A proof-of-concept randomized controlled study of gabapentin: effects on cannabis use, withdrawal and executive function deficits in cannabis-dependent adults.
Open accessAbstract
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.
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CB1 agonists, gabapentin, and N-acetylcysteine have been shown to produce improvements in some symptoms of CUD in single studies.
“Some drugs, such as CB1 agonists, gabapentin, and N-acetylcysteine, have been shown to produce improvements in some symptoms of CUD in single studies”
From Psychosocial and pharmacological interventions for the treatment of cannabis use disorder (2018) · cites this paper as [47]
The Discussion (page not provided) reports that gabapentin reduced cannabis use and withdrawal symptoms compared with placebo in this single study. The paper does not report a study of N-acetylcysteine, and its mention of agonist treatments does not establish the claimed symptom improvements for CB1 agonists. (LLM, conf=0.88)
Experimental — accuracy not yet measuredGabapentin reduced cannabis use and withdrawal symptoms in adults with CUD.
“the anticonvulsant gabapentin, a GABA/calcium channel modulator, reduced cannabis use and withdrawal symptoms in adults with CUD 47.”
From Psychosocial and pharmacological interventions for the treatment of cannabis use disorder (2018) · cites this paper as [47]
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- Authors
- Mason, B. J., Crean, R., Goodell, V., Light, J. M., Quello, S., Shadan, F., Buffkins, K., Kyle, M., Adusumalli, M., Begovic, A., & Rao, S.
- Affiliations
- Scripps Research Institute (US)
- Oregon Research Institute (US)
- Scripps Green Hospital (US)
- Corresponding author
- Mason, Barbara J
- ORCID
- Light, John M
- Venue
- Neuropsychopharmacology
- Published
- 2012-02-29
- Volume
- 37
- Issue
- 7
- Pages
- 1689-1698
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3358737
- OpenAlex
- W2044958137
- Cited by
- 242
- References
- 45
- Citations by year
- 2026: 13 · 2025: 14 · 2024: 16 · 2023: 13 · 2022: 30 · 2021: 20 · 2020: 16 · 2019: 21 · 2018: 18 · 2017: 14 · 2016: 20 · 2015: 16 · 2014: 20 · 2013: 9 · 2012: 2
- FWCI
- 11.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- National Institutes of Health
- National Institute on Drug Abuse (DA020766, R21DA020766, DA024194, P20DA024194, R01DA026758)
- Johnson and Johnson Pharmaceutical Research and Development
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- gabapentin, cannabis use disorder, cannabis withdrawal, executive dysfunction, calcium channel modulators, addiction treatment
- MeSH terms
- Gabapentin, Adolescent, Adult, Amines, Calcium Channel Blockers, Cannabis, Marijuana Abuse, Counseling, Cyclohexanecarboxylic Acids, Double-Blind Method, Female, gamma-Aminobutyric Acid, Humans, Male, Middle Aged, Substance Withdrawal Syndrome, Treatment Outcome, Executive Function
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