Psilocybin for Obsessive-Compulsive Disorder

Recruiting at 3 trial locations

Overseen By Benjamin Kelmendi, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Yale University

Must not be taking: Psychotropic medications

Disqualifiers: Schizophrenia, Bipolar, Substance use, 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: 7

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how psilocybin, a compound in certain mushrooms, might reduce symptoms of obsessive-compulsive disorder (OCD). Researchers aim to determine if repeated doses can benefit individuals who haven’t found relief from standard OCD treatments. Participants will begin treatment either immediately or after a short waiting period. Those who have tried at least one OCD treatment without success and do not have certain medical conditions might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any psychotropic medications for OCD or other psychiatric conditions at least 8 weeks before starting the trial and refrain from taking them until 4 weeks after the second dose of psilocybin.

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

Research has shown that psilocybin, when administered in varying doses, is usually well-tolerated. For instance, one study found that a 10 mg oral dose was well-tolerated by individuals with OCD. Another study found that a 25 mg dose, given with psychological support, was safe and helped improve symptoms.

Psilocybin has been tested in various contexts, including for OCD, with an emphasis on safety and tolerability. These studies suggest that psilocybin is generally safe for humans when used in controlled settings. However, since this trial is in an early stage, it primarily focuses on safety, and researchers are still gathering detailed safety information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for Obsessive-Compulsive Disorder (OCD), like SSRIs and cognitive behavioral therapy, require weeks to show effectiveness. But psilocybin works differently, targeting serotonin receptors in the brain in a unique way that might lead to faster relief. Researchers are excited about psilocybin because it has the potential to provide lasting benefits from just a few dosing sessions, rather than needing ongoing daily medication. This psychedelic compound could offer a new approach to managing OCD symptoms, potentially transforming treatment strategies for those who haven't found success with traditional methods.

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

Research has shown that psilocybin might help treat obsessive-compulsive disorder (OCD). One study demonstrated that a single 10 mg dose of psilocybin significantly reduced OCD symptoms, particularly compulsions. Another study found that all participants experienced a noticeable decrease in their OCD symptoms, with improvements ranging from 23% to 100%. In this trial, participants in the immediate treatment arm will receive psilocybin treatment right away, while those in the waitlist control/delayed treatment arm will receive the same treatment after a waitlist phase. These results suggest that psilocybin could reduce the severity of OCD symptoms, offering potential relief for those affected by the condition. ^{1 6 7 8 9}

Who Is on the Research Team?

Christopher Pittenger, MD, PhD

Principal Investigator

Yale University

Benjamin Kelmendi, MD

Principal Investigator

Yale University

Terence Ching, PhD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults with a primary diagnosis of OCD, who have tried at least one standard treatment without success. Participants must be fluent in English, able to take oral pills, not on psychotropic medications or psychotherapy for 8 weeks prior to the study and agree not to start any during the study. They should provide an emergency contact and commit to all procedures including lifestyle changes.

Inclusion Criteria

Agree to commit to all study procedures

English fluency

If participant is of childbearing potential, must have a negative pregnancy test at study entry and prior to each dosing session

Exclusion Criteria

I do not have any health conditions that could make the study unsafe for me.

Active suicidal intent or suicidal or non-suicidal self-injurious behaviors

Unwillingness or inability to abstain from alcohol use at least 24 hours prior to the days of dosing, up to 24 hours after each dosing day (or corresponding intervals for waitlist group)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Immediate Treatment

Participants receive two doses of oral psilocybin separated by one week, with preparatory and integration sessions

2 weeks

4 visits (in-person)

Waitlist Control/Delayed Treatment

Participants enter a waitlist phase for 7 weeks, followed by the same treatment as the immediate group

7 weeks

1 visit (in-person) for rescreening

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (virtual)

Long-term Follow-up

Participants have follow-up visits up to 12 months post-second dose

12 months

Periodic visits (virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview The trial tests how repeated doses of psilocybin affect OCD symptoms compared to a waitlist group. It's randomized and includes blinded ratings. The goal is also to understand psychological processes that might explain psilocybin's potential benefits in treating OCD.

How Is the Trial Designed?

Group I: Immediate Treatment Experimental Treatment 1 Intervention

Participants randomized to this condition will receive treatment immediately, facilitated by two study staff members, and which consists of two preparatory sessions, followed by the first dosing session and two integration sessions, then the second dosing session and two integration sessions. This is followed by follow-up and long-term follow-up visits up to 12 months post-second dose.

Group II: Waitlist Control/Delayed Treatment Active Control 1 Intervention

Participants randomized to this condition will first enter a waitlist phase that lasts for 7 weeks, after which rater unblinding will occur, and participants will be rescreened. If participants remain eligible at this time, they will begin their treatment phase. During their treatment phase, participants in this condition will receive the same treatment as described for participants in the immediate treatment group. This is followed by follow-up and long-term follow-up visits up to 12 months post-second dose.

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?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Steven & Alexandra Cohen Foundation

Collaborator

Trials

10

Recruited

320+

Steven & Alexandra Cohen Foundation

Collaborator

Trials

5

Recruited

150+

Published Research Related to This Trial

Psilocybin may offer a promising and safe treatment option for obsessive-compulsive disorder (OCD), which is often inadequately addressed by current therapies.

The chapter discusses the mechanisms of action of psilocybin and its potential efficacy in treating OCD, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin for the Treatment of Obsessive-Compulsive Disorders. Ehrmann, K., Allen, JJB., Moreno, FA.[2022]

1-methylpsilocin has been identified as a selective agonist for the h5-HT(2C) receptor, which is important for developing new treatments targeting this receptor.

