Studies on CBD Oil & Epilepsy [Research Simplified]

Epilepsy is considered to be a common neurological disorder, characterized primarily by sudden bouts of seizures and convulsions.

It is so common that it, in fact, affects around 50 million people worldwide each year, or at least, that’s what the World Health Organization (WHO) estimates. According to their data, this neurological condition affected around 1.2% of the American population in the United States in 2015 alone.

Not only is its incidence so common, but it is also a misunderstood disorder, owing mostly due to the confusion over its actual causes and misleading symptoms. Apart from seizures and convulsions (that is not accompanied by fever), epilepsy may also cause:

  • Sudden and short-spanned black-outs and memory loss
  • Sudden, yet brief periods of unresponsive behavior
  • Compulsive chewing or fluttering of eyelids
  • Panic attacks or sudden bouts of anxiety
  • Incoherence in speech and thought process, coupled with powerlessness over a person’s own senses

Often the normal course of treatment or rather the conventional forms of treatment fail to help these patients. Moreover, the conventional methods also come at a price – not by just a pinch to the pocket, but also with adverse side effects for the patients.

Perhaps this is why for the first time on June 25, 2018, the US Food and Drug Administration (FDA) approved [2, 11] Epidiolex [*1], an oral solution containing cannabidiol (CBD), for the treatment of seizures caused by two specific types of epilepsy — Lennox-Gastaut syndrome (LGS) and Dravet syndrome – among patients who are at least 2 years of age.

The drug’s approval was based on three clinical trials, involving 516 patients with either of the syndromes. The trials showed a positive effect on patients who took Epidiolex. There was a significant drop in the number of seizures they experienced compared to those who took a placebo.

Incidentally, this is the first drug approved by the FDA to treat seizures associated with Dravet syndrome.

The CBD oral solution, Epidiolex, is a drug that is extracted from the marijuana plant, which is probably the most controversial and oft misunderstood source of medicine and food supplement. FDA approved this medication for adults and children above the age of 2 years only in cases when the usual medications have no positive impact on the patients.

However, it has been seen that CBD oil is effective on epileptic seizures only when taken alongside the standard anti-epilepsy medications. No clinical trials have been conducted on epilepsy patients to assess the impact on CBD oil alone.

The confusion over the causes of epilepsy

Our brain is wired to send and receive messages according to stimuli received from our environment and controls our bodily functions with the help of neurotransmitters. Epilepsy is believed to be caused by the faulty and erratic transmission of messages to and from the brain, leading to uncontrolled physical movements that could be coupled with lapses in consciousness.

In most cases, epilepsy is believed to be congenital, i.e., either it was genetically inherited or caused due to prenatal complications, like brain damage due to lack of oxygen. That is why it is often manifested within the first two years of a child’s life. However, it may also develop later on in life due to some traumatic head injury, stroke, or infectious diseases, such as AIDS and viral encephalitis. This usually appears after the age of 60-65 years.

What’s amiss in the conventional methods of treatment

Most types of epilepsy are not curable. However, it is treatable by means of either surgery (if it is caused by a correctable brain condition) or medication. Most of these medications basically target the key symptoms, like seizures.

The most common anti-epileptic drugs (AEDs) are:

  • Valproic acid (Depakene, Depakote)
  • Lamotrigine (Lamictal)
  • Topiramate (Topamax).
  • Carbamazepine (Tegretol)
  • Phenytoin (Dilantin)
  • Oxcarbazepine (Trileptal)
  • Ethosuximide (Zarontin).
  • Phenobarbital

But these medications come with quite a few side effects – from drowsiness and dizziness to even depression and suicidal tendencies.

Often patients are found to be immune to the intended effects of prescribed medicine, forcing doctors to recommend another medication, and so on.

In the process, the patient experiences all the adverse side effects of the medicines that have already been prescribed to him or her.

This is the reason why there is so much interest among the medical fraternity as well as patients across the US about cannabidiol’s effectiveness [7, 8] in treating epilepsy.  

What does science say about CBD for epilepsy?

Although, it isn’t completely clear why CBD seems to reduce seizures among epilepsy patients, what we do know is that cannabinoids have a biochemical impact on the nerve cells that control movement, among other functions, in both humans and animals. Research and clinical tests on its impact are still ongoing.

