Understanding Effects of Cannabis Use and Abstinence on Neural Glutamate Homeostasis

NCT05664763 | Terminated Early Phase 1 Results FDA Drug

• 2 other identifiers: 2000033244K23DA045957
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cannabis Use Disorder

Keywords

Cannabis; neuroimaging; marijuana; glutamate; tetrahydrocannabinol (THC)

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• Change in Neurocognitive Function Using CogState Cognitive Battery

  Baseline and Day 28

• Change in Verbal Memory Measured Using Electroencephalography (EEG)

  Baseline and Day 28

Study Arms (2)

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.

Drug: [18F]FPEB with PET; Behavioral: Cannabis abstinence

Healthy control

EXPERIMENTAL

Healthy control participants undergo neuroimaging, cognitive testing, and EEG at baseline.

Drug: [18F]FPEB with PET

Interventions

[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

Cannabis use disorder; Healthy control

Cannabis abstinence BEHAVIORAL

Motivational enhancement and contingency management (CM) to promote and maintain cannabis abstinence after the baseline scan.

Cannabis use disorder

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

The Anlyan Center

New Haven, Connecticut, 06510, United States

Location

MeSH Terms

Conditions

Marijuana Abuse

Interventions

2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Results Point of Contact

• Title: Stephen R Baldassarri, M.D.
• Organization: Yale University

stephen.baldassarri@yale.edu

203-785-3627

Study Officials

• Stephen R Baldassarri, M.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: December 14, 2022
• First Posted: December 27, 2022
• Study Start: March 1, 2023
• Primary Completion: July 3, 2024
• Study Completion: July 3, 2024
• Last Updated: August 19, 2025
• Results First Posted: August 19, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)