Pregnenolone and Marijuana Dependence
Condition: Marijuana Dependence
MeSH terms: Marijuana Abuse
Intervention: Pregnenolone; Placebo
Intervention description: Pregnenolone is a steroid that occurs naturally in the body, and early studies have shown that pregnenolone may block the effects of marijuana intoxication; Inactive comparator
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      The cannabinoid delta 9-tetrahydrocannabinol (THC) is the primary psychoactive component of
      marijuana. THC is believed to be a significant factor in the addictive potential associated
      with marijuana use. In addition, attenuated levels of endogenous endocannabinoids have been
      found in alcohol-dependent individuals as compared to social drinkers, suggesting that
      changes in the sensitivity of the endogenous endocannabinoid system play a role in the
      transition from recreational drug use to substance use disorders. Thus, pharmacotherapies
      that target the cannabinoid system may be effective strategies for reducing marijuana use and
      dependence. Recent preclinical data demonstrate that the neurosteroid pregnenolone (PREG)
      inhibits THC activation of cannabinoid receptors and decreases symptoms of marijuana
      intoxication. In addition, other studies show that PREG inhibits drug-seeking behavior. This
      pilot study will provide important preliminary data on the effect of an acute dose of PREG on
      cue-related craving in individuals with cannabis use disorder.
    

Eligibility criteria:

        General Inclusion / Exclusion Criteria Inclusion Criteria

          1. Subjects must be able to provide informed consent and function at an intellectual
             level sufficient to allow accurate completion of all assessment instruments.

          2. Subjects must meet DSM-5 criteria for current cannabis use disorder (within the past
             three months). While individuals may endorse use of other substances, they must
             identify marijuana as their primary substance of abuse and must not meet criteria for
             any other substance use disorder (except nicotine) within the last 60 days. Due to the
             high comorbidity of marijuana and alcohol use disorder, subjects who meet criteria for
             mild alcohol use disorder will be included.

          3. Subjects must consent to remain abstinent from alcohol for 24 hours and other drugs of
             abuse (except nicotine and marijuana) for three days immediately prior to the study
             visit. Subjects must abstain from marijuana for 24 hours prior to the study visit. By
             restricting marijuana use as proposed, subjects should not be under the acute effects
             of marijuana.

          4. Subjects must consent to random assignment.

        Exclusion Criteria

          1. Women who are pregnant, nursing or of childbearing potential and not practicing an
             effective means of birth control.

          2. Individuals taking exogenous gonadal steroids including estrogens, progestins and
             testosterone. This includes hormonal contraception and replacement therapy.

          3. Subjects with evidence of or a history of significant hematological, endocrine,
             cardiovascular, pulmonary, renal, gastrointestinal, neurological disease including
             diabetes or cancer, as these conditions may affect study outcomes.

          4. Subjects with a history of or current psychotic disorder or bipolar affective disorder
             as these may interfere with subjective measurements.

          5. Subjects taking any psychotropic medications, including SRI's or other
             antidepressants, opiates or opiate antagonists because these may affect test response.
             Individuals who take stimulants for treatment of ADHD will be allowed to participate.

          6. Subjects with any acute illness or fever. Individuals who otherwise meet study
             criteria will be rescheduled for evaluation for participation.

          7. Subjects who are unwilling or unable to maintain abstinence from alcohol and marijuana
             for 24 hours and other drugs of abuse (except nicotine) for three days prior to the
             study visit.

          8. Subjects meeting DSM-5 criteria for a substance use disorder (other than nicotine,
             marijuana, or alcohol) within the past 60 days.