- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01964404
Cannabis, Schizophrenia and Reward: Self-Medication and Agonist Treatment?
Study Overview
Status
Intervention / Treatment
Detailed Description
Substance use disorders are strikingly common in patients with schizophrenia and contribute to its morbidity and cost to society. We have proposed a neurobiological formulation suggesting that cannabis and other substance use in these patients may ameliorate a dysfunction in the brain reward circuit(thus serving a "self-medication" function), while also worsening the symptoms and course of schizophrenia.
In this translational research proposal, based on our formulation, we seek to confirm and expand upon data obtained in our pilot study suggesting that cannabis and the cannabinoid agonist dronabinol, given in low dose to patients with schizophrenia and co-occurring cannabis use disorder, will in fact ameliorate the brain reward circuit dysregulation in these patients and, thereby, provide evidence in support of the role of cannabis as a "self-medication" agent for them. Also, by also testing the full range of effects produced by dronabinol (effects on brain reward circuitry assessed with task-based function MRI and resting state connectivity), as well as on reward responsiveness, mood, craving, cognition, psychiatric and extrapyramidal symptoms), we will provide clues as to whether dronabinol should be tried in low doses as an adjunctive agent (with an antipsychotic medication) to limit cannabis use in patients with schizophrenia.
This study will involve 8 groups of 25 participants each. Groups 1-3 will have diagnoses of schizophrenia and cannabis use disorder; Group 4 will have schizophrenia only, Groups 5-7 will have cannabis use disorder only and Group 8 will be healthy control participants. Following screening and baseline neuropsychiatric testing, participants will have two tests days (T1 and T2) that will include task-based functional MRI, including assessment of resting state connectivity, and measuring a number of other parameters including reward responsiveness, mood, craving, symptoms and cognition. The assessments at T1 will be virtually the same for all groups. At T2 Groups 1-3, and Groups 5-7 will be randomly assigned to one of the following conditions prior to the assessments: receiving 15mg of dronabinol and smoking a placebo marijuana cigarette, receiving a placebo pill and smoking a real marijuana cigarette, or receiving a placebo pill and smoking a placebo marijuana cigarette. Group 4 and Group 8 will receive no drug or placebo at T2. Participants receiving drug will have safety assessments before the drug is administered, after the drug is administered but before leaving the research clinic for the day, and again a week later.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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New Hampshire
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Lebanon, New Hampshire, United States, 03756
- Dartmouth Hitchcock Medical Center
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Vermont
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Burlington, Vermont, United States, 05401
- University of Vermont
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Groups 1-3 Participants with schizophrenia and a cannabis use disorder
- Ages 18 - 55 years
- Diagnosis of schizophrenia
- Diagnosis of cannabis abuse or dependence
- Use of cannabis within the month prior to screening
- Willing to remain abstinent for the 14 days before the baseline assessments and throughout the two scans.
- Psychiatrically stable
- Treated with a stable dose of an antipsychotic medication (except clozapine) for the past month
- Not seeking treatment for their cannabis use disorder.
Group 4 - Control participants with schizophrenia
- Ages 18 - 55 years
- Diagnosis of schizophrenia
- Willing to remain abstinent as described above
- Psychiatrically stable
- Treated with a stable dose of an antipsychotic medication (except clozapine) for the past month
Groups 5-7 - Control participants with cannabis use disorder
- Ages 18 - 55 years
- Diagnosis of cannabis abuse or dependence
- Use of cannabis within the month prior to screening
- Willing to remain abstinent as described above
- Not seeking treatment for their cannabis use disorder.
Group 8 - Healthy control participants
- Ages 18 - 55 years
- Willing to remain abstinent as described above
Exclusion criteria:
Groups 1-3 with schizophrenia and a cannabis use disorder
- Positive symptoms of psychosis (> 4 [moderate]) on any item of the Positive and Negative Syndrome Scale psychosis subscale (once abstinent) except for the hallucination item. We will exclude for a rating > 5 for this item.
- Cocaine/stimulant use disorder
- Pharmacological treatment for addiction
- Mental retardation
- History of head injury
- Metal objects within the body that would contraindicate and MRI
- Pregnancy or currently nursing
- Uncontrolled medical condition
- Taking clozapine
- Any condition that would contraindicate use of cannabis or dronabinol.
- History of a seizure disorder
Group 4 - Control participants with schizophrenia
- Positive symptoms of psychosis (> 4 [moderate]) on any item of the Positive and Negative Syndrome Scale psychosis subscale (once abstinent) except for the hallucination item. We will exclude for a rating > 5 for this item.
- Any history of a substance use disorder other than nicotine
- Pharmacological treatment for addiction
- Mental retardation
- History of head injury
- Metal objects within the body that would contraindicate and MRI
- Pregnancy or currently nursing
- Uncontrolled medical condition
- Taking clozapine
Groups 5-7 - Control participants with cannabis use disorder
- Axis I psychiatric diagnosis other than a cannabis use disorder
- Taking any psychotropic medication
- Pharmacological treatment for addiction
- Mental retardation
- History of head injury
- Metal objects within the body that would contraindicate and MRI
- Pregnancy or currently nursing
- Uncontrolled medical condition
- History of a seizure disorder
Group 8 - Healthy control participants
- Any Axis I psychiatric diagnosis
- Taking any psychotropic medication
- Pharmacological treatment for addiction
- Mental retardation
- History of head injury
- Metal objects within the body that would contraindicate and MRI
- Pregnancy or currently nursing
- Uncontrolled medical condition
- Current tobacco smokers
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Marijuana cigarette and placebo capsule
3-5% tetrahydrocannabinol cannabis cigarette smoked immediately prior to the second functional MRI and a placebo capsule (for dronabinol) by mouth taken approximately 2.75 hours prior to the second functional MRI.
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Smoked plant with THC
Other Names:
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Experimental: Dronabinol and placebo cigarette
Dronabinol 15mg 3-5% by mouth taken approximately 2.75 hours prior to the second functional MRI and a placebo cigarette (for marijuana) smoked immediately prior to the second functional MRI.
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Capsule with THC
Other Names:
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Placebo Comparator: Placebo cigarette and placebo capsule
Placebo cigarette (for marijuana) smoked immediately prior to the second functional MRI and a placebo capsule (for dronabinol) by mouth taken approximately 2.75 hours prior to the second functional MRI.
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Capsule with no active ingredient
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Brain Reward Circuit Activation
Time Frame: 3 hours
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Activation of the Brain Reward Circuit (particularly the nucleus accumbens) in anticipation of monetary reward.
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3 hours
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Resting State Connectivity
Time Frame: 3 hours
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Resting state connectivity within the brain reward circuit
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3 hours
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Mary F Brunette, MD, Dartmouth College
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Chemically-Induced Disorders
- Pathologic Processes
- Substance-Related Disorders
- Schizophrenia Spectrum and Other Psychotic Disorders
- Schizophrenia
- Disease
- Psychotic Disorders
- Mental Disorders
- Marijuana Abuse
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Analgesics, Non-Narcotic
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Psychotropic Drugs
- Hallucinogens
- Cannabinoid Receptor Agonists
- Cannabinoid Receptor Modulators
- Dronabinol
Other Study ID Numbers
- D14061
- 1R01DA034699-01A1 (U.S. NIH Grant/Contract)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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