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

Trial Summary

What is the purpose of this trial?

This pilot study will evaluate the therapeutic potential of psilocybin in people with Cannabis Use Disorder (CUD). This study will examine the impact of psilocybin treatment on cannabis use and related variables in 12 people with CUD. This is an open-label proof-of-concept trial in which participants will complete a 12-week course of study treatment including two psilocybin sessions with psychological support, and follow-up assessments 3 and 6 months after the first psilocybin session.

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 psilocybin safe for human use?

Psilocybin, found in magic mushrooms, is generally considered safe under controlled conditions, but it can cause hallucinations and other effects on the nervous system. It is important to use it carefully, as higher doses or improper use can lead to adverse effects, and there is a risk of confusing it with poisonous mushrooms. ^{1 2 3 4 5}

How is the drug psilocybin unique in treating cannabis use disorder?

Psilocybin is unique because it works by affecting serotonin receptors in the brain, which can lead to altered perceptions and potentially help change behavior patterns related to cannabis use. Unlike traditional treatments, psilocybin is a psychedelic compound that can produce profound changes in consciousness and is being explored for its potential to treat various mental health conditions. ^{1 2 6 7 8}

Research Team

Albert Garcia-Romeu, Ph.D.

Principal Investigator

Johns Hopkins University

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

References

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

The pharmacology of psilocybin. [2016]

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

[Hallucinogenic mushrooms]. [2018]

3. England 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. [2021]

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

Intravenous mushroom poisoning. [2019]

5. Scotland pubmed.ncbi.nlm.nih.gov

The danger of hallucinogenic mushrooms. [2017]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Extensive Collection of Psychotropic Mushrooms with Determination of Their Tryptamine Alkaloids. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Simultaneous Production of Psilocybin and a Cocktail of β-Carboline Monoamine Oxidase Inhibitors in "Magic" Mushrooms. [2021]

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

Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice. [2023]