For kids with uncontrolled seizures, a technically illegal drug offers hope. But is it scientifically sound?
Desperate for relief, parents are taking unusual steps to help children plagued with seizures. The relief, however, comes in a most unlikely form: marijuana.
As many as 30 percent of people with epilepsy—or about one million Americans—still have seizures while on Food and Drug Administration (FDA)-approved treatments. It’s left many who suffer from uncontrollable seizures—or their parents, as many of them are children—turning to medical marijuana and its derivatives in an attempt to take back control of a disease with no cure.
A seizure is an abnormal electrical storm in the brain that causes sudden alteration in consciousness, sensation and behavior that can manifest from an eye flicker to full