Psilocybin for Opioid Use Disorder

Overseen By Anna Rose Childress, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Anna Rose Childress, Ph.D.

Must be taking: Buprenorphine, Methadone

Must not be taking: Antidepressants, others

Disqualifiers: Schizophrenia, Bipolar, Cardiovascular, 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: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how psilocybin, a compound found in certain mushrooms, might aid individuals with opioid use disorder by affecting brain circuits linked to addiction and decision-making. Participants receive either a low or high dose of psilocybin, and researchers use brain scans to detect changes that might reduce the risk of drug relapse. Individuals diagnosed with opioid use disorder who are already in a stable treatment program might be suitable for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial requires participants to stay on their current opioid treatment medications like BUP-NX or methadone. However, you cannot take any psychoactive medications, such as antidepressants, during the study.

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

Research has shown that psilocybin might be safe for humans. Studies have linked psilocybin to a lower risk of opioid addiction, suggesting it could aid those with addiction issues. Some research also indicates that psilocybin therapy can reduce symptoms in individuals with substance use disorders (SUDs). However, larger studies are still testing these findings to better understand its effects.

Psilocybin is generally considered safe, with most people experiencing mild effects like changes in mood or perception. Serious side effects are rare. The current study is in an early phase, so researchers are closely monitoring safety. They observe participants for any negative effects to ensure their well-being. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for opioid use disorder?

Unlike the standard treatments for opioid use disorder, which often include medications like methadone or buprenorphine, psilocybin offers a completely different approach by acting on serotonin receptors in the brain. Researchers are excited about psilocybin because it has the potential to create profound psychological experiences that could help reset harmful patterns of thinking and behavior associated with addiction. Additionally, psilocybin might offer benefits with just a single or a few doses, contrasting with the daily regimen required by current medications. The high-dose and low-dose psilocybin arms aim to explore the optimal balance between effectiveness and minimal side effects, offering promising alternatives for those seeking new paths to recovery.

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

Research has shown that psilocybin might help treat addiction, including opioid use disorder. This trial will compare the effects of high-dose and low-dose psilocybin on opioid use disorder. Studies have found that therapy using psilocybin can lessen symptoms of substance use disorder (SUD). Early results suggest it may reduce opioid cravings by affecting serotonin receptors, which influence mood and behavior. Additionally, some studies have found that using psychedelics like psilocybin is linked to a lower risk of opioid dependence. These promising findings suggest that psilocybin could be a potential treatment for opioid addiction. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-60 in the Philadelphia area with opioid use disorder. Participants must be able to come to the office for multiple visits, including therapy sessions and medical tests. They'll also need to stay in an inpatient program for about two weeks during the study.

Inclusion Criteria

An informed consent document voluntarily signed and dated by the subject

IQ score of greater than or equal to 80

I am 18-60 years old, healthy, and seeking treatment for opioid addiction.

Exclusion Criteria

Seizure disorder or history of seizures not related to drug or alcohol withdrawal

At Screening or Baseline have elevated blood pressure as defined as: Screening blood pressure SBP greater than 135 mmHg or DBP greater than 85 mmHg on three separate readings; or Baseline blood pressure SBP greater than 140 mmHg or DBP greater than 90 mmHg on three separate readings

I have been diagnosed with bipolar disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Multiple visits (in-person)

Inpatient Psilocybin Treatment

Participants are admitted to an inpatient program for psilocybin treatment, including pre-dose preparation, dosing, and post-dose therapy

2 weeks

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including fMRI and behavioral assessments

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview The study is testing how low (1mg) or high (25mg) doses of psilocybin affect brain circuits related to addiction and cognitive flexibility using fMRI scans before and after dosing. The participants will be randomly assigned to one of these dose groups.

How Is the Trial Designed?

Group I: High dose psilocybin Experimental Treatment 1 Intervention

25 mg PEX010 capsule, single dose

Group II: Low dose psilobyin 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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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 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]

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]

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]

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]

Citations

1. 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 ...

2. 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) ( ...

3. hopkinsmedicine.org hopkinsmedicine.org/psychiatry/research/psychedelics-research

Psychedelics Research and Psilocybin Therapy Upcoming studies will determine the effectiveness of psilocybin as a new therapy for opioid addiction, Alzheimer's disease, post-traumatic stress disorder ...

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

Associations between classic psychedelics and opioid use ... demonstrated that classic psychedelic use conferred 27% reduced risk of past-year opioid dependence and 40% reduced risk of past-year opioid ...

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. 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.

7. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2023.1183740/full

Psychedelic therapy in the treatment of addiction (33) looked at 44,000 individuals with a history of illicit opioid use and found psychedelic use to be associated with a 27% reduced risk of past-year opioid ...