Psilocybin for PTSD

Overseen By Adam Levin, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Ohio State University

Must not be taking: Antidepressants, Psychoactive, Serotonergic

Disqualifiers: Pregnancy, Cardiovascular, Epilepsy, Diabetes, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether psilocybin, a psychedelic compound, can safely and effectively treat post-traumatic stress disorder (PTSD) in U.S. military Veterans. Participants will receive two doses of psilocybin, paired with therapy sessions before and after. This opportunity is for Veterans with a PTSD diagnosis who aren't currently on antidepressants and have minimal past use of hallucinogens. The trial seeks better treatment options for those struggling with trauma's impacts. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group, offering Veterans a chance to contribute to groundbreaking PTSD treatment advancements.

Do I have to stop taking my current medications to join the trial?

Yes, you must stop taking any psychoactive prescription medications and those with a primary centrally-acting serotonergic effect, like Monoamine oxidase inhibitors, to join the trial.

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

Research has shown that psilocybin could be a safe treatment option. In studies, participants generally tolerated a single 25 mg dose of psilocybin combined with therapy well. Importantly, no serious harmful effects were reported. These findings align with other studies that also found psilocybin safe when used with psychological support. Participants in these studies did not experience major negative health effects. While researchers continue to study the treatment, current evidence suggests that psilocybin is safe for human use in controlled settings. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for PTSD, which often involve antidepressants and psychotherapy, psilocybin-assisted therapy uses a psychedelic compound found in certain mushrooms. Researchers are excited about psilocybin because it acts on serotonin receptors in the brain, potentially leading to profound changes in perception and mood. This treatment is unique because it combines two doses of psilocybin with therapy sessions, which might offer faster and more lasting relief compared to traditional methods. Additionally, psilocybin may help patients process traumatic memories in a new way, offering hope for those who haven't found success with other treatments.

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

Research has shown that psilocybin can help treat PTSD by enabling deeper emotional processing. One study found that a single dose of psilocybin led to consistent improvements in PTSD symptoms, daily functioning, and overall quality of life. The study also reported that psilocybin was well tolerated, with no serious side effects. In this trial, participants will receive psilocybin-assisted therapy, which includes two doses of psilocybin approximately two weeks apart, along with preparatory and post-psilocybin therapy sessions. These findings suggest that therapy using psilocybin could be a promising treatment for PTSD. ^{1 2 5 6 7}

Who Is on the Research Team?

Alan K Davis, PhD

Principal Investigator

Ohio State University

Are You a Good Fit for This Trial?

This trial is for US military Veterans aged 21-64 with PTSD, who have a high school education or equivalent and are medically stable. They must not be on antidepressants, have a significant history of drug abuse, severe mental health conditions like schizophrenia or bipolar disorder, cardiovascular issues, diabetes, obesity, or epilepsy.

Inclusion Criteria

US military Veteran

Have at least a high-school level of education or equivalent

I am between 21 and 64 years old.

Exclusion Criteria

I am currently taking medication that affects serotonin in my brain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparatory Therapy

Participants meet with session facilitators for preparatory therapy sessions before the first psilocybin session

1-2 weeks

Up to 4 meetings

Psilocybin Treatment

Participants receive two doses of psilocybin, approximately 2 weeks apart, with post-psilocybin therapy sessions

4 weeks

2 psilocybin sessions, 2 post-therapy sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Visits at 1 and 2 weeks, and 1, 3, and 6 months post-treatment

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview

The study is testing the safety and effectiveness of psilocybin-assisted therapy in treating PTSD in veterans. Psilocybin is given under controlled conditions to see if it helps reduce PTSD symptoms more than standard treatments.

How Is the Trial Designed?

Group I: Psilocybin-assisted therapy Experimental Treatment 1 Intervention

Participants will receive two doses of psilocybin, approximately 2 weeks apart, in conjunction with preparatory and post-psilocybin therapy sessions

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?

