Psilocybin for Perception Disorders

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

Trial Summary

What is the purpose of this trial?

The long-term objective of this project is to characterize how psilocybin affects visual perception and the brain's representation of the visual environment. It is known that psilocybin alters aspects of visual perception, but the underlying brain mechanisms contributing to these effects are poorly understood. The proposed work will address these questions in a large, diverse sample of healthy human subjects by using functional magnetic resonance imaging (fMRI) to measure the brain's responses to visual stimuli. The proposed research will document which brain areas mediate the effects of psilocybin. The technique of fMRI will be employed to measure brain activity in different brain areas while subjects are performing a visual perceptual task.

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.

What evidence supports the effectiveness of the drug psilocybin for perception disorders?

Research shows that psilocybin has been studied in clinical trials for various psychiatric disorders, including depression and anxiety, with some patients experiencing significant long-term improvements. Although more research is needed, these initial findings suggest potential benefits for perception disorders as well. ^{1 2 3 4 5}

Is psilocybin generally safe for humans?

Psilocybin, found in 'magic mushrooms,' can cause rapid effects on the central nervous system, including hallucinations and physical symptoms like vomiting and muscle pain. While it has been used in research for various conditions, its potential for abuse and adverse reactions like hyperpyrexia (high fever) and hypoxemia (low blood oxygen) highlight the need for careful medical supervision. ^{4 6 7 8 9}

How is the drug psilocybin unique in treating perception disorders?

Psilocybin is unique because it works by activating serotonin receptors in the brain, particularly the 5-HT2A receptor, which can lead to psychedelic effects. Unlike traditional treatments, psilocybin is a naturally occurring compound found in certain mushrooms and is known for its rapid onset of effects, typically within 30 minutes to an hour after ingestion. ^{4 10 11 12 13}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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-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 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]

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 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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Psilocybin in Palliative Care: An Update. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Dose-response relationships of psilocybin-induced subjective experiences in humans. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

[Treatment with psilocybin: applications for patients with psychiatric disorders]. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

DARK Classics in Chemical Neuroscience: Psilocybin. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

The pharmacology of psilocybin. [2016]

8. United States pubmed.ncbi.nlm.nih.gov

Intravenous mushroom poisoning. [2019]

9. Germany pubmed.ncbi.nlm.nih.gov

Occurrence of psilocybin in various higher fungi from several European countries. [2007]

10. United States pubmed.ncbi.nlm.nih.gov

Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice. [2023]

11. Germany pubmed.ncbi.nlm.nih.gov

Genetic Survey of Psilocybe Natural Products. [2022]

12. Germany pubmed.ncbi.nlm.nih.gov

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

13. Ireland pubmed.ncbi.nlm.nih.gov

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