Cannabis, Schizophrenia and Reward: Self-Medication and Agonist Treatment?
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|ClinicalTrials.gov Identifier: NCT01964404|
Recruitment Status : Recruiting
First Posted : October 17, 2013
Last Update Posted : April 2, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Schizophrenia Dual Diagnosis Psychotic Disorder Cannabis Use Disorder||Drug: Marijuana Drug: Dronabinol Drug: Placebo||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||240 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Primary Purpose:||Basic Science|
|Official Title:||Cannabis, Schizophrenia and Reward: Self-Medication and Agonist Treatment?|
|Study Start Date :||July 2014|
|Estimated Primary Completion Date :||March 2020|
|Estimated Study Completion Date :||April 2020|
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.
Other Name: Cannabis
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.
Other Name: Marinol
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.
- Brain Reward Circuit Activation [ Time Frame: 3 hours ]Activation of the Brain Reward Circuit (particularly the nucleus accumbens) in anticipation of monetary reward.
- Resting State Connectivity [ Time Frame: 3 hours ]Resting state connectivity within the brain reward circuit
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01964404
|Contact: Mary Hynes||603-646-7057||Mary.L.Hynes@Hitchcock.ORG|
|United States, New Hampshire|
|Dartmouth Hitchcock Medical Center||Recruiting|
|Lebanon, New Hampshire, United States, 03756|
|Contact: Mary Hynes 603-646-7057 Mary.L.Hynes@Hitchcock.ORG|
|United States, Vermont|
|University of Vermont||Recruiting|
|Burlington, Vermont, United States, 05401|
|Contact: Scott Mackey 802-847-8767 firstname.lastname@example.org|
|Principal Investigator: Hugh Garavan, PhD|
|Principal Investigator:||Alan I Green, MD||Dartmouth College|