Brain Imaging of Cannabinoid Receptors

• ClinicalTrials.gov Identifier: NCT03204305
• Recruitment Status: Completed
• First Posted: July 2, 2017
• Results First Posted: March 21, 2023
• Last Update Posted: March 21, 2023
• Sponsor: Johns Hopkins University
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

Brief Summary:

All participants will be healthy volunteers and all procedures will be completed for research purposes only. Two groups will be recruited, females who use cannabis (marijuana, MJ), and female who do not use cannabis (controls). Female MJ users will be enrolled in a protocol that includes an outpatient drug administration session and a 4-day/3-night inpatient stay on the Johns Hopkins Bayview Clinical Research Unit (CRU). During outpatient visits, MJ users will have an MRI, and complete MJ self-administration and cognitive performance sessions. MJ users will then reside on the CRU,and complete MJ abstinence, and self-report instruments for withdrawal discomfort. A positron emission tomography (PET) scan of brain cannabinoid type 1 receptors will also be completed. Non-users will complete MRI, PET imaging and cognitive testing under an outpatient protocol (no MJ administration).

Condition or disease	Intervention/treatment	Phase
Cannabis Use Disorder; Cannabis Dependence, Continuous	Drug: 11C-OMAR; Drug: Cannabis	Early Phase 1

Detailed Description:

The primary goals of this project are to examine whether use of cannabis alters brain cannabinoid type 1 receptor (CB1R) availability in females, and if severity of cannabis withdrawal is correlated with CB1 receptor availability. CB1R are widely distributed in the human brain and can be quantified using PET imaging with the radiotracer 11C-OMAR (Carbon-11-OMAR). The effects MJ use on brain CB1R have not been studied in females. The current study will enroll 10 female MJ users in an inpatient protocol that includes administration of smoked MJ, followed by monitored abstinence with daily behavioral assessments, and PET imaging with 11C-OMAR. PET data will collected in 10 matched controls for comparison. The proposed study is an important first step to determine whether localized CB1R changes in female MJ users help explain, and provide a neurobiological target for intervention. Results will increase knowledge of cannabinoid mechanisms of cannabis use and severity of dependence in females, an understudied population.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 28 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Two groups will be recruited. Female cannabis users and nonusers.
• Masking: Single (Participant)
• Masking Description: Cannabis THC content (dose) is masked for participant
• Primary Purpose: Basic Science
• Official Title: Brain Imaging of Cannabinoid Receptors in Women
• Actual Study Start Date: September 14, 2017
• Actual Primary Completion Date: March 31, 2020
• Actual Study Completion Date: March 31, 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Cannabis users; Smoked Cannabis plant material (0 and 25 mg THC) will be administered to volunteers who are regular cannabis users. Cannabis users will also complete a PET scan where 20 millicurie of 11C-OMAR	Drug: 11C-OMAR; 11C-OMAR is a PET radiotracer that binds to cannabinoid type 1 receptors (CB1R). It is an analog of the CB1R antagonist/inverse agonist rimonabant. 11C-OMAR was developed, synthesized and validated for inhuman use at the Johns Hopkins University PET center.; Other Name: JHU75528; Drug: Cannabis; Cannabis will be administered to cannabis users. Doses include 0 and 25 mg THC.; Other Name: Marijuana
Active Comparator: Nonuser controls; No cannabis administration. Non-user controls will complete a PET scan where 20 millicuries of 11C-OMAR	Drug: 11C-OMAR; 11C-OMAR is a PET radiotracer that binds to cannabinoid type 1 receptors (CB1R). It is an analog of the CB1R antagonist/inverse agonist rimonabant. 11C-OMAR was developed, synthesized and validated for inhuman use at the Johns Hopkins University PET center.; Other Name: JHU75528

Outcome Measures

Primary Outcome Measures :

1. Distribution Volume (VT) [ Time Frame: Collected during 90-min PET study ]
   Distribution Volume (VT) is the quantification of 11C-OMAR binding to the CB1R; Per our statistical plan we examined VT for eight volumes of interest in the brain (ventral striatum, amygdala, putamen, cingulate, globus pallidus, insula, frontal cortex, and hippocampus) as well as the composite VT for the brain. The unit of measure is mL/cm^3.

Secondary Outcome Measures :

1. Peak Change From Baseline Marijuana Withdrawal Discomfort Score [ Time Frame: Up to 5 days ]
   Marijuana withdrawal discomfort will be self-reported using the marijuana withdrawal checklist, available via PhenXToolkit.org. Items are: depressed mood, irritability, nervousness/anxiety, restlessness, increased aggression, increased anger, violent outbursts, nausea, decreased appetite, stomach pain, shakiness, sweating, sleep difficulty, strange/wild dreams, craving to smoke cannabis, diarrhea/loose stools, dizziness, muscle spasms/aches, hiccups, stuffy nose, feverish feeling, hot flashes, chills, increased appetite, headaches, fatigue/tiredness, yawning, difficulty concentrating, general physical discomfort, and other. Each item is rated as 0=none, 1=mild, 2=moderate, or 3=severe. A sum score is calculated from items that are valid, reliable cannabis withdrawal symptoms (Budney et al, 2003, Journal of Abnormal Psychology,112(3): 393-402). A higher score represents more severe withdrawal. Scores range from 0-36.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

• Female, healthy adult volunteers who are either MJ users and nonusers (controls)
• 18-45 years of age
• serum creatinine and hepatic enzymes (AST, ALT) must be within the normal limits

• Women of child bearing potential must meet one of the following three criteria:

  1. negative pregnancy test by serum pregnancy test 2 .Following a reliable method of birth control 3. Agreeing to follow a reliable method of birth control during the study and for 1 month following all study procedures

Additional inclusion criteria for MJ users

• Regular MJ use
• present MJ positive urine
• meet Diagnostic and Statistical Manual, version 5 (DSM-5) criteria for cannabis use disorder (CUD)

Additional inclusion non-users

• report no MJ use
• present a MJ-negative urine

Exclusion Criteria:

• < 5th grade reading level
• Current Diagnostic and Statistical Manual, version 5 (DSM-5) psychiatric disorder;
• Current DSM-5 alcohol or substance use disorder (excluding MJ or nicotine)
• Recent Illicit drug use or positive drug test
• Using MJ under the guidance of MD;
• History of seizures, closed head trauma;
• unstable hypertension;
• conditions preventing magnetic resonance imaging (MRI) such as implanted metal, claustrophobia, or anatomical abnormalities (e.g., enlarged ventricles, brain lesions);
• Use of medications or herbal supplements which may be counter indicated as determined by study physician
• Have had exposure to ionizing radiation that in combination with the study's estimated radiation exposure would result in a cumulative exposure that exceeds recommended exposure limits of 5 rem per year.
• Presence or history of drug allergy, or allergic disease diagnosed and treated by a physician.
• any serious medical condition in whom participation is contraindicated.

Contacts and Locations

Locations

United States, Maryland

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, United States, 21224

Sponsors and Collaborators

Johns Hopkins University

National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Elise Weerts, Ph.D.; Johns Hopkins University

  Study Documents (Full-Text)

Documents provided by Johns Hopkins University:

Study Protocol and Statistical Analysis Plan  [PDF] August 15, 2017

More Information

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT03204305
• Other Study ID Numbers: IRB00101744; R21DA043963 ( U.S. NIH Grant/Contract )
• First Posted: July 2, 2017
• Results First Posted: March 21, 2023
• Last Update Posted: March 21, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Johns Hopkins University:

Marijuana; cannabis; cannabinoid receptor

Additional relevant MeSH terms:

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