rescues cognitive flexibility impairments caused by aberrant prefrontal error signaling.bioRxiv : the preprint server for biology · 2026Article
- Psilocybin-Assisted Therapy for Adolescent Anorexia Nervosa: Clinical Considerations and Emerging Models of Care.Current psychiatry reports · 2026Review
- Psilocybin ameliorates neuropathic pain-like behaviour in mice and facilitates gabapentin-mediated analgesia.Communications biology · 2026Article
- Effects of psilocybin and chronic mild stress on microglial activation in rat spinal cord: an ex vivo analysis.Pharmacological reports : PR · 2026Article
- Cognitive control as a transdiagnostic mechanism of action in psychedelic effects.Cognitive, affective & behavioral neuroscience · 2026Review
- The Complex Role of Serotonin-Dopamine-Glutamate Receptors in Major Depression.Advances in experimental medicine and biology · 2026Review
- Case Report: Repeated low doses of psilocybin reduce perceived symptom severity but fail to restore cognitive flexibility in a case of severe obsessive-compulsive disorder: an observational case study of identical twins.Frontiers in psychiatry · 2026Article
- The ABCs of psychedelics: a preclinical roadmap for drug discovery.Trends in pharmacological sciences · 2025Review
- Exploring the therapeutic potential of psychedelics in treating substance use disorders.Molecular psychiatry · 2025Review
- Psychedelics in the Treatment of Neurologic and Psychiatric Disorders: Coincidence or a New Point of View.Molecular neurobiology · 2025Review
- How to Improve Cognitive Flexibility: Evidence From Noninvasive Neuromodulation Techniques.CNS neuroscience & therapeutics · 2025Review
- Psychedelics and the Serotonin Hypothesis of Eating Disorders.Brain sciences · 2025Review
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4 authors at 1 institution in 1 country.
Funding
Abstract
Psilocybin has been shown to improve symptoms of depression and anxiety when combined with psychotherapy or other clinician-guided interventions. To understand the neural basis for this pattern of clinical efficacy, experimental and conceptual approaches that are different than traditional laboratory models of anxiety and depression are needed. A potential novel mechanism is that acute psilocybin improves cognitive flexibility, which then enhances the impact of clinician-assisted interventions. Consistent with this idea, we find that acute psilocybin robustly improves cognitive flexibility in male and female rats using a task where animals switched between previously learned strategies in response to uncued changes in the environment. Psilocybin did not influence Pavlovian reversal learning, suggesting that its cognitive effects are selective to enhanced switching between previously learned behavioral strategies. The serotonin (5HT) 2 A receptor antagonist ketanserin blocked psilocybin's effect on set-shifting, while a 5HT2C-selective antagonist did not. Ketanserin alone also improved set-shifting performance, suggesting a complex relationship between psilocybin's pharmacology and its impact on flexibility. Further, the psychedelic drug 2,5-Dimethoxy-4-iodoamphetamine (DOI) impaired cognitive flexibility in the same task, suggesting that this effect of psilocybin does not generalize to all other serotonergic psychedelics. We conclude that the acute impact of psilocybin on cognitive flexibility provides a useful behavioral model to investigate its neuronal effects relevant to its positive clinical outcome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.