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Cannabis, Schizophrenia and Reward: Self-Medication and Agonist Treatment?

Primary Purpose

Schizophrenia, Dual Diagnosis, Psychotic Disorder

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Marijuana
Dronabinol
Placebo
Sponsored by
Dartmouth-Hitchcock Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Schizophrenia focused on measuring Dronabinol, Schizophrenia, Dual Diagnosis, Substance Abuse, Cannabis Use Disorder

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Groups 1-3 Participants with schizophrenia and a cannabis use disorder

  1. Ages 18 - 55 years
  2. Diagnosis of schizophrenia
  3. Diagnosis of cannabis abuse or dependence
  4. Use of cannabis within the month prior to screening
  5. Willing to remain abstinent for the 14 days before the baseline assessments and throughout the two scans.
  6. Psychiatrically stable
  7. Treated with a stable dose of an antipsychotic medication (except clozapine) for the past month
  8. Not seeking treatment for their cannabis use disorder.

Group 4 - Control participants with schizophrenia

  1. Ages 18 - 55 years
  2. Diagnosis of schizophrenia
  3. Willing to remain abstinent as described above
  4. Psychiatrically stable
  5. Treated with a stable dose of an antipsychotic medication (except clozapine) for the past month

Groups 5-7 - Control participants with cannabis use disorder

  1. Ages 18 - 55 years
  2. Diagnosis of cannabis abuse or dependence
  3. Use of cannabis within the month prior to screening
  4. Willing to remain abstinent as described above
  5. Not seeking treatment for their cannabis use disorder.

Group 8 - Healthy control participants

  1. Ages 18 - 55 years
  2. Willing to remain abstinent as described above

Exclusion criteria:

Groups 1-3 with schizophrenia and a cannabis use disorder

  1. 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.
  2. Cocaine/stimulant use disorder
  3. Pharmacological treatment for addiction
  4. Mental retardation
  5. History of head injury
  6. Metal objects within the body that would contraindicate and MRI
  7. Pregnancy or currently nursing
  8. Uncontrolled medical condition
  9. Taking clozapine
  10. Any condition that would contraindicate use of cannabis or dronabinol.
  11. History of a seizure disorder

Group 4 - Control participants with schizophrenia

  1. 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.
  2. Any history of a substance use disorder other than nicotine
  3. Pharmacological treatment for addiction
  4. Mental retardation
  5. History of head injury
  6. Metal objects within the body that would contraindicate and MRI
  7. Pregnancy or currently nursing
  8. Uncontrolled medical condition
  9. Taking clozapine

Groups 5-7 - Control participants with cannabis use disorder

  1. Axis I psychiatric diagnosis other than a cannabis use disorder
  2. Taking any psychotropic medication
  3. Pharmacological treatment for addiction
  4. Mental retardation
  5. History of head injury
  6. Metal objects within the body that would contraindicate and MRI
  7. Pregnancy or currently nursing
  8. Uncontrolled medical condition
  9. History of a seizure disorder

Group 8 - Healthy control participants

  1. Any Axis I psychiatric diagnosis
  2. Taking any psychotropic medication
  3. Pharmacological treatment for addiction
  4. Mental retardation
  5. History of head injury
  6. Metal objects within the body that would contraindicate and MRI
  7. Pregnancy or currently nursing
  8. Uncontrolled medical condition
  9. Current tobacco smokers

Sites / Locations

  • Dartmouth Hitchcock Medical Center
  • University of Vermont

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Marijuana cigarette and placebo capsule

Dronabinol and placebo cigarette

Placebo cigarette and placebo capsule

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Brain Reward Circuit Activation
Activation of the Brain Reward Circuit (particularly the nucleus accumbens) in anticipation of monetary reward.

Secondary Outcome Measures

Resting State Connectivity
Resting state connectivity within the brain reward circuit

Full Information

First Posted
October 15, 2013
Last Updated
October 11, 2021
Sponsor
Dartmouth-Hitchcock Medical Center
Collaborators
Columbia University, Harvard Medical School (HMS and HSDM), Massachusetts Institute of Technology, Massachusetts General Hospital, Nathan Kline Institute for Psychiatric Research, University of Vermont, National Institute on Drug Abuse (NIDA)
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1. Study Identification

Unique Protocol Identification Number
NCT01964404
Brief Title
Cannabis, Schizophrenia and Reward: Self-Medication and Agonist Treatment?
Official Title
Cannabis, Schizophrenia and Reward: Self-Medication and Agonist Treatment?
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
July 2014 (undefined)
Primary Completion Date
September 18, 2021 (Actual)
Study Completion Date
September 18, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dartmouth-Hitchcock Medical Center
Collaborators
Columbia University, Harvard Medical School (HMS and HSDM), Massachusetts Institute of Technology, Massachusetts General Hospital, Nathan Kline Institute for Psychiatric Research, University of Vermont, National Institute on Drug Abuse (NIDA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Dual Diagnosis, Psychotic Disorder, Cannabis Use Disorder
Keywords
Dronabinol, Schizophrenia, Dual Diagnosis, Substance Abuse, Cannabis Use Disorder

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
261 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Marijuana cigarette and placebo capsule
Arm Type
Experimental
Arm Description
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.
Arm Title
Dronabinol and placebo cigarette
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo cigarette and placebo capsule
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Marijuana
Other Intervention Name(s)
Cannabis
Intervention Description
Smoked plant with THC
Intervention Type
Drug
Intervention Name(s)
Dronabinol
Other Intervention Name(s)
Marinol
Intervention Description
Capsule with THC
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Capsule with no active ingredient
Primary Outcome Measure Information:
Title
Brain Reward Circuit Activation
Description
Activation of the Brain Reward Circuit (particularly the nucleus accumbens) in anticipation of monetary reward.
Time Frame
3 hours
Secondary Outcome Measure Information:
Title
Resting State Connectivity
Description
Resting state connectivity within the brain reward circuit
Time Frame
3 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mary F Brunette, MD
Organizational Affiliation
Dartmouth College
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dartmouth Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
University of Vermont
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States

12. IPD Sharing Statement

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Cannabis, Schizophrenia and Reward: Self-Medication and Agonist Treatment?

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