Psilocybin-Assisted Psychotherapy for Cannabis Use Disorder

(PSI_CUD Trial)

Overseen By Maryam Rahat, Ph.D Candiate

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: McMaster University

Must not be taking: Stimulants, Antipsychotics, Benzodiazepines, others

Disqualifiers: Bipolar, Schizophrenia, Panic, 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: Unknown

Duration: 8 weeks

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether psilocybin, a compound in certain mushrooms, can help people reduce or stop cannabis use when combined with therapy sessions. The main goal is to determine if this combination is safe and effective for those struggling with Cannabis Use Disorder (CUD), a condition where cannabis use negatively affects work, school, and relationships. Participants with a moderate or severe CUD diagnosis who want to cut down or quit cannabis might be a good fit for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking certain medications, such as stimulants, anti-psychotic agents, benzodiazepines, and tri-cyclic anti-depressants. However, if you are on Selective Serotonin Reuptake Inhibitors or Serotonin Noradrenalin Reuptake Inhibitors, you can continue as long as your dose has been stable for 4 weeks and remains stable during the study.

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

Research has shown that psilocybin might help treat substance use disorders. One review found that psilocybin helped people with alcohol use disorder drink less or stop drinking, suggesting it could aid in treating other addictions as well.

Regarding safety, studies indicate that psilocybin is generally safe when used in controlled settings. Although concerns exist about recreational use, the risk of addiction to psychedelics remains low. However, the strength of psilocybin can vary, so its effects depend on the dose and the individual.

Overall, researchers consider psilocybin safe for study, especially when administered in a controlled environment with professional supervision. ^{1 2 3 4 5}

Why are researchers excited about this possible treatment for Cannabis Use Disorder?

Unlike traditional treatments for cannabis use disorder, which often involve counseling and medications like naltrexone or bupropion, psilocybin-assisted psychotherapy uses a psychedelic compound derived from certain types of mushrooms. This treatment is unique because psilocybin targets serotonin receptors in the brain, potentially altering mood and perception in a way that can lead to profound behavioral change. Researchers are excited about psilocybin because it may offer rapid, transformative effects after just a few sessions, unlike standard treatments that can take much longer to show results. This novel approach could provide a breakthrough for individuals struggling with cannabis dependency, offering hope where conventional therapies might fall short.

What evidence suggests that psilocybin-assisted psychotherapy might be an effective treatment for Cannabis Use Disorder?

Research has shown that psilocybin, when used in therapy, may help treat substance use disorders (SUDs). In several studies, therapy with psilocybin reduced addiction symptoms, including those related to substance use. Specifically, research suggests that psilocybin could be effective for various SUDs, though larger studies are needed to confirm these benefits. Early evidence indicates that psilocybin might help people manage their cannabis use, possibly reducing dependency. While more research is needed, psilocybin's role in therapy could offer a new way to treat Cannabis Use Disorder. Participants in this trial will receive psilocybin-assisted psychotherapy as part of their 9-week intervention. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals aged 18-65 with Cannabis Use Disorder who want to reduce or stop cannabis use. They must be fluent in English, medically healthy as confirmed by tests, and have a stable residence during the study. Participants need to agree to protocol requirements and provide regular medical updates.

Inclusion Criteria

I am willing to follow the study's rules and requirements.

I have been diagnosed with a moderate or severe cannabis use disorder.

I can provide proof of my identity.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 doses of 25 mg psilocybin as part of an 8-week Motivational Enhancement Therapy (MET) and supportive therapy

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview The trial is testing psilocybin-assisted psychotherapy for treating Cannabis Use Disorder. It involves two doses of psilocybin (25 mg each) combined with an 8-week Motivational Enhancement Therapy program. The focus is on assessing feasibility, safety, tolerability, and potential therapeutic effects.

How Is the Trial Designed?

Group I: Single Arm Experimental Treatment 1 Intervention

This is an open-label single arm intervention trial. Participants in this arm will be offered both drug and psychotherapy as part of their 9-week intervention.

Who Is Running the Clinical Trial?

McMaster University

Lead Sponsor

Trials

936

Recruited

2,630,000+

Center for Medicinal Cannabis Research

Collaborator

Trials

19

Recruited

630+

Peter Boris Centre for Addictions Research (PBCAR)

Collaborator

Trials

2

Recruited

40+

Published Research Related to This Trial

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 28-year-old female with complex D-PTSD experienced a remarkable 98.5% reduction in dissociative symptoms after 10 sessions of cannabis-assisted psychotherapy (CAP) over 5 months, indicating strong efficacy for this novel treatment.

The patient not only no longer met the criteria for D-PTSD but also reported sustained improvements for over 2 years, suggesting that CAP may offer long-lasting benefits similar to those seen with classic psychedelics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabis-assisted psychotherapy for complex dissociative posttraumatic stress disorder: A case report. Ragnhildstveit, A., Kaiyo, M., Snyder, MB., et al.[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]

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/S0376871624014273

Associations between psychedelic use and cannabis ... Lifetime LSD and psilocybin use were each associated with higher rates of past year CUD. Psilocybin had the strongest association with pathological cannabis ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6987443/

Persisting Reductions in Cannabis, Opioid, and Stimulant ... Observational data and preliminary studies suggest serotonin 2A agonist psychedelics may hold potential in treating a variety of substance use disorders (SUDs), ...

4. colorado.edu colorado.edu/asmagazine/2025/08/07/study-using-cannabis-and-psilocybin-together-may-increase-dependence

Study: Using cannabis and psilocybin together may ... As expected, the research data demonstrated that psilocybin users showed mild signs of marijuana dependence, while non-psilocybin users did not, ...

5. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2023.1144276/full

Systematic review and rationale of using psychedelics in ... Regarding the risk of addiction, development of a psychedelic use disorder is relatively low among recreational users, and in therapeutic ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10330760/

Systematic review and rationale of using psychedelics in ... Regarding the risk of addiction, development of a psychedelic use disorder is relatively low among recreational users, and in therapeutic ...

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

Psychedelics Research and Psilocybin Therapy Online survey of over 300 people with Alcohol Use Disorder reported reducing or abstaining alcohol use after taking a psychedelic drug such as psilocybin, LSD ...

8. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/2840625

Psilocybin Outside the Clinic: Public Health Challenges ... Testing data from decriminalized regions indicate more than 20-fold variability in psilocybin potency and inconsistent levels of minor ...