Psilocybin for Cannabis Use Disorder

Overseen By Albert Garcia-Romeu, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Johns Hopkins University

Must be taking: SSRIs, SNRIs, Bupropion

Must not be taking: Antipsychotics, MAO inhibitors, Lithium

Disqualifiers: Substance use disorder, Cardiovascular, Schizophrenia, 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: 10

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore whether psilocybin, a psychedelic compound, can help individuals with Cannabis Use Disorder (CUD) reduce their cannabis consumption. Participants will engage in two psilocybin sessions, each supported by psychological guidance, over a 12-week period. The trial seeks individuals diagnosed with CUD who are medically stable, meaning they do not have other significant health issues that could interfere with the study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

Will I have to stop taking my current medications?

You can continue taking certain medications like SSRIs, SNRIs, and bupropion (up to 300mg/day) if you've been stable on them for at least two months before the trial. However, you cannot participate if you're taking antipsychotics, MAO inhibitors, or other antidepressants.

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

Research has shown that psilocybin has been well-tolerated in past studies. In one study, a single dose of psilocybin caused no serious side effects. Another study found no unexpected safety issues with psilocybin, according to a safety review board. These results suggest that psilocybin is generally safe for humans. However, as it is still under investigation for various conditions, individuals should consider their own health and consult a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Psilocybin is unique because it offers a novel approach to treating cannabis use disorder by targeting the brain's serotonin receptors, potentially altering patterns of addiction. Unlike traditional treatments, which often focus on behavioral therapy or medications like naltrexone and bupropion, psilocybin may directly influence the brain's neural pathways associated with dependency. Researchers are excited because psilocybin might provide rapid and profound changes in perception and behavior, potentially reducing cannabis use with just a couple of sessions, rather than requiring ongoing medication.

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

Research has shown that psilocybin, a compound found in certain mushrooms, may help treat substance use disorders, such as alcohol and tobacco addictions. Studies have found that psilocybin can significantly reduce addiction severity and decrease drug use frequency. In this trial, participants will receive psilocybin to evaluate its potential for treating Cannabis Use Disorder (CUD). Although few studies specifically address psilocybin for CUD, its success with other addictions suggests it might be beneficial. Psilocybin appears to work by altering perceptions and thoughts about addiction, encouraging individuals to reconsider their relationship with substances. Early research suggests that psilocybin could help reduce or eliminate cannabis use by changing thoughts and feelings about addiction. ^{6 7 8 9 10}

Who Is on the Research Team?

Albert Garcia-Romeu, Ph.D.

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for individuals who struggle with Cannabis Use Disorder, meaning they have a problematic pattern of cannabis use. Participants will be involved in a 12-week study with follow-ups at 3 and 6 months after treatment begins.

Inclusion Criteria

Currently meets criteria for The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of Cannabis Use Disorder

Capable of providing written informed consent for participation into the study

Willingness to allow the study team to review past medical records

Exclusion Criteria

Transaminases greater than x2 the upper limit of normal lab reference range

I am not fluent in English.

Meeting DSM-5 criteria for another moderate or severe substance use disorder (excluding tobacco) within the past 5 years

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Preparatory Meetings

Participants undergo 4 weekly preparatory meetings including targeted cognitive behavioral therapy (CBT) intervention for CUD

4 weeks

4 visits (in-person or virtual)

Psilocybin Treatment

Participants receive two psilocybin sessions with psychological support, with doses administered in weeks 5 and 7

8 weeks

2 visits (in-person) for dosing, weekly meetings (in-person or virtual)

End of Treatment

Participants complete post-session assessments at the end of the 12-week treatment period

1 week

1 visit (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 3 and 6 months after the first psilocybin session

6 months

2 visits (in-person or virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview The trial is testing the effects of psilocybin, which is thought to potentially help treat Cannabis Use Disorder. It includes two sessions where psilocybin is administered with psychological support over a course of 12 weeks.

How Is the Trial Designed?

Group I: Psilocybin Experimental Treatment 1 Intervention

Open-label psilocybin will be administered with psychological support to each participant at two dosing sessions approximately 2 weeks apart.

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?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Center for Psychedelic and Consciousness Research

Collaborator

Trials

1

Recruited

10+

Published Research Related to This Trial

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]

A study analyzed 226 mushroom samples from seven genera to measure concentrations of psilocybin and other tryptamine alkaloids, revealing significant variability in their levels, particularly in Psilocybe species.

The variability in tryptamine concentrations poses a risk of overdose for consumers and complicates the interpretation of medicinal effects compared to standardized psilocybin therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extensive Collection of Psychotropic Mushrooms with Determination of Their Tryptamine Alkaloids. Gotvaldová, K., Borovička, J., Hájková, K., et al.[2022]

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]

There is a growing trend among young people to consume wild Psilocybin mushrooms for their hallucinogenic effects, but this practice carries risks.

