Quetiapine Pharmacotherapy for Cannabis Dependence
Condition: Cannabis Dependence
MeSH terms: Marijuana Abuse
Intervention: Quetiapine; Placebo
Intervention description: Quetiapine pharmacotherapy for cannabis dependence; placebo capsules
Intervention MeSH terms: Quetiapine Fumarate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 130.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: cannabis; marijuana; pharmacotherapy

Summary:

      Despite a benign public perception, marijuana use disorders represent a significant public
      health problem. The development of safe and effective pharmacotherapies for marijuana
      dependence is an important unmet public health need. Quetiapine, an effective atypical
      antipsychotic that acts by blocking serotonin type 2A, dopamine type 2, histamine type 1, and
      adrenergic receptors, is a promising treatment for substance use disorders. In animal models,
      quetiapine blocks the enhancement of reward by cocaine, which is likely due to its actions on
      both dopamine and non-dopamine neurotransmission. Clinical studies of quetiapine have shown
      benefit for the treatment of alcohol and cocaine use disorders.

      Conceptually, the clinically prominent effects of quetiapine, namely sedation, anxiolysis,
      mood stabilization and appetite stimulation, are a good match for the symptoms of marijuana
      withdrawal. Most importantly, an open-label dose-finding study of quetiapine for the
      treatment of marijuana dependence conducted by our research group determined that quetiapine
      was well-tolerated and associated with reductions in marijuana use indicating that it is a
      promising agent deserving of further study in marijuana-dependent outpatients.

      The proposed research project is a randomized double-blind placebo-controlled clinical trial
      to evaluate the efficacy of quetiapine for the treatment of marijuana dependence over a
      12-week period. All participants will receive Medical Management, a medication adherence
      focused psychosocial intervention that facilitates compliance with study medication and other
      study procedures, promotes abstinence from marijuana and other substances, and encourages
      mutual-support group attendance. All participants will receive voucher incentives for
      compliance with study visit attendance, returning study medication bottles, and completing
      other study procedures, with the objective of achieving a highly compliant sample. The goal
      of this phase II clinical trial is to build on our promising open-label pilot study results
      and examine the efficacy of quetiapine on participants' marijuana consumption under
      placebo-controlled double-blind conditions using an abstinence-initiation model, where
      participants will be using marijuana regularly at study entry, reduce their use, and then
      achieve abstinence. The specific aims of the projects are to determine whether quetiapine is
      superior to placebo in 1) reducing marijuana use and 2) achieving abstinence.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Meets DSM-IV-TR criteria for current marijuana dependence

          2. Reports using marijuana an average of 5 days per week over the past 28 days

          3. Between the ages of 18 and 60

          4. Able to provide informed consent and comply with study procedures

          5. Seeking treatment for cannabis dependence

        Exclusion Criteria:

          1. Lifetime DSM-IV diagnosis of schizophrenia, schizoaffective disorder, or bipolar
             disorder.

          2. Current DSM-IV criteria for any other psychiatric disorder that may, according to
             investigator's judgment, require either pharmacological or non-pharmacological
             intervention over the course of the study.

          3. Patients prescribed psychotropic medications.

          4. History of allergic reaction, intolerance, or hypersensitivity to Quetiapine.

          5. Pregnancy, lactation, or failure to use adequate contraceptive methods in female
             patients who are currently engaging in sexual activity with men.

          6. Unstable medical conditions, such as poorly controlled hypertension which might make
             participation hazardous.

          7. Diabetes (whether controlled or not), meeting criteria for metabolic syndrome as
             defined by the NCEP (any 3 of the following: a. obesity [waist circumference > 40
             inches], b. hyperglycemia [fasting glucose > 100 mg/dl or Rx], c. dyslipidemia [TG >
             150 mg/dl or Rx], d. dyslipidemia [HDL cholesterol; 40 mg/dl (male), 50 mg/dl (female)
             or Rx], e. hypertension [130 mmHg systolic or > 85 mmHg diastolic or Rx]. Participants
             with a BMI > 35 will be excluded.

          8. Current DSM-IV diagnosis of an alcohol or substance use disorder (abuse or dependence)
             other than marijuana or nicotine dependence.

          9. Positive confirmed result on urine toxicology screen.

         10. Are legally mandated to participate in a substance use disorder treatment program.

         11. Increased risk for suicide.

         12. QTc prolongation (screening electrocardiogram with Qtc > 450 msec for men, QTc > 470
             msec for women) or history of QTc prolongation or using concomitant medications which
             prolong QTc interval.