Marijuana has been utilized as a medicinal plant to treat a variety of conditions for nearly five millennia. Over the past few years, there has been an unprecedented interest in using cannabis extracts to treat epilepsy, spurred on by a few refractory pediatric cases featured in the media that had an almost miraculous response to cannabidiol-enriched marijuana extracts. This review attempts to answer the most important questions a clinician may have regarding the use of marijuana in epilepsy. First, we review the preclinical and human evidences for the anticonvulsant properties of the different cannabinoids, mainly tetrahydrocannabinol (THC) and cannabidiol (CBD). Then, we explore the safety data from animal and human studies. Lastly, we attempt to reconcile the controversy regarding physicians’ and patients’ opinions about whether the available evidence is sufficient to recommend the use of marijuana to treat epilepsy.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Papers of particular interest, published recently, have been highlighted as: • Of importance•• Of major importance
Petersen, R.C., Marihuana research findings. 1976. Summary. NIDA Res Monogr. 1977:14:1–37.
Koppel BS et al. Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2014;82(17):1556–63. Koppel et al. reviewed the available literature on medical marijuana to treat symptoms of multiple sclerosis, epilepsy and movement disorders. It found sufficient articles with class I evidence to support a role for cannabis in the symptomatic treatment of multiple sclerosis (MS), but its efficacy in Huntington disease (HD), Parkinson disease (PD) and epilepsy is unknown.
WG, Epilepsy and other chronic convulsive disorders. Churchill, 1881.
Reynolds, J., Epilepsy: its symptoms, treatment, and relation to other chronic convulsive diseases. John Churchill, 1861
Consroe P, Wolkin A. Cannabidiol—antiepileptic drug comparisons and interactions in experimentally induced seizures in rats. J Pharmacol Exp Ther. 1977;201(1):26–32.
Consroe P et al. Effects of cannabidiol on behavioral seizures caused by convulsant drugs or current in mice. Eur J Pharmacol. 1982;83(3–4):293–8.
Wallace MJ et al. Assessment of the role of CB1 receptors in cannabinoid anticonvulsant effects. Eur J Pharmacol. 2001;428(1):51–7.
Wallace MJ, Martin BR, DeLorenzo RJ. Evidence for a physiological role of endocannabinoids in the modulation of seizure threshold and severity. Eur J Pharmacol. 2002;452(3):295–301.
Jones NA et al. Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo. J Pharmacol Exp Ther. 2010;332(2):569–77.
Karler R, Cely W, Turkanis SA. Anticonvulsant properties of delta 9-tetrahydrocannabinol and other cannabinoids. Life Sci. 1974;15(5):931–47.
Porter BE, Jacobson C. Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy Behav. 2013;29(3):574–7.
Saade D, Joshi C. Pure cannabidiol in the treatment of malignant migrating partial seizures in infancy: a case report. Pediatr Neurol. 2015;52(5):544–7.
Maa E, Figi P. The case for medical marijuana in epilepsy. Epilepsia. 2014;55(6):783–6.
Press CA, Knupp KG, Chapman KE. Parental reporting of response to oral cannabis extracts for treatment of refractory epilepsy. Epilepsy Behav. 2015;45:49–52.
Grelotti DJ, Kaptchuk TJ. Placebo by proxy. BMJ. 2011;343:d4345.
Benedetti F et al. Conscious expectation and unconscious conditioning in analgesic, motor, and hormonal placebo/nocebo responses. J Neurosci. 2003;23(10):4315–23.
Martin P, Consroe P. Cannabinoid induced behavioral convulsions in rabbits. Science. 1976;194(4268):965–7.
Stadnicki SW et al. Delta9-tetrahydrocannabinol: subcortical spike bursts and motor manifestations in a Fischer rat treated orally for 109 days. Life Sci. 1974;14(3):463–72.
Devinsky O et al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia. 2014;55(6):791–802. This manuscript is an evidence-based review of the preclinical and clinical evidence for the use Cannabidiol (CBD) in epilepsy and other neuropsychiatric disorders. The authors highlighted the limited evidence supporting medical marijuana and CBD to treat epilepsy and acknowledged the encouraging preclinical evidence and called for rigorous research.
Matsuda LA et al. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature. 1990;346(6284):561–4.
