Synthetic Cannabinoids for Substance Use Disorders

(CB1R in Spice Trial)

Overseen By Deepak C D'Souza, M.D.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Disqualifiers: Mri metal, Claustrophobia, Education, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how synthetic cannabinoids, like those in products such as Spice or K2, affect the brain. Researchers aim to determine if these substances alter the brain's CB1R levels, which relate to the body's response to cannabinoids. Participants will receive a special tracer called [11-C]OMAR, an imaging agent, to help measure these effects. The trial seeks frequent users of synthetic cannabinoids, particularly those who regularly use products like Spice or K2. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research on the effects of synthetic cannabinoids.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that this method is safe for synthetic psychoactive cannabinoid users?

Research has shown that [11-C]OMAR is a radiotracer, a tool used in imaging to view the body's interior. Although specific safety information for [11-C]OMAR in humans is not available, it is crucial to understand that it differs from synthetic cannabinoids like K2 or Spice.

Synthetic cannabinoids have been linked to serious health risks, including severe bleeding and even death. They differ from natural cannabis and can be much more dangerous. Users of these substances have experienced more health problems compared to those using natural cannabis.

While [11-C]OMAR itself may lack clear safety data, the research examines its interaction with synthetic cannabinoids, which are known to pose significant health risks. Consulting healthcare professionals before joining any study is essential. They can provide guidance on what to expect and any potential risks involved. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for substance use disorders focus on behavior modification or substitute one substance for another. But [11-C]OMAR works differently, targeting the brain's cannabinoid receptors directly with a synthetic compound. This approach could offer a new avenue for managing dependence on synthetic cannabinoids like spice or K2, which don’t respond well to standard treatments. Researchers are excited because this could mean more effective, targeted interventions for users who haven't found success with current options.

What evidence suggests that [11-C]OMAR might be an effective treatment for substance use disorders?

Research has shown that [11-C]OMAR, which participants in this trial will receive, can detect changes in brain receptors in people who use synthetic drugs like Spice or K2. Studies have found that individuals with cannabis use disorders have fewer CB1 receptors in their brains. This is significant because CB1 receptors are part of the system that influences mood and behavior. By using [11-C]OMAR to measure these changes, scientists can better understand how synthetic drugs affect the brain. This knowledge could aid in developing treatments for substance use disorders. ^{6 7 8 9 10}

Who Is on the Research Team?

Deepak C D'Souza, M.D.

Principal Investigator

Yale University

Mohini Ranganathan, M.D.

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-55 who currently use synthetic psychoactive cannabinoids and can give written consent. It's not suitable for individuals with less than a high school education or those who cannot undergo MRI due to metal in their body or fear of enclosed spaces.

Inclusion Criteria

Able to provide written consent

Current Synthetic Psychoactive Cannabinoids consumption

Exclusion Criteria

MRI metal exclusions and claustrophobia

Education completed is less than 12 years

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging and Cognitive Testing

Participants undergo PET imaging and cognitive testing to assess CB1R availability and cognitive functions

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging and testing

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• [11-C]OMAR

Trial Overview [11-C]OMAR, a substance used in imaging studies, is being tested to see if it shows lower CB1R availability in the brains of people using synthetic psychoactive cannabinoids compared to non-users.

How Is the Trial Designed?

Group I: Synthetic Psychoactive Cannabinoid Users Experimental Treatment 1 Intervention

Synthetic Psychoactive Cannabinoid dependent subjects who are frequent spice/K2 users will receive the radiotracer \[11-C\]OMAR.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Citations

1. mdpi.com mdpi.com/2218-273X/12/3/396

Biomarkers of the Endocannabinoid System in Substance ... The results showed that [11C]OMAR VT was lower in the Amy, caudate, Hipp, hypothalamus, insula, putamen pallidum, frontal, parietal, occipital, and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11473150/

Cannabis use disorder: from neurobiology to treatment - PMC This Review will cover this topic from a variety of perspectives, with a particular emphasis on neurobiological findings and innovative treatment approaches.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4742341/

Rapid Changes in CB1 Receptor Availability in Cannabis ... Compared to HCs, [11C]OMAR VT was 15% lower in CDs (effect size Cohen's d=−1.11) at baseline in almost all brain regions. However, these group ...

4. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/2781289

Association of Cannabis Use During Adolescence With ... This cohort study examines the degree to which magnetic resonance imaging–assessed cerebral cortical thickness development is associated with cannabis use.

5. pubs.acs.org pubs.acs.org/doi/10.1021/acs.analchem.6b02600

Detection and Activity Profiling of Synthetic Cannabinoids and ... Chronic abuse of "Spice" has linked with signs of addiction syndrome and withdrawal symptoms similar to syndromes obsd. in cannabis abuse. These ...

6. dea.gov dea.gov/factsheets/spice-k2-synthetic-marijuana

Spice/ K2, Synthetic Marijuana These products are being abused for their psychoactive properties and are packaged without information as to their health and safety risks.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10377539/

Toxicity of Synthetic Cannabinoids in K2/Spice: A Systematic ... Evidence shows that using SCs products leads to greater health risks than cannabis. They have been associated with greater toxicity and higher ...

8. dea.gov dea.gov/sites/default/files/2020-06/K2-spice-2020.pdf

Drug Fact Sheet: K2/Spice These products are being abused for their psychoactive properties and are packaged without information as to their health and safety risks. Synthetic ...

9. dhs.wisconsin.gov dhs.wisconsin.gov/chemical/synthetic-cannabinoids.htm

Synthetic Cannabinoids (K2, Spice) | Wisconsin Department of ... A substance often called "fake weed," "K2," and "spice" can cause severe bleeding and possibly death. These products are found across the US.

10. nyc.gov nyc.gov/assets/doh/downloads/pdf/han/advisory/2025/han-advisory-21-k2.pdf

Increases in Synthetic Cannabinoid (K2) While rare, synthetic cannabinoid use can result in death. • Data from the NYC Health Department indicate a sustained elevation in synthetic.