- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05664763
Understanding Effects of Cannabis Use and Abstinence on Neural Glutamate Homeostasis
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Estimated)
Phase
- Early Phase 1
Contacts and Locations
Study Contact
- Name: Stylianos Mysirlidis, B.S.
- Phone Number: 203-415-5297
- Email: cannabis.study@yale.edu
Study Locations
-
-
Connecticut
-
New Haven, Connecticut, United States, 06510
- Recruiting
- The Anlyan Center
-
Contact:
- Stephen R Baldassarri, M.D.
- Phone Number: 203-785-3627
- Email: stephen.baldassarri@yale.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
HC and CUD Group:
- Voluntary, written, informed consent
- Physically healthy by medical history, physical, neurological, ECG and laboratory exams
- No personal or first-degree relative history of psychiatric disorders (outside of cannabis use for CUD group)
- Full scale and verbal IQs > 80 (Wechsler Adult Intelligence Scale, Fourth Edition; WAIS-IV).
CUD group:
- Cannabis use disorder as determined by DSM-5 structured interviews
- Urine toxicology evidence of cannabinoid use
HC group:
- lifetime cannabis exposure less than 20 times
- no cannabis use in the past 2 years by self-report
- a negative urine drug screen.
Exclusion Criteria:
- Other substance use disorder within 1 year, except for nicotine
- Another primary DSM-5 Axis I major psychiatric disorder (e.g., schizophrenia, bipolar disorder, major depression, etc.) per SCID-5
- Urine toxicology results positive for other drugs such as opiates / opiate metabolites (e.g., methadone, buprenorphine, etc.)
- A history of significant medical (cardiac, infectious, metabolic) or neurological illness (e.g., cerebrovascular disease, traumatic brain injury)
- A history of seizures/epilepsy
- Current use of psychotropic and/or potentially psychoactive prescription medications
- Medical contraindications to MRI imaging (e.g., ferromagnetic implants/foreign bodies, claustrophobia, etc.)
- Pregnancy or breastfeeding (women).
- Subjects will be excluded for major medical or neurological illness or laboratories consistent with these illnesses or suggesting contraindication to PET or MR imaging
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
|
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
Motivational enhancement and contingency management (CM) to promote and maintain cannabis abstinence after the baseline scan.
|
Experimental: Healthy control
Healthy control participants undergo neuroimaging, cognitive testing, and EEG at baseline.
|
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
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Metabotropic Glutamate Receptor 5 (mGluR5) Availability
Time Frame: Baseline and Day 28
|
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
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Neurocognitive Function using CogState Cognitive Battery
Time Frame: Baseline and Day 28
|
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
|
Change in Verbal Memory measured using Electroencephalography (EEG)
Time Frame: Baseline and Day 28
|
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
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Stephen R Baldassarri, M.D., Yale University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2000033244
- K23DA045957 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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