Psilocybin for Perception Disorders

Overseen By BCSP Staff

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, Berkeley

Must not be taking: Antidepressants, Antipsychotics, Mood stabilizers, others

Disqualifiers: Psychiatric disorder, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how psilocybin, a psychedelic compound, affects visual perception and the brain's response to visual stimuli. Researchers will use fMRI to identify which brain regions activate when participants perform tasks after taking psilocybin. The trial seeks healthy individuals who can swallow capsules and are willing to attend all study visits. It is not suitable for those with current psychiatric disorders or certain medical conditions that might affect safety. As a Phase 1 trial, this research focuses on understanding how psilocybin works in people, offering participants the opportunity to be among the first to receive this treatment.

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications. The trial excludes participants who regularly use psychotropic medications like antidepressants, antipsychotics, and mood stabilizers. Additionally, some medications must not be used within 48 hours of the study drug administration.

Is there any evidence suggesting that psilocybin is likely to be safe for humans?

Research shows that psilocybin, the treatment under study, is usually well-tolerated in a controlled setting. In earlier studies, a single dose of psilocybin, administered with psychological support, proved safe for most people, with side effects being mostly mild and temporary. This suggests that, when used correctly, psilocybin is considered safe in a clinical setting. It is important to note that this study is in an early phase, focusing on safety and determining the right dose. The results from this trial will provide a better understanding of how psilocybin affects the brain, particularly in terms of visual perception. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about psilocybin for perception disorders because it offers a novel approach compared to traditional treatments. Unlike standard medications that often focus on neurotransmitter balance, psilocybin is a psychedelic compound that may alter perception by affecting serotonin receptors in the brain. This unique mechanism could potentially lead to rapid improvements in symptoms, providing a faster alternative to treatments that typically take weeks to show effects. Additionally, psilocybin's potential for inducing lasting changes in perception and cognition is generating excitement about its transformative impact on mental health conditions.

What evidence suggests that psilocybin might be an effective treatment for perception disorders?

Research shows that psilocybin can alter perception by affecting the brain's processing of visual information. Studies have found that psilocybin, often used in psychedelic therapy, can lessen symptoms of major depression, indicating strong effects on the brain. In trials with individuals whose depression is hard to treat, psilocybin led to a clear reduction in depressive symptoms, likely due to changes in brain function. This trial will explore psilocybin's impact on perception disorders, with one arm using psilocybin as an experimental treatment and another as a comparator. While most research focuses on depression, psilocybin's alteration of brain activity might also illuminate its impact on perception. Early findings suggest that psilocybin could help researchers understand how the brain interprets visual information. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for healthy adults over 21 who can swallow capsules and agree to birth control if applicable. They must attend all study visits, have a support person for post-dosing safety, and inform researchers of medical changes. Excluded are those with poor liver or kidney function, recent drug use including psychedelics, certain medication use, psychiatric disorders, MRI contraindications like metal implants or claustrophobia, uncontrolled hypertension or heart issues.

Inclusion Criteria

I agree to use effective birth control during the study.

I can swallow pills.

I can commit to all study requirements, including visits and evaluations.

Exclusion Criteria

I haven't taken any vasoactive drugs like sildenafil or calcium channel blockers in the last 48 hours.

I haven't taken any drugs linked to serotonin syndrome within 48 hours.

Have a current psychiatric disorder, general medical condition, or other problem or abnormality that, in the opinion of the study clinician or PI, could compromise safety, render them unsuitable for the study, or would make them unable to comply with study activities

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive psilocybin (0-14 mg) before undergoing fMRI measurement to assess visual perception and brain activity

1 day

1 visit (in-person)

Data Collection and Analysis

Functional MRI recordings and perceptual measurements are collected and analyzed to assess the effects of psilocybin

2 hours for fMRI, additional time for data analysis

Follow-up

Participants are monitored for any delayed effects and data is further analyzed for statistical testing

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview

The trial studies how psilocybin affects visual perception by using fMRI scans while participants do visual tasks. It aims to identify brain areas involved in the altered perception caused by psilocybin in a diverse group of healthy subjects.

How Is the Trial Designed?

Group I: Experimental Experimental Treatment 1 Intervention

Psilocybin 0-14 mg, before fMRI measurement

Group II: Comparator Experimental Treatment 1 Intervention

Psilocybin 0-14 mg, before fMRI measurement

Psilocybin is already approved in United States, European Union for the following indications:

Approved in United States as Psilocybin for:

• Treatment-resistant depression (TRD) under Breakthrough Therapy designation

Approved in European Union as Psilocybin for:

• Treatment-resistant depression (TRD) under PRIME designation

Who Is Running the Clinical Trial?

