Brain Imaging for Cannabis Use Effects in Older Adults

Recruiting at 1 trial location

Overseen By Angerlyk Frytz, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Yale University

Must not be taking: Anticoagulants

Disqualifiers: Pregnancy, Lactation, Bleeding disorder, 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: 1

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how cannabis affects the brain in older adults. Researchers will use a special brain scan called [11C]UCB-J PET (an imaging agent) to measure changes in brain connections. Participants will be divided into two groups: healthy older adults and older adults who use cannabis. The trial seeks individuals aged 50 and above who do not have major medical issues and have used cannabis. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

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

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

What prior data suggests that [11C]UCB-J PET imaging is safe for older adults?

Research shows that the [11C]UCB-J PET scan, used in this trial, is generally safe and well-tolerated. Previous studies have used this method to examine brain activity without causing serious side effects.

Detailed safety data for this specific study is not yet available, as the treatment is in the early stages of testing (Phase 1 and Phase 2). Researchers are closely monitoring it for safety. Any side effects are likely mild and manageable, as treatments must pass safety checks before advancing to later stages. Participants who underwent the PET scan in past studies did not report major problems, making it a relatively safe choice for those considering joining this clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it uses a cutting-edge brain imaging technique with [11C]UCB-J PET to explore how cannabis affects older adults' brains. Unlike traditional methods that might focus on behavioral or self-reported data, this approach provides a clear, direct view of brain activity. By targeting synaptic density, [11C]UCB-J PET offers insights that could lead to a deeper understanding of cannabis use's impact on the aging brain, potentially guiding future therapeutic strategies.

What evidence suggests that [11C]UCB-J PET imaging is effective for studying cannabis use effects in older adults?

Research shows that the [11C]UCB-J PET scan effectively views connections between brain cells and measures their communication. Studies have found it can detect changes in individuals with mild memory problems, such as early Alzheimer's, revealing a 41% drop in brain cell activity. In this trial, researchers use the [11C]UCB-J PET scan to study cannabis's effects on these brain connections. Participants include healthy controls and cannabis-using older adults. This method could reveal significant changes in brain function, particularly in older adults who use cannabis. ^{1 2 5 6 7}

Who Is on the Research Team?

Deepak C D'Souza, MBBS, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for men and women over the age of 50 who can consent to participate. They must not have significant medical or neurological diseases, and women able to bear children should agree to use birth control during the study. People cannot join if they've recently donated blood, are pregnant or lactating, have been exposed to a lot of radiation, or have bleeding disorders.

Inclusion Criteria

Able to provide informed consent

I am 50 years old or older.

BMI ≤ 50

Exclusion Criteria

Subjects who have donated blood within 8 weeks of the present study

I've been exposed to radiation levels higher than recommended due to this study.

I am currently pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

PET Imaging

Subjects undergo a single PET scan using [11C]UCB-J to measure synaptic density

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the PET scan

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• [11C]UCB-J PET

Trial Overview The study is looking at how cannabis affects brain connections in older adults by using a special PET scan called [11C]UCB-J PET imaging. It aims to understand changes in synaptic density related to cannabis use.

How Is the Trial Designed?

Group I: Healthy controls Experimental Treatment 1 Intervention

Subjects undergo a single PET scan using \[11C\]UCB-J

Group II: Cannabis using older adults Experimental Treatment 1 Intervention

Subjects undergo a single PET scan using \[11C\]UCB-J

[11C]UCB-J PET is already approved in United States, European Union for the following indications:

Approved in United States as [11C]UCB-J for:

• Research use for synaptic density imaging in neurodegenerative diseases and epilepsy

Approved in European Union as [11C]UCB-J for:

• Research use for synaptic density imaging in neurodegenerative diseases

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

Regular cannabis users show neuroanatomic alterations in brain regions rich in cannabinoid receptors, particularly with higher doses and earlier onset of use, based on a review of 31 studies.

THC appears to exacerbate these neuroanatomic changes, while CBD may offer protective effects, highlighting the need for more standardized methods to assess cannabis use in research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Cannabinoids in Neuroanatomic Alterations in Cannabis Users. Lorenzetti, V., Solowij, N., Yücel, M.[2022]

A study using magnetic resonance spectroscopy on 26 chronic cannabis users and 24 controls found no significant differences in brain metabolite concentrations, suggesting that cannabis use may not drastically alter brain chemistry in the short term.