Currently, oral CBD solution may only be recommended for controlling seizures associated with LGS and Dravet syndrome, and not for treating any other type of epilepsy.

It has been seen that when taken with other anti-seizure medications, CBD reduces the frequency and severity of seizures substantially in epilepsy patients.

  • According to a 2019 review [1], Epidiolex showed a 30 and 63 percent decrease in the frequency of seizures in such patients, besides a decrease in its severity by half. These patients also manifested a much better comeback after the seizures have passed.
  • A 2018 [3] study on the impact on Epidiolex on Lennox-Gastaut Syndrome patients showed a substantial drop in seizures. In this trial, randomized double-blind, placebo-controlled trial (gold standard) was conducted on a total of 225 patients suffering from LGS at 30 clinical centers.

Among these patients, aged between 2 to 55 years, 76 patients were given 20 mg CBD oil per kilogram of body weight, 73 were given 10 mg CBD oil per kilogram of body weight, while 76 were given placebo – all for 14 weeks.

During the course of treatment, it was seen that there was a 41.9% drop in seizures among the 20-mg CBD oil group of patients, while the drop was by 37.2% in the 10-mg CBD group. The placebo group showed a drop in seizures by 17.2%. [Note that all these patients were also taking their regular pharmaceutical medication.]

However, the researchers concluded that the 20mg dose may be a bit too much for some patients, as 6 out of the 76 patients taking this dosage left the clinical trial owing to side effects, which included sleepiness, diarrhea, and loss of appetite.

  • Another clinical trial [4], conducted in May 2017, tested the efficacy of this FDA-approved drug on 120 Dravet Syndrome patients (both children and young adults). While one group of patients were given (20mg CBD per kg of body weight) Epidiolex, the rest were given placebo. Both groups were administered their regular seizure medications for the entire course of treatment that continued for 14 weeks.

The test results showed that 43% of patients taking CBD experienced a 50% decrease in the frequency of convulsive-seizures, while 27% of patients taking placebo displayed the same dip in frequency of seizures, owing mostly to the standard anti-epilepsy drugs which were being administered to all patients.

However, there was no significant improvement in the frequency of non-convulsive seizures.

Around 3% of patients in this test stopped taking CBD due to some side effects that included diarrhea, vomiting, fatigue, fever, sleepiness, and abnormal results on liver function tests.

  • According to the 2015 study [5], published in Lancet Neurology in 2015, 214 people who were given Epidiolex (99% CBD) for over 12 weeks experienced a drop in seizures by 54%. These patients were aged between 2 and 26 years. Note that there was no placebo control in this test. Besides, patients who were on anti-seizure medication clobazam (Onfi) displayed better response to CBD than those who were not on this medication.
  • Yet another study, conducted in Israel using a product that has CBD and THC in 20:1 part on children up to 18 years of age with hard-to-control epilepsy, showed a significant reduction in seizures. The test that was published in the journal Seizure [6] in 2016 did not use any placebo control.
  • A 2014 study [9] from the Children’s Hospital Colorado also found evidence of CBD’s efficiency in reducing seizures. It was found that 57% of patients experienced a decrease in seizures to some extent, while at least 33% experienced reduction by 50% or more.
  • Another study, conducted on 38 patients in Mexico in March 2017 [10], examined the efficacy of CBD in treating patients with Lennox-Gastaut Syndrome. A pure form of CBD oil was used for the test. The researchers found that 86% of patients reported a 50% decrease in motor seizures, while over half the patients reported a 75% reduction in overall seizures and about 13% of them experienced total remission of seizures. Not only did the patients show a general improvement in their condition, but none of the patients also experienced any negative side effects.
  • A 2018 study [13], published in the journal Drugs, also pointed to a positive impact of CBD oil on epilepsy patients. For this study, four trials, involving 550 patients with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) were examined. Patients of the 20-mg group experienced a 19.9% reduction in seizures, while the 10-mg group experienced a decrease by 19.5% when compared to those who were given placebo. [Also read 14]

Besides, some research has also suggested that CBD can help treat complications arising from epilepsy, like neuro-degeneration, neuronal injury, and psychiatric diseases.

Several clinical tests [12] to examine the efficacy of CBD on epilepsy patients are still going on. Hopefully, CBD oil will soon become legally available for the treatment of more types of epilepsy in the near future.

