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

Phase 2

Terminated

Conditions: Cannabis Dependence
Marijuana Dependence

Interventions: Drug: Placebo
Drug: Dronabinol
Drug: Clonidine

Registration Number: NCT01598896

Lead Sponsor: Mclean Hospital

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 12

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo
Dronabinol + Clonidine	Clonidine	Dronabinol titrated to 5 mg three times daily, Clonidine 0.1 mg twice daily
Dronabinol + Clonidine	Dronabinol	Dronabinol titrated to 5 mg three times daily, Clonidine 0.1 mg twice daily

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Cannabis Use at 10 Weeks	At 10 weeks	Subject self-report hits of marijuana per day at week 10

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Cannabis Use at 14 Weeks	At 14 weeks	Self-report cannabis use at 14 weeks after initiating the study.
Change in Craving Symptoms From Baseline at 14 Weeks	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.
Change in Craving Symptoms From Baseline at 10 Weeks	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.