Abstract
The purpose of this chapter is to review the evidence for the efficacy and safety of anticonvulsants for reducing cannabis use and withdrawal symptoms, compared to placebo. A comprehensive literature search of PubMed and related databases and reference lists of obtained publications was performed. The search yielded four completed prospective pilot studies evaluating divalproex sodium (Depakote), gabapentin (Neurontin), and topiramate (Topamax) for therapeutic potential in cannabis use disorder. For three studies the average age was 30.1 years; one study targeted youth. About 78% of study participants were male. Studies were double-blind, placebo-controlled with random assignment to treatments. Cannabis use was measured by both urine toxicology and self-report. Medication adherence was verified by drug plasma level. Divalproex and topiramate generally did not show efficacy for reducing cannabis use and were poorly tolerated. Both drugs were associated with adverse drug reactions involving neurocognitive impairment and symptoms of negative affect such as depression, anxiety, and irritability. Gabapentin showed benefits over placebo in decreasing cannabis use and withdrawal symptoms, including cannabis craving, negative affect, and sleep disturbance, and was well-tolerated. Findings support further evaluation of gabapentin as a treatment for cannabis use disorder.
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References
AbbVie Inc. Depakote (divalproex sodium) tablets, for oral use. 2017. http://www.rxabbvie.com/pdf/depakote.pdf. Accessed 18 May 2018.
Albanese MJ, Clodfelter RC Jr, Khantzian EJ. Divalproex sodium in substance abusers with mood disorder. J Clin Psychiatry. 2000;61:916–21.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed., text rev. Washington, DC: American Psychiatric Association; 2000.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013.
American Psychiatric Association. Practice guideline for the pharmacological treatment of patients with alcohol use disorder. American Psychiatric Association. 2017. http://psychiatryonline.org/doi/pdf/10.1176/appi.books.9781615371969. Accessed 21 May 2018.
Anton RF, Myrick H, Baros AM, Latham PK, Randall PK, Wright TM, et al. Efficacy of a combination of flumazenil and gabapentin in the treatment of alcohol dependence: relationship to alcohol withdrawal symptoms. J Clin Psychopharmacol. 2009;29:334–42.
Anton RF, Myrick H, Wright TM, Latham PK, Baros AM, Waid LR, et al. Gabapentin combined with naltrexone for the treatment of alcohol dependence. Am J Psychiatry. 2011;168:709–17.
Apelt S, Emrich HM. Sodium valproate in benzodiazepine withdrawal. Am J Psychiatry. 1990;7:950–1.
Bisaga A, Evans SM. The acute effects of gabapentin in combination with alcohol in heavy drinkers. Drug Alcohol Depend. 2006;83:25–32.
Brady KT, Myrick H, Henderson S, Coffey SF. The use of divalproex in alcohol relapse prevention: a pilot study. Drug Alcohol Depend. 2002;67:323–30.
Brower KJ, Myra Kim H, Strobbe S, Karam-Hage MA, Consens F, Zucker RA. A randomized double-blind pilot trial of gabapentin versus placebo to treat alcohol dependence and comorbid insomnia. Alcohol Clin Exp Res. 2008;32:1429–38.
Carpenter KM, McDowell D, Brooks DJ, Cheng WY, Levin FR. A preliminary trial: double-blind comparison of nefazodone, bupropion-SR, and placebo in the treatment of cannabis dependence. Am J Addict. 2009;18:53–64.
Chiappini S, Schifano F. A decade of gabapentinoid misuse: an analysis of the European Medicines Agency’s ‘suspected adverse drug reactions’ database. CNS Drugs. 2016;30:647–54.
Crean RD, Crane NA, Mason BJ. An evidence based review of acute and long-term effects of cannabis use on executive cognitive functions. J Addict Med. 2011;5:1–8.
Donovan SJ, Stewart JW, Nunes EV, Quitkin FM, Parides M, Daniel W, et al. Divalproex treatment for youth with explosive temper and mood lability: a double-blind, placebo-controlled crossover design. Am J Psychiatry. 2000;157:818–20.
