Feature Article: Treating epilepsy with marijuana: All that has changed in the last few years as explained by Dr. Firas Taha
Dr. Firas Taha was born and raised in New Jersey. He completed his Doctor of Medicine at Ross University School of Medicine in Dominica. He trained in Pediatrics Residency at Saint Peter's University Hospital in New Brunswick, NJ followed by his Child Neurology Residency at the Mayo Clinic Florida in Jacksonville, FL. Subsequently he received specialized EEG and epilepsy training at New York University during his Clinical Neurophysiology Fellowship. He is Board Certified in Clinical Neurophysiology and Neurology with Special Qualification in Child Neurology. Dr. Taha is a certified marijuana prescriber in the State of New Jersey where he prescribes medical marijuana for patients with refractory epilepsy. His research interests include childhood epilepsy syndromes, psychogenic non-epileptic spells in children and intractable epilepsy. He sees patients in Jersey City and Hackensack, New Jersey.
We are fortunate to have Dr. Taha today making sense of the exciting and sometimes controversial topic of medicinal marijuana in the treatment of epilepsy.
Where do we stand regarding medicinal marijuana in the state of NJ?
Medical Cannabis was first legalized in New Jersey by Governor Jon Corzine in 2010, with seizure disorder listed as one of the permissible diagnoses. In 2013, Governor Chris Christie expanded the program to allow medical marijuana access for sick children as well.
The use of the Medical Marijuana Program of New Jersey has been expanding, with more than 70,000 registered patients enrolled, including many with epilepsy. I would consider the program successful, however there have been some limitations to the New Jersey program as compared to other states. These drawbacks include high prices and the relative lack of edible options such as oils for administration that does not require smoking. There has also been concern about the small number of medical marijuana dispensaries, of which there are only 6 in the state.
A recent positive development occurred in July 2019 with the signing by Governor Phil Murphy of the Jake Honig Compassionate Use Medical Cannabis Act, which attempts to expand the program and expand patient access. Patients can now be authorized for medical cannabis for up to 12 months based on a physician's clinical judgment, the amount of cannabis allowed was increased, and edible cannabis is now permitted for adult patients. This will hopefully encourage the dispensaries to stock more edible forms of cannabis.
In December 2019, six businesses were selected to open new medical marijuana dispensaries, which will bring the total to 12 in the state. And the Department of Health is currently seeking new applicants to operate up to 24 additional Alternative Treatment Centers. These future developments should greatly improve access and to this form of treatment.
How is marijuana that is used to treat medical conditions and that is prescribed by a medical doctor different than marijuana used for illicit/recreational purposes?
Recreational Marijuana and Medical Marijuana are derived from the same species of plant: the cannabis plant. The most important difference between recreational marijuana and illicit marijuana is the oversight provided by the government, and the ability for a patient and physician to understand what type of strain the patient is receiving, with exact contents of each strain provided. Cannabis which is obtained from sources other than a dispensary may contain chemicals, other contaminants, or be laced with dangerous substances, and is not safe for consumption.
Can you give us a background about cannabis plants, discuss what different types of cannabis exist and how they vary in their contents and effects?
The most studied and well known chemical compounds in cannabis plants are Δ(9) -- tetrahydrocannabinol (THC) and Cannabidiol (CBD). Recreational marijuana is more likely to be high in THC, which tends to alter one's state of consciousness and may provide a "high". Strains of cannabis that are high in CBD, such as hemp strains, do not alter consciousness. These largely correlate with the two main species of cannabis: cannabis sativa, and cannabis indica. The most notable contrast between the two is that sativa strains will have high concentrations of CBD, whereas indica strains will have higher concentrations of THC.
Several strains of both species of the cannabis plant occur in nature and have also been cultivated specifically by humans for different uses. It has been used industrially for its strong fibers for rope and cloth. So, if you have heard of hemp, now you know that this is actually a cannabis plant. Cannabis has been used as medicine for centuries; in fact, specifically for epilepsy it was used by Islamic physicians as long ago as the medieval period. In recent years, it has been rediscovered to be effective against seizures and epilepsy, with most of the research so far pointing to CBD as effective for seizure control.
