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

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.

Study Overview

• Status: Terminated
• Conditions: Cannabis Dependence; Marijuana Dependence
• Intervention / Treatment: Drug: Dronabinol; Drug: Clonidine; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • McLean Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mclean Hospital
• Collaborators: Brain & Behavior Research Foundation
• Investigators: Principal Investigator: Kevin P Hill, MD, MHS, McLean Hospital

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): August 1, 2017
• Study Completion (Actual): August 1, 2017

Study Registration Dates

• First Submitted: May 11, 2012
• First Submitted That Met QC Criteria: May 14, 2012
• First Posted (Estimate): May 15, 2012

Study Record Updates

• Last Update Posted (Actual): August 29, 2018
• Last Update Submitted That Met QC Criteria: July 31, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Schizophrenia; Dronabinol; Clonidine; Marijuana Dependence; Cannabis Dependence; Cannabis Use Disorders; Cannabis Withdrawal
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Marijuana Abuse; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Psychotropic Drugs; Hallucinogens; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Sympatholytics; Dronabinol; Clonidine
• Other Study ID Numbers: 2010P-002262; Brain and Behavior Research (Other Identifier: Brain and Behavior Research Foundation)