ArticleTranslational psychiatry2021
Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder.
Article in Translational psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06798636 (Investigating the Effects of a Psychedelic-augmented Mental Imagery-based Intervention for Young People With Self-harm Behaviour), which is not on this map. Cited by 177 papers, 13 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Investigating the Effects of a Psychedelic-augmented Mental Imagery-based Intervention for Young People With Self-harm Behaviour: an Experimental Medicine Study
Who cites it
177 citing papers in PubMed, 13 syntheses or guidelines pooled it, 321 citations in OpenAlex.
- Predictors of therapeutic response to psychedelic-assisted therapy: A systematic review.Journal of psychopharmacology (Oxford, England) · 2026Pooled it
- Psychedelics and ketamine/esketamine in depressive disorders: biological mechanisms and associated neuroimaging and clinical changes.Translational psychiatry · 2025Pooled it
- Can ketamine and other glutamate receptor modulators be considered entactogens?Psychiatry research · 2025Pooled it
- Acute effects of psilocybin on attention and executive functioning in healthy volunteers: a systematic review and multilevel meta-analysis.Psychopharmacology · 2025Pooled it
- Catalyst for change: Psilocybin's antidepressant mechanisms-A systematic review.Journal of psychopharmacology (Oxford, England) · 2025Pooled it
- Evaluating the effectiveness of psilocybin in alleviating distress among cancer patients: A systematic review.Palliative & supportive care · 2025Pooled it
- Impact of psilocybin on cognitive function: A systematic review.Psychiatry and clinical neurosciences · 2024Pooled it
- Cognitive functioning associated with acute and subacute effects of classic psychedelics and MDMA - a systematic review and meta-analysis.Scientific reports · 2024Pooled it
- Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis.BMJ (Clinical research ed.) · 2024Pooled it
- The association between diverse psychological protocols and the efficacy of psilocybin-assisted therapy for clinical depressive symptoms: a Bayesian meta-analysis.Frontiers in psychiatry · 2024Pooled it
- Default Mode Network Modulation by Psychedelics: A Systematic Review.The international journal of neuropsychopharmacology · 2023Pooled it
- Therapeutic uses of psychedelics for eating disorders and body dysmorphic disorder.Journal of psychopharmacology (Oxford, England) · 2023Pooled it
- A Systematic Review of Neurocognitive Effects of Subanesthetic Doses of Intravenous Ketamine in Major Depressive Disorder, Post-Traumatic Stress Disorder, and Healthy Population.Clinical drug investigation · 2022Pooled it
- Acute and post-acute neurobehavioral responses to lysergic acid diethylamide in healthy subjects: a randomized controlled study.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Trial
- Spatiotemporal mapping of brain organisation following the administration of 2C-B and psilocybin.Molecular psychiatry · 2026Trial
- Effects of psilocybin on personality, psychiatric symptoms, and values: Exploring mediating effects of the acute psychedelic experience.Journal of psychopharmacology (Oxford, England) · 2026Trial
- Psilocybin or Nicotine Patch for Smoking Cessation: A Pilot Randomized Clinical Trial.JAMA network open · 2026Trial
- Negative affective bias in depression following treatment with psilocybin or escitalopram - a secondary analysis from a randomized trial.Translational psychiatry · 2025Trial
- Psilocybin therapy for mood dysfunction in Parkinson's disease: an open-label pilot trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Trial
- Multimodal creativity assessments following acute and sustained microdosing of lysergic acid diethylamide.Psychopharmacology · 2025Trial
117 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Psilocybin has shown promise for the treatment of mood disorders, which are often accompanied by cognitive dysfunction including cognitive rigidity. Recent studies have proposed neuropsychoplastogenic effects as mechanisms underlying the enduring therapeutic effects of psilocybin. In an open-label study of 24 patients with major depressive disorder, we tested the enduring effects of psilocybin therapy on cognitive flexibility (perseverative errors on a set-shifting task), neural flexibility (dynamics of functional connectivity or dFC via functional magnetic resonance imaging), and neurometabolite concentrations (via magnetic resonance spectroscopy) in brain regions supporting cognitive flexibility and implicated in acute psilocybin effects (e.g., the anterior cingulate cortex, or ACC). Psilocybin therapy increased cognitive flexibility for at least 4 weeks post-treatment, though these improvements were not correlated with the previously reported antidepressant effects. One week after psilocybin therapy, glutamate and N-acetylaspartate concentrations were decreased in the ACC, and dFC was increased between the ACC and the posterior cingulate cortex (PCC). Surprisingly, greater increases in dFC between the ACC and PCC were associated with less improvement in cognitive flexibility after psilocybin therapy. Connectome-based predictive modeling demonstrated that baseline dFC emanating from the ACC predicted improvements in cognitive flexibility. In these models, greater baseline dFC was associated with better baseline cognitive flexibility but less improvement in cognitive flexibility. These findings suggest a nuanced relationship between cognitive and neural flexibility. Whereas some enduring increases in neural dynamics may allow for shifting out of a maladaptively rigid state, larger persisting increases in neural dynamics may be of less benefit to psilocybin therapy.
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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.