Furieri FA, Nakamura-Palacios EM. Gabapentin reduces alcohol consumption and craving: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2007;68:1691–700.
Ghaemi SN, Katzow JJ, Desai SP, Goodwin FK. Gabapentin treatment of mood disorders: a preliminary study. J Clin Psychiatry. 1998;59:426–9.
Giakas WJ, Seibyl JP, Mazure CM. Valproate in the treatment of temper outbursts. J Clin Psychiatry. 1990;51:525.
Goldstein RZ, Volkow ND. Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. Am J Psychiatry. 2002;159:1642–52.
Gorelick DA. Pharmacological treatment of cannabis-related disorders: a narrative review. Curr Pharm Des. 2016;22:6409–19.
Haney M, Hart CL, Vosburg SK, Nasser J, Bennett A, Zubaran C, et al. Marijuana withdrawal in humans: effects of oral THC or divalproex. Neuropsychopharmacology. 2004;29:158–70.
Harden CL, Lazar LM, Pick LH, Nikolov B, Goldstein MA, Carson D, et al. A beneficial effect on mood in partial epilepsy patients treated with gabapentin. Epilepsia. 1999;40:1129–34.
Janssen Pharmaceuticals Inc. Topamax (topiramate) tablets for oral use. AbbVie Inc. Depakote (divalproex sodium) tablets, for oral use. 2009. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020844s041lbl.pdf. Accessed 21 May 2018.
Johnson RM, Fairman B, Gilreath T, Xuan Z, Rothman EF, Parnham T, et al. Past 15-year trends in adolescent marijuana use: differences by race/ethnicity and sex. Drug Alcohol Depend. 2015;155:8–15.
Jonas DE, Amick HR, Feltner C, Bobashev G, Thomas K, Wines R, et al. Pharmacotherapy for adults with alcohol use disorders in outpatient settings: a systematic review and meta-analysis. JAMA. 2014;311:1889–900.
Karam-Hage M, Brower KJ. Gabapentin treatment for insomnia associated with alcohol dependence. Am J Psychiatry. 2000;157:151.
Karam-Hage M, Brower KJ. An open pilot study of gabapentin vs. trazodone to treat insomnia in alcoholic outpatients. Psychiatry Clin Neurosci. 2003;57:542–4.
Ketter TA, Frye MA, Corá-Locatelli G, Kimbrell TA, Post RM. Metabolism and excretion of mood stabilizers and new anticonvulsants. Cell Mol Neurobiol. 1999;19:511–32.
Koob GF, Le Moal M. Cannabinoids. In:Neurobiology of addiction. 1st ed. Cambridge, MA: Elsevier Academic Press; 2006. p. 289–337.
Laprevote V, Schwan R, Schwitzer T, Rolland B, Thome J. Is there a place for off-label pharmacotherapy in cannabis use disorder? A review on efficacy and safety. Curr Pharm Des. 2015;21:3298–305.
Levin FR, McDowell D, Evans SM, Nunes E, Akerele E, Donovan S, et al. Pharmacotherapy for marijuana dependence: a double-blind, placebo-controlled pilot study of divalproex sodium. Am J Addict. 2004;13:21–32.
Lo HS, Yang CM, Lo HG, Lee CY, Ting H, Tzang BS. Treatment effects of gabapentin for primary insomnia. Clin Neuropharmacol. 2010;33:84–90.
Maldonado R, Berrendero F, Ozaita A, Robledo P. Neurochemical basis of cannabis addiction. Neuroscience. 2011;181:1–17.
Marshall K, Gowing L, Ali R, Le Foll B. Pharmacotherapies for cannabis dependence. Cochrane Database Syst Rev. 2014; https://doi.org/10.1002/14651858.CD008940.pub2.
Mason BJ, Light JM, Williams LD, Drobes DJ. Proof-of-concept human laboratory study for protracted abstinence in alcohol dependence: effects of gabapentin. Addict Biol. 2009;14:73–83.
