Brain Imaging of Cannabinoid Receptors

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).

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.

Eligibility 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.