A Proof-of-Concept Randomized Controlled Study of Gabapentin: Effects on Cannabis Use, Withdrawal and Executive Function Deficits in Cannabis-Dependent Adults

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 37; no. 7; pp. 1689 - 1698
• Main Authors: Mason, Barbara J, Crean, Rebecca, Goodell, Vivian, Light, John M, Quello, Susan, Shadan, Farhad, Buffkins, Kimberly, Kyle, Mark, Adusumalli, Murali, Begovic, Adnan, Rao, Santosh
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.06.2012
• Subjects: Abstinence; Addictions; Addictive behaviors; Adolescent; Adult; Adult and adolescent clinical studies; Amines - pharmacology; Amines - therapeutic use; Biological and medical sciences; Brain research; Calcium Channel Blockers - pharmacology; Calcium Channel Blockers - therapeutic use; Cannabis - adverse effects; Clinical trials; Counseling; Cyclohexanecarboxylic Acids - pharmacology; Cyclohexanecarboxylic Acids - therapeutic use; Desintoxication. Drug withdrawal; Double-Blind Method; Drug addiction; Drug therapy; Drug use; Drug withdrawal; Executive function; Executive Function - drug effects; FDA approval; Female; gamma-Aminobutyric Acid - pharmacology; gamma-Aminobutyric Acid - therapeutic use; Humans; Male; Marijuana; Marijuana Abuse - drug therapy; Marijuana Abuse - psychology; Marijuana Abuse - therapy; Medical sciences; Middle Aged; Neurosciences; Original; Pilot projects; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Research centers; Substance Withdrawal Syndrome - drug therapy; Substance Withdrawal Syndrome - psychology; Substance Withdrawal Syndrome - therapy; Tetrahydrocannabinol; THC; Toxicology; Treatment Outcome; Treatments; La Jolla California; United States > US; Human; Drug addiction; cannabis dependence; Executive function; Poison withdrawal; Cognitive disorder; addiction treatment; Gabapentin; Controlled therapeutic trial; Cannabidaceae; Anticonvulsant; randomized controlled trial; Cannabis; Analgesic; Addiction; marijuana withdrawal; Dicotyledones; Angiospermae; Dependence; Adult; Marijuana; Spermatophyta; Drug of abuse; Recreational drug
• DOI: 10.1038/npp.2012.14
• ISSN: 0893-133X; 1740-634X

There are no FDA-approved pharmacotherapies for cannabis dependence. Cannabis is the most widely used illicit drug in the world, and patients seeking treatment for primary cannabis dependence represent 25% of all substance use admissions. We conducted a phase IIa proof-of-concept pilot study to examine the safety and efficacy of a calcium channel/GABA modulating drug, gabapentin, for the treatment of cannabis dependence. A 12-week, randomized, double-blind, placebo-controlled clinical trial was conducted in 50 unpaid treatment-seeking male and female outpatients, aged 18-65 years, diagnosed with current cannabis dependence. Subjects received either gabapentin (1200 mg/day) or matched placebo. Manual-guided, abstinence-oriented individual counseling was provided weekly to all participants. Cannabis use was measured by weekly urine toxicology and by self-report using the Timeline Followback Interview. Cannabis withdrawal symptoms were assessed using the Marijuana Withdrawal Checklist. Executive function was measured using subtests from the Delis-Kaplan Executive Function System. Relative to placebo, gabapentin significantly reduced cannabis use as measured both by urine toxicology (p=0.001) and by the Timeline Followback Interview (p=0.004), and significantly decreased withdrawal symptoms as measured by the Marijuana Withdrawal Checklist (p<0.001). Gabapentin was also associated with significantly greater improvement in overall performance on tests of executive function (p=0.029). This POC pilot study provides preliminary support for the safety and efficacy of gabapentin for treatment of cannabis dependence that merits further study, and provides an alternative conceptual framework for treatment of addiction aimed at restoring homeostasis in brain stress systems that are dysregulated in drug dependence and withdrawal.