Psilocybin for Opioid Use Disorder

Not yet recruiting at 5 trial locations

Overseen By Michael Bogenschutz, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NYU Langone Health

Must be taking: Methadone

Must not be taking: Psychotropics, others

Disqualifiers: Seizure disorder, Cardiovascular disease, Schizophrenia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether psilocybin, a psychedelic compound, can assist individuals who continue using opioids despite methadone treatment. Researchers will administer different doses of psilocybin to determine its effectiveness in helping participants stop using illegal opioids. The trial aims to identify the safest and most effective dose. Individuals who have been in methadone treatment for at least six months but still use illegal opioids may be suitable candidates for this study. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not require you to stop taking prescribed psychotropic medications or any other medically necessary medications. However, you must stop taking non-prescription medications and supplements for at least 1 week before the psilocybin session, unless approved by the study investigator.

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

In a previous study, psilocybin showed potential in reducing opioid and nicotine use, though results were mixed for other substance use disorders. Psilocybin affects certain brain areas related to mood and perception. Some early findings suggest it might lower opioid cravings through this action.

While psilocybin has shown promise, more research is needed to fully understand its safety and effectiveness. Some reports suggest it might reduce the chances of developing opioid use disorder, indicating potential benefits. However, a complete picture of its safety is not yet available.

This trial is in phase 2, meaning psilocybin has already passed initial safety tests in earlier trials. This phase aims to explore its safety and effectiveness further, assessing how well people tolerate it. Encouraging evidence exists, but participating in the trial will help gather more concrete safety data. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike traditional treatments for opioid use disorder, which often rely on medications like methadone or buprenorphine to manage withdrawal symptoms and cravings, psilocybin offers a novel approach. Researchers are excited about psilocybin because it acts on serotonin receptors in the brain, potentially promoting new perspectives and insights that could reduce dependence on opioids. Additionally, psilocybin is administered in controlled, supervised settings, which may lead to transformative experiences with lasting effects from just a single session. This unique mechanism of action and the potential for rapid results make psilocybin a promising candidate in the fight against opioid addiction.

What evidence suggests that this trial's treatments could be effective for opioid use disorder?

Studies have shown that psilocybin might help people with opioid use disorder (OUD). Research has found that individuals using psilocybin were less likely to experience opioid-related problems. Early findings suggest that psilocybin might reduce opioid cravings by affecting specific brain regions. Clinical trials demonstrated that therapy involving psilocybin alleviated symptoms of substance use disorders. These results position psilocybin as a promising option for those struggling with opioid addiction. Participants in this trial will receive varying doses of psilocybin—high, medium, and control—to evaluate its effectiveness in treating OUD. ^{4 5 6 7 8}

Who Is on the Research Team?

Michael Bogenschutz, MD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

This trial is for individuals with Opioid Use Disorder who continue to use opioids despite being on methadone treatment. Participants will be part of a study evaluating the effects of different doses of psilocybin.

Inclusion Criteria

Diagnosis of Opioid Use Disorder (OUD) based on DSM 5 criteria

Taken methadone at least 25 out of the last 30 days

Had at least one urine drug screen positive for non-prescribed opioids in the past 30 days

Exclusion Criteria

History of hallucinogen use disorder or hallucinogen persisting perception disorder

Any other disorder likely to interfere with study participation

I am not allergic to any medications used in this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stage 1 Treatment

Participants receive a single administration of psilocybin (30 mg, 20 mg, or 1 mg) and remain under supervision for 8 hours

1 day

1 visit (in-person)

Stage 1 Follow-up

Participants are monitored for safety and effectiveness, with interim analysis to determine continuation to Stage 2

24 weeks

Stage 2 Treatment

Participants receive a single administration of psilocybin (30 mg or 20 mg) and remain under supervision for 8 hours

1 day

1 visit (in-person)

Stage 2 Follow-up

Participants are monitored for safety and effectiveness, with assessments including craving and affect scales

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview The trial tests moderate (20 mg) and high (30 mg) doses of psilocybin against a low-dose control (1 mg) in a two-stage process, assessing safety and potential efficacy in reducing opioid use over 24 weeks.

How Is the Trial Designed?

Group I: Stage 2: Psilocybin 30 mg (high dose) Experimental Treatment 1 Intervention

Participants will receive a single IP administration (30 mg) session and remain under supervision at the facility for 8 hours.

Group II: Stage 2: Psilocybin 20 mg (medium dose) Experimental Treatment 1 Intervention

Participants will receive a single IP administration (20 mg) session and remain under supervision at the facility for 8 hours.

Group III: Stage 1: Psilocybin 30 mg (high dose) Experimental Treatment 1 Intervention

Participants will receive a single IP administration (30 mg) session and remain under supervision at the facility for 8 hours.

Group IV: Stage 1: Psilocybin 20 mg (medium dose) Experimental Treatment 1 Intervention

Participants will receive a single IP administration (20 mg) session and remain under supervision at the facility for 8 hours.

Group V: Psilocybin 1 mg (control) Active Control 1 Intervention

Participants will receive a single IP administration (1 mg) session and remain under supervision at the facility for 8 hours.

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

Lifetime use of psilocybin is associated with significantly lower odds of developing opioid use disorder (OUD), with an adjusted odds ratio of 0.70 based on a large sample of 214,505 participants from the National Survey on Drug Use and Health.

