Treatment of Schizophrenia and Comorbid Cannabis Use Disorder: Comparing Clozapine to Treatment-as-Usual

Individuals with schizophrenia have a high risk of becoming addicted to drugs; between 13 to
42% of schizophrenics are addicted to marijuana. These individuals often have difficulties
adhering to a substance abuse treatment program, and have an increased chance of marijuana
relapse. Marijuana use by schizophrenics has also been associated with clinical
exacerbations, noncompliance with antipsychotic medications, poor global functioning, and
increased rehospitalization rates. While antipsychotic medications are often effective in
controlling symptoms of schizophrenia, they are not always effective in preventing substance
abuse. Clozapine, an atypical antipsychotic drug, is currently used to treat schizophrenia.
Preliminary research has shown that clozapine is more successful at reducing drug relapse
rates in individuals with schizophrenia, as compared to other antipsychotic medications,
including olanzapine and risperidone. The purpose of this study is to compare the
effectiveness of clozapine as compared to other oral antipsychotic treatment, including
combinations of up to two antipsychotics, in reducing marijuana use in schizophrenic
individuals.

This study will enroll individuals with schizophrenia who are currently taking any oral
antipsychotic other than clozapine, including those taking up to two oral antipsychotic, and
who are also addicted to marijuana. The study will begin with a 1-week assessment phase,
during which all participants will continue taking olanzapine or risperidone. Participants
will undergo a physical examination and have blood drawn for laboratory tests. Information
pertaining to their medical, psychiatric, and substance use history will also be collected.
Urine tests and breathalyzers will be used to screen for the presence of alcohol and drugs.
Following the assessment phase, participants will be randomly assigned to switch to clozapine
or remain on their prestudy antipsychotic for 12 weeks. Participants remaining on their
prestudy antipsychotic treatment will continue to receive the same dose for the entire study.
Participants taking clozapine will initially receive a daily dose of 12.5 mg, which will be
increased to a maximum of 400 mg per day, as tolerated. Study visits will take place once a
week. At each visit, medication side effects, physical and psychological symptoms, substance
use, treatment services received, and living situation will be assessed. Blood will be drawn
for laboratory tests. Drug and alcohol levels will be monitored three times a week through
urine and breathalyzer tests. Quality of life questionnaires will be administered once a
month.

Inclusion Criteria:

- Meets Diagnostic and Statical Manual of Mental Disorders IV (DSM-IV) diagnostic
criteria for schizophrenia or schizoaffective disorder

- Meets diagnostic criteria for marijuana use disorder, as determined by a rating of 3
or higher on the Drug Use Scale (Abuse or Dependence)

- Used marijuana on 5 or more days during the 3 weeks prior to study entry

- Taking any oral antipsychotic other than clozapine in the month prior to study entry.
(Patients may take a second oral antipsychotic medication, if approved by the
Medication Adjustment Group)

- If female, willing to use effective contraception throughout the study

Exclusion Criteria:

- Unable to take clozapine for medical reasons, including previous clozapine-induced
granulocytopenia, myeloproliferative disorder, white blood cell count less than
3500/mm3, or history of seizures

- Currently taking clozapine

- Currently taking other psychotropic medications for the treatment of substance use
(e.g., disulfiram, naltrexone, acamprosate, inderol, tegretol, topiramate, and
pramipexole)

- Participated in a clinical trial of an investigational drug within 30 days of study
entry

- Currently participating in a psychosocial intervention clinical trial

- Has medical or legal problems that may entail a jail or hospital stay during the study

- Has a developmental disability that would make study participation difficult

- Currently enrolled in a live-in treatment program for substance use disorders

- Pregnant or plans to become pregnant during the study