Psilocybin for Brain Function in Healthy Subjects

(OPTE Trial)

Overseen By Ceyda Sayali, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Johns Hopkins University

Must not be taking: Psychoactive medications, MAO inhibitors

Disqualifiers: Cardiovascular conditions, Epilepsy, Schizophrenia, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

15 Participants Needed

Trial Summary

Do I need to stop taking my current medications for the trial?

The trial requires that participants do not take any psychoactive prescription medications regularly. If you take such medications intermittently, you must wait until at least 5 half-lives of the medication have passed after your last dose before participating in a session. Additionally, you must refrain from using any nonprescription medications, nutritional supplements, or herbal supplements for one week before each session, unless approved by the study investigators.

What data supports the effectiveness of the drug psilocybin for brain function in healthy subjects?

Research shows that psilocybin can improve mood and mental health in both healthy individuals and those with major depressive disorder. It also increases brain activity and connectivity, which might help explain its potential benefits for brain function. ^{1 2 3 4 5}

Is psilocybin safe for healthy humans?

Psilocybin is generally safe for healthy people when given in moderate doses in a controlled setting. Some people may experience temporary anxiety or mood changes, but these are usually manageable with support and do not require medication. Long-term negative effects have not been observed in healthy subjects. ^{2 5 6 7 8}

How is the drug psilocybin unique for brain function in healthy subjects?

Psilocybin is unique because it is a naturally occurring hallucinogenic compound that can induce profound changes in mood, perception, and thought, which are generally described as pleasurable and enriching. Unlike other treatments, it affects brain activity by increasing sensory responses and altering blood flow in specific brain regions, potentially offering new insights into brain function. ^{1 2 4 5 9}

What is the purpose of this trial?

This open-label pilot psilocybin administration study investigates the influence of psilocybin on brain function and cognitive control functions in clinically and psychiatrically healthy volunteers. Participants will undergo experimental drug administration sessions after careful screening and preparation. Participants will also have brain activity measured using electroencephalogram (EEG) also during non-invasive brain stimulation using Transcranial Magnetic Stimulation (TMS).

Research Team

Ceyda Sayali, PhD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for right-handed, English-speaking adults aged 22-55 who are medically and psychologically healthy. They must have finished high school, consented in writing, and used hallucinogens at least twice before. Participants can't wear metal near their head during sessions and must avoid psychoactive substances and smoking prior to drug administration.

Inclusion Criteria

I am between 22 and 55 years old.

I have completed high school.

I have signed a consent form.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparation

Participants undergo preparation for psilocybin administration

1 week

Treatment

Participants receive 25 mg psilocybin and undergo TMS while brain activity is measured using EEG

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after psilocybin administration

1-2 weeks

Treatment Details

Interventions

• Psilocybin
• Transcranial Magnetic Stimulation (TMS)

Trial Overview The study tests the effects of a single dose of Psilocybin (25 mgs) on brain function in healthy volunteers using EEG monitoring alongside Transcranial Magnetic Stimulation (TMS). It aims to understand how psilocybin influences cognitive control functions.

Participant Groups

Group I: Psilocybin and TMS Experimental Treatment 2 Interventions

All participants will be administered 25 mg psilocybin and undergo TMS

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Findings from Research

In a phase 2 trial with 104 participants, a single dose of psilocybin significantly reduced depression scores compared to a niacin placebo, showing a mean difference of -12.3 points on the MADRS scale by day 43, indicating strong efficacy.

Psilocybin treatment led to a significant reduction in functional disability as measured by the Sheehan Disability Scale, with no serious adverse events reported, suggesting it is a safe option when combined with psychological support for treating major depressive disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial. Raison, CL., Sanacora, G., Woolley, J., et al.[2023]

In a study of 953 psilocybin microdosers and 180 non-microdosing comparators over 30 days, participants reported small- to medium-sized improvements in mood and mental health, consistent across different demographics.

Combining psilocybin with lion's mane mushrooms and niacin showed specific psychomotor performance benefits in older adults, suggesting potential advantages of this combination, although further research is needed to confirm these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin microdosers demonstrate greater observed improvements in mood and mental health at one month relative to non-microdosing controls. Rootman, JM., Kiraga, M., Kryskow, P., et al.[2022]

In a study of 27 patients with moderate to severe major depressive disorder, psilocybin-assisted treatment showed significant and lasting antidepressant effects, with 75% of participants experiencing a treatment response and 58% achieving remission after 12 months.

There were no serious adverse events related to psilocybin, indicating a favorable safety profile, and participants reported meaningful personal and spiritual experiences that correlated with increased well-being, although these did not directly predict improvements in depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. Gukasyan, N., Davis, AK., Barrett, FS., et al.[2022]

A systematic review of 16 studies found that psilocybin is generally well-tolerated, with the most common side effects being transient nausea and headache, and no reports of severe long-term issues like psychosis.

Psilocybin shows promise as a safe treatment option for psychiatric and substance-dependence conditions, particularly for patients who do not respond to standard therapies, as it has demonstrated both acute and long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Tolerability and Safety of Psilocybin in Psychiatric and Substance-Dependence Conditions: A Systematic Review. Kaminski, D., Reinert, JP.[2023]

References

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

Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial. [2023]

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

Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies. [2016]

3. England pubmed.ncbi.nlm.nih.gov

Psilocybin microdosers demonstrate greater observed improvements in mood and mental health at one month relative to non-microdosing controls. [2022]

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

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Acute psilocybin increased cortical activities in rats. [2023]

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

The Tolerability and Safety of Psilocybin in Psychiatric and Substance-Dependence Conditions: A Systematic Review. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Trajectory of Antidepressant Effects after Single- or Two-Dose Administration of Psilocybin: A Systematic Review and Multivariate Meta-Analysis. [2022]

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

The administration of psilocybin to healthy, hallucinogen-experienced volunteers in a mock-functional magnetic resonance imaging environment: a preliminary investigation of tolerability. [2016]

9. England pubmed.ncbi.nlm.nih.gov

Neuroimaging: a scanner, colourfully. [2021]