However, the analysis indicated that monthly cannabis use and sex may influence certain metabolites, with males showing a stronger relationship between cannabis use and glutamate levels, highlighting the need for further research with larger sample sizes to explore these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Investigation of Neurochemical Changes in Chronic Cannabis Users. Newman, SD., Cheng, H., Schnakenberg Martin, A., et al.[2023]

This review highlights that delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), the two main cannabinoids in cannabis, have different effects on brain metabolites, which are important for understanding their therapeutic and harmful impacts.

Current research, although limited, suggests that THC and CBD may influence brain metabolite levels in unique ways, indicating the need for more detailed studies to explore these differences and their implications for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of cannabinoids on brain metabolites: A review of animal and human studies. Ma, J., Lyoo, IK., Renshaw, PF., et al.[2023]

Chronic use of Δ9-tetrahydrocannabinol (THC) in older adults is associated with poorer performance on cognitive tasks, specifically inhibitory control, compared to cannabidiol users and non-users, indicating potential negative effects on cognitive function.

THC users exhibited altered cerebral glucose metabolism, showing lower overall metabolism and increased activity in specific brain regions, which suggests that long-term THC use may impact brain function in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in Inhibitory Control and Resting Brain Metabolism between Older Chronic Users of Tetrahydrocannabinol (THC) or Cannabidiol (CBD)-A Pilot Study. Rudroff, T., Workman, CD., Gander, PE., et al.[2022]

In a pilot study of 56 older adults, including 28 current cannabis users with an average of 23.55 years of use, cannabis users showed greater regional brain volume in areas like the left putamen and rostral middle frontal cortex compared to nonusers.

Despite these regional differences, there were no significant impacts on overall brain volume or cognitive performance between cannabis users and nonusers, suggesting that cannabis use may not adversely affect overall brain structure in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary results from a pilot study examining brain structure in older adult cannabis users and nonusers. Thayer, RE., YorkWilliams, SL., Hutchison, KE., et al.[2020]

Chronic exposure to vaporized cannabis high in Δ9-THC provided effective pain relief without developing tolerance, but did not improve anxiety or cognitive function, indicating its potential as an analgesic for older adults.

In contrast, chronic use of CBD enhanced brain network connectivity, effects that persisted even after stopping the drug, suggesting it may have long-term benefits for brain health, although its behavioral implications are still unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of inhaled cannabis high in Δ9-THC or CBD on the aging brain: A translational MRI and behavioral study. Sadaka, AH., Canuel, J., Febo, M., et al.[2023]

The study demonstrated that the CB2R PET ligand [11C]-NE40 is safe and well-tolerated in six healthy male subjects, with no adverse events reported during the imaging process.

[11C]-NE40 showed a favorable biodistribution, with high uptake in the spleen and rapid kinetics in the brain, indicating its potential for studying neuroinflammatory disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole-body biodistribution and radiation dosimetry of the cannabinoid type 2 receptor ligand [11C]-NE40 in healthy subjects. Ahmad, R., Koole, M., Evens, N., et al.[2021]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18F]MK-9470 PET measurement of cannabinoid CB1 receptor availability in chronic cannabis users. Ceccarini, J., Kuepper, R., Kemels, D., et al.[2016]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05465538

Study Details | NCT05465538 | SV2A in Older Adults The 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. Official Title.

2. withpower.com withpower.com/trial/phase-2-cannabis-use-6-2022-9251c

Brain Imaging for Cannabis Use Effects in Older Adults The 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 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1568163724000151

In vivo imaging of synaptic density in neurodegenerative ... In this systematic review, we provide a discussion of in vivo SV2A PET imaging research for quantitative assessment of synaptic density in various dementia ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6894376/

In Vivo Synaptic Density Imaging with 11C-UCB-J Detects ... Recently, we conducted 11C-UCB-J PET on patients with mild cognitive impairment or early AD, revealing a 41% mean decrease in specific binding in the ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03995121

NCT03995121 | SV2 PET Imaging With [11C]APP311 The aim of this study is to evaluate a new SV2A tracer, [11C]APP311, in healthy aging and neuropsychiatric disorders including psychotic disorders and cannabis ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2667325824001596

Advances in synaptic PET imaging and intervention with ... Researchers have found an age-dependent mitochondrial dysfunction and synaptic loss in the caudate of healthy volunteers in a clinical multi-tracer study, where ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40878905/

Associations between fluid biomarkers and PET imaging ... SV2A ([11C]UCB-J) PET was used to quantify synaptic density. Reductions of synaptic density were associated with CSF synaptic biomarker levels. Keywords: ...