Quetiapine Pharmacotherapy for Cannabis Dependence
Condition: Cannabis Dependence
MeSH terms: Marijuana Abuse
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      In a 12-week randomized double-blind placebo-controlled clinical trial, we will evaluate the
      efficacy of quetiapine for the treatment of marijuana dependence in 150 outpatients.
      Participants will be randomly assigned to treatment under double-blind conditions with either
      a fixed dosing schedule of quetiapine or placebo. All participants will receive Medical
      Management, a medication adherence focused psychosocial intervention that facilitates
      compliance with study medication and other study procedures, and promotes abstinence from
      marijuana and other substances. All participants will receive progressive voucher incentives
      for compliance with study visit attendance and completing other study procedures, with the
      objective of achieving a highly compliant sample.

      The results of a dose-finding pilot study of quetiapine for the treatment of marijuana
      dependence (see Preliminary Studies) suggests that the ideal dosing for the proposed project
      is a single 300 mg dose every evening, achieved after a gradual three-week titration.
      Clinical experience with this medication for treatment of marijuana dependence indicates that
      a gradual upward titration of dose is advisable to maximize tolerability and that morning
      dosing was poorly tolerated. Quetiapine (immediate release formulation) will be administered
      in 25 and 100 mg capsules; placebo capsules will appear identical to the quetiapine capsules.
      Participants in both treatment arms will take the same number of pills on the same schedule.
      Study medication will be dispensed on a weekly basis starting with the baseline visit.
      Quetiapine will be titrated over a three-week period to the target dose of 300 mg or the
      maximum tolerated dose. The research psychiatrist will make dose reductions for tolerability
      if necessary.
    

Intervention name(s): Quetiapine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Quetiapine pharmacotherapy for cannabis dependence; placebo capsules
Other intervention name(s): Seroquel; Matched Placebo
Intervention MeSH terms: Quetiapine Fumarate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: cannabis; marijuana; pharmacotherapy