Situations when CBD isn’t safe for epilepsy patients

While Epidiolex has been proved to be suitable for treating two specific types of epilepsy – LGS and Dravet Syndrome – there are some situations when it has been noticed to be not suitable for epileptic patients.

Studies show benefits may fade with time:

The effect of CBD liquid, which has proven effective against seizures in most cases, seems to dull in about one-third of patients, who develop tolerance towards the drug. This was revealed by a study, presented at the American Epilepsy Society’s annual meeting in New Orleans on December 2, 2018.

In this study, 92 children and young adults (aged of 1 and 37 years) suffering from treatment-resistant seizures were administered cannabis oil extract, containing 20:1 CBD-to-THC ratio, for an average of 19.8 months. It was seen that 32.6% of patients developed tolerance to CBD, reported Shimrit Uliel-Sibony, MD, head of the pediatric epilepsy service at Tel Aviv Sourasky Medical Center’s Dana-Dwek Children’s Hospital in Israel.

Interaction with other drugs:

In the course of research to study the effectiveness of CBD oil in treating epilepsy syndromes, scientists have noticed some drug-to-drug interactions. It was revealed:

  • Some patients taking valproic acid (VPA) – a commonly used anti-seizure medication, along with CBD oil, showed increased levels of liver enzymes (by up to three times or more than normal). This condition may put such people under an increased risk of liver failure. While this is not true for all patients taking VPA with CBD, a part or byproduct of VPA may be interacting with CBD when it (VPA) is broken down.
  • Another anti-epilepsy drug, clobazam (Onfi), has also been seen to react with CBD at times. When broken down, a major component of clobazam appears to interact with CBD in some people, leading to extreme tiredness.
  • Some studies have also raised concerns on the risk of increased blood pressure levels among some patients combining AEDs and CBD oil.
  1. Effect of THC: THC or tetrahydrocannabinol has a halluciniatory effect on humans. Although Epidiolex is a regulated drug, not all products available in the market are regulated. So, it is not safe for epilepsy patients to self-medicate themselves with any product containing CBD oil, since it may contain high traces of THC. THC is also known to worsen seizures in some patients.
  2. Side effects like diarrhea & stomach cramps:

Any oil-based product, even placebos, can cause these side effects. So, any epilepsy patients, previously or currently suffering from stomach problems would do well to stay away from CBD oil altogether.

  1. Pregnancy: Pregnant women are always among the risk groups who should avoid experimenting with CBD if they are already on anti-epilepsy drugs. Although not many studies in this connection are available, it is better to be safe than sorry.   

Editor’s Takeaway

CBD oils and related products have different dosages and health benefits. Although CBD may seem to have the potential to help manage a variety of conditions, never buy any product without proper research.

As far as epilepsy is concerned, Epidiolex is expected to pave the way for more FDA-approved CBD products for other forms of epilepsy and their associated seizures in the future. While there are many unregulated CBD products in the market, we can only hope to see more clinical trials and many more good results soon.

Meanwhile, as patients or caretakers of patients with epilepsy, we need to stick to the standard methods of epilepsy treatment and only abide by what the doctor prescribes.

If you or someone close to you is suffering from the two specific types of epilepsy, LGS or Dravet Syndrome, for which Epidiolex has been approved, you can ask your doctor if he deems it necessary for you to try out this drug.

But remember: NEVER self-medicate an epilepsy patient!

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Notes:

*1. Epidiolex is produced by Greenwich Biosciences, a US subsidiary of UK-based company GW Pharmaceuticals, which also produces Sativex, another CBD-based product.

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Reference links:

