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

Gabapentin for Restoring GABA/Glutamate Homeostasis in Co-occurring Bipolar and Cannabis Use Disorders: A Randomized, Double-blind, Placebo-controlled, Parallel-group, MRI Study

This research study evaluates the effects of an FDA-approved medication Gabapentin in individuals with Bipolar Disorder who smoke marijuana. Participants in the study will will be assigned to take either Gabapentin or a matched placebo. Study medication will be taken for 17 days. There will be 5 study visits, with 2 MRI brain imaging scans completed. Questionnaires and clinical interview measures will be completed at study visits along with consistent assessment of potential side effects from study medication.

Study Overview

• Status: Recruiting
• Conditions: Bipolar Disorder; Cannabis Use; Bipolar I Disorder; Cannabis Use Disorder, Mild; Cannabis Use Disorder, Moderate; Cannabis Use Disorder, Severe; Bipolar II Disorder; Schizoaffective Disorder, Bipolar Type
• Intervention / Treatment: Drug: Gabapentin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 68
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sara Hix; Phone Number: 843-792-7500; Email: hixs@musc.edu

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
      • Contact: Sara Hix; Phone Number: 843-792-0572; Email: hixs@musc.edu
      • Principal Investigator: James J Prisciandaro, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Ages 18-65 years
2. 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
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 complete assessment 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 than cannabis or tobacco) within the past 60 days
3. Any uncontrolled neurological condition (e.g., epilepsy) that could confound the results 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 (in the past 3 months)
6. Any uncontrolled medical condition that may adversely affect the conduct of the study 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 times the normal range
9. 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
10. Concomitant use of opioid medications, benzodiazepines, barbiturates, chloral hydrate, sodium oxybate, or any other medication deemed to be hazardous if taken with gabapentin
11. Azelastine, orphenadrine, oxomemazine, paraldehyde, and thalidomide are generally contraindicated in patients taking gabapentin; as such, individuals taking these medications will be excluded
12. Women of childbearing potential who are pregnant, lactating, or refuse adequate forms of contraception
13. Current suicidal or homicidal risk
14. Baseline scores greater than 35 on the Montgomery-Asberg Depression Rating Scale or greater than 25 on the Young Mania Rating Scale
15. Has taken gabapentin in the last month or experienced adverse effects/allergic reaction (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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A - Gabapentin	Drug: Gabapentin; After group assignment but before taking any study medication, and again 17 days later, participants will have a Magnetic Resonance Imaging (MRI) exam after completing various assessments (clinical interview, questionnaires, etc.). Group A will receive gabapentin 2-3 times a day for a total of 17 days.
Placebo Comparator: Group B - Placebo	Drug: Placebo; After group assignment but before taking any study medication, and again 17 days later, participants will have a Magnetic Resonance Imaging (MRI) exam after completing various assessments (clinical interview, questionnaires, etc.). Group A will receive placebo 2-3 times a day for a total of 17 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 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.	Baseline to end of treatment, approximately 17 days

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

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2022
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: September 22, 2021
• First Submitted That Met QC Criteria: September 22, 2021
• First Posted (Actual): October 1, 2021

Study Record Updates

• Last Update Posted (Estimated): July 24, 2023
• Last Update Submitted That Met QC Criteria: July 20, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Mood Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Bipolar and Related Disorders; Psychotic Disorders; Bipolar Disorder; 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: 00112593; R01DA054275 (U.S. NIH Grant/Contract)

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