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| ID | Type | Description | Link |
|---|---|---|---|
| K23DA045957 | U.S. NIH Grant/Contract | View source |
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Insufficient funding
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| Name | Class |
|---|---|
| National Institute on Drug Abuse (NIDA) | NIH |
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This study will be the first in vivo human multimodal neuroimaging study exploring the relationship between mGluR5 availability (PET), neural oscillations (EEG), and cognitive function in people with CUD. The goal is to test the overall hypothesis that mGluR5 availability is higher in people with CUD compared with HC. In Aim 1, the investigators will determine differences in mGluR5 availability between people with CUD and HC in the fronto-limbic brain circuit. Aim 2 examines the associations between mGluR5 availability, CUD severity, neural oscillations, and cognitive function in CUD subjects. Aim 3 will determine how prolonged abstinence from chronic cannabis use affects mGluR5 availability, neural oscillations, and cognitive function in CUD subjects.
Cannabis use and availability continue to rise significantly in the US. It is critical to expand our knowledge of the negative and positive effects of cannabis to "catch up" to the current reality of widespread and growing use. Cannabis and tetrahydrocannabinol (THC), its primary psychoactive chemical, have widespread effects on neural glutamate homeostasis, and specifically metabotropic glutamate receptor 5 (mGluR5). mGluR5 regulates transmission of glutamate and plays a critical role in neural plasticity (i.e., long-term potentiation; LTP), memory, learning, mood, and addiction. Specifically, it is thought that mGluR5 activation by glutamate initiates production of endocannabinoids (i.e., 2-AG) that bind retrograde to presynaptic cannabinoid receptor 1. This pathway inhibits further glutamate release and modulates synaptic plasticity diffusely in the brain. However, cannabis use disrupts this normal mechanism of glutamate homeostasis. While the relationship between cannabis use and glutamate regulation has been explored in preclinical models, it has not been well-characterized in humans, and particularly in people with cannabis use disorder (CUD).
The goal is to test the overall hypothesis that mGluR5 availability is higher in people with CUD compared with HC. This study will advance our understanding of cannabis effects on the neural glutamate system in humans and may lead to the development of novel therapeutics and biomarkers to treat people with CUD. Aim 1 will determine differences in mGluR5 availability between people with CUD and HC in the fronto-limbic brain circuit. Aim 2 examines the associations between mGluR5 availability, CUD severity, neural oscillations, and cognitive function in CUD subjects. Aim 3 will determine how prolonged abstinence from chronic cannabis use affects mGluR5 availability, neural oscillations, and cognitive function in CUD subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cannabis use disorder | Experimental | CUD participants participants undergo neuroimaging, cognitive testing, and EEG at baseline and following cannabis abstinence at 4 weeks follow-up. Participants will receive motivational enhancement and contingency management during the 4-week abstinence period. |
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| Healthy control | Experimental | Healthy control participants undergo neuroimaging, cognitive testing, and EEG at baseline. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [18F]FPEB with PET | Drug | radioactive tracer [18F]FPEB administered by bolus infusion over up to 2 hours with PET performed in the last 30 minutes of infusion with Positron emission tomography (PET) neuroimaging |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Metabotropic Glutamate Receptor 5 (mGluR5) Availability | Participants will undergo a Positron Emission Tomography (PET) scan to visualized mGluR5 availability in the regions of interest (ROIs): orbitofrontal cortex (OFC), anterior cingulate, ventromedial prefrontal cortex (vmPFC), dorsolateral prefrontal cortex (dlPFC), hippocampus, and amygdala. Only done at baseline for HC group. | Baseline and Day 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Neurocognitive Function Using CogState Cognitive Battery | A battery of neuropsychological tests from the well-validated CogState Cognitive Battery are sensitive to detecting cognitive deficits in mood disorders, executive control and working memory. The entire battery takes approximately 30 minutes. Change in CUD group at baseline and day 28 compared to HC at baseline. | Baseline and Day 28 |
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Inclusion Criteria:
HC and CUD Group:
CUD group:
HC group:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Stephen R Baldassarri, M.D. | Yale University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Anlyan Center | New Haven | Connecticut | 06510 | United States |
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No healthy controls were enrolled.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cannabis Use Disorder | CUD participants participants undergo neuroimaging, cognitive testing, and EEG at baseline and following cannabis abstinence at 4 weeks follow-up. Participants will receive motivational enhancement and contingency management during the 4-week abstinence period. |