University of California, Berkeley

Lead Sponsor

Trials

193

Recruited

716,000+

Published Research Related to This Trial

Psilocybin, a serotonergic psychedelic, has shown promise in treating various psychiatric disorders, including depression and substance use disorders, with 9 clinical trials conducted between 2000 and 2020.

The treatment is generally well tolerated with limited side effects, and some patients with treatment-resistant conditions have experienced significant long-term improvements after just a few sessions, indicating its potential efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment with psilocybin: applications for patients with psychiatric disorders]. Breeksema, JJ., Koolen, MHB., Somers, M., et al.[2021]

Psilocybin shows promising effects in alleviating anxiety, depression, and emotional distress in palliative care patients, with a favorable safety profile, based on recent studies and reports.

Despite its potential benefits, psilocybin is not yet approved for therapeutic use in the U.S., and significant barriers exist for access, particularly for vulnerable populations like the elderly and those in palliative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin in Palliative Care: An Update. Whinkin, E., Opalka, M., Watters, C., et al.[2023]

A meta-analysis of psilocybin studies found that higher doses of psilocybin are associated with stronger subjective experiences, particularly in areas like perceptual alterations and ego dissolution, based on data from standardized questionnaires.

Challenging experiences were less affected by dose, suggesting that individual and environmental factors also play a significant role in the psilocybin experience, indicating that these findings are most relevant in controlled settings rather than recreational use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-response relationships of psilocybin-induced subjective experiences in humans. Hirschfeld, T., Schmidt, TT.[2022]

Psilocybin, a compound found in 'magic mushrooms', has shown potential in recent studies for treating various mental health conditions, including obsessive-compulsive disorder, alcohol and tobacco addiction, and major depressive disorder, particularly in terminally ill cancer patients.

Despite its classification as a Schedule I drug in 1970, which halted much research, there is a renewed interest in psilocybin's therapeutic effects, highlighting its importance in both historical and contemporary neuroscience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DARK Classics in Chemical Neuroscience: Psilocybin. Geiger, HA., Wurst, MG., Daniels, RN.[2019]

In a study with 15 rats, psilocybin was successfully distinguished from saline, showing that it has a specific discriminative cue at a dose of 1.0 mg/kg.

The effects of psilocybin generalized to psilocin and LSD but not to mescaline, suggesting that not all hallucinogens may function similarly in terms of their effects, indicating that the classification of 'hallucinogen' may not accurately reflect their mechanisms in nonhuman studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin as a discriminative stimulus: lack of specificity in an animal behavior model for 'hallucinogens'. Koerner, J., Appel, JB.[2019]

Psilocybin-containing mushrooms, commonly known as hallucinogenic or 'magic' mushrooms, rapidly affect the central nervous system within 0.5-1 hour of ingestion, leading to effects such as ataxia, hyperkinesis, and hallucinations.

The review discusses the significant toxicity associated with these mushrooms, highlighting the need for awareness and understanding of their pharmacology, clinical effects, and potential treatment for adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. Reingardiene, D., Vilcinskaite, J., Lazauskas, R.[2018]

Psilocybin is primarily a pro-drug that converts to the active compound psilocin in the body, which then interacts with serotonin receptors to produce its hallucinogenic effects.

The metabolism of psilocybin and psilocin varies significantly among individuals, affecting their dose-response and potential toxicity, highlighting the need for personalized approaches in therapeutic settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance. Dinis-Oliveira, RJ.[2018]

Psilocybin, a hallucinogenic compound found in certain mushrooms, has been associated with increasing rates of drug abuse, highlighting the need for comprehensive pharmacological understanding.

Despite its historical use in the 1960s for experimental medical purposes, recent research has only begun to uncover the pharmacological properties of psilocybin, indicating a gap in knowledge that needs to be addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacology of psilocybin. Passie, T., Seifert, J., Schneider, U., et al.[2016]

A study analyzed over 100 species of fungi from Europe for the presence of psilocybin and related compounds, identifying several genera that contain these hallucinogenic substances.

Only two species, Psilocybe semilanceata and Panaeolus subbalteatus, were found in sufficient quantities in Middle and Northern Europe to potentially be abused for their psilocybin content.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Occurrence of psilocybin in various higher fungi from several European countries. Stijve, T., Kuyper, TW.[2007]

Psilocybin, a prodrug for psilocin, shows strong agonist activity at the serotonin 5-HT2A receptor, which is responsible for its psychedelic effects, and has been shown to have nanomolar affinity for various serotonin receptor subtypes in both in vitro and in vivo studies.