The report highlights seven cases of mushroom overdosage, stressing that while Psilocybin mushrooms are generally considered harmless, there is a significant danger of accidentally consuming toxic mushroom species that can cause serious harm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The danger of hallucinogenic mushrooms. Mills, PR., Lesinskas, D., Watkinson, G.[2017]

Research on four species of Psilocybe mushrooms revealed the presence of β-carbolines, such as harmane and harmine, which are derived from l-tryptophan and contribute to the mushrooms' psychoactive effects.

These β-carbolines act as potent inhibitors of monoamine oxidases, which not only affect the degradation of psilocybin but also suggest a complex interaction of natural compounds that enhance the pharmacological effects of the mushrooms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous Production of Psilocybin and a Cocktail of β-Carboline Monoamine Oxidase Inhibitors in "Magic" Mushrooms. Blei, F., Dörner, S., Fricke, J., et al.[2021]

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]

In a study examining the effects of Psilocybe cubensis and Panaeolus cyanescens mushrooms on heart cells, the extracts did not worsen hypertrophy caused by endothelin-1 and provided protection against TNF-α-induced cell injury.

The findings suggest that these mushroom extracts can be safely used in controlled conditions for potential therapeutic benefits in heart disease, although caution is advised with higher concentrations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects and safety of Psilocybe cubensis and Panaeolus cyanescens magic mushroom extracts on endothelin-1-induced hypertrophy and cell injury in cardiomyocytes. Nkadimeng, SM., Steinmann, CML., Eloff, JN.[2021]

A 30-year-old man experienced severe symptoms, including vomiting and muscle pain, after receiving an intravenous injection of Psilocybe mushroom extract, highlighting the potential dangers of using hallucinogenic substances in non-traditional ways.

The patient showed rapid improvement with supportive care, suggesting that while the effects of Psilocybe mushrooms can be serious, timely medical intervention can effectively manage the symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous mushroom poisoning. Curry, SC., Rose, MC.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8901083/

Analysis of Psilocybin-Assisted Therapy in Medicine This review analyzes the potential of psilocybin in the treatment of addiction, depression, and end-of-life mood disorders.

2. compasspathways.com compasspathways.com/our-work/comp360-psilocybin-treatment-in-trd/

COMP360 psilocybin treatment in TRD This trial assessed the safety and efficacy of COMP360 psilocybin treatment in three doses: 1mg, 10mg, 25mg. The results, published in the New England ...

3. mdpi.com mdpi.com/1648-9144/61/2/278

The Therapeutic Potential of Psychedelics in Treating ... Recent studies suggest that psilocybin holds potential for treating mental health conditions like depression, anxiety, obsessive–compulsive disorder, and SUD.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2772392522000207

Classic and non‐classic psychedelics for substance use ... A significant decrease in addiction severity outcomes, drug use, alcohol use ... psilocybin may be effective for AUD and tobacco use disorder. THC and ...

5. researchgate.net researchgate.net/publication/358887616_The_therapeutic_potential_of_psilocybin_a_systematic_review

The therapeutic potential of psilocybin: a systematic review Results: Findings revealed that individuals who had recently used psilocybin had greater cannabis dependence scores than those who had not used ...

6. psychiatrictimes.com psychiatrictimes.com/view/comp360-psilocybin-for-treatment-resistant-depression-positive-phase-3-efficacy-data

COMP360 Psilocybin for Treatment-Resistant Depression Compass Pathways reports significant progress in psilocybin research, showing promise for treatment-resistant depression in a pivotal phase 3 trial.

7. ir.compasspathways.com ir.compasspathways.com/News--Events-/news/news-details/2025/Compass-Pathways-Successfully-Achieves-Primary-Endpoint-in-First-Phase-3-Trial-Evaluating-COMP360-Psilocybin-for-Treatment-Resistant-Depression/default.aspx

News Details ... Data Safety Monitoring Board (DSMB) reviewed safety data for COMP360 and found no unexpected safety findings and no clinically meaningful ...

8. theeducatedpatient.com theeducatedpatient.com/view/psilocybin-shows-promise-for-hard-to-treat-depression-in-new-study

Psilocybin Shows Promise for Hard-to-Treat Depression in ... A single dose of COMP360 psilocybin significantly reduced depression symptoms in people with treatment-resistant depression, according to new ...

9. 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 ...

10. investingnews.com investingnews.com/compass-pathways-announces-publication-of-results-from-phase-2-study-of-comp360-psilocybin-for-post-traumatic-stress-disorder/

Compass Pathways Announces Publication of Results from ... Open-label Phase 2 study shows a single 25 mg COMP360 psilocybin dose was well tolerated, with no serious adverse events observed, ...