Gabapentin for Bipolar & Cannabis Use Disorders

Bipolar disorder (BD) is the Axis I condition most strongly associated with cannabis use
disorder (CUD); there is a six-fold increase in the prevalence of CUD in individuals with BD
relative to the general population. Individuals with co-occurring CUD and BD (CUD+BD) have
substantially worse clinical outcomes than those with either BD or CUD alone. Response to
mood stabilizing medications appears to be poor, yet little is known about optimal treatment
for CUD+BD, as there have been no randomized medication trials for CUD+BD to date. Convergent
evidence supports dysregulated brain γ-Aminobutyric acid (GABA)/glutamate homeostasis as a
candidate target for pharmacological intervention in CUD+BD. Preclinical and clinical studies
have demonstrated that CUD and BD are each associated with prefrontal GABA and glutamate
disturbances and that impulsivity, a core neurobehavioral feature of both CUD and BD and a
key Research Domain Criteria (RDoC) construct, is causally related to GABAergic/glutamatergic
functioning. Gabapentin has been consistently shown in preclinical research to modulate GABA
and glutamate transmission. In human Proton Magnetic Resonance Spectroscopy (1H-MRS) studies,
both acute and chronic gabapentin dosing have been shown to increase brain GABA levels,
however, few studies have investigated gabapentin effects on glutamate levels. Researchers
propose that gabapentin may impact clinical outcomes in CUD+BD individuals both directly and
indirectly through their impact on impulsivity.

Inclusion Criteria:

- Meets DSM-V criteria for Bipolar Disorder

- Meets DSM-V criteria for Cannabis Use Disorder

- Using at least one mood stabilizing medication

Exclusion Criteria:

- Serious medical or non-inclusionary psychiatric disease

- Concomitant use of benzodiazepine medications or any medications hazardous if taken
with gabapentin

- History of clinically significant brain injury

- Presence of non-MRI safe material, or clinically significant claustrophobia.