Psilocybin for Obsessive-Compulsive Disorder

Overseen By Yale OCD Clinic Psilocybin Study

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Yale University

Must not be taking: Antidepressants, Antipsychotics, Mood stabilizers, others

Disqualifiers: Schizophrenia, Bipolar, Substance use, others

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

Compensation: Varies

Number of Visits: 27

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how psilocybin, a compound found in certain mushrooms, might reduce symptoms of Obsessive-Compulsive Disorder (OCD). Researchers aim to determine if psilocybin can affect the brain to ease OCD. Participants will receive either psilocybin or a placebo, such as niacin (Vitamin B3), to compare results. This trial suits those with OCD who have not found relief from standard treatments and are not currently taking certain psychiatric medications. As a Phase 1 trial, the research focuses on understanding how psilocybin works in people, offering participants the chance to be among the first to receive this innovative treatment.

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

Yes, you will need to stop taking psychiatric medications like antidepressants and antipsychotics during the study. You also need to avoid certain other medications on the day of dosing and stop using SSRIs at least 8 weeks before the trial.

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

Research has shown that psilocybin, a substance found in certain mushrooms, is generally safe and well-tolerated. Studies have identified common side effects as mild, including temporary changes in mood, perception, and thinking, which usually resolve on their own. No serious problems have been reported with the doses typically used in research. As this trial is in the early stages, it primarily focuses on assessing the safety of psilocybin for participants. Safety remains a top priority, and researchers will closely monitor for any possible side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for OCD?

Unlike the standard treatments for Obsessive-Compulsive Disorder (OCD), which often include selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy, psilocybin presents a novel approach. Psilocybin is unique because it is a psychedelic compound that may offer therapeutic effects by promoting new neural connections and altering perceptions and thought patterns. Researchers are excited because psilocybin has the potential to work more rapidly than traditional medications, possibly providing relief in just a few sessions rather than over weeks or months. Additionally, its effects on neuroplasticity could offer long-term benefits, making it a promising option for those who do not respond well to current treatments.

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

Research has shown that psilocybin, one of the treatments studied in this trial, might help reduce symptoms of obsessive-compulsive disorder (OCD). One study found that a single dose of psilocybin significantly lessened OCD symptoms, particularly repetitive behaviors. Other studies suggest that psilocybin can improve flexible thinking, which is often challenging for people with OCD. Additionally, psilocybin is a mind-altering substance that is not physically addictive, a positive factor for long-term treatment. While more research is needed, these findings suggest that psilocybin could be a promising option for managing OCD symptoms. Participants in this trial may receive either psilocybin or a placebo comparator, niacin. ^{6 7 8 9 10}

Who Is on the Research Team?

Christopher Pittenger, MD, PhD

Principal Investigator

Yale University

Benjamin Kelmendi, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults with Obsessive-Compulsive Disorder (OCD) who have tried at least one standard treatment without success. Participants must not be taking certain psychiatric medications, including SSRIs, and should have a support person available. They cannot join if they have a history of certain mental disorders, recent psychedelic use, or conditions that make MRI scans unsafe.

Inclusion Criteria

You have a score of 18 or more on the YBOCS evaluation, which measures the severity of obsessive-compulsive disorder symptoms.

Willingness to sign a medical release for direct communication between research staff and external provider(s) about the participant's treatment and medical histories

I haven't taken SSRIs for at least 8 weeks.

Exclusion Criteria

You have Obsessive-Compulsive Personality Disorder (OCPD) or Borderline Personality Disorder (BPD).

I do not have uncontrolled diabetes, high blood pressure, heart issues, or a history of seizures or severe headaches.

You are currently feeling extremely sad or hopeless and have thoughts of wanting to harm yourself.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either psilocybin or niacin as an active placebo, with inpatient admission for at least 3 nights/4 days surrounding drug administration

1 week

Inpatient stay for 3 nights/4 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at multiple time points

12 weeks

Multiple follow-up visits at 24 hours, 48 hours, 1 week, 2 weeks, 1 month, and 3 months post-drug

Open-label extension (optional)

Participants who received active-placebo-control are offered the option to receive open-label psilocybin

What Are the Treatments Tested in This Trial?

Interventions

• Niacin
• Psilocybin

Trial Overview The study tests the impact of psilocybin on OCD symptoms compared to niacin as a placebo. It's double-blind, meaning neither participants nor researchers know who gets the real drug versus placebo during the trial. The goal is to understand how psilocybin might affect brain function related to OCD.

How Is the Trial Designed?

Group I: Psilocybin Experimental Treatment 1 Intervention

Psilocybin (0.25mg/kg)

Group II: Niacin Placebo Group 1 Intervention

Niacin (250mg)

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+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Heffter Research Institute

Collaborator

Trials

15

Recruited

520+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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 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 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]

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]

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. yalemedicine.org yalemedicine.org/clinical-trials/neural-correlates-of-the-effects-of-psilocybin-in-obsessive-compulsive-disorder

Efficacy of Psilocybin in OCD: a Double-Blind, Placebo- ... This study aims to investigate the effects of oral psilocybin on OCD symptomatology and provide the first evidence of the neural mechanism that may mediate ...

5. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00450-X/fulltext

Considerations and cautions for the integration of ... In line with these two studies, the first therapeutic study was also published in 2006, and demonstrated an acute reduction of symptom severity in 9 patients ...

6. en.wikipedia.org en.wikipedia.org/wiki/Psilocybin

Psilocybin Psilocybin, also known as 4-phosphoryloxy-N,N-dimethyltryptamine (4-PO-DMT), is a naturally occurring tryptamine alkaloid and investigational drug found in ...

7. pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.gov/compound/Psilocybin

Psilocybin | C12H17N2O4P | CID 10624 - PubChem - NIH Psilocybin is a tryptamine alkaloid that is N,N-dimethyltryptamine carrying an additional phosphoryloxy substituent at position 4. The major hallucinogenic ...

8. webbook.nist.gov webbook.nist.gov/cgi/cbook.cgi?ID=520-52-5

Psilocybine - the NIST WebBook Formula · C12H17N2O4P ; Molecular weight · 284.2481 ; Permanent link for this species. Use this link for bookmarking this species for future reference.

9. en.wikipedia.org en.wikipedia.org/wiki/Psilocin

Psilocin Psilocin, also known as 4-hydroxy-N,N-dimethyltryptamine (4-HO-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic.

10. consensus.app consensus.app/home/blog/what-is-psilocybin-other-names-psilocibin-psilocybine-psilocin-phosphate-ester/

Psilocibin, Psilocybine, Psilocin Phosphate Ester Psilocybin is a naturally occurring psychedelic compound found in certain species of mushrooms, commonly referred to as “magic mushrooms.”