Gabapentin for Bipolar & Cannabis Use Disorders

NCT ID: NCT03334721

Last Updated: 2020-11-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-01
• Study Completion Date: 2019-07-01

Brief Summary

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.

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.

Conditions

Bipolar I Disorder; Bipolar II Disorder; Cannabis Use Disorder; Substance Use Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

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).

Group Type: EXPERIMENTAL

Gabapentin

Intervention Type: DRUG

5 day trial of gabapentin with titration to 1,200mg

Placebo Oral Capsule

Intervention Type: DRUG

5 day trial of matched placebo

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).

Group Type: EXPERIMENTAL

Gabapentin

Intervention Type: DRUG

5 day trial of gabapentin with titration to 1,200mg

Placebo Oral Capsule

Intervention Type: DRUG

5 day trial of matched placebo

Interventions

Gabapentin

5 day trial of gabapentin with titration to 1,200mg

Intervention Type: DRUG

Placebo Oral Capsule

5 day trial of matched placebo

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

James J. Prisciandaro

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

James J Prisciandaro, PhD

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Locations

Medical University of South Carolina

Charleston, South Carolina, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34390300 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

R21DA04391701A1

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

69905

Identifier Type: -

Identifier Source: org_study_id