Mason BJ, Crean R, Goodell V, Light JM, Quello S, Shadan F, et al. A proof-of-concept randomized controlled study of gabapentin: effects on cannabis use, withdrawal and executive function deficits in cannabis-dependent adults. Neuropsychopharmacology. 2012;37:1689–98.
Mason BJ, Quello S, Goodell V, Shadan F, Kyle M, Begovic A. Gabapentin treatment for alcohol dependence. A randomized clinical trial. JAMA Intern Med. 2014;174:70–7.
Mason BJ, Quello S, Shadan F. Gabapentin for the treatment of alcohol use disorder. Expert Opin Investig Drugs. 2018;27:113–24.
McRae-Clark AL, Carter RE, Killeen TK, Carpenter MJ, Wahlquist AE, Simpson SA, et al. A placebo-controlled trial of buspirone for the treatment of marijuana dependence. Drug Alcohol Depend. 2009;105:132–8.
McRae-Clark AL, Carter RE, Killeen TK, Carpenter MJ, White KG, Brady KT. A placebo-controlled trial of atomoxetine in marijuana-dependent individuals with attention deficit hyperactivity disorder. Am J Addict. 2010;19:481–9.
Miranda R Jr, Treloar H, Blanchard A, Justus A, Monti PM, Chun T, et al. Topiramate and motivational enhancement therapy for cannabis use among youth: a randomized placebo-controlled pilot study. Addict Biol. 2016;22:79–90.
Myrick H, Brady KT, Malcolm R. Divalproex in the treatment of alcohol withdrawal. Am J Drug Alcohol Abuse. 2000;26:155–60.
Myrick H, Anton R, Voronin K, Wang W, Henderson S. A double-blind evaluation of gabapentin on alcohol effects and drinking in a clinical laboratory paradigm. Alcohol Clin Exp Res. 2007;31:221–7.
Poddar MK, Bhattacharyya KC, Ghosh JJ. Potentiating effect of cannabidiol on delta0-tetrahydrocannabinol-induced changes in hepatic enzymes. Biochem Pharmacol. 1974;23:758–9.
Roberto M, Gilpin NW, O’Dell LE, Cruz M, Morse AC, Siggins GR, et al. Cellular and behavioral interactions of gabapentin with alcohol dependence. J Neurosci. 2008;28:5762–71.
Rodríguez de Fonseca F, Carrera MR, Navarro M, Koob GF, Weiss F. Activation of corticotropin-releasing factor in the limbic system during cannabinoid withdrawal. Science. 1997;276:2050–4.
Rosenberg G. The mechanisms of action of valproate in neuropsychiatric disorders: can we see the forest for the trees? Cell Mol Life Sci. 2007;64:2090–103.
Salinsky MC, Storzbach D, Spencer DC, Oken BS, Landry T, Dodrill CB. Effects of topiramate and gabapentin on cognitive abilities in healthy volunteers. Neurology. 2005;64:792–8.
Sherman BJ, McRae-Clark AL. Treatment of cannabis use disorder: current science and future outlook. Pharmacotherapy. 2016;36:511–35.
Sills GJ. The mechanisms of action of gabapentin and pregabalin. Curr Opin Pharmacol. 2006;6:108–13.
Smith RV, Havens JR, Walsh SL. Gabapentin misuse, abuse and diversion: a systematic review. Addiction. 2016;111:1160–74.
United Nations Office on Drugs and Crime. World drug report 2010. New York: United Nations; 2010.
Volkow ND, Baler RD, Compton WM, Weiss SRB. Adverse health effects of marijuana use. N Engl J Med. 2014;370:2219–27.
Walther L, Gantner A, Heinz A, Majic T. Evidence-based treatment options in cannabis dependency. Dtsch Arztebl Int. 2016;113:653–9.
Wilcox J. Divalproex sodium in the treatment of aggressive behavior. Ann Clin Psychiatry. 1994;6:17–20.
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Appreciation is expressed to Sam Reed for his editorial assistance in the preparation of this chapter.
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Mason, B.J. (2019). Anticonvulsants to Treat Cannabis Use Disorder. In: Montoya, I., Weiss, S. (eds) Cannabis Use Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-90365-1_21
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