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

Subjects will receive either the combination of dronabinol and clonidine or placebo in
addition to medical management (MM) over a 10-week treatment period. Following treatment
completion, subjects will have follow-up visits until 14 weeks after treatment initiation.
This pilot study will evaluate the feasibility of the combination of dronabinol and clonidine
for cannabis dependence and will establish effect sizes for a larger trial.

Cannabis use disorders are highly prevalent in the United States and rising among high school
seniors, making the identification of efficacious treatments for cannabis dependence of
critical clinical and public health significance. Schizophrenia is overrepresented among
those with cannabis dependence. At the completion of this study, the investigators hope to
have improved our understanding of the relationship of the pharmacotherapy combination of
dronabinol and clondine on cannabis use.

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.