Cannabis and Epilepsy

Epilepsy describes a class of neurological disorders characterized by recurring seizures, which can vary dramatically in frequency and intensity. Approximately 3.4 million people in the U.S. suffer from epilepsy,[1] and most of these patients can achieve seizure control using antiepileptic drugs such as valproate or carbamazepine.[2] However, while there are more than two dozen anti-seizure drugs currently available,[3] 20%–30% of people with epilepsy have a condition that is drug-resistant—meaning that approximately one million Americans suffer from uncontrolled seizures. Patients suffering from severe epilepsy can sustain injuries from seizures and this condition has a major impact on the quality of life for patients, families, and caregivers. New therapies are required to reduce seizure frequency and severity and to improve quality of life.[4]

Cannabis has been used to treat epilepsy throughout history, possibly spanning 4000 years. Some researchers suggest that the first documented evidence of cannabis use for epilepsy can be found on stone Assyrian tablets, dating to the second millennium BCE.[5]

In India, cannabis use for epilepsy can be traced back to the 1st millennium BCE. In one documented example, patients are instructed to insert the juice of cannabis leaves into the nostrils, a route of administration that is appropriate during acute attacks (when an oral preparation can be difficult to administer and dangerous to the patient—this example also suggests that this raw preparation was comprised predominantly of THCa and not THC).[6]

The first modern investigations of cannabis as a treatment for epilepsy began in the 19th century, when William O'Shaughnessy studied the uses of cannabis in Ayurvedic therapies. O'Shaughnessy reported success when using cannabis to treat his own patients and subsequently inspired other physicians to treat and to report their own successes. This treatment would soon make its way across the Atlantic and cannabis became a common treatment for epileptic patients prior to U.S. cannabis prohibition.[7]

Cannabis use as a medicine began to decline in the early 20th century, and cannabis prohibition prevented patients from access to this treatment modality for over six decades. However, new research, combined with cannabis legalization, high profile cases with pediatric epilepsy patients, and anecdotal evidence from patients experimenting with cannabis have generated intense interest in cannabis-based medications for people with refractory epilepsy.

In fact, the use of cannabis as a treatment for pediatric epilepsy has made a significant impact on the public perception of legal cannabis. In 2013, CNN released a cannabis documentary with their chief medical correspondent, Sanjay Gupta. The documentary illustrated how cannabis virtually cured 5-year-old Charlotte Figi, who suffered with Dravet syndrome. Figi was wheelchair-bound, on a feeding tube, and suffering from 300 grand mal seizures every week. Her parents started experimenting with high-CBD cannabis oil in 2012, which reduced her seizures to approximately four per month.

Three additional CNN cannabis documentaries followed, and in 2014 the New York Times published a week of editorials in support of medical cannabis. Ten states now have legal adult-use cannabis, and all but 5 states have some type of medical cannabis laws. It’s impossible to deny the impact that Figi’s story—and others like it—has had on the legalization of cannabis in the U.S.

And, as more data becomes available, it appears that cannabis as a therapeutic treatment for epilepsy has promise, especially for patients who do not respond to FDA-approved anti-epileptic drugs.

In an observational study[8] with 272 epileptic patients in California, Washington, and Maine, physicians reported seizure reduction in 235 of the patients using cannabis preparations. Most patients used preparations consisting primarily of CBD, though some patients also used preparations that included a small amount of THC or THCa.

Of the 235 patients who experienced some relief, 45 patients had at least a 50% reduction in seizures, and 75 patients had at least a two-thirds reduction in seizures. Twenty-six patients had complete seizure remission. Thirty-seven patients (about 14%) had no seizure relief using cannabis preparations. In this study, over half the patients experienced—at minimum—50% fewer seizures using cannabis. Patients and families reported that adverse effects were mild, infrequent, and well tolerated. Some patients reported side effects that were beneficial, such as increased alertness.

Recently, the U.S. FDA approved Epidiolex,[9] an oral solution for the treatment of seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome. Epidiolex is the first FDA-approved drug that contains a purified compound—CBD—that is derived from a cannabis plant. Epidiolex was studied in three randomized, double-blind, placebo-controlled clinical trials with a total of 516 patients. Epidiolex, when used as an adjunct medication to other conventional medications, demonstrated efficacy in reducing seizure frequency when compared with a placebo.[10]

Despite these advancements, challenges remain for patients using cannabis.

