Cannabis, Schizophrenia and Reward: Self-Medication and Agonist Treatment?
Condition: Schizophrenia; Dual Diagnosis; Psychotic Disorder; Cannabis Use Disorder
MeSH terms: Marijuana Abuse; Schizophrenia; Psychotic Disorders
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

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.
    

Intervention name(s): Marijuana; Dronabinol; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Smoked plant with THC; Capsule with THC; Capsule with no active ingredient
Other intervention name(s): Cannabis; Marinol
Intervention MeSH terms: Dronabinol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Dronabinol; Schizophrenia; Dual Diagnosis; Substance Abuse; Cannabis Use Disorder