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.
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.
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.Google Scholar
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.PubMedCentralCrossRefPubMedGoogle Scholar
WG, Epilepsy and other chronic convulsive disorders. Churchill, 1881.Google Scholar
Reynolds, J., Epilepsy: its symptoms, treatment, and relation to other chronic convulsive diseases. John Churchill, 1861Google Scholar
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.PubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar
Wallace MJ et al. Assessment of the role of CB1 receptors in cannabinoid anticonvulsant effects. Eur J Pharmacol. 2001;428(1):51–7.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar
Matsuda LA et al. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature. 1990;346(6284):561–4.CrossRefPubMedGoogle Scholar
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.PubMedCentralCrossRefPubMedGoogle Scholar
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.PubMedGoogle Scholar
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).Google Scholar
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.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar
Yamaori S et al. Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6. Drug Metab Dispos. 2011;39(11):2049–56.CrossRefPubMedGoogle Scholar
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).Google Scholar
Bruno P.e.a. Effect of cannabidiol on the antiepileptic drug clobazam. (Abst. 2.428).Google Scholar
Gross DW et al. Marijuana use and epilepsy: prevalence in patients of a tertiary care epilepsy center. Neurology. 2004;62(11):2095–7.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar