Combination of Dronabinol and Clonidine for Cannabis Dependence in Patients With Schizophrenia

Inclusion Criteria: 1. Age range 18-45 years 2. DSM-IV diagnosis of cannabis dependence, based on the Structured Clinical Interview for DSM-IV (SCID) 3. DSM-IV diagnosis of schizophrenia or schizoaffective disorder, based on the Structured Clinical Interview for DSM-IV (SCID) 4. express a desire to quit cannabis use within the next 30 days 5. have used cannabis on ≥20 days within the past 30 days (i.e., an average of ≥5 day per week) 6. identify cannabis as their primary drug of abuse; 6) stable on antipsychotic medication for ≥1 month 7. for women of childbearing age, a negative pregnancy test at screening with agreement to use adequate contraception to prevent pregnancy and monthly pregnancy tests 8. consent for us to communicate with their prescribing clinician if one exists 9. furnish the names of 2 locators, who would assist study staff in locating them during the study period 10. live close enough to McLean Hospital to attend study visits 11. plan to stay in the Boston area for the next 3 months 12. are willing and able to sign informed consent. Exclusion Criteria: 1. Current diagnosis of other drug or alcohol dependence (excluding nicotine) 2. significant cardiac disease as indicated by history or suspected by abnormal ECG or history of cardiac symptoms 3. Positive and Negative Syndrome Scale (PANSS) subscale for positive symptoms of psychosis item \> 3 (moderate) at baseline evaluation 4. current medical condition that could prevent regular study attendance 5. liver function tests \>3 times the upper limit of normal range 6. history of seizure disorder or history of head trauma or CNS insult that could predispose the subject to seizures 7. taking clozapine 8. current suicidal risk 9. bradycardia less than or equal to 50 bpm, supine blood pressure of less than or equal to 100/65, a seated blood pressure of less than or equal to 90/60, or orthostatic change of \>20 systolic or \>10 diastolic on standing, at screening or any pre-dose assessment, or symptoms attributable to low BP (i.e. lightheadedness or dizziness on standing) 10. mental retardation or organic mental disorder 11. currently in a residential treatment setting in which substance use is monitored and restricted, since the restricted access to drugs could represent an important confounding variable 12. pregnant, nursing, or, if a woman of childbearing potential, not using a form of birth control judged by the investigator to be effective 13. concomitant treatment with opioid analgesics, sedative hypnotics, or other known CNS depressants 14. known hypersensitivity to cannabinoids or sesame oil or clonidine 15. disease of the gastrointestinal system, liver, or kidneys that may impede metabolism or excretion of dronabinol 16. inability to read or write in English that would hinder their ability to follow study procedures 17. history of seizures or a family history of seizures.