Psilocybin for OCD

Overseen By Eliza Miller

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Johns Hopkins University

Must not be taking: Psychoactive, Serotonergic, MAOIs

Disqualifiers: Cardiovascular conditions, Epilepsy, Type 1 diabetes, 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: 3

Duration: 4 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether psilocybin, a compound in certain mushrooms, can help treat obsessive-compulsive disorder (OCD). Researchers aim to determine its safety and effectiveness for individuals who have struggled with OCD for at least a year and have tried other treatments. Participants will receive psilocybin either immediately or after a waiting period. This study may suit someone experiencing OCD symptoms that disrupt daily life and who is not currently on antidepressants. As an Early Phase 1 trial, this research focuses on understanding how psilocybin works in people, offering participants a chance to explore this new treatment option.

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

Yes, you will need to stop taking any regular psychoactive prescription medications or those with a primary centrally-acting serotonergic effect before participating in the trial. There is a required period of approximately five half-lives (time it takes for the drug's active substance to reduce by half in the body) after the last dose before starting psilocybin sessions.

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

Research has shown that psilocybin can be safely used in people with OCD. In one study, patients tolerated a single 10 mg dose well. Another study found that a 25 mg dose, administered with psychological support, was also safe and well-tolerated. Both studies reported improvements in symptoms.

Additionally, psilocybin has been used safely in a controlled clinical setting, demonstrating reductions in OCD symptoms. While these findings are promising, this treatment is still under study to confirm its safety and effectiveness. ^{1 2 3 4 5}

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

Researchers are excited about psilocybin for treating OCD because it offers a completely different approach compared to traditional treatments like SSRIs or cognitive-behavioral therapy. Unlike these standard options, psilocybin works by interacting with serotonin receptors in the brain, potentially leading to profound changes in perception and mood. This mechanism could result in rapid symptom relief, possibly after just one or two sessions, which is much quicker than the weeks or months typically needed for conventional treatments to show effects. Additionally, the unique psychoactive properties of psilocybin might help patients gain new insights into their thoughts and behaviors, offering a novel pathway to managing OCD symptoms.

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

Research has shown that psilocybin might help lessen symptoms of OCD (obsessive-compulsive disorder). One study found a 10 mg dose of psilocybin to be safe and potentially effective for people with OCD. In this trial, participants in the Immediate Psilocybin arm will first receive two sessions of psilocybin (20 mg in the first session and then, if well tolerated, 30 mg). Meanwhile, participants in the Delayed Psilocybin arm will receive psilocybin after a waiting period. Brain scans have shown that psilocybin can decrease activity in certain brain areas and improve connections between different regions, which may help with symptoms. Psilocybin also supports neuroplasticity, helping the brain adapt and change positively. Overall, psilocybin has shown a relatively safe profile and promising results in reducing symptoms according to most psychiatric evaluations. ^{1 6 7 8 9}

Who Is on the Research Team?

David B Yaden, PhD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for adults with Obsessive Compulsive Disorder (OCD) who have tried treatment before. Participants should not have used hallucinogens often, be at low risk of suicide, and agree to avoid certain medications and substances before sessions. Women must use effective birth control if applicable.

Inclusion Criteria

Be judged by study team clinicians to be at low risk for suicidality

Agree to consume approximately the same amount of caffeine-containing beverage (e.g., coffee, tea) that he/she consumes on a usual morning, before arriving at the research unit on the mornings of drug session days. If the participant does not routinely consume caffeinated beverages, he/she must agree not to do so on session days

Have a Y-BOCS score of 18 or more

Exclusion Criteria

I cannot go without nicotine for 8-10 hours.

Clinically significant transaminitis (AST or ALT greater than two times normal value)

BMI < 18

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1-2 visits (in-person)

Treatment

Participants receive two doses of psilocybin approximately two weeks apart

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview The study tests the safety and potential effectiveness of psilocybin as a treatment for OCD. It's an early-stage trial to see if larger studies are warranted, focusing on how this intervention might affect cognitive processes and brain function in OCD patients.

How Is the Trial Designed?

Group I: Immediate Psilocybin Experimental Treatment 1 Intervention

This arm will receive two sessions of psilocybin first (20mg in first session and then, if well tolerated, 30mg).

Group II: Delayed Psilocybin Active Control 1 Intervention

Waitlist control. This arm will receive psilocybin after the waiting period is over (20mg in first session and then, if well tolerated, 30mg).

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?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Usona Institute

Collaborator

Trials

18

Recruited

1,100+

Published Research Related to This Trial

The hallucinogenic mushroom Inocybe aeruginascens contains a newly identified compound called aeruginascin, which is a quaternary ammonium derivative of psilocybin.

Aeruginascin is structurally related to bufotenidine, a potent agonist of the 5-HT3 receptor, suggesting it may have significant effects on serotonin receptors, which could be relevant for understanding its psychoactive properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aeruginascin, a trimethylammonium analogue of psilocybin from the hallucinogenic mushroom Inocybe aeruginascens. Jensen, N., Gartz, J., Laatsch, H.[2006]

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 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]

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 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]

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]

A study analyzed over 100 species of fungi from Europe for the presence of psilocybin and related compounds, identifying several genera that contain these hallucinogenic substances.

Only two species, Psilocybe semilanceata and Panaeolus subbalteatus, were found in sufficient quantities in Middle and Northern Europe to potentially be abused for their psilocybin content.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Occurrence of psilocybin in various higher fungi from several European countries. Stijve, T., Kuyper, TW.[2007]

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]

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 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]

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]

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-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]

Citations

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Single-dose (10 mg) psilocybin reduces symptoms in ... A 10 mg dose of oral psilocybin was found to be well-tolerated and potentially efficacious in patients with OCD.

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/PMC12030455/

The Emergence of Psilocybin in Psychiatry and Neuroscience Neuroimaging studies indicate psilocybin reduces default mode network (DMN) activity, increases brain network integration, and may promote neuroplasticity.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8055489/

What is the clinical evidence on psilocybin for the treatment of ... Psilocybin has shown a relatively safe profile and very promising results, with reductions found on most of the psychiatric rating scales' scores.

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

Clinical Research Protocol This study is an open-label, proof of concept study investigating the use of psilocybin- assisted psychotherapy (PAP) in treating TR-OCD. The findings of this ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06258031

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 ...

7. 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 ...

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

Safety, tolerability, and efficacy of psilocybin in 9 patients ... Conclusions: In a controlled clinical environment, psilocybin was safely used in subjects with OCD and was associated with acute reductions in core OCD symptoms ...

9. 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.