Cannabis, Schizophrenia and Reward: Self-Medication and Agonist Treatment?
| Status: | Recruiting |
|---|---|
| Conditions: | Schizophrenia, Psychiatric, Psychiatric, Psychiatric |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - 55 |
| Updated: | 4/4/2019 |
| Start Date: | July 2014 |
| End Date: | April 2020 |
| Contact: | Mary Hynes |
| Email: | Mary.L.Hynes@Hitchcock.ORG |
| Phone: | 603-646-7057 |
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.
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.
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
We found this trial at
2
sites
1 Medical Center Dr
Lebanon, New Hampshire 03756
Lebanon, New Hampshire 03756
(603) 650-5000
Phone: 603-646-7057
Dartmouth Hitchcock Medical Center Dartmouth-Hitchcock is a national leader in patient-centered health care and building...
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85 S Prospect St
Burlington, Vermont 5405
Burlington, Vermont 5405
(802) 656-3131
Principal Investigator: Hugh Garavan, PhD
Phone: 802-847-8767
University of Vermont The University of Vermont combines faculty-student relationships most commonly found in a...
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