| FG001 | Healthy Control | Healthy control participants undergo neuroimaging, cognitive testing, and EEG at baseline. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Cannabis Use Disorder | CUD participants participants undergo neuroimaging, cognitive testing, and EEG at baseline and following cannabis abstinence at 4 weeks follow-up. Participants will receive motivational enhancement and contingency management during the 4-week abstinence period. |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Metabotropic Glutamate Receptor 5 (mGluR5) Availability | Participants will undergo a Positron Emission Tomography (PET) scan to visualized mGluR5 availability in the regions of interest (ROIs): orbitofrontal cortex (OFC), anterior cingulate, ventromedial prefrontal cortex (vmPFC), dorsolateral prefrontal cortex (dlPFC), hippocampus, and amygdala. Only done at baseline for HC group. | Posted | Mean | Standard Deviation | ml/cm^3 | Baseline and Day 28 |
|
28 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cannabis Use Disorder | CUD participants participants undergo neuroimaging, cognitive testing, and EEG at baseline and following cannabis abstinence at 4 weeks follow-up. Participants will receive motivational enhancement and contingency management during the 4-week abstinence period. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Stephen R Baldassarri, M.D. | Yale University | 203-785-3627 | stephen.baldassarri@yale.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 23, 2024 | May 8, 2025 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Mar 13, 2024 | May 8, 2025 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D002189 | Marijuana Abuse |
| ID | Term |
|---|---|
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C062942 | 2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole |
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| Cannabis abstinence | Behavioral | Motivational enhancement and contingency management (CM) to promote and maintain cannabis abstinence after the baseline scan. |
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| Change in Verbal Memory Measured Using Electroencephalography (EEG) | Theta band power and coherence will be assessed. EEG data are collected in three separate conditions. In the passive listening condition, subjects will passively listen to a list of 15 words (presented one at a time) six times in a row. In the memory encoding condition, subjects will be administered a list of 15 words played one at a time, five times, and will be told to try and remember the list and to repeat as many words as possible after each list. Twenty minutes after the end of the encoding phase, subjects will be asked to repeat as many words as they can from the original list of words. In the computerized recognition condition, subjects will hear words from the (1) original memorized list, (2) the distractor list, and (3) novel words not heard that day. Subjects will respond with a three-choice button box to indicate from which list each word originated. Change in CUD group at baseline and day 28 compared to HC at baseline. | Baseline and Day 28 |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Secondary | Change in Neurocognitive Function Using CogState Cognitive Battery | A battery of neuropsychological tests from the well-validated CogState Cognitive Battery are sensitive to detecting cognitive deficits in mood disorders, executive control and working memory. The entire battery takes approximately 30 minutes. Change in CUD group at baseline and day 28 compared to HC at baseline. | Due to limitations in the availability of trained staff, data for the secondary outcomes were not collected. The project was scaled down to assess only the primary outcome, as reported above. All available data from this project have been reported. Data collection and analysis for this measure will not be conducted in the future. | Posted | Baseline and Day 28 |
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| Secondary | Change in Verbal Memory Measured Using Electroencephalography (EEG) | Theta band power and coherence will be assessed. EEG data are collected in three separate conditions. In the passive listening condition, subjects will passively listen to a list of 15 words (presented one at a time) six times in a row. In the memory encoding condition, subjects will be administered a list of 15 words played one at a time, five times, and will be told to try and remember the list and to repeat as many words as possible after each list. Twenty minutes after the end of the encoding phase, subjects will be asked to repeat as many words as they can from the original list of words. In the computerized recognition condition, subjects will hear words from the (1) original memorized list, (2) the distractor list, and (3) novel words not heard that day. Subjects will respond with a three-choice button box to indicate from which list each word originated. Change in CUD group at baseline and day 28 compared to HC at baseline. | Due to limitations in the availability of trained staff, data for the secondary outcomes were not collected. The project was scaled down to assess only the primary outcome, as reported above. All available data from this project have been reported. Data collection and analysis for this measure will not be conducted in the future. | Posted | Baseline and Day 28 |
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