Psilocybin use was linked to reduced odds of meeting seven out of eleven DSM-IV criteria for OUD, suggesting its potential as a therapeutic option, although further clinical trials are necessary to establish a causal relationship.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associations between classic psychedelics and opioid use disorder in a nationally-representative U.S. adult sample. Jones, G., Ricard, JA., Lipson, J., et al.[2022]

In a pilot study involving 15 participants, those who underwent psilocybin-facilitated smoking cessation reported significant insights into their self-identity and reasons for smoking, which contributed to their ability to quit smoking.

Participants experienced lasting positive changes beyond smoking cessation, such as increased altruism and pro-social behavior, suggesting that the therapeutic effects of psilocybin may extend beyond the immediate treatment context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychedelic therapy for smoking cessation: Qualitative analysis of participant accounts. Noorani, T., Garcia-Romeu, A., Swift, TC., et al.[2019]

In a study of 27 patients with moderate to severe major depressive disorder, psilocybin-assisted treatment showed significant and lasting antidepressant effects, with 75% of participants experiencing a treatment response and 58% achieving remission after 12 months.

There were no serious adverse events related to psilocybin, indicating a favorable safety profile, and participants reported meaningful personal and spiritual experiences that correlated with increased well-being, although these did not directly predict improvements in depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. Gukasyan, N., Davis, AK., Barrett, FS., et al.[2022]

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]

Psilocybin has shown significant therapeutic effects in reducing symptoms of depression and anxiety in patients with life-threatening diseases, based on a systematic review and meta-analysis of clinical trials involving 92 patients.

The results indicate that psilocybin may be a safe and effective treatment option, particularly for cases resistant to conventional therapies, with significant improvements measured by the Beck Depression Inventory and State-Trait Anxiety Inventory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases-A Systematic Review and Meta-Analysis of Clinical Trials. Vargas, AS., Luís, Â., Barroso, M., et al.[2020]

Psilocybin, found in 'magic mushrooms', shows promise as a non-addictive alternative for treating mental health disorders like major depressive disorder and addiction, potentially addressing the urgent need for new therapies amid rising addiction and suicide rates.

Current research indicates that psilocybin may offer therapeutic benefits without the overdose risks associated with traditional mind-altering substances, suggesting a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin Therapeutic Research: The Present and Future Paradigm. Kargbo, RB.[2021]

Methamphetamine use disorder is a serious condition with high relapse rates and limited effectiveness of current treatments, highlighting the need for new therapeutic options.

Psilocybin-assisted psychotherapy shows promise as a potential treatment for methamphetamine use disorder, based on early experiences from four clinical trials, although no published studies currently exist on this specific application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring psilocybin-assisted psychotherapy in the treatment of methamphetamine use disorder. Brett, J., Knock, E., Korthuis, PT., et al.[2023]

A study involving 28 Black individuals with Opioid Use Disorder revealed that while most had heard of psilocybin, only a small number had actually used it, indicating limited exposure to this potential treatment.

Despite a willingness to consider psilocybin therapy, over 80% of participants perceived significant risks associated with its use, highlighting the need for culturally informed education and outreach to improve understanding and acceptance of psilocybin as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin use patterns and perception of risk among a cohort of Black individuals with Opioid Use Disorder. Clifton, JM., Belcher, AM., Greenblatt, AD., et al.[2023]

In a proof-of-concept study involving 10 alcohol-dependent participants, psilocybin administration led to a significant increase in abstinence rates after treatment, with effects maintained for up to 36 weeks.

Participants experienced no significant adverse events, suggesting that psilocybin is safe for use in this context, and the intensity of the psilocybin effects predicted positive changes in drinking behavior and cravings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. Bogenschutz, MP., Forcehimes, AA., Pommy, JA., et al.[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]

A systematic review of 16 studies found that psilocybin is generally well-tolerated, with the most common side effects being transient nausea and headache, and no reports of severe long-term issues like psychosis.

Psilocybin shows promise as a safe treatment option for psychiatric and substance-dependence conditions, particularly for patients who do not respond to standard therapies, as it has demonstrated both acute and long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Tolerability and Safety of Psilocybin in Psychiatric and Substance-Dependence Conditions: A Systematic Review. Kaminski, D., Reinert, JP.[2023]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165178125000952

The therapeutic effects of psychedelics for opioid use ... Most of these studies showed the effectiveness of psychedelics in reducing opioid withdrawal signs (in some cases naloxone/naltrexone-induced withdrawal) ( ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05242029

Psilocybin for Opioid Use Disorder in Patients on ... This study will investigate whether psilocybin administered under supportive conditions can reduce illicit opioid use and improve quality of life.

3. 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 ...

4. 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 ...

5. pharmacytimes.com pharmacytimes.com/view/the-promise-of-psilocybin-assisted-therapy-for-opioid-use-disorder

The Promise of Psilocybin-Assisted Therapy for Opioid Use ... Preliminary findings suggest that psilocybin may help reduce opioid cravings by agonism at serotonergic receptors, particularly 5-HT2A, and to a lesser extent, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06796062

NCT06796062 | Psilocybin for Opioid Use Disorder (OUD) The study will proceed to Stage 2 if at least one of the active dosages of psilocybin demonstrates 1) acceptable safety, based on analysis of safety data from ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0149763425001630

Efficacy and safety of psilocybin for the treatment ... Early findings suggest psilocybin's potential in reducing opioid and nicotine use, though results remain mixed for other SUDs.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40245969/

Efficacy and safety of psilocybin for the treatment ... Psilocybin, a serotonergic psychedelic, may have therapeutic benefits for Substance Use Disorders (SUDs), but its overall efficacy and safety remain uncertain.