In recent years, CBD oil and Hemp oil have been popularized by the media as treatments for epilepsy. The latter is a cannabis plant that has been cultivated by humans for thousands of years as medicine and for industrial uses such as fiber for rope and cloth. It is actually a cannabis sativa plant. Under the 2018 Farm Bill, the federal definition of hemp was changed to encompass any cannabis plant or product derived from a cannabis plant that contains less than 0.3% THC by dry weight. This is the reason why many of our patient's may have noticed that their pharmacy or local shops are carrying CBD oil or hemp oil.
Medical Cannabis dispensaries with the New Jersey state medical marijuana program stock strains of both cannabis indica and sativa species, as well as hybrids, with different concentrations of CBD and THC. Our epilepsy patients will typically be recommended to receive a high CBD strain, as CBD has now been extensively shown to reduce seizure frequency. THC has also been shown to be helpful in other conditions, such as treating anxiety and nausea or lack of appetite associated with cancer, so these strains are also available at the dispensaries.
Where can a patient find a certified provider and a certified dispensary?
New Jersey has created a great website https://www.nj.gov/health/medicalmarijuana/ where patients, caregivers, and physicians can read the program rules, and find the answers to frequently asked questions. Through this website, patients can find a participating local doctor. For our NEREG patients with refractory epilepsy, if your epilepsy specialist feels that medical marijuana is a good choice for you, we are able to register appropriate patients in both NJ and NY and can set up a consultation with one of our participating physicians.
Is that the only way to obtain medicinal marijuana?
In terms of other forms of medicinal marijuana or medical cannabis derivatives, there are actually two other avenues that can be pursued.
One option we have already mentioned is over the counter CBD oils or hemp oils. These can be purchased online or in a pharmacy. Many different products are available, with variable, quality. Some of these brands are well known such as Charlotte's Web and Haleigh's Hope. As CBD is considered a supplement, it is not regulated strongly and independent testing has shown that many of these over the counter CBD products are either contaminated or have very little actual CBD. It is advisable to discuss with your doctor first, and to start any treatment under the guidance of your physician. They may have certain brands they trust or are familiar with.
Another option we have now for some of our patients is an FDA approved pharmaceutical cannabis derivative called Epidiolex. This is something many of our patients have heard about as well.
Can you tell us some more about Epidiolex?
In June 2018, the FDA approved a pharamaceutical drug Epidiolex for the treatment of seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome, in patients two years of age and older.
Epidiolex contains cannabidiol (CBD), which is extracted from the cannabis plant and is the first FDA-approved drug to contain a purified extract from the plant. It is dispensed as an oil but requires a special authorization process through a specialty pharmacy. Here at NEREG, we have many patients who are currently receiving Epidiolex.
What research has been conducted on the effectiveness of marijuana in treating epilepsy?
The gold standard for evaluating effectiveness of a medication is a double-blind placebo-controlled trial. In these types of trials, the outcome of patients taking the medication is compared to the outcome of patients taking placebo, and neither the patients or the researchers are aware who gets which. Two such studies evaluating the efficacy of Epidiolex in Dravet Syndrome and Lennox Gastaut Syndrome (LGS) were performed in 2017 and 2018, and reported in the New England Journal of Medicine. These studies showed that in patients with LGS, drop seizures decreased up to 41.9% with Epidiolex, and in Dravet Syndrome 43% of patients had a 50% reduction or more in their seizure frequency.
In 2018, a Canadian open-label trial evaluated the use of a combination of CBD and THC at a ratio of 50:1 in children with Dravet Syndrome. The study involved only 19 children, but the study found a median motor seizure reduction of 70.6% and a 50% decrease in seizures for 63% of patients. Even though it was relatively small and not a double-blind placebo trial, this study suggests that THC-containing cannabinoid preparations are also effective and provided safety and dosing information.
There have not been vigorous prospective studies which evaluated the use of New Jersey's or any other US state's medical marijuana programs. However, small retrospective studies (studies which look back and analyze data that has already occurred) have been performed in epilepsy centers and shown positive results. It should be noted that it is difficult to extrapolate the results to any of the below studies to our NJ MMP patients as the available preparations in different states and country vary and are not standardized in the same manner as a pharmaceutical preparation.
