Psilocybin-Enhanced Psychotherapy for Methamphetamine Addiction

Overseen By Bianca Watt, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Portland VA Research Foundation, Inc

Must not be taking: Psilocybin interactors

Disqualifiers: Hypertension, Cardiovascular disease, Seizure, 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: 74

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether psilocybin, a compound found in certain mushrooms, can help people overcome methamphetamine addiction when combined with therapy. Researchers compare this approach to usual treatment methods in a residential rehab setting. The focus is on veterans with moderate to severe methamphetamine addiction who want to reduce or quit their use. Participants should not have uncontrolled high blood pressure, certain heart conditions, or a history of specific mental health disorders. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants a chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial excludes participants who are taking certain medications that may interact with psilocybin, so you might need to stop some medications. However, the protocol does not specify which medications these are.

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

Research has shown that psilocybin, the active ingredient in "magic mushrooms," may help treat methamphetamine addiction. Studies have found that psilocybin is generally safe and well-tolerated by participants, with low toxicity, meaning it doesn't cause significant harm to the body.

A small study specifically tested psilocybin-assisted therapy for methamphetamine addiction, assessing its safety and practicality in real-world settings. The results indicated that the therapy was safe for the participants involved.

So far, participants have handled psilocybin well, with few serious issues reported. Like any treatment, side effects can occur, but research suggests these are manageable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about psilocybin-enhanced psychotherapy for methamphetamine addiction because it offers a novel approach compared to traditional treatments like behavioral therapies and medications that focus on withdrawal symptoms. Unlike these options, psilocybin is a psychedelic compound that may help rewire the brain's reward systems, potentially reducing cravings and promoting long-term abstinence. Additionally, psilocybin is administered in just a couple of sessions, which could provide faster results compared to the ongoing nature of standard therapies. This new mechanism of action and the potential for rapid improvement make psilocybin an intriguing alternative for addressing methamphetamine addiction.

What evidence suggests that psilocybin-enhanced psychotherapy could be an effective treatment for methamphetamine addiction?

Research shows that therapy using psilocybin, a compound found in certain mushrooms, might help treat substance use disorders like methamphetamine addiction. In this trial, participants will receive either psilocybin-enhanced psychotherapy or treatment-as-usual. Studies have found that psilocybin therapy can lessen symptoms related to addiction. One study showed that people who received this treatment had fewer cravings for methamphetamine. Psilocybin has also helped with depression and anxiety, which often occur alongside addiction. These findings suggest that psilocybin could be a promising tool for managing methamphetamine use disorder. ^{1 2 4 6 7}

Who Is on the Research Team?

Chris Stauffer, MD

Principal Investigator

Oregon Health and Science University

Are You a Good Fit for This Trial?

This trial is for individuals with moderate to severe methamphetamine use disorder who want to stop or cut down on their use. It's not suitable for those with uncontrolled high blood pressure, significant heart disease, seizures in adulthood, poorly controlled diabetes, certain medication regimes, bipolar I disorder, active eating disorders with purging behaviors, persistent psychotic disorders (like schizophrenia), hallucinogen use disorder, or those who are pregnant or breastfeeding.

Inclusion Criteria

Moderate to severe methamphetamine use disorder using the DSM-V diagnostic criteria

United States military Veteran

Desire to cease or reduce methamphetamine use

Exclusion Criteria

I have had seizures as an adult.

I am not on medications that interact with psilocybin.

History of hallucinogen use disorder

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparatory Therapy

Participants undergo 4 preparatory therapy visits before psilocybin sessions

2 weeks

4 visits (in-person)

Psilocybin Sessions

Participants receive 2 psilocybin sessions (25mg & 30mg two weeks apart)

2 weeks

2 visits (in-person)

Integration Therapy

Participants attend 8 integration therapy visits following psilocybin sessions

2 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

180 days

Follow-up assessments at 60 and 180 days post-discharge

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview The study is testing if psilocybin-enhanced psychotherapy can help people with methamphetamine addiction better than the usual treatment methods. Participants will be randomly assigned to receive either the new therapy involving psilocybin or continue with standard treatments without it.

How Is the Trial Designed?

Group I: Treatment-as-Usual Experimental Treatment 1 Intervention

Treatment-as-usual while admitted to a residential rehabilitation treatment program.

Group II: Psilocybin-enhanced psychotherapy Experimental Treatment 2 Interventions

Psilocybin will be administered twice (25mg \& 30mg two weeks apart) in addition to a 6-week psychotherapy protocol while admitted to a residential rehabilitation treatment program.

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?

Portland VA Research Foundation, Inc

Lead Sponsor

Trials

2

Recruited

50+

Steven & Alexandra Cohen Foundation

Collaborator

Trials

10

Recruited

320+

Steven & Alexandra Cohen Foundation

Collaborator

Trials

5

Recruited

150+

Published Research Related to This Trial

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]

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 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 compound found in certain mushrooms, is being studied for its potential therapeutic effects in treating conditions like addiction, anxiety, and depression, primarily through its active metabolite psilocin, which interacts with the 5HT2A receptor.

While psilocybin shows promise as a treatment agent in neuropsychiatry, careful consideration of its safety and potential for harm is necessary to determine its clinical use, highlighting the need for a responsible approach in this research area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin in neuropsychiatry: a review of its pharmacology, safety, and efficacy. Dodd, S., Norman, TR., Eyre, HA., et al.[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-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]

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, 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]

Methylenedioxymethamphetamine (MDMA) showed a strong positive effect in reducing symptoms of post-traumatic stress disorder (PTSD) compared to active controls, with a significant effect size of -0.86 based on four studies.

Psilocybin demonstrated effectiveness in treating anxiety and depression in life-threatening diseases, being superior to a wait-list control, and showed comparable efficacy to escitalopram in long-standing depression, indicating its potential as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic literature review and meta-analysis of the effect of psilocybin and methylenedioxymethamphetamine on mental, behavioural or developmental disorders. Kisely, S., Connor, M., Somogyi, AA., et al.[2023]

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]

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.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10043240/

Exploring psilocybin-assisted psychotherapy in the treatment ... Early phase clinical trials of psilocybin-assisted psychotherapy have demonstrated promising results for treatment of other substance use ...

3. researchgate.net researchgate.net/publication/395696941_Psilocybin-assisted_psychotherapy_for_methamphetamine_use_disorder_A_pilot_open-label_safety_and_feasibility_study

A pilot open-label safety and feasibility study Methamphetamine craving was also observed to be lower while quality of life, depression, anxiety, and stress were observed to be higher at days ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S027858462500003X

Clinical and preclinical evidence of psilocybin as ... Clinical trials have revealed that psilocybin has a large, rapid, and persistent effect in the improvement of symptoms of depression and anxiety.

5. mdpi.com mdpi.com/1424-8247/18/4/555

The Emergence of Psilocybin in Psychiatry and ... This suggests psilocybin may support improvements in social cognition, particularly in disorders marked by social withdrawal or emotional numbing [38].

6. withpower.com withpower.com/clinical-trials/using-psilocybin

Top Treatment for Psilocybin Clinical Trials | Power This trial tests if psilocybin pills, combined with counseling, are safe for adults addicted to methamphetamine. Psilocybin can change brain function ...

7. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/cns.14054

Psilocin suppresses methamphetamine‐induced ... In this study, we want to explore the effects of psilocin on methamphetamine (METH)-induced alterations of behavior in mice and its molecular mechanisms.