42 Participants Needed

[11C]APP311 for Cannabis Use Disorder

KC
KD
AK
Overseen ByAnika Kumar
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

The main purpose of this study is to determine whether hippocampal synaptic vesicle density estimated by hippocampal \[11C\]APP-311/\[11C\]UCB-J binding in individuals diagnosed with cannabis use disorder (CUDs) improves with at least 4 weeks of confirmed abstinence from cannabis, in comparison to healthy controls (HCs). Furthermore, any change in synaptic vesicle density will be placed in functional context by measuring verbal memory, which is sensitive to hippocampal function, before and after at least 4 weeks of confirmed abstinence. Finally, the relationship between hippocampal \[11C\]UCB-J binding in CUDs with measures of cannabis exposure (e.g., age of initiation, cumulative lifetime dose) will be explored.

Will I have to stop taking my current medications?

The trial requires that participants do not take medications that could alter synaptic density, as these could affect the study results. If you are on such medications, you may need to stop taking them to participate.

How does the drug [11C]APP311 differ from other treatments for Cannabis Use Disorder?

[11C]APP311 is unique because it is a radioligand used in imaging studies to measure the availability of CB1 receptors in the brain, which are affected by cannabis use. This approach is different from typical treatments as it focuses on understanding the brain's receptor changes rather than directly treating the disorder.12345

Who Is on the Research Team?

DC

Deepak C D'Souza

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-75 with moderate to severe cannabis use disorder, who are physically healthy and not using other drugs. They must be willing to attempt quitting cannabis, agree to birth control if applicable, and have no metal implants that could interfere with MRI scans or a history of significant medical conditions.

Inclusion Criteria

Diagnosis of DSM-5 cannabis use disorder (≥ moderate, i.e., ≥ 4 [of 11] symptoms)
I am willing to try quitting cannabis.
Able to provide informed consent
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Exclusion Criteria

Have implanted or embedded metal objects or fragments in the head or body that would present a risk during the MRI scanning procedure, or have worked with ferrous metals either as a vocation or hobby
Laboratory tests with clinically significant abnormalities or positive urine toxicology screen with exception of cannabinoids
I am currently pregnant or breastfeeding.
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Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline MRI and PET scans and cognitive assessments

1 week
1 visit (in-person)

Abstinence and Monitoring

CUD participants abstain from cannabis for 4 weeks, with PET scans and cognitive assessments before and after abstinence

4 weeks
2 visits (in-person)

Extended Monitoring

A subset of CUD participants undergoes additional PET scan after 8 weeks of abstinence

4 weeks
1 visit (in-person)

Follow-up

Participants are monitored for any long-term changes in synaptic density and cognitive function

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • [11C]APP311
Trial Overview The study tests whether stopping cannabis improves brain function related to memory by measuring changes in hippocampal synaptic vesicle density using [11C]APP-311/[11C]UCB-J binding. It compares individuals with CUD abstaining from cannabis for at least 4 weeks against healthy controls.
How Is the Trial Designed?
2Treatment groups
Active Control
Group I: CUD GroupActive Control1 Intervention
Group II: Healthy ControlsActive Control1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials
1,963
Recruited
3,046,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials
2,658
Recruited
3,409,000+

Published Research Related to This Trial

Chronic cannabis users showed a significant decrease in cerebral CB1 receptor availability, with an overall reduction of 11.7% compared to healthy controls, indicating potential neuroadaptive changes due to prolonged cannabis exposure.
Specific brain regions, including the temporal lobe and cingulate cortex, exhibited even greater reductions in CB1 receptor availability, suggesting that these changes could be linked to cannabis tolerance and dependence, and may inform future treatment strategies for cannabis addiction.
[18F]MK-9470 PET measurement of cannabinoid CB1 receptor availability in chronic cannabis users.Ceccarini, J., Kuepper, R., Kemels, D., et al.[2016]
Alcohol dependence in humans is linked to a significant reduction (20-30%) in cannabinoid CB1 receptor binding in the brain, which persists for at least 2-4 weeks after abstinence, indicating a potential biomarker for alcohol use disorders.
The study found that individuals with a specific genetic variation (C allele at rs2023239) had higher CB1 receptor binding, suggesting that genetic factors may influence cannabinoid receptor density and potentially the risk of alcohol dependence.
Reduced cannabinoid CB1 receptor binding in alcohol dependence measured with positron emission tomography.Hirvonen, J., Zanotti-Fregonara, P., Umhau, JC., et al.[2021]
In a study involving 32 participants (18 healthy volunteers and 14 cannabis users), it was found that cannabis users had 12% lower levels of the FAAH enzyme in their brains, which is responsible for breaking down the endocannabinoid anandamide.
This finding was replicated in a younger cohort, suggesting that even with less cumulative cannabis exposure, lower FAAH levels are associated with increased cannabis use, indicating a potential impact of cannabis on endocannabinoid metabolism.
Fatty acid amide hydrolase is lower in young cannabis users.Jacobson, MR., Watts, JJ., Da Silva, T., et al.[2022]

Citations

[18F]MK-9470 PET measurement of cannabinoid CB1 receptor availability in chronic cannabis users. [2016]
Reduced cannabinoid CB1 receptor binding in alcohol dependence measured with positron emission tomography. [2021]
Fatty acid amide hydrolase is lower in young cannabis users. [2022]
Molecular brain differences and cannabis involvement: A systematic review of positron emission tomography studies. [2023]
Imaging the brain marijuana receptor: development of a radioligand that binds to cannabinoid CB1 receptors in vivo. [2022]
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