Clozapine for Cannabis Use in Schizophrenia
Condition: Schizophrenia; Cannabis Abuse; Cannabis Dependence; Dual Diagnosis
MeSH terms: Marijuana Abuse; Schizophrenia
Study type: Interventional
Phase: Phase 4

Summary: 
      Many individuals with schizophrenia also suffer from marijuana addiction that worsens their
      problems related to schizophrenia. Most of the medications prescribed for schizophrenia have
      no effect on reducing marijuana use. Preliminary data suggests that clozapine, an atypical
      antipsychotic, may limit marijuana use in people diagnosed with schizophrenia, but it is not
      commonly used due to its side effects and is reserved for people who do not respond to other
      antipsychotic medications.

      In the proposed study, 132 individuals who are diagnosed with both schizophrenia and a
      cannabis use disorder will be randomized to a 12-week treatment course with either clozapine
      or risperidone (another commonly prescribed antipsychotic medication) to test the hypothesis
      that patient treated with clozapine will have decreased cannabis use as compared to patients
      treated with risperidone.

      Should this study indicate that clozapine will lessen marijuana use in persons diagnosed with
      schizophrenia more than risperidone, it will provide evidence needed to begin to shift
      clinical practice toward its use in this population.
    

Detailed description: 
      Cannabis use disorder (CUD), which is up to ten times more common in patients with
      schizophrenia (SCZ) than in the general population, worsens the course of this severe
      psychiatric disorder. Since SCZ occurs in 1% of the population, the co-occurrence of CUD in
      13% to 42% of people with this disorder presents society with an important public health
      problem. Unfortunately, most antipsychotics available for treatment of patients with SCZ do
      not appear to limit their cannabis use. Moreover, the one antipsychotic that preliminary data
      suggest may well limit cannabis use in these patients, clozapine (CLOZ), is not used for this
      purpose; it is reserved for patients whose psychosis is treatment resistant.

      The overarching idea behind this proposal, however, is that CLOZ's use is being unreasonably
      restricted and should be made more widely available for patients with SCZ who have a
      co-occurring CUD but whose psychosis is not necessarily treatment resistant. This notion is
      supported by our preliminary clinical and animal data on the effects of CLOZ, as well as our
      neurobiological model of the basis of cannabis use in patients with SCZ that provides a
      pharmacologic rationale for this effect of CLOZ.

      Even given all the arguments favoring the potential benefits of CLOZ in patients with SCZ and
      CUD, however, its side effect profile will likely limit its use until a fully powered study
      demonstrates its ability to decrease cannabis use in patients with SCZ. This proposal aims to
      launch such a study. If, as we hypothesize, this study confirms and extends our previous
      preliminary data of the effects of CLOZ in patients with SCZ and CUD, it will provide a
      strong impetus to expand the use of CLOZ in this population.

      In the proposed study, 132 patients who are comorbid for both SCZ and CUD will be randomized
      to a 12-week treatment course with either CLOZ or risperidone (RISP) to test the hypothesis
      that patients treated with CLOZ will have decreased cannabis use as compared to patients
      treated with RISP. In addition, the study will determine whether patients treated with CLOZ
      will have improvements in psychiatric symptoms, quality of life neuropsychological functions
      as compared to those taking RISP. We will also explore whether patients taking CLOZ show
      improved reward responsiveness as compared to those taking RISP. Finally, this study will
      explore whether those patients with the val/val genotype at the Catechol-O-methyltransferase
      (COMT) Val158Met locus are more likely to decrease cannabis use during CLOZ treatment than
      are those without the val/val COMT genotype.

      Should this study indicate that CLOZ will lessen cannabis use in patients with SCZ more than
      RISP, it will provide evidence needed to begin to shift clinical practice toward its use in
      these patients.
    

Intervention name(s): Clozapine; Risperidone
Intervention type(s): Drug; Drug
Intervention description(s): Clozapine: target dose of 400mg per day with a maximum dose of 550mg per day; Clozapine: target dose of 4mg per day with a maximum dose of 6mg per day
Other intervention name(s): Clozaril; Risperdal
Intervention MeSH terms: Risperidone; Clozapine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Schizophrenia; Cannabis Abuse; Cannabis Dependence; Dual Diagnosis; Clozapine; Risperidone