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Home/Research/Psilocybin/Neurocognitive Disorders

Psilocybin for Neurocognitive Disorders

18 papers and 11 clinical trials exploring psilocybin as a treatment for neurocognitive disorders.

CompoundClassic Psychedelic

Psilocybin

Psilocybin is a naturally occurring tryptamine psychedelic that acts as a prodrug to psilocin, a potent 5-HT2A receptor agonist. It is the furthest advanced psychedelic in clinical development, with two positive Phase III trials in treatment-resistant depression and expanding regulated access in Australia, Germany, and US states.

Full Psilocybin profile
Indication55M+ people living with dementia worldwide

Neurocognitive Disorders

Neurocognitive disorders, including dementia, Alzheimer's disease, Parkinson's disease and traumatic brain injury, involve a progressive decline in memory, thinking and everyday function. Interest in psychedelics here rests on a strong biological rationale and early human safety signals, not on proven treatment: no completed controlled trial yet shows that psychedelics treat dementia or restore lost cognition.

Full Neurocognitive Disorders profile

Academic Research

18 papers
Open Accessindividual

Cognitive outcomes following psilocybin-assisted therapy in treatment-resistant depression: A post-hoc analysis of a randomized, waitlist-controlled trial

This secondary analysis (n=26) of adults with treatment-resistant depression from an open-label psilocybin-assisted psychotherapy trial found statistically significant improvements in processing speed and executive function at two weeks post-treatment, with gains on Trail Making Tests remaining significant after adjusting for depressive symptoms; however, reliable change indices showed that the proportion of participants achieving meaningful improvement (4.2–12.5%) did not exceed chance expectations, suggesting observed gains may reflect practice effects rather than genuine procognitive benefits.

Published
December 1, 2025
Journal
Progress in Neuro-Psychopharmacology and Biological Psychiatry
Authors
Johnson, D. E., Meshkat, S., Kaczmarek, E. S., Rabin, J. S., Brudner, R. M., Chisamore, N., Doyle, Z., Bawks, J., Riva-Cambrin, J., Mansur, R. B., Lipsitz, O., McIntyre, R. S., Lanctôt, K. L., Rosenblat, J. D.
Open Accessindividual

Cross-Species Evidence for Psilocin-Induced Visual Distortions: Apparent Motion Is Perceived by Both Humans and Rats

This cross-species experimental study (n=21 humans; n=10 rats) finds that psilocin (18.2mg/70kg for humans; 0.3mg/kg for rats) impairs the ability to distinguish between static and moving images in both humans and rats. In humans, the impairment aligns with psilocin plasma levels and self-reported hallucination intensity. In rats, the effect is specific to motion perception, providing the first evidence of psilocin-induced visual distortions across species.

Published
September 1, 2025
Journal
Biological Psychiatry
Authors
Vejmola, C., Šíchová, K., Syrová, K., Janečková, L., Koudelka, V., Tesař, M., Nikolič, M., Viktorin, V., Viktorinová, M., Tylš, F., Korčák, J., Kelemen, E., Nekovářová, T., Brunovský, M., Horáček, J., Kuchař, M., Páleníček, T.
Open Accessindividual

Psilocybin treatment extends cellular lifespan and improves survival of aged mice

This mouse study (n=58) provides the first experimental evidence that psilocin extends cellular lifespan and that psilocybin promotes increased longevity in aged mice. The findings suggest psilocybin may have geroprotective potential, though the molecular mechanisms remain unclear.

Published
July 8, 2025
Journal
npj Aging
Authors
Kato, K., Kleinhenz, J. M., Shin, Y. J., Coarfa, C., Zarrabi, A. J., Hecker, L.
Open Accessindividual

Psilocybin therapy for mood dysfunction in Parkinson's disease: an open-label pilot trial

In an open‑label pilot of 12 people with mild–moderate Parkinson’s disease and comorbid depression/anxiety, two psilocybin doses combined with psychotherapy were well tolerated with no serious adverse events. Participants showed clinically meaningful, sustained improvements in depression and anxiety and gains in non‑motor, motor and select cognitive measures up to three months post‑treatment, indicating psilocybin therapy in PD warrants further study.

Published
April 9, 2025
Journal
Neuropsychopharmacology
Authors
Bradley, E. R., Sakai, K., Fernandes-Osterhold, G., Szigeti, B., Ludwig, C., Ostrem, J. L., Tanner, C. M., Bock, M. A., Llerena, K., Finley, P. R., O'donovan, A., Rafael, J., Zuzuarregui, P., Busby, Z., Mckernan, A., Penn, A. D., Wang, A. C. C., Rosen, R. C., Woolley, J. D.
Open Accessmeta

Side Effects of Microdosing Lysergic Acid Diethylamide and Psilocybin: A Systematic Review of Potential Physiological and Psychiatric Outcomes

This systematic review (s=31) examines the side effects of microdosing LSD and psilocybin, finding that adverse effects are typically dose-dependent, mild, and short-lived. Common side effects include increased blood pressure, anxiety, and cognitive impairment. The review highlights the lack of standardised reporting on side effects and calls for future studies to provide more systematic and transparent assessments.

