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

Inclusion Criteria:

1. Ages 18-65 years

2. Meet DSM-5 criteria for moderate or severe cannabis use disorder (CUD; within thepast 3 months), provide a positive urine cannabinoid screen at baseline, andidentify cannabis as the primary substance of abuse

3. Meet DSM-5 criteria for bipolar I or II disorder (BD) or Schizoaffective Disorder,Bipolar Type

4. Able to provide informed consent and read, understand, and accurately completeassessment instruments

5. Willing to commit to medication treatment and follow-up assessments

6. Prescribed daily use of at least one mood stabilizing medication (i.e., lithium,divalproex sodium, lamotrigine, carbamazepine, 2nd generation antipsychotic)

Exclusion Criteria:

1. A primary psychiatric diagnosis other than BD (e.g., Schizophrenia)

2. Meet DSM-5 criteria for moderate or severe substance use disorder (other thancannabis or tobacco) within the past 60 days

3. Any uncontrolled neurological condition (e.g., epilepsy) that could confound theresults of the study

4. Any history of brain injury with loss of consciousness greater than 5 minutes

5. Any history of mental retardation, dementia, or recent electroconvulsive therapy (inthe past 3 months)

6. Any uncontrolled medical condition that may adversely affect the conduct of thestudy or jeopardize the safety of the participant

7. Hepatocellular disease as indicated by plasma levels of liver transaminases (aspartate transaminase, alanine transaminase) greater than 3 times the normal range

8. Renal insufficiency as indicated by plasma levels of creatinine greater than 2 timesthe normal range

9. Concomitant use of medications that could interfere with glutamatergic/GABAergictransmission (e.g., benzodiazepines, ceftriaxone, riluzole, memantine, ketamine,topiramate, vigabatrin), due to potential confounding effects

10. Concomitant use of opioid medications, benzodiazepines, barbiturates, chloralhydrate, sodium oxybate, or any other medication deemed to be hazardous if takenwith gabapentin

11. Azelastine, orphenadrine, oxomemazine, paraldehyde, and thalidomide are generallycontraindicated in patients taking gabapentin; as such, individuals taking thesemedications will be excluded

12. Women of childbearing potential who are pregnant, lactating, or refuse adequateforms of contraception

13. Current suicidal or homicidal risk

14. Baseline scores greater than 35 on the Montgomery-Asberg Depression Rating Scale orgreater than 25 on the Young Mania Rating Scale

15. Has taken gabapentin in the last month or experienced adverse effects/allergicreaction (e.g., angioedema) from it at any time

16. Significant claustrophobia and/or past negative experiences with MRI

17. Presence of non-MRI safe materials in the body (e.g., ferrous metal implants,pacemaker)