Psilocybin for Brain Function in Healthy Subjects

(OPTE Trial)

Overseen By Eli Weisman

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how psilocybin affects brain function and cognitive control in individuals who are physically and mentally healthy. Participants will receive a dose of psilocybin and undergo a brain activity test using techniques like EEG (which measures brain waves) and TMS (Transcranial Magnetic Stimulation, a non-invasive method to stimulate the brain). The trial seeks right-handed individuals who are medically and mentally healthy, fluent in English, and have used hallucinogens like LSD or psilocybin at least twice before. Participants must be comfortable removing metal objects from their head area and abstain from smoking and other psychoactive substances around session times. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that psilocybin is generally safe in a controlled environment. One study found that, under medical supervision, a single dose does not cause serious physical or mental harm in healthy individuals. Another study indicated that psilocybin might affect brain activity more than other substances, but it does not cause lasting damage.

For Transcranial Magnetic Stimulation (TMS), research has demonstrated its safety and tolerability, with serious side effects being rare. TMS uses magnets to stimulate brain cells and is often used to treat depression.

Both treatments are considered safe when used correctly, with psilocybin requiring careful supervision. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using psilocybin for brain function because it offers a novel approach by potentially enhancing brain connectivity and flexibility. Unlike traditional methods that might involve medications like antidepressants or cognitive enhancers, psilocybin is a psychedelic compound that can create profound changes in perception and cognition during its effects. Additionally, this trial combines psilocybin with transcranial magnetic stimulation (TMS), a non-invasive brain stimulation technique, which could further enhance brain function and mood regulation in ways that current treatments do not. This innovative combination might unlock new possibilities for improving mental health and cognitive performance.

What evidence suggests that this trial's treatments could be effective for brain function?

Research has shown that psilocybin can strongly affect the brain. One study found that it changes brain connections more than some other substances, potentially influencing how people feel emotions and experience their senses. Another study found that psilocybin might enhance emotional empathy, helping people understand others' feelings better. In this trial, all participants will receive both psilocybin and Transcranial Magnetic Stimulation (TMS). Studies have shown that TMS can improve brain function and enhance cognitive abilities, especially in those with cognitive issues. Together, psilocybin and TMS could offer new ways to enhance brain function and thinking skills. ^{1 2 3 6 7}

Who Is on the Research Team?

Ceyda Sayali, PhD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11612538/

Impact of psilocybin on cognitive function: A systematic ... Psilocybin was observed to enhance emotional empathy without significantly altering cognitive empathy and social cognition. Cognitive ...

2. nature.com nature.com/articles/s41586-024-07624-5

Psilocybin desynchronizes the human brain Psilocybin massively disrupted functional connectivity (FC) in cortex and subcortex, acutely causing more than threefold greater change than methylphenidate.

3. hopkinsmedicine.org hopkinsmedicine.org/psychiatry/research/psychedelics-research

Psychedelics Research and Psilocybin Therapy The brain scans after psilocybin use showed that the claustrum was less active, meaning the area of the brain believed responsible for setting attention and ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0149763425002398

Neurocognitive effects of psilocybin: A systematic and ... Psilocybin effects on the brain were associated with acute alterations in self-experience, sensory and emotional processing, and sustained effects on mood, ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1111/pcn.13741

Impact of psilocybin on cognitive function: A systematic ... Emotional processing was positively modified, particularly in TRD patients. Psilocybin was observed to enhance emotional empathy without ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S277240852400125X

Safety pharmacology of acute psilocybin administration in ... These findings suggest that a single administration of psilocybin is safe with regard to acute psychological and physical harm in healthy participants in a ...

7. frontiersin.org frontiersin.org/journals/systems-neuroscience/articles/10.3389/fnsys.2025.1585367/full

Neurobiology of psilocybin: a comprehensive overview and ... Psilocybin could help combat mild neurodegeneration by increasing synaptic density and supporting neuronal growth. With low risk for addiction and adverse ...