Psilocybin for Opioid Use Disorder

Overseen By Gustavo Angarita, MD, MHS

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Yale University

Must not be taking: Psychotropic medications

Disqualifiers: Schizophrenia, Bipolar, Hypertension, Cardiovascular disease, 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: 2

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a single dose of psilocybin, a compound found in certain mushrooms, might aid individuals who have detoxified from opioid dependence. Researchers aim to assess psilocybin's effects on the brain using specialized brain scans before and after administration. Suitable candidates have an opioid use disorder, are medically healthy, and have been opioid-free for over a week. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking any psychotropic or potentially psychoactive prescription medications that could interfere with psilocybin. If you're on such medications, you may need to stop them to participate.

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

Research has shown that psilocybin has been studied for its safety in treating various conditions. For individuals with depression unresponsive to other treatments, psilocybin has reduced symptoms without major safety concerns. Studies have also examined its effects on substance use disorders, showing positive results without serious safety issues.

In the case of opioid use disorder (OUD), psilocybin remains under investigation. As this study is in an early stage, researchers are closely monitoring safety. Experts are watching for any side effects or negative reactions, a common practice in early studies to ensure safety before proceeding.

Psilocybin is already known for its use in controlled settings, and past studies suggest it is generally well-tolerated. However, because this study is in its early stages, its complete safety for OUD cannot yet be confirmed. Participants should feel encouraged by the promise psilocybin has shown in related areas, but also understand that more data is needed to confirm its safety for OUD. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Psilocybin is unique because it taps into the power of psychedelics to potentially reset the brain's response to addiction. Unlike standard opioid use disorder treatments, which often rely on medication-assisted therapies like methadone or buprenorphine to manage cravings and withdrawal symptoms, psilocybin may offer a new mechanism by promoting profound psychological insights and altering neural pathways. Researchers are excited about psilocybin because it could provide rapid and lasting relief with just a single dose, potentially transforming the way we approach addiction treatment.

What evidence suggests that psilocybin might be an effective treatment for opioid use disorder?

Research has shown that psilocybin might help lower the risk of developing opioid use disorder (OUD). One study found that individuals who had used psilocybin at some point in their lives were 30% less likely to develop OUD. In this trial, all participants will receive a dose of psilocybin to evaluate its potential in treating OUD. Although clinical data remains limited, early results suggest psilocybin could be beneficial for treating OUD. Importantly, initial studies showed no serious side effects or changes in opioid cravings or withdrawal symptoms after taking psilocybin. While most evidence comes from observations, these findings are promising for psilocybin as a possible treatment for OUD. ^{6 7 8 9 10}

Who Is on the Research Team?

Gustavo Angarita, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults with Opioid Use Disorder who are physically healthy, have been abstinent for over a week, and can provide informed consent. Women must not be pregnant. People with other substance use disorders (except nicotine), major psychiatric conditions, significant medical issues, or those on certain medications cannot participate.

Inclusion Criteria

I have not used alcohol or drugs for over a week.

Physically healthy by medical history, physical, neurological, ECG, and laboratory examinations

Documented evidence (by urine toxicology) of opioid use (upon screening)

Exclusion Criteria

Arterial Line Exclusion: Blood donation within eight weeks of the start of the study

I am not on any medication that could affect my safety or the study results.

I do not have a bleeding disorder and am not on blood thinners.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Outpatient visits at CNRU

Inpatient Treatment

Participants undergo inpatient detoxification, baseline PET scan, psilocybin administration, and overnight observation

1-2 weeks

Inpatient stay

Outpatient Monitoring

Participants return twice weekly for urine toxicology testing to confirm abstinence before the second PET scan

1-2 weeks

2 visits per week (outpatient)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in synaptic density and vital signs

up to 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview The study tests the effects of psilocybin on brain connections in people recovering from opioid addiction. Participants will receive psilocybin and undergo PET scans before and after treatment to measure changes in their brain.

How Is the Trial Designed?

