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

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)