Published
February 26, 2025
Journal
Neuropharmacology
Authors
Modzelewski, S., Waszkiewicz, N., Lukasiewicz, K., Stankiewisz, A.
Open Accessmeta

Default Mode Network Modulation by Psychedelics: A Systematic Review

This systematic review shows that classical psychedelics (LSD, psilocybin, ayahuasca) consistently cause acute disruption of resting-state connectivity within the Default Mode Network and increase cross-network functional connectivity, but it remains unclear how central DMN modulation is to their therapeutic effects. The article synthesises existing evidence and highlights gaps to guide future mechanistic research.

Published
October 22, 2022
Journal
International Journal of Neuropsychopharmacology
Authors
Gattuso, J. J., Perkins, D., Ruffell, S. G. D., Lawrence, A. J., Hoyer, D., Jacobson, L. H., Timmermann, C., Castle, D., Rossell, S. L., Downey, L., Pagni, B. A., Galvão-Coelho, N. L., Nutt, D. J., Sarris, J.

Clinical Trials

11 trials
Not yet recruitingPhase II

The Efficacy of Psilocybin Therapy for Depression in Parkinson's Disease

This Phase II, randomised, quadruple-masked, parallel-group trial (n=40) will evaluate oral psilocybin therapy for depression in people with Parkinson’s disease. The study will assess whether two psilocybin administration sessions, delivered in a monitored setting with psychotherapeutic support, improve depressive symptoms and other clinical outcomes in participants with early to moderate Parkinson’s disease and moderate or greater depression. Participants with Hoehn and Yahr stage 1–3 Parkinson’s disease and a baseline Beck Depression Inventory-2 score of at least 20 will receive one dose of psilocybin ranging from low (“microdose”) to high in each of two drug administration sessions, with preparation psychotherapy before and integration sessions after. Outcomes will include change in depression measured by the Montgomery-Asberg Depression Rating Scale from baseline to 30 days after the first dose, as well as safety, tolerability, non-motor and motor symptoms of Parkinson’s disease, cognitive performance, and quality of life, with follow-up continuing for 3 months after the second session.

Started
May 1, 2026
Type
interventional
Blinding
quadruple
Randomized
Yes
Registry ID
NCT07610369
RecruitingPhase I

Effects of Psilocybin in Patients With Amyotrophic Lateral Sclerosis

This open-label trial (n=24) will assess the feasibility of psilocybin therapy in patients with Amyotrophic Lateral Sclerosis (ALS) experiencing depressed mood. Participants will undergo an 8-week treatment course, including two psilocybin sessions (15 mg in week 4 and 15 or 25 mg in week 6), with follow-up assessments at 1, 3, and 6 months post-treatment.

Started
February 28, 2025
Type
interventional
Blinding
none
Randomized
No
Registry ID
NCT06656702
CompletedPhase NA

Evaluation of the Effect of a Single Dose of Psilocybin on Neural Correlates of Cognitive Control in Patients with Psychogenic Nonepileptic Seizures (CRIPSY)

Open-label single-group interventional study (n=4) assessing a single 25 mg oral dose of psilocybin with MRI pre/post to evaluate neural correlates of cognitive control in patients with PNES.

Started
November 1, 2024
Type
interventional
Blinding
none
Randomized
No
Registry ID
NCT06647056
RecruitingPhase I

Treatment of Persistent Post-concussive Symptoms With Psilocybin Assisted Therapy (PatACT)

This randomised, quadruple-blind, placebo-controlled trial (n=40) will evaluate the safety, feasibility, and efficacy of psilocybin-assisted therapy in adults aged 18–65 with persistent post-concussion symptoms (PPCS). Participants will receive either a high dose (25mg) or a low dose (1mg) of psilocybin and undergo 5–6 weekly sessions of BrainACT, an adapted form of Acceptance and Commitment Therapy (ACT) for individuals with acquired brain injury.

Started
October 30, 2024
Type
interventional
Blinding
quadruple
Randomized
Yes
Registry ID
NCT06615908
RecruitingPhase II

Psilocybin Therapy for Depression in Parkinson’s Disease (PDP2)

This randomised controlled trial (n=60) will assess the efficacy of oral psilocybin therapy for depression in individuals with Parkinson’s disease.

Started
July 1, 2024
Type
interventional
Blinding
quadruple
Randomized
Yes
Registry ID
NCT06455293
Active not recruitingPhase II

Does Psilocybin Change Synaptic Density in Amnestic Mild Cognitive Impairment

This Phase II interventional trial (n=60) aims to investigate whether psilocybin affects synaptic vesicular density (SVD) in individuals with amnestic Mild Cognitive Impairment (aMCI) compared to healthy participants.

Started
November 27, 2023
Type
interventional
Blinding
quadruple
Randomized
Yes
Registry ID
NCT06041152

Explore further

Search all Psilocybin papers Search all Neurocognitive Disorders trials Full Psilocybin profile Full Neurocognitive Disorders profile