In mouse experiments, psilocybin and related compounds induced head twitch responses, a sign of psychedelic activity, which were blocked by a 5-HT2A antagonist, confirming the involvement of this receptor in their effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice. Glatfelter, GC., Pottie, E., Partilla, JS., et al.[2023]

Genomic analysis of five species of Psilocybe mushrooms revealed a much greater metabolic diversity than previously understood, indicating potential for discovering new compounds beyond psilocybin and psilocin.

Two species, P. cyanescens and P. mexicana, were identified as producers of aeruginascin, along with other metabolites like lumichrome and verpacamide A, which may help explain the pharmacological and toxicological effects associated with these mushrooms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic Survey of Psilocybe Natural Products. Dörner, S., Rogge, K., Fricke, J., et al.[2022]

A 30-year-old man experienced severe symptoms, including vomiting and muscle pain, after receiving an intravenous injection of Psilocybe mushroom extract, highlighting the potential dangers of using hallucinogenic substances in non-traditional ways.

The patient showed rapid improvement with supportive care, suggesting that while the effects of Psilocybe mushrooms can be serious, timely medical intervention can effectively manage the symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous mushroom poisoning. Curry, SC., Rose, MC.[2019]

P. samuiensis, a newly identified psychoactive mushroom species from Thailand, shows rapid mycelial growth and contains significant levels of psilocybin and psilocin, similar to other psychoactive fungi.

Laboratory analyses revealed that psilocybin concentrations in P. samuiensis ranged from 0.23% to 0.90%, with the highest levels found in the caps, indicating its potential for psychoactive effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ethnomycology, biochemistry, and cultivation of Psilocybe samuiensis Guzmán, Bandala and Allen, a new psychoactive fungus from Koh Samui, Thailand. Gartz, J., Allen, JW., Merlin, MD.[2019]

Citations

1.

psychiatrist.com

psychiatrist.com/wp-content/uploads/2025/02/long-term-observational-follow-up-study-single-dose-psilocybin-treatment-resistant-episode-major-depressive-disorder-24m15449.pdf

long-term-observational-follow-up-study-single-dose- ...

In terms of safety, psilocybin was deemed well-tolerated. Adverse events, including suicidal ideation and behavior, were reported in all dose.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12226623/

Psilocybin therapy for treatment resistant depression

MADRS score change at week 3 was the primary outcome of the study though a large reduction in depressive symptoms was evident on the day following psilocybin ...

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40047545/

Results From a Long-Term Observational Follow-Up Study ...

Over 52 weeks, a single administration of 25 mg psilocybin suggested longer maintenance of antidepressant effect than both 1 mg and 10 mg.

4.

compasspathways.com

compasspathways.com/our-work/comp360-psilocybin-treatment-in-trd/

COMP360 psilocybin treatment in TRD

This trial assessed the safety and efficacy of COMP360 psilocybin treatment in three doses: 1mg, 10mg, 25mg. The results, published in the New England Journal ...

5.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0165032724020494

The role of the psychedelic experience in psilocybin ...

Several exploratory trials have suggested that an exemplar, psilocybin, can reduce symptoms of major depressive disorder (MDD), including in ...

6.

journals.sagepub.com

journals.sagepub.com/doi/10.1177/02698811251362390

Investigating the safety and tolerability of single-dose ...

In this trial, COMP360 psilocybin administered in a single session with psychological support was found to be generally well-tolerated and ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12001667/

A Modern Overview of the Potential Therapeutic Effects ...

Psilocybin is considered safe when used in a controlled and supervised environment. According to the UK Independent Scientific Committee on ...

8.

mdpi.com

mdpi.com/1424-8247/18/4/555

The Emergence of Psilocybin in Psychiatry and ...

This suggests psilocybin may support improvements in social cognition, particularly in disorders marked by social withdrawal or emotional numbing [38].

9.

psychiatryonline.org

psychiatryonline.org/doi/10.1176/appi.ajp.20230884

Compass Psychological Support Model for COMP360 ...

The CPSM was designed to support participant safety in clinical trials involving COMP360 psilocybin treatment and to address the requisite ...

10.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05481736

Study Details | NCT05481736 | Efficacy and Safety of ...

This study aims to explore the efficacy and safety of COMP360 25 mg as compared to COMP360 1 mg (control condition) administered with psychological support