Many patients live in states where it’s impossible to procure safe, tested products. Often, these patients must reply on hemp-derived products that are unregulated and that often contain heavy metals, pesticides, mold, bacteria, and other toxins. Even in states with medical laws, products can often contain toxic additives, such as propylene glycol, ethylene glycol, flavor additives, corn syrup, and artificial colors. Sometimes it is difficult to find information about how cannabis ingredients are extracted, and many products contain residual amounts of hydrocarbons (such as butane, hexane, and propane) or isopropyl alcohol.

Even in states like Colorado and California, it can be challenging to consistently obtain the same medication, and given that most of these medications are artisanal, inconsistencies often occur among batches. Labeling can be misleading, incorrect, or can lack important information that patients require. There are few healthcare professionals available to guide cannabis patients, and many patients receive medical advice from retail workers and product manufacturers. And, incredibly, families using cannabis for pediatric patients can face legal retribution from child protective services and other government agencies, even when those families comply with all state laws.

Despite these challenges, many families are considering cannabis as a possible treatment option. And, given the side effects of many anti-seizure drugs, which can include blindness, liver damage, and increased risk of death with long-term use, it’s easy to understand their motivation. And, while cannabis can certainly have adverse side effects (such as fatigue, lethargy, and euphoria), these side effects are mostly dose dependent. Overall, cannabis has a much higher safety profile than many prescription medications used to treat epilepsy.

Of course, patients and families pursuing cannabis as a treatment modality should always get medical advice from a healthcare professional (HCP), especially when treating a condition as serious as epilepsy. A competent healthcare professional can provide a comprehensive intake meeting to review the condition and assess prescription medications to identify potential contraindications with cannabis. HCPs can help patients learn how to administer medicines, how to use devices, and can discuss the benefits and potential side effects of products. And, HCPs can provide ongoing support to help patients navigate the complexities of cannabis treatment, local laws, and access issues.

Finally, the medical community must accept that, regardless of a healthcare professional’s personal opinion about cannabis, patients are currently using and will continue to use cannabis to treat a broad range of conditions and disease. Cannabis must be treated like any other medication, and the medical community cannot allow for patients to continue receiving healthcare advice from unlicensed retail workers. With the release of the FDA-approved product Epidiolex, perhaps more healthcare professionals will pursue education about the endocannabinoid system and cannabinoid-based medicines.

Sources:

[1] https://www.cdc.gov/epilepsy/about/fast-facts.htm

[2] Stockings E, Zagic D, Campbell G, et al Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence J Neurol Neurosurg Psychiatry 2018;89:741-753.

[3] https://www.epilepsysociety.org.uk/list-anti-epileptic-drugs#.W-oYP3pKjOQ

[4] Romy Mahrer-Imhof, Sabina Jaggi, Armanda Bonomo, Hannele Hediger, Priska Eggenschwiler, Gu¨nther Kra¨mer, Erich Oberholzer, Seizure, March 2013, pages 128-135.

[5] Russo, Ethan. (2016). Cannabis and epilepsy: An ancient treatment returns to the fore. Epilepsy & behavior : E&B. 70. 10.1016/j.yebeh.2016.09.040.

[6] Russo, Ethan. (2016). Cannabis and epilepsy: An ancient treatment returns to the fore. Epilepsy & behavior : E&B. 70. 10.1016/j.yebeh.2016.09.040.

[7] Russo, Ethan. (2016). Cannabis and epilepsy: An ancient treatment returns to the fore. Epilepsy & behavior : E&B. 70. 10.1016/j.yebeh.2016.09.040.

[8] Sulak, Saneto, and Goldstein, “The current status of artisanal cannabis for the treatment of epilepsy in the United States,”

Epilepsy & Behavior , Volume 70 , 328 - 333

[9] FDA news release, “FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy,” June 25, 2018.

[10] FDA News Release, “FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy,” June 25, 2018.