The phosphate derivative, 1-methylpsilocybin, demonstrated efficacy in an animal model for obsessive-compulsive disorder, indicating potential therapeutic applications for 5-HT(2C) agonists in mental health treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SAR of psilocybin analogs: discovery of a selective 5-HT 2C agonist. Sard, H., Kumaran, G., Morency, C., et al.[2016]

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]

Five cases of poisoning from the Hikageshibiretake mushroom, which contains psilocybin, exhibited symptoms similar to those caused by pure psilocybin, including acute stupor, amnesia, and vivid hallucinations.

While the toxic effects were generally short-lived, patients experienced significant anxiety and panic reactions, highlighting the need for careful management of emotional and behavioral issues during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poisoning by hallucinogenic mushroom hikageshibiretake (Psilocybe argentipes K. Yokoyama) indigenous to Japan. Musha, M., Ishii, A., Tanaka, F., et al.[2019]

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 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]

This study is the first randomized controlled trial investigating the safety and efficacy of psilocybin for treating obsessive-compulsive disorder (OCD) in 30 adult participants who have not responded to standard treatments.

Participants will receive either a single dose of psilocybin or a placebo, with outcomes measured through OCD symptom scales and neuroimaging, aiming to uncover both clinical effects and the underlying neural mechanisms of psilocybin's action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and clinical and neural effects of single-dose psilocybin in obsessive-compulsive disorder: protocol for a randomized, double-blind, placebo-controlled, non-crossover trial. Ching, THW., Grazioplene, R., Bohner, C., et al.[2023]

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 case study of a patient with refractory obsessive-compulsive disorder (OCD) showed significant improvement in symptoms after treatment with psilocybin, with the Yale-Brown Obsessive Compulsive Scale (YBOCS) score decreasing from 24 to 0-2 over a year.

The treatment not only reduced OCD symptoms but also led to positive changes in the patient's emotional well-being, social interactions, and overall quality of life, highlighting the potential of psilocybin as a therapeutic option for OCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose psilocybin for treatment-resistant obsessive-compulsive disorder: A case report. Kelmendi, B., Kichuk, SA., DePalmer, G., et al.[2023]

In a study involving 9 patients with obsessive-compulsive disorder (OCD), psilocybin was administered in varying doses, and it was found to be safe with only one instance of transient hypertension, indicating a good safety profile.

All subjects experienced significant reductions in OCD symptoms, with decreases in Yale-Brown Obsessive Compulsive Scale (YBOCS) scores ranging from 23% to 100%, suggesting that psilocybin may be an effective treatment for OCD in a controlled setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. Moreno, FA., Wiegand, CB., Taitano, EK., et al.[2022]

A case study of a male adult with Obsessive Compulsive Disorder (OCD) demonstrated a significant reduction in symptoms after consuming psilocybin-containing mushrooms, suggesting potential therapeutic benefits.

This case adds to the growing evidence that psilocybin may be an effective treatment option for OCD, highlighting the need for further research to assess its safety and efficacy in larger populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Amelioration of OCD Symptoms in a Patient with Chronic Consumption of Psilocybin-containing Mushrooms. Lugo-Radillo, A., Cortes-Lopez, JL.[2022]

There is a growing trend among young people to consume wild Psilocybin mushrooms for their hallucinogenic effects, but this practice carries risks.

The report highlights seven cases of mushroom overdosage, stressing that while Psilocybin mushrooms are generally considered harmless, there is a significant danger of accidentally consuming toxic mushroom species that can cause serious harm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The danger of hallucinogenic mushrooms. Mills, PR., Lesinskas, D., Watkinson, G.[2017]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0010440X25000471

Single-dose (10 mg) psilocybin reduces symptoms in ... In this study, a single 10 mg dose of oral psilocybin was found to be effective in reducing obsessive-compulsive symptoms (specifically compulsions) at the one- ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06258031?term=ocd&cond=psilocybin&viewType=Table&rank=9

PsilOCD: A Pharmacological-Challenge Feasibility Study The purpose of this study is to assess the impact of psilocybin on cognitive inflexibility and neural plasticity in a cohort of people with obsessive-compulsive ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11387457/

Psilocybin in pharmacotherapy of obsessive-compulsive ... Recent discoveries suggest that psilocybin, a non-physically addictive psychoactive substance, may ameliorate disease symptoms.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05624268

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.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/17196053/

Safety, tolerability, and efficacy of psilocybin in 9 patients ... Marked decreases in OCD symptoms of variable degrees were observed in all subjects during 1 or more of the testing sessions (23%-100% decrease in YBOCS score).

6. journals.sagepub.com journals.sagepub.com/doi/10.1177/02698811251362390

Investigating the safety and tolerability of single-dose ... Psilocybin at a dose of 25 mg, administered with psychological support, may be safe, well-tolerated and associated with symptomatic improvement ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05312151

NCT05312151 | The Safety and Tolerability of COMP360 in ... The Safety and Tolerability of COMP360 in Participants With Post-traumatic Stress Disorder. ClinicalTrials.gov ID NCT05312151. Sponsor COMPASS Pathways.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10166878/

Safety, tolerability, and clinical and neural effects of single ... This first-of-its-kind trial aims to evaluate the feasibility, safety, and tolerability of psilocybin in the treatment of OCD.

9. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/19/NCT06299319/Prot_SAP_000.pdf

Clinical Research Protocol Evaluating the feasibility, clinical effects, and safety of psilocybin-assisted psychotherapy for treatment-resistant obsessive-compulsive disorder: An open- ...