Gabapentin for Bipolar & Cannabis Use Disorders

The proposed 2-week, double-blind, crossover, proof of concept study aims to measure and manipulate core neurochemical (i.e., dysregulated brain GABA/glutamate homeostasis) and neurobehavioral (i.e., elevated impulsivity) dysfunctions characteristic of individuals with cannabis use disorder (CUD) and Bipolar Disorder (BD), using a medication that has been shown to increase cortical GABA (i.e., gabapentin) levels in past research, and to evaluate medication-related changes in response inhibition (go no-go) and cannabis cue reactivity functional Magnetic Resonance Imaging tasks, as well as cannabis use, mood symptoms (including anxiety and sleep), and impulsivity in individuals with CUD+BD.

Study Overview

• Status: Completed
• Conditions: Substance Use Disorders; Bipolar I Disorder; Cannabis Use Disorder; Bipolar II Disorder
• Intervention / Treatment: Drug: Gabapentin; Drug: Placebo Oral Capsule

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gabapentin, Then Placebo Oral Capsule; Week 1: 1-week condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (i.e., 1,200mg gabapentin) (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Week 2: 1-week condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (Days 1-5), MRI (Day 5), and medication washout (Days 5-7).	Drug: Gabapentin; 5 day trial of gabapentin with titration to 1,200mg; Drug: Placebo Oral Capsule; 5 day trial of matched placebo
Experimental: Placebo Oral Capsule, Then Gabapentin; Week 1: 1-week condition will consist of an in-person study visit for assessment and dispensing of medication (Day 1), titration to maximum dose (Days 1-5), MRI (Day 5), and medication washout (Days 5-7). Week 2: 1-week condition will consist of an in-person study visit for assessment and dispensing of Gabapentin medication (Day 1), titration to maximum dose (i.e., 1,200mg gabapentin) (days 1-5), MRI (Day 5), and medication washout (Days 5-7).	Drug: Gabapentin; 5 day trial of gabapentin with titration to 1,200mg; Drug: Placebo Oral Capsule; 5 day trial of matched placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 5 of each experimental condition

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: James J Prisciandaro, PhD, Medical University of South Carolina

Publications and helpful links

General Publications

• Prisciandaro JJ, Mellick W, Squeglia LM, Hix S, Arnold L, Tolliver BK. Results from a randomized, double-blind, placebo-controlled, crossover, multimodal-MRI pilot study of gabapentin for co-occurring bipolar and cannabis use disorders. Addict Biol. 2022 Jan;27(1):e13085. doi: 10.1111/adb.13085. Epub 2021 Aug 14.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2017
• Primary Completion (Actual): July 1, 2019
• Study Completion (Actual): July 1, 2019

Study Registration Dates

• First Submitted: September 29, 2017
• First Submitted That Met QC Criteria: November 6, 2017
• First Posted (Actual): November 7, 2017

Study Record Updates

• Last Update Posted (Actual): November 13, 2020
• Last Update Submitted That Met QC Criteria: October 21, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Substance-Related Disorders; Disease; Marijuana Abuse; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Anti-Anxiety Agents; Anticonvulsants; Antimanic Agents; Gabapentin
• Other Study ID Numbers: 69905; R21DA04391701A1 (Other Grant/Funding Number: NIDA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No