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

Study Overview
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Brief Summary
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Cannabis use disorders are an important public health problem in the United States, but no effective pharmacotherapies are available to treat these disorders. People with schizophrenia are more likely than healthy people to abuse cannabis. Cannabis use may worsen clinical outcomes in this group, making the identification of pharmacotherapy to treat cannabis dependence in those with schizophrenia important. The investigators intend to test the combination of dronabinol, a cannabinoid agonist, and the α2-adrenergic agonist clonidine, for cannabis dependence in subjects with schizophrenia. The combination of dronabinol and clonidine may alleviate cannabis withdrawal symptoms while allowing treatment-seeking outpatients to benefit from medical management (MM) sessions when they are trying to stop using cannabis. The investigators propose to assess the relationship of dronabinol and clonidine, when added to MM, on cannabis use patterns in cannabis-dependent patients with schizophrenia. Hypothesis: The investigators predict that combination pharmacotherapy of dronabinol and clonidine will significantly reduce cannabis use compared to those receiving placebo.

Detailed Description
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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.

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

Conditions
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Cannabis Dependence, Marijuana Dependence

Intervention / Treatment
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* Drug: Dronabinol
* Drug: Clonidine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age range 18-45 years DSM-IV diagnosis of cannabis dependence, based on the Structured Clinical Interview for DSM-IV (SCID) DSM-IV diagnosis of schizophrenia or schizoaffective disorder, based on the Structured Clinical Interview for DSM-IV (SCID) express a desire to quit cannabis use within the next 30 days have used cannabis on ≥20 days within the past 30 days (i.e., an average of ≥5 day per week) identify cannabis as their primary drug of abuse; 6) stable on antipsychotic medication for ≥1 month for women of childbearing age, a negative pregnancy test at screening with agreement to use adequate contraception to prevent pregnancy and monthly pregnancy tests consent for us to communicate with their prescribing clinician if one exists furnish the names of 2 locators, who would assist study staff in locating them during the study period live close enough to McLean Hospital to attend study visits plan to stay in the Boston area for the next 3 months are willing and able to sign informed consent. Exclusion Criteria: Current diagnosis of other drug or alcohol dependence (excluding nicotine) significant cardiac disease as indicated by history or suspected by abnormal ECG or history of cardiac symptoms Positive and Negative Syndrome Scale (PANSS) subscale for positive symptoms of psychosis item > 3 (moderate) at baseline evaluation current medical condition that could prevent regular study attendance liver function tests >3 times the upper limit of normal range history of seizure disorder or history of head trauma or CNS insult that could predispose the subject to seizures taking clozapine current suicidal risk 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) mental retardation or organic mental disorder 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 pregnant, nursing, or, if a woman of childbearing potential, not using a form of birth control judged by the investigator to be effective concomitant treatment with opioid analgesics, sedative hypnotics, or other known CNS depressants known hypersensitivity to cannabinoids or sesame oil or clonidine disease of the gastrointestinal system, liver, or kidneys that may impede metabolism or excretion of dronabinol inability to read or write in English that would hinder their ability to follow study procedures history of seizures or a family history of seizures.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dronabinol + Clonidine<br>Dronabinol titrated to 5 mg three times daily, Clonidine 0.1 mg twice daily | Drug: Dronabinol<br>* Dronabinol titrated to 5 mg three times daily<br>* Other names: Marinol, CSA Drug Code 7369, Schedule III, NDC 54868-3189-0;Drug: Clonidine<br>* Clonidine 0.1 mg twice daily<br>* Other names: Catapres, NDC 16590-266-30;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* One placebo capsule by mouth twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Cannabis Use at 10 Weeks | Subject self-report hits of marijuana per day at week 10 | At 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Craving Symptoms From Baseline at 10 Weeks | Scores on the Marijuana Craving Questionnaire (MCQ) (Heishman et al. 2009) - The 4 Factor Total Score. Maximum Score = 84 Minimum Score = 12 The higher the score, the more severe marijuana craving symptoms endorsed by the subject. | At 10 weeks | 
| Change From Baseline in Cannabis Use at 14 Weeks | Self-report cannabis use at 14 weeks after initiating the study. | At 14 weeks | 
| Change in Craving Symptoms From Baseline at 14 Weeks | Scores on the Marijuana Craving Questionnaire (Heishman et al. 2009) - The 4 Factor Total Score Maximum Score = 84 Minimum Score = 12 The higher the score, the more severe marijuana craving symptoms endorsed by the subject. | At 14 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cannabis Dependence, Marijuana Dependence, Cannabis Use Disorders, Cannabis Withdrawal, Dronabinol, Clonidine, Schizophrenia