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?

This trial explores whether abstaining from cannabis for at least four weeks can improve brain function, particularly in areas related to memory. Researchers compare individuals with cannabis use disorder to non-users to identify differences in brain activity and memory changes. The study targets daily cannabis users who are willing to quit for the trial's duration. Participants will undergo brain scans using [11C]APP311, a radiotracer used in imaging, to track changes. As an Early Phase 1 trial, this research aims to understand how a cannabis break affects brain function, offering participants the opportunity to contribute to groundbreaking insights.

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.

What prior data suggests that [11C]APP311 is safe for use in humans?

Research has shown that [11C]APP311 is being tested for safety and effectiveness in people with cannabis use disorder. Results so far suggest that [11C]APP311 is generally well-tolerated, with most participants not experiencing serious side effects.

The goal of using [11C]APP311 is to understand changes in the brain's synaptic density, which are the connections between nerve cells, in individuals who have stopped using cannabis. In earlier studies, [11C]APP311 examined brain activity in other conditions and did not show major negative effects.

As this is an early-phase study, the main focus is to ensure the treatment's safety for humans. Although detailed safety information is limited, researchers are closely monitoring for any potential issues. This phase is crucial to ensure the treatment's safe use in larger groups in the future.12345

Why are researchers excited about this trial?

Researchers are excited about [11C]APP311 for Cannabis Use Disorder because it offers a novel approach by using a radiolabeled compound in PET scans to explore brain activity associated with cannabis use. Unlike traditional treatments that primarily focus on behavioral therapy or medications like naltrexone or bupropion, this method aims to provide deeper insights into the brain's response to cannabis, potentially leading to more targeted interventions. By highlighting specific brain areas affected by cannabis use, [11C]APP311 could pave the way for developing new, more effective treatments for those struggling with cannabis addiction.

What evidence suggests that [11C]APP311 is effective for cannabis use disorder?

Studies have shown that cannabis use can reduce the number of connections between brain cells in the hippocampus, a region important for memory. This is where [11C]APP311 plays a role. This special imaging tool measures these changes in the brain. Early research suggests that it can help scientists observe how these connections change in individuals with cannabis use disorder. In this trial, researchers will scan participants in the CUD Group using [11C]APP311 to observe these brain changes. Although direct evidence on [11C]APP311's effectiveness in treating cannabis use disorder is limited, its ability to reveal brain changes might enhance understanding of the condition. This could eventually lead to new treatments that improve brain function in cannabis users.678910

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
See 4 more

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.
See 4 more

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

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]
The novel radioligand [123I]AM281 has been developed for imaging cannabinoid CB1 receptors in the living human brain, showing rapid brain passage and specific binding properties, making it suitable for in vivo studies.
Preclinical studies in baboons and mice demonstrated that [123I]AM281 effectively binds to CB1 receptors and its binding can be inhibited by known cannabinoid receptor ligands, indicating its potential for exploring the physiological roles of these receptors and the effects of marijuana dependence.
Imaging the brain marijuana receptor: development of a radioligand that binds to cannabinoid CB1 receptors in vivo.Gatley, SJ., Lan, R., Volkow, ND., et al.[2022]
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

Brain Imaging for Cannabis Use Effects in Older AdultsThe aim of the study is to examine the effect of cannabis use on brain synaptic density among older adults using \[11C\]UCB-J PET imaging. Show more. Do I need ...
Preliminary in vivo evidence of lower hippocampal synaptic ...Whether similar alterations exist in human cannabis users, has not yet been demonstrated in vivo. Positron emission tomography (PET) and [11C]UCB-J, a ...
Trial | NCT05472818The main purpose of this study is to determine whether hippocampal synaptic vesicle density estimated by hippocampal \[11C\]APP-311/\[11C\]UCB-J binding in ...
NCT03995121 | SV2 PET Imaging With [11C]APP311The aim of this study is to evaluate a new SV2A tracer, [11C]APP311, in healthy aging and neuropsychiatric disorders including psychotic disorders and cannabis ...
Exploring the influence of synaptic density and anxiety on pain ...Structural and functional brain alterations may be associated with pain and anxiety. We hypothesized that synaptic density (measured in vivo with [11C]UCB-J ...
NCT03995121 | SV2 PET Imaging With [11C]APP311The overall goal of this protocol is to study synaptic density in two psychiatric disorders (namely schizophrenia and other psychotic disorders, and cannabis ...
[11C]APP311 for Cannabis Use DisorderThis Phase < 1 medical study run by Yale University is evaluating whether [11C]APP311 will have tolerable side effects & efficacy for patients with Cannabis ...
NCT03104257 | The Neural Correlates of Cannabis UseThe purpose of this research study is to determine the temporal course of recovery of CB1R availability and neural oscillations, in cannabis-dependent ...
SV2A Density Cannabis Use Disorder... [11C]APP-311/[11C]UCB-J binding in individuals diagnosed with cannabis use disorder (CUDs) improves with at least 4 weeks of confirmed ...
Advances in synaptic PET imaging and intervention with ...In this review, first we detail the progress of synaptic density imaging including tracer development and preclinical/clinical application.
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