Brain Imaging of Cannabinoid Receptors

Cannabis Use Disorder Clinical Trial

Official title:

Brain Imaging of Cannabinoid Receptors in Women

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03204305
• Other study ID #: IRB00101744
• Secondary ID: R21DA043963
• Status: Completed
• Phase: Early Phase 1
• Start date: September 14, 2017
• Est. completion date: March 31, 2020

Study information

• Verified date: March 2023
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: March 31, 2020
• Est. primary completion date: March 31, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

• 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.

Related Conditions & MeSH terms

• Cannabis Dependence, Continuous
• Cannabis Use Disorder
• Marijuana Abuse

Intervention

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.
• Cannabis
Cannabis will be administered to cannabis users. Doses include 0 and 25 mg THC.

Locations

Country	Name	City	State
United States	Johns Hopkins Bayview Medical Center	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Distribution Volume (VT)	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.	Collected during 90-min PET study
Secondary	Peak Change From Baseline Marijuana Withdrawal Discomfort Score	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.	Up to 5 days