Pacher P, Mechoulam R. Is lipid signaling through cannabinoid 2 receptors part of a protective system? Prog Lipid Res. 2011;50(2):193–211.
Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol. 2008;153(2):199–215.
Cilio MR, Thiele EA, Devinsky O. The case for assessing cannabidiol in epilepsy. Epilepsia. 2014;55(6):787–90.
Gloss D, Vickrey B. Cannabinoids for epilepsy. Cochrane Database Syst Rev. 2014;3:CD009270. This article is an evidence-based systematic review that screened randomized controlled studies using cannabinoids for the treatment of epilepsy. Four studies met their inclusion criteria. Although two of the studies found limited improvements, all four suffered from methodological issues, including small sample size and, in some cases, inadequate blinding. The authors could not draw any reliable conclusions regarding the efficacy of cannabinoids in epilepsy based on the available evidence. They also acknowledged the lack of significant side effects in any of the patients studied except in one study (Ames 1985) which reported mild drowsiness.
Devinsky O. et al. Efficacy and safety of Epidiolex (cannabidiol) in children and young adults with treatment-resistant epilepsy: Initial data from an expanded access program. 2014.(Abst. 3.303).
Wheless JW. Intractable epilepsy: a survey of patients and caregivers. Epilepsy Behav. 2006;8(4):756–64.
Keeler MH, Reifler CB. Grand mal convulsions subsequent to marijuana use. Case report. Dis Nerv Syst. 1967;28(7 Pt 1):474–5.
Volkow ND et al. Adverse health effects of marijuana use. N Engl J Med. 2014;370(23):2219–27.
Zalesky A et al. Effect of long-term cannabis use on axonal fibre connectivity. Brain. 2012;135(Pt 7):2245–55.
Bolla KI et al. Dose-related neurocognitive effects of marijuana use. Neurology. 2002;59(9):1337–43.
Fried P et al. Current and former marijuana use: preliminary findings of a longitudinal study of effects on IQ in young adults. CMAJ. 2002;166(7):887–91.
Wolff V et al. Cannabis-related stroke: myth or reality? Stroke. 2013;44(2):558–63.
Yamaori S et al. Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: role of phenolic hydroxyl groups in the resorcinol moiety. Life Sci. 2011;88(15–16):730–6.
Yamaori S et al. Comparison in the in vitro inhibitory effects of major phytocannabinoids and polycyclic aromatic hydrocarbons contained in marijuana smoke on cytochrome P450 2C9 activity. Drug Metab Pharmacokinet. 2012;27(3):294–300.
Yamaori S et al. Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6. Drug Metab Dispos. 2011;39(11):2049–56.
Friedman D.e.a. The effect of Epidiolex (cannabidiol) on serum levels of concomitant anti-epileptic drugs in children and young adults with treatment-resistant epilepsy in an expanded access program. 2014(Abst. 2.309).
Bruno P.e.a. Effect of cannabidiol on the antiepileptic drug clobazam. (Abst. 2.428).
Hamerle M et al. Cannabis and other illicit drug use in epilepsy patients. Eur J Neurol. 2014;21(1):167–70.
Gross DW et al. Marijuana use and epilepsy: prevalence in patients of a tertiary care epilepsy center. Neurology. 2004;62(11):2095–7.
Mathern GW, Beninsig L, Nehlig A. Fewer specialists support using medical marijuana and CBD in treating epilepsy patients compared with other medical professionals and patients: result of Epilepsia’s survey. Epilepsia. 2015;56(1):1–6.
Compliance with Ethics Guidelines
Conflict of Interest
Kamil Detyniecki has received research grants from Eisai, Lundbeck, and Sunovion and an honoraria payment from Eisai.
Lawrence Hirsch has received consultancy fees from Lundbeck, Upsher-Smith, and GlaxoSmithKline, grants from UCB-Pharma, Upsher-Smith, Lundbeck, Eisai, and Sunovion, and royalty payments from UpToDate, Inc. and Medlink Corporation.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
This article is part of the Topical Collection on Epilepsy
About this article
Cite this article
Detyniecki, K., Hirsch, L. Marijuana Use in Epilepsy: The Myth and the Reality. Curr Neurol Neurosci Rep 15, 65 (2015). https://doi.org/10.1007/s11910-015-0586-5