On June 25th, 2018, the Food and Drug Administration approved the very first drug that was developed using one of the active components in marijuana plants. The drug, Epidiolex, is considered a reliable treatment for people who have seizures relative to a few really rare forms of epilepsy.
Lennox-Gastaut syndrome and Dravet syndrome are the two rare forms of epilepsy this new drug treats, and even better, the medication can be used to treat patients as young as two years old. But most surprising for many is the active ingredient in this new medication: cannabidiol (CBD).
Epediolex is expected to be only the first of several CBD-based drugs. The University of Mississippi submitted an Investigational New Drug Application to the FDA in 2017 in efforts to begin a new clinical study on a CBD extract for epileptic children.
In general terms, epilepsy is a neurological condition that affects the brain. People who have epilepsy tend to have sudden disruptions in electrical activity and pulses that should be transitioned to keep the body in a functional state. People who have epilepsy often experience symptoms like:
There are different forms of epilepsy, each with specific symptoms and attributes that classify them. The two forms of epilepsy that are known to be helped through CBD treatment are Lennox-Gastaut syndrome and Dravet syndrome.
Lennox Gastaut Syndrome is one of the most severe types of epilepsy, usually begins early in a child's life, and is accompanied most often by intellectual disabilities and frequent seizures of different types. Dravet syndrome is one of the rarest and most catastrophic forms of epilepsy and is often referred to as Severe Myoclonic Epilepsy of Infancy (SMEI). This epilepsy starts early in infancy, usually within the first year of life, and is characterized by a genetic dysfunction that is present in the brain without other physiological causes. The seizures with Dravet syndrome occur frequently and are often associated by a spike in bodily temperature.
Approximately 30 percent of people with epilepsy who are on traditional medications for seizure control still experience regular seizures, according to Vital Record. Up until recently, the primary ways to treat the most severe forms of epilepsy had been to prevent seizures with medications or even by removing sections of the brain, according to UCLA.
Research of cannabis constituents has been ongoing for a while, but the recent changes in legal statuses of different cannabinoids have opened the way for many new clinical studies to be performed in scientific settings. Here, we will examine the multitude of clinical trials, scientific research, and informational releases that have been published by physicians, medical institutions, and universities on the effectiveness of CBD for epilepsy.
The Journal of Pharmacology and Experimental Therapeutics proposed an abstract study titled "Cannabidiol-Antiepileptic Drug Comparisons and Interactions in Experimentally Induced Seizures in Rats." The study was on the anticonvulsant and neurotoxic effects of CBD in 1977. The study was performed on rats as animal models who were experimentally induced into having controlled seizures. The resulting data showed that CBD was:
"...an effective anticonvulsant with a specificity more comparable to drugs clinically effective in major than minor seizures."
The study further stated that CBD seemed to both enhance and reduce the effects of certain antileptic drugs.
There are some studies that emerged early in the 2000s that were performed on rats as well. In 2003, a study by researchers at Virginia Commonwealth University was performed on chronically epileptic rats by injecting them with combinations of:
The study found that rats that received either marijuana extract or synthetic drugs with the same psychoactive ingredients as marijuana actually completely stopped the seizures the rats were having within ten hours.
While treatment on animals was a good indicator of the effectiveness of CBD for epilepsy, well-organized studies on humans did not come about until much later. In fact, UConn Today published an article in 2016 that stated while CBD showed promise, there was a great need for further studies on larger groups of patients with epilepsy before any real conclusions could be drawn.
A report titled "Cannabinoids in the Treatment of Epilepsy: Hard Evidence at Last?" was published in December 2017 by the Journal of Epilepsy Research offered an in-depth look at the multiple documented studies of CBD, as well as other cannabinoids. In this report, there were multiple references given to show CBD could be considered a form of anticonvulsant treatment, that the component was free from adverse psychoactive effects, and lacks the abuse potential associated with THC.
A systematic review of controlled and observational evidence was published in July 2018 by the Journal of Neurology, Neurosurgery, and Psychiatry that also showed great evidence to support cannabinoids for epilepsy. It was noted that outcomes of studies done in 2017 were 50 percent seizure reduction, complete freedom of seizures in some cases, and even improved quality of life. It was further notated then that pediatric-onset epilepsy and epilepsy that resisted most drugs could potentially see reduced seizure frequency with CBD.
There have been multiple reports of patients with various forms of epilepsy having success with CBD treatment. According to a PDF published by DCRX, a survey of parents of children with severe forms of early-onset epilepsy was performed. Sixteen out of nineteen of those parents reported that cannabidiol-enriched cannabis reduced the numbers of seizures their children were having. Two of those respondents stated their children actually stopped having seizures altogether. Eight others said that there was at least an 80 percent drop in the number of seizures their children experienced.
