Gabapentin for Restoring GABA/Glutamate Homeostasis in Co-occurring Bipolar and Cannabis Use Disorders

Study Overview
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Brief Summary
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This research study evaluates the effects of an FDA-approved medication Gabapentin in individuals with Bipolar Disorder who smoke marijuana. Participants in the study will will be assigned to take either Gabapentin or a matched placebo. Study medication will be taken for 17 days. There will be 5 study visits, with 2 MRI brain imaging scans completed. Questionnaires and clinical interview measures will be completed at study visits along with consistent assessment of potential side effects from study medication.

Official Title
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Gabapentin for Restoring GABA/Glutamate Homeostasis in Co-occurring Bipolar and Cannabis Use Disorders: A Randomized, Double-blind, Placebo-controlled, Parallel-group, MRI Study

Conditions
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Bipolar Disorder, Cannabis Use, Schizoaffective Disorder, Bipolar Type, Bipolar I Disorder, Bipolar II Disorder, Cannabis Use Disorder, Mild, Cannabis Use Disorder, Moderate, Cannabis Use Disorder, Severe

Intervention / Treatment
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* Drug: Gabapentin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages 18-65 years Meet DSM-5 criteria for moderate or severe cannabis use disorder (CUD; within the past 3 months), provide a positive urine cannabinoid screen at baseline, and identify cannabis as the primary substance of abuse Meet DSM-5 criteria for bipolar I or II disorder (BD) or Schizoaffective Disorder, Bipolar Type Able to provide informed consent and read, understand, and accurately complete assessment instruments Willing to commit to medication treatment and follow-up assessments Prescribed daily use of at least one mood stabilizing medication (i.e., lithium, divalproex sodium, lamotrigine, carbamazepine, 2nd generation antipsychotic) Exclusion Criteria: A primary psychiatric diagnosis other than BD (e.g., Schizophrenia) Meet DSM-5 criteria for moderate or severe substance use disorder (other than cannabis or tobacco) within the past 60 days Any uncontrolled neurological condition (e.g., epilepsy) that could confound the results of the study Any history of brain injury with loss of consciousness greater than 5 minutes Any history of mental retardation, dementia, or recent electroconvulsive therapy (in the past 3 months) Any uncontrolled medical condition that may adversely affect the conduct of the study or jeopardize the safety of the participant Hepatocellular disease as indicated by plasma levels of liver transaminases (aspartate transaminase, alanine transaminase) greater than 3 times the normal range Renal insufficiency as indicated by plasma levels of creatinine greater than 2 times the normal range Concomitant use of medications that could interfere with glutamatergic/GABAergic transmission (e.g., benzodiazepines, ceftriaxone, riluzole, memantine, ketamine, topiramate, vigabatrin), due to potential confounding effects Concomitant use of opioid medications, benzodiazepines, barbiturates, chloral hydrate, sodium oxybate, or any other medication deemed to be hazardous if taken with gabapentin Azelastine, orphenadrine, oxomemazine, paraldehyde, and thalidomide are generally contraindicated in patients taking gabapentin; as such, individuals taking these medications will be excluded Women of childbearing potential who are pregnant, lactating, or refuse adequate forms of contraception Current suicidal or homicidal risk Baseline scores greater than 35 on the Montgomery-Asberg Depression Rating Scale or greater than 25 on the Young Mania Rating Scale Has taken gabapentin in the last month or experienced adverse effects/allergic reaction (e.g., angioedema) from it at any time Significant claustrophobia and/or past negative experiences with MRI Presence of non-MRI safe materials in the body (e.g., ferrous metal implants, pacemaker)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A - Gabapentin<br> | Drug: Gabapentin<br>* After group assignment but before taking any study medication, and again 17 days later, participants will have a Magnetic Resonance Imaging (MRI) exam after completing various assessments (clinical interview, questionnaires, etc.). Group A will receive gabapentin 2-3 times a day for a total of 17 days.<br>|
| Placebo Comparator: Group B - Placebo<br> | Drug: Placebo<br>* After group assignment but before taking any study medication, and again 17 days later, participants will have a Magnetic Resonance Imaging (MRI) exam after completing various assessments (clinical interview, questionnaires, etc.). Group A will receive placebo 2-3 times a day for a total of 17 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in prefrontal GABA concentrations through Proton Magnetic Resonance Spectroscopy | Concentrations of GABA, normalized to water and corrected for CSF%, in dorsal anterior cingulate measured via Proton Magnetic Resonance Spectroscopy. | Baseline to end of treatment, approximately 17 days |