Epilepsy is one of the most common chronic brain diseases. It is a neurological disorder characterized by recurrent seizures. Seizures occur due to abnormal electrical activity in the brain, which can cause a variety of symptoms depending on the type of seizure. There are many different types of epilepsy, and treatment options include antiepileptic drugs (AEDs) and surgery. The efficacy and tolerability of AEDs vary depending on the type of epilepsy and the patient’s age, but it is notable that many do not respond or cannot withstand the side effects of conventional treatment. Almost one-third of patients have drug-resistant epilepsy (DRE). Up to 30% of children with epilepsy will be refractory to standard anticonvulsant therapy, and those with epileptic encephalopathy can be particularly challenging to treat.

Cannabis-based therapies have been used for millennia to treat a variety of diseases, including epilepsy. There have been reports of cannabis improving seizure control for over 2000 years. This historical record justifies scientific studies for the ongoing preclinical and clinical exploration of the anti-seizure properties of cannabinoids and other components of the cannabis plant.

Several studies have already shown that CBD, both in isolation as a pharmaceutical-grade preparation or as part of a CBD-enriched cannabis herbal extract, is beneficial in decreasing seizure frequency in children with treatment-resistant epilepsy, with herbal extracts (e.g., full-spectrum oils) appearing to provide greater efficacy.

Over 200 research papers, including fifteen double-blind placebo-controlled clinical trials, have examined components of the endocannabinoid system in the treatment of epilepsy. CBD-based therapeutics have shown potential therapeutic benefits in over 40 clinical experiments. Recent reviews report CBD-based therapeutics’ efficacy in treating epilepsy, mounting to a relatively solid scientific foundation. CBD has been shown to have an anti-seizure effect and is being used as a treatment for epilepsy, particularly in patients with drug-resistant epilepsy such as Dravet Syndrome, Lennox-Gastaut Syndrome, and seizures associated with tuberous sclerosis complex. CBD has been proven effective in reducing various types of seizures in animal seizure and epilepsy models, and recent randomized, placebo-controlled trials have confirmed its effectiveness in patients with drug-resistant epilepsy.

A review of 50 studies encompassing 4791 participants was published in Therapeutic  Advances in Neurological Disorders a few months ago. It concluded that cannabidiol treatment of Durg Resistant Epilepsy has stable efficacy and fewer adverse events than conventional therapies in the early period. Long-term use may have decreased efficacy and increased adverse events. Furthermore, cannabidiol use may reduce the dosage of other ASMs without reducing efficacy, thereby reducing adverse effects. Cannabidiol may have similar effects in various epilepsy syndromes.

The studies suggest that endocannabinoids play a role in synaptic transmission and the regulation of neuronal firing. Accordingly, there is evidence that the endocannabinoid system is altered in various animal models with epilepsy.  According to Gaston (2018), the mechanisms of action of cannabis include possible indirect modulation of endocannabinoid receptors via blocking the breakdown of anandamide, activation of the transient receptor potential of vanilloid type-1 (TRPV1), antagonist action at GPR55, targeting of abnormal sodium channels, blocking of T-type calcium channels, modulation of adenosine receptors, modulation of voltage-dependent anion-selective channel protein (VDAC1), and modulation of tumor necrosis factor-alpha release.

Research indicates that CBD-rich drugs are generally well-tolerated with a favorable safety profile. Common side effects reported in some studies include fatigue, changes in appetite, and diarrhea, but these are typically mild and transient. Parents and caregivers consistently report improvements in seizure control with minimal side effects, especially when compared to the debilitating common side effects of conventional drugs.

Preclinical and clinical studies have not identified any significant adverse effects on vital physiological functions within normal dosage ranges. Nevertheless, it is crucial to note that individual responses to cannabis may vary, and consulting with healthcare professionals is advisable, especially for those taking other medications.

The ongoing research on cannabis and epilepsy represents a crucial step in providing alternative treatment options for people who may not respond adequately to traditional antiepileptic medications.

References

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Friedman, D., & Sirven, J. I. (2017). Historical perspective on the medical use of cannabis for epilepsy: Ancient times to the 1980s. Epilepsy & behavior : E&B, 70(Pt B), 298–301. https://doi.org/10.1016/j.yebeh.2016.11.033

Gaston, T. E., & Szaflarski, J. P. (2018). Cannabis for the Treatment of Epilepsy: an Update. Current neurology and neuroscience reports, 18(11), 73. https://doi.org/10.1007/s11910-018-0882-y

Hidding, U., Mainka, T., & Buhmann, C. (2023). Therapeutic use of medical Cannabis in neurological diseases: a clinical update. Journal of neural transmission (Vienna, Austria : 1996), 10.1007/s00702-023-02719-1. Advance online publication. https://doi.org/10.1007/s00702-023-02719-1

Huntsman, R. J., Tang-Wai, R., & Shackelford, A. E. (2020). Cannabis for Pediatric Epilepsy. Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society, 37(1), 2–8. https://doi.org/10.1097/WNP.0000000000000641

Lattanzi S, Trinka E, Striano P, Rocchi C, Salvemini S, Silvestrini M, Brigo F. Highly Purified Cannabidiol for Epilepsy Treatment: A Systematic Review of Epileptic Conditions Beyond Dravet Syndrome and Lennox-Gastaut Syndrome. CNS Drugs. 2021 Mar;35(3):265-281. doi: 10.1007/s40263-021-00807-y. Epub 2021 Mar 22. PMID: 33754312; PMCID: PMC8005394.

Liu S, He Z, Li J. Long-term efficacy and adverse effects of cannabidiol in adjuvant treatment of drug-resistant epilepsy: a systematic review and meta-analysis. Ther Adv Neurol Disord. 2023 Oct 30;16:17562864231207755. doi: 10.1177/17562864231207755. PMID: 37915501; PMCID: PMC10617284.

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