In that same report by DCRX, there is mention of a case involving a child who had Dravet syndrome to a severe degree. A developed strain of Cannabis that had a high concentration of CBD and lower concentration of THC reduced the child's seizure frequency form nearly 50 every day to only a few nocturnal convulsions in a 30-day period.
It is noted in the report released by DCRX that four small trials were done between the late 1970s and early 1990s on CBD for seizures as well. One particular study was done in 1978 on nine patients with seizures. They were given 200 mg. of CBD or a placebo for three months. Two of four of the patients who were given CBD became completely seizure-free by the time the trial concluded. Those who were given a placebo experienced no change.
A multi-center study hosted by the researchers from UCSF Benioff Children’s Hospital San Francisco and published in 2015 also had impressive results. Out of 162 children and young adults who were treated with Epediolex during the study, there was a 36.5 percent decrease in monthly motor seizures. UCSF was the very first initial testing conductor to ever give Epediolex to a child who was suffering from epilepsy.
There have been a handful of studies geared toward how effective CBD could be for treating seizures relative to Lennox-Gastaut Syndrome (LGS) over the last several years. One small trial conducted by the Children's Hospital of Philidelphia on 25 patients between the ages of 3 and 19 who had either LGS or the Dravet Syndrome was one of the first performed in 2015. The results showed that patients treated had a range of experiences, including a dramatic reduction in the incidence of seizures and many patients showed improvements in cognitive function and walking abilities.
An infographic published by Greenwich Biosciences and funded by GW Pharmaceuticals (developer of Epidiolex), which was performed by professionals from prestigious organizations like the Nationwide Children's Hospital, University College of London, and The Pediatric Neurosciences Research Group, found dropped seizure frequency in people who suffered from Lennox-Gastaut Syndrome. The patients were given 20 mg. and 10 mg. per day of CBD in addition to their usual care.
Those patients who were given 20 mg/per kg. body weight per day through the primary treatment period saw a 42 percent decrease in the instances of seizures. Those provide with a 10 mg./per kg. of bodyweight dose during the treatment period saw a 37 percent decrease. The patients who participated in this study were between 2 and 55 years of age.
In an article published by the U.S. Academic Health Center about the study published by Greenwich Biosciences on CBD for Lennox-Gastaut Syndrome, it was stated that the study is a historic one, and provides scientific evidence that CBD is safe for epilepsy, as well as effective. It was largely thanks to this study that the FDA did eventually approve Epidiolex for epilepsy treatment.
In 2015, The New England Journal of Medicine published a review article on Cannabinoids in the treatment of Epilepsy. The purpose of the review was to show that CBD could be considered a potential pharmaceutical for epilepsy. They stated:
"The pharmacologic and biochemical features of cannabinoids make them candidates for antiseizure medications."
In 2017, The New England Journal of Medicine published the results of a trial of CBD for drug-resistant seizures in the Dravet Syndrome. The trial was double-blind and placebo-controlled for accuracy and involved 120 children as well as younger adults. Each patient had been diagnosed with the Dravet syndrome and had some degree of drug-resistant seizures.
The patients involved in the trial were given 20 mg. per kilogram of body weight in addition to their usual antileptic medications and treatment. The number of convulsive seizures dropped from 12.4 per month to 5.9 with CBD treatment. Five percent of the patients in the trial actually became seizure-free. Professor Ingrid Scheffer, University of Melbourne Chair of Paediatric Neurology and Austin Health Director of Paediatrics, said about the study published by The New England Journal of Medicine:
“I am delighted that we finally have high-level evidence that cannabidiol is effective for uncontrolled seizures in Dravet syndrome,”
Initially, CBD was only available for patients who lived in states who had legalized medical marijuana on some level. For instance, in 2014 CBD was not available for parents of children with epilepsy outside of states like Colorado, so many parents were moving out of states like Pennsylvania and Utah just to get CBD treatment legally. Even though CBD is now legal in all 50 states, every state has its own laws governing how the CBD is allowed to be distributed to patients.
One such example is in the state of Texas, according to TMC News, who states the laws in the state are pretty restrictive compared to many others. Even though patients legally have access to CBD, they are only allowed to be prescribed the oil if they get a recommendation from two treating physicians, and not many doctors are onboard with helping. Plus, the patient's epilepsy must be “intractable” epilepsy, which basically means two other traditional antileptic medications have been unhelpful. As an added challenge, there are only 3 licensed CBD dispensaries in the state.
More time and attention is being designated to conducting further clinical trials of cannabidiol for people with epilepsy, with some organizations actively recruiting patients who would be interested in taking part in their trials. The Health University of Utah was recruiting trial participants as of August 2018 who had been diagnosed with medication-resistant epilepsy.