Ohio State University

Lead Sponsor

Trials

891

Recruited

2,659,000+

Published Research Related to This Trial

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 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]

In a study involving 12 healthy adults, escalating doses of psilocybin (0.3, 0.45, and 0.6 mg/kg) were administered safely, with no serious adverse events reported, indicating a favorable safety profile for this psychedelic compound.

The pharmacokinetics of psilocin, the active metabolite of psilocybin, were linear across the tested doses, with an elimination half-life of about 3 hours, suggesting that no dose adjustments are necessary for individuals with mild to moderate renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. Brown, RT., Nicholas, CR., Cozzi, NV., et al.[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]

A single dose of psilocybin significantly reduced fear responses in mice, indicating its potential to facilitate fear extinction, which is crucial for treating PTSD.

Psilocybin promoted hippocampal neuroplasticity by improving dendritic complexity, spine density, and levels of neuroplasticity-related proteins, suggesting it could enhance the effectiveness of exposure-based therapies for PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin facilitates fear extinction in mice by promoting hippocampal neuroplasticity. Du, Y., Li, Y., Zhao, X., et al.[2023]

A single dose of 5-MeO-DMT, derived from the bufotoxin of the Sonoran Desert Toad, resulted in significant and sustained improvements in PTSD symptoms for a 23-year-old female patient, with effects lasting up to 12 months.

The treatment was generally safe, with no serious adverse events reported, although the patient did experience some side effects like nausea and night terrors, highlighting the need for further research to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-MeO-DMT for post-traumatic stress disorder: a real-world longitudinal case study. Ragnhildstveit, A., Khan, R., Seli, P., et al.[2023]

A single dose of psilocybin (0.5-20 mg/kg) significantly increases the expression of genes related to neuroplasticity in the prefrontal cortex and hippocampus, suggesting its potential therapeutic effects for mental health disorders.

The study highlights that psilocybin's effects on gene expression are dose-dependent and predominantly observed in the prefrontal cortex, emphasizing the need to assess both gene expression and protein translation to understand its rapid effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcriptional regulation in the rat prefrontal cortex and hippocampus after a single administration of psilocybin. Jefsen, OH., Elfving, B., Wegener, G., et al.[2022]

In a survey of 1993 individuals who experienced challenging psilocybin trips, 39% rated their experience as one of the most difficult of their lives, with 11% reporting risks of physical harm, particularly influenced by dose and lack of support.

Despite the challenges, 84% of respondents felt they benefited from the experience, suggesting that while adverse effects can occur, the overall incidence of serious psychological distress is low, especially in controlled settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. Carbonaro, TM., Bradstreet, MP., Barrett, FS., et al.[2018]

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]

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]

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]

Citations

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ir.compasspathways.com/News--Events-/news/news-details/2025/Compass-Pathways-Announces-Publication-of-Results-from-Phase-2-Study-of-COMP360-Psilocybin-for-Post-Traumatic-Stress-Disorder/default.aspx

News Details

Open-label Phase 2 study shows a single 25 mg COMP360 psilocybin dose was well tolerated, with no serious adverse events observed, ...

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journals.sagepub.com/doi/10.1177/02698811251362390

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

Secondary outcomes (PTSD symptom severity, functional impairment and quality of life) revealed consistent and durable pre-post treatment ...

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Studies have shown that psilocybin can facilitate profound psychological experiences characterised by heightened emotional processing and ...

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clinicaltrials.gov

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Efficacy, Safety, and Tolerability of COMP360 in ...

This is a phase III, international, multi-centre, randomised, parallel group, fixed single-dose, double-blind, placebo-controlled study.

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finance.yahoo.com/news/compass-pathways-announces-publication-results-103000296.html

Compass Pathways Announces Publication of Results from ...

Open-label Phase 2 study shows a single 25 mg COMP360 psilocybin dose was well tolerated, with no serious adverse events observed, ...

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A nonrandomized open-label clinical trial

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Safety and Tolerability of COMP360 in Post-traumatic ...

The study results showed that the safety and tolerability of COMP360 in PTSD was consistent with the known safety profile from other COMP360 studies. The most ...