Psilocybin for Opioid Use Disorder

Overseen By Megan Ivey, MS

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Anna Rose Childress, Ph.D.

Must be taking: MAT for OUD

Must not be taking: Psychoactive medications

Disqualifiers: Schizophrenia, Bipolar, Severe MDD, 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: 16

Duration: 1 day

36 Participants Needed

Trial Summary

What is the purpose of this trial?

Investigators will recruit 36 individuals on MAT for OUD for a double-blind, placebo-controlled design to determine whether PEX010 (25-mg/d) shows preliminary efficacy on neural correlates of neurocognition and on clinical outcomes. Participants will be randomized to either (single dose) 25-mg (PEX010-25 group) or 1-mg (PPEX010-1 group) PEX010 in a 2:1 ratio. Brain and behavioral testing sessions will precede Psilocybin (PSI) dosing day by 24-48 hours and will follow PSI dosing by 1 week. After an initial 6 phases, participants will come into the lab to submit a urine screen 2x/week and to complete a short survey in order to collect data on drug use, MAT adherence, and mental health symptoms. The investigators hypothesize the PEX010-25 (vs. PEX010-1) group will have better clinical outcomes (e.g., lower average percent positive urine drug screens, more late relapses, higher MAT adherence). There are research follow ups every three months out to one year post dose.

Will I have to stop taking my current medications?

The trial requires participants to continue taking their current medication for opioid use disorder, such as buprenorphine or methadone, as part of the study. However, you may need to avoid other psychoactive medications, like antidepressants, unless approved by the study's medical director.

What data supports the effectiveness of the drug psilocybin for treating opioid use disorder?

Research suggests that psilocybin, a component of 'magic mushrooms', may help treat various addiction disorders, including smoking and potentially methamphetamine use disorder. While specific studies on opioid use disorder are not mentioned, psilocybin has shown promise in treating other substance use disorders and mental health conditions like major depressive disorder. ^{1 2 3 4 5}

Is psilocybin generally safe for humans?

Psilocybin is generally considered safe when used in controlled settings with proper support, although some people may experience challenging psychological effects. In studies, the risk of serious harm is low, especially when participants are screened and supported. ^{5 6 7 8 9}

How is the drug psilocybin different from other treatments for opioid use disorder?

Psilocybin is unique because it is a psychedelic substance that may help reduce opioid use disorder by altering perception and consciousness, unlike traditional treatments that often focus on managing withdrawal symptoms or blocking opioid effects. It has shown promise in reducing the odds of opioid use disorder, which is not commonly seen with other classic psychedelics. ^{1 10 11 12 13}

Eligibility Criteria

This trial is for individuals on Medication-Assisted Treatment (MAT) for Opioid Use Disorder. Participants must be willing to undergo brain and behavioral testing, submit urine screens twice a week, and complete surveys regularly. The study excludes those who don't meet these requirements.

Inclusion Criteria

Voluntary enrollment in the residential addiction treatment facility

Intention on residing within residential addiction treatment facility for the duration of the Pre/Post PSI dosing period

Meet criteria for opioid use disorder (based on DSM-5 criteria) as primary diagnosis and voluntarily seeking treatment

Exclusion Criteria

Meets DSM-5 criteria for moderate to severe substance use disorder for substances other than cocaine, alcohol, marijuana, or nicotine

Participation in clinical trial and receipt of investigational drug(s) during 30 days prior to the research study, except as explicitly approved by the Principal Investigator

History of serious head trauma, seizures not related to withdrawal, or presence of certain prosthetics in the body

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment Testing

Brain and behavioral testing sessions conducted 24-48 hours before Psilocybin dosing

1 week

Treatment

Participants receive a single dose of either 25 mg or 1 mg PEX010

1 day

Post-Treatment Testing

Brain and behavioral testing sessions conducted 1 week after Psilocybin dosing

1 week

Outcomes Phase

Participants submit urine screens twice a week and complete surveys to collect data on drug use, MAT adherence, and mental health symptoms

8 weeks

16 visits (in-person)

Follow-up

Research follow-ups every three months to monitor long-term outcomes

1 year

Treatment Details

Interventions

• Psilocybin

Trial Overview The trial tests the efficacy of PEX010 (Psilocybin), comparing two doses: 25-mg and 1-mg. It's double-blind, meaning neither participants nor researchers know who gets which dose. The goal is to see if Psilocybin improves neurocognition and clinical outcomes in OUD patients.

Participant Groups

Group I: High Dose Psilocybin Experimental Treatment 1 Intervention

25 mg PEX010 capsule, single dose

Group II: Low Dose Psilocybin Active Control 1 Intervention

1 mg PEX010 capsule, single dose

Who Is Running the Clinical Trial?

Anna Rose Childress, Ph.D.

Lead Sponsor

Trials

3

Recruited

70+

Findings from Research

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]

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]

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]

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]

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]

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]

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 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 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]

References

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

Psychedelic therapy for smoking cessation: Qualitative analysis of participant accounts. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Exploring psilocybin-assisted psychotherapy in the treatment of methamphetamine use disorder. [2023]

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

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

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

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. [2022]

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

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

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

Optimal dosing for psilocybin pharmacotherapy: Considering weight-adjusted and fixed dosing approaches. [2022]

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

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. [2018]

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

Hallucinogenic mushrooms. [2017]

9. Switzerland 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. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Associations between classic psychedelics and opioid use disorder in a nationally-representative U.S. adult sample. [2022]

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

Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. [2022]

12. Netherlands pubmed.ncbi.nlm.nih.gov

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

13. Hungary pubmed.ncbi.nlm.nih.gov

Psilocybin use patterns and perception of risk among a cohort of Black individuals with Opioid Use Disorder. [2023]