A study of 74 patients in Israel using a 20:1 CBD:THC ratio formulation showed 52% of patients had more than 50% reduction of seizures. Another Israeli study of 54 patients using a similar formulation showed 56% of patients having a 50 % or more reduction of their seizures. A retrospective study of 108 pediatric patients using CBD oil at Vanderbilt University in Tennessee revealed 39% of patients with 50% or more reduction of seizures.
These studies above all showed similar positive results, but we should also mention a 2019 prospective study from Colorado, which followed 32 children with refractory epilepsy who began and continued a CBD preparation for 12 weeks. The 50% seizure reduction rate was only 24% which is not considered a success, as this is similar to placebo rates. One explanation for this result is that the doses of CBD achieved in this study were very low (1mg/kg/day) compared to the Israeli studies and the Epidiolex trials (10-20mg/kg/day). This result highlights both the importance of adequate dosing, and the need for further study.
Are there particular conditions, seizure types, epilepsy types that are best suited for treatment with marijuana?
Medical marijuana, CBD oil or even the FDA approved Epidiolex are not considered first line treatments for epilepsy at this point. Most neurologists would consider these therapies appropriate for patients who are not responding to typical anti-epileptic therapies. If a patient has drug-resistant epilepsy, at that point their neurologist should consider alternate therapies such as dietary therapy, neurostimulation, epilepsy surgery, and cannabis derivatives, including both Epidiolex and medical marijuana. The clinical trials to date have been primarily in patients with drug-resistant epilepsy.
Is medical marijuana used for all ages?
Medical Marijuana is not the first line medication for any age. However, if a patient's epilepsy has been resistant to medications, then it is reasonable for their doctor to consider medical marijuana for their case, even in children. In some cases, we have used medical marijuana in children less than 2 years of age. Epidiolex is approved for ages 2 and up for Dravet Syndrome and Lennox Gastaut Syndrome.
How do you determine what dose to use?
In regard to Epidiolex, there is a standard weight-based dosing. In regard to medical marijuana obtained through the NJ State program, I prefer to use a liquid formulation, and calculate similar weight-based dosing based on the Epidiolex studies. In both cases, the tendency is to start low dose and increase as tolerated. It should be noted that the doses that we can achieve using Epidiolex are much higher than through the NJ State program. As with any medication, compliance and regular dosing intervals are very important.
Are there any side effects or dangers to using this treatment?
Like any medication or drug, there are possible side effects. The most common reported are sleepiness, sedation and lethargy, decreased appetite, diarrhea, rash, fatigue, malaise and weakness, and insomnia. Treatment with medical marijuana or CBD may also affect liver function, so your doctor will most likely check bloodwork while on these medications.
In addition, CBD and medical marijuana can have interactions with many of the antiepileptic medications by slowing down their metabolism in the liver. Levels of other medications can be monitored with bloodwork, and dose reductions are sometimes necessary to prevent side effects such as excessive sleepiness.
Where do you see treatment with medicinal marijuana in the future? Is there room for growth or will it reach a plateau soon?
With the growing acceptance both within the medical community and on a larger scale culturally, I think that the use of medicinal marijuana will continue to grow. There is already strong evidence that CBD is beneficial for certain types of refractory epilepsy, and studies are ongoing in evaluating its efficacy for other conditions such as epilepsy associated with Tuberous Sclerosis, and more broadly there will continue be more accumulated data on CBD on epilepsy in general. New Jersey will continue to improve its medical marijuana program and expand access and expand their menus to easier to administer options.
The limiting factors for the growth of the use of medical marijuana may be the cost to the patient due to not being covered by insurance, and the lack of strong protections in the workplace for patients who are using medical marijuana.
An exciting thing to think about for the future is that that there are hundreds of chemical compounds in the cannabis plant, and they interact with a whole system of neurotransmitters (the endocannabinoid system) that we now know plays a role in epilepsy. Many of these compounds are being studied (such as CBDV and CBGV) and will likely lead to new pharmaceutical epilepsy treatments in the future. It is likely that cannabinoids and cannabis derivatives will form a class of several epilepsy medications, not just the single pharmaceutical we currently have. Interestingly, if it turns out that several compounds in the cannabis plant are proven effective in epilepsy, it may reinforce the importance of whole plant cannabis extracts such as those used in the state medical programs.
Thank you Dr. Taha for your kind attention to this matter and for explaining it so well for all our readers.