Group I: Current OUD diagnosis + psilocybin Experimental Treatment 1 Intervention

All participants will receive a \[11C\]-UCB-J PET scan and fMRI with in 1-2 weeks pre and post treatment with one dose of Psilocybin. Intravenous lines will be used for phlebotomy and administration of the \[11C\]-UCB-J radiotracer. On the PET scanning day, a radial arterial catheter may be inserted.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

Psilocybin, a compound found in 'magic mushrooms', has shown potential in recent studies for treating various mental health conditions, including obsessive-compulsive disorder, alcohol and tobacco addiction, and major depressive disorder, particularly in terminally ill cancer patients.

Despite its classification as a Schedule I drug in 1970, which halted much research, there is a renewed interest in psilocybin's therapeutic effects, highlighting its importance in both historical and contemporary neuroscience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DARK Classics in Chemical Neuroscience: Psilocybin. Geiger, HA., Wurst, MG., Daniels, RN.[2019]

Psilocybin is primarily a pro-drug that converts to the active compound psilocin in the body, which then interacts with serotonin receptors to produce its hallucinogenic effects.

The metabolism of psilocybin and psilocin varies significantly among individuals, affecting their dose-response and potential toxicity, highlighting the need for personalized approaches in therapeutic settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance. Dinis-Oliveira, RJ.[2018]

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 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]

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 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 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11661506/

Psilocybin for Opioid Use Disorder in Two Adults Stabilized ... Preliminary data pertaining to the safety, clinical outcomes, and subjective effects of psilocybin were collected. Main Findings: Two ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06796062

NCT06796062 | Psilocybin for Opioid Use Disorder (OUD) The primary aims are to 1) Evaluate safety and efficacy outcomes in Stage 1 subjects in order to optimize design of the Stage 2, 2) Determine whether treatment ...

3. nature.com nature.com/articles/s41598-022-08085-4

Associations between classic psychedelics and opioid use ... Lifetime psilocybin use was associated with lowered odds of OUD (aOR: 0.70; 95% CI [0.60, 0.83]). No other substances, including other classic ...

4. journals.sagepub.com journals.sagepub.com/doi/abs/10.1089/psymed.2023.0012

Psilocybin for Opioid Use Disorder in Two Adults Stabilized ... There were no serious adverse events or significant baseline changes on measures of opioid craving or withdrawal, and the subjective effects associated with ...

5. link.springer.com link.springer.com/article/10.1007/s00018-024-05519-2

Effects of psychedelics on opioid use disorder: a scoping ... Limited preliminary clinical studies suggest specific psychedelics might aid OUD treatment, though most clinical evidence remains observational, with few ...

6. psychiatrictimes.com psychiatrictimes.com/view/comp360-psilocybin-for-treatment-resistant-depression-positive-phase-3-efficacy-data

COMP360 Psilocybin for Treatment-Resistant Depression COMP360 showed a statistically significant reduction in TRD symptom severity compared to placebo, with a clinically meaningful MADRS score ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9947277/

Therapeutic effect of psilocybin in addiction: A systematic ... All four clinical trials indicated a beneficial effect of psilocybin-assisted therapy on SUD symptoms. Larger RCTs in patients with SUDs need to evaluate ...

8. assets.lgcstandards.com assets.lgcstandards.com/sys-master%2Fpdfs%2Fh36%2Fh94%2F10954396336158%2FSDS_LPM-PSI-411-FB-100_ST-WB-MSDS-6734148-1-1-1.PDF

SAFETY DATA SHEET Precautionary Statements - Response. IF exposed or concerned: Call a POISON CENTER or doctor. Get medical advice/attention if you feel unwell.

9. imgcdn.mckesson.com imgcdn.mckesson.com/CumulusWeb/Click_and_learn/SDS_CERILL_CONTROL_PSILOCYBIN_1.0MG_ML_D_S_2025.pdf

SAFETY DATA SHEET P241. Use explosion-proof electrical/ ventilating/ lighting/ equipment. P242. Use only non-sparking tools. P243. Take precautionary measures ...

10. en.wikipedia.org en.wikipedia.org/wiki/Psilocybin

Psilocybin Psilocybin is being studied as a possible medicine in the treatment of psychiatric disorders such as depression, substance use disorders, obsessive–compulsive ...