Psilocybin for OCD

Overseen By Jeremy Scott, BA

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

Trial Summary

What is the purpose of this trial?

This study will test the feasibility, safety, and evidence for efficacy of psilocybin administration in participants with obsessive compulsive disorder (OCD). This will serve as a preliminary proof of concept study for future larger studies aimed to investigate the utility, cognitive mechanisms, and neural correlates of this intervention.

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.

What evidence supports the effectiveness of the drug psilocybin for treating OCD?

Research suggests that psilocybin may be a safe and effective treatment for OCD, with some studies showing marked, long-term improvements in patients, even those with treatment-resistant conditions. However, more research is needed to fully understand its benefits and how best to use it. ^{1 2 3 4 5}

Is psilocybin generally safe for humans?

Psilocybin, found in certain mushrooms, can cause hallucinations and other effects on the brain, but these effects are usually short-lived. While it has been studied for its potential in treating conditions like depression, it can also lead to anxiety and panic reactions, especially in high doses or when used recreationally. ^{3 6 7 8 9}

How does the drug psilocybin differ from other treatments for OCD?

Psilocybin is unique because it works by activating serotonin receptors in the brain, particularly the 5-HT2A receptor, which is different from traditional OCD treatments that often focus on serotonin reuptake inhibition. This drug is being explored for its potential to provide psychedelic effects that might help in treating OCD, offering a novel approach compared to standard medications. ^{3 10 11 12 13}

Research Team

David B Yaden, PhD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

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)

I am not pregnant or nursing.

Timeline

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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, 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]

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-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]

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]

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 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]

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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Psilocybin for the Treatment of Obsessive-Compulsive Disorders. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Dose-response relationships of psilocybin-induced subjective experiences in humans. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

The pharmacology of psilocybin. [2016]

4. Netherlands pubmed.ncbi.nlm.nih.gov

[Treatment with psilocybin: applications for patients with psychiatric disorders]. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Psilocybin in Palliative Care: An Update. [2023]

6. Scotland pubmed.ncbi.nlm.nih.gov

The danger of hallucinogenic mushrooms. [2017]

7. Switzerland pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. [2018]

8. Japan pubmed.ncbi.nlm.nih.gov

Poisoning by hallucinogenic mushroom hikageshibiretake (Psilocybe argentipes K. Yokoyama) indigenous to Japan. [2019]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice. [2023]

11. England pubmed.ncbi.nlm.nih.gov

SAR of psilocybin analogs: discovery of a selective 5-HT 2C agonist. [2016]

12. Germany pubmed.ncbi.nlm.nih.gov

Aeruginascin, a trimethylammonium analogue of psilocybin from the hallucinogenic mushroom Inocybe aeruginascens. [2006]

13. Germany pubmed.ncbi.nlm.nih.gov

Occurrence of psilocybin in various higher fungi from several European countries. [2007]