Brain Imaging of Cannabinoid Receptors

Sponsor
Johns Hopkins University (Other)
Overall Status
Completed
CT.gov ID
NCT03204305
Collaborator
National Institute on Drug Abuse (NIDA) (NIH)
17
1
2
30.5
0.6

Study Details

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
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
Actual Enrollment :
17 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Two groups will be recruited. Marijuana users and nonusers.Two groups will be recruited. Marijuana users and nonusers.
Masking:
Single (Participant)
Masking Description:
marijuana THC content (dose) is masked for participant
Primary Purpose:
Basic Science
Official Title:
Brain Imaging of Cannabinoid Receptors in Women
Actual Study Start Date :
Sep 14, 2017
Actual Primary Completion Date :
Mar 31, 2020
Actual Study Completion Date :
Mar 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 Names:
  • JHU75528
  • Drug: Cannabis
    Cannabis will be administered to cannabis users. Doses include 0 and 25 mg THC.
    Other Names:
  • 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 Names:
  • JHU75528
  • Outcome Measures

    Primary Outcome Measures

    1. Non-displaceable binding potential (BPND) [Collected during 90-min PET study; up to 1 day]

      quantification of 11C-OMAR binding to the CB1R

    Secondary Outcome Measures

    1. Peak Marijuana Withdrawal Discomfort Score [Cannabis users only ; Up to 5 days, group data analysis year 2]

      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, and general physical discomfort. Participants can describe symptoms not listed on the questionnaire (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).

    Eligibility Criteria

    Criteria

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

    Site City State Country Postal Code
    1 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)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Johns Hopkins University
    ClinicalTrials.gov Identifier:
    NCT03204305
    Other Study ID Numbers:
    • IRB00101744
    • R21DA043963
    First Posted:
    Jul 2, 2017
    Last Update Posted:
    May 20, 2020
    Last Verified:
    May 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    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
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of May 20, 2020