  1. Epidiolex as an adjunct therapy for the treatment of refractory epilepsy: a comprehensive review with a focus on adverse effects; F1000Research Review; Krithiga Seka; https://f1000research.com/articles/8-234/v1
  2. FDA Briefing Document; Peripheral and Central Nervous System Drugs; Advisory Committee Meeting; April 19, 2018; https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PeripheralandCentralNervousSystemDrugsAdvisoryCommittee/UCM604736.pdf
  3. Effect of Cannabidiol on Drop Seizures in the Lennox–Gastaut Syndrome; The New England Journal of Medicine; May 17, 2018; Orrin Devinsky, M.D., Anup D. Patel, M.D., J. Helen Cross, M.B., Ch.B., Ph.D., Vicente Villanueva, M.D., Ph.D., Elaine C. Wirrell, M.D., Michael Privitera, M.D., Sam M. Greenwood, Ph.D., Claire Roberts, Ph.D., Daniel Checketts, M.Sc., Kevan E. VanLandingham, M.D., Ph.D., and Sameer M. Zuberi, M.B., Ch.B., M.D. for the GWPCARE3 Study Group*; https://www.nejm.org/doi/10.1056/NEJMoa1714631
  4. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome; The New England Journal of Medicine; Orrin Devinsky, M.D., J. Helen Cross, Ph.D., F.R.C.P.C.H., Linda Laux, M.D., Eric Marsh, M.D., Ian Miller, M.D., Rima Nabbout, M.D., Ingrid E. Scheffer, M.B., B.S., Ph.D., Elizabeth A. Thiele, M.D., Ph.D., and Stephen Wright, M.D. for the Cannabidiol in Dravet Syndrome Study Group*; May 25, 2017; https://www.nejm.org/doi/full/10.1056/NEJMoa1611618
  5. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial; Lancet Neurology; Dec 24, 2015; Devinsky O, Marsh E, Friedman D, Thiele E, Laux L, Sullivan J, Miller I, Flamini R, Wilfong A, Filloux F, Wong M, Tilton N, Bruno P, Bluvstein J, Hedlund J, Kamens R, Maclean J, Nangia S, Singhal NS, Wilson CA, Patel A, Cilio MR.; https://www.ncbi.nlm.nih.gov/pubmed/26724101
  6. CBD-enriched medical cannabis for intractable pediatric epilepsy: The current Israeli experience; Seizure; Jan 6; 2016; Tzadok M1, Uliel-Siboni S2, Linder I3, Kramer U2, Epstein O4, Menascu S2, Nissenkorn A5, Yosef OB5, Hyman E4, Granot D6, Dor M7, Lerman-Sagie T3, Ben-Zeev B5; https://www.ncbi.nlm.nih.gov/pubmed/26800377  
  7. Cannabinoids in the Treatment of Epilepsy: Hard Evidence at Last?; Journal of Epilepsy Research; Dec 31, 2017; Emilio Perucca; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5767492/
  8. Cannabidiol for Treatment of Childhood Epilepsy–A Cross-Sectional Survey; Frontiers in Neurology; Sep 7, 2018; Kerstin A. Klotz, Andreas Schulze-Bonhage, Victoria San Antonio-Arce, and Julia Jacobs; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143823/
  9. The Use of Cannabis to Treat Children with Epilepsy; Epilepsy Foundation of Colorado; March 2014; https://www.epilepsycolorado.org/news-research/medical-marijuana/efco-report-to-the-community/
  10. STUDY RESULTS: MEDICAL MARIJUANA, INC. SUBSIDIARY HEMPMEDS® MEXICO ANNOUNCES RELEASE OF STUDY USING ITS REAL SCIENTIFIC HEMP OIL-X™ TO TREAT EPILEPTIC CHILDREN; Medical Marijuana, Inc.; March 14, 2017; https://investors.medicalmarijuanainc.com/study-results-medical-marijuana-inc-subsidiary-hempmeds-mexico-announces-release-study-using-real-scientific-hemp-oil-x-treat-epiletic-children/
  11. Epilepsy Foundation Statement from President and CEO Philip Gattone on the U.S. Food & Drug Administration’s Approval of EPIDIOLEX®; Epilepsy Foundation; Monday, June 25, 2018; https://www.epilepsy.com/release/2018/6/epilepsy-foundation-statement-president-and-ceo-philip-gattone-us-food-drug
  12. Epilepsy Foundation; Find a Clinical Trial;  https://www.epilepsy.com/clinical_trials
  13. Efficacy and Safety of Cannabidiol in Epilepsy: A Systematic Review and Meta-Analysis; Drugs. Nov 2018; Lattanzi S, Brigo F, Trinka E, Zaccara G, Cagnetti C, Del Giovane C, Silvestrini M; https://www.ncbi.nlm.nih.gov/pubmed/30390221
  14. Epilepsy and Cannabis: A Literature Review; Cureus. September 2018,  Monitoring Editor: Alexander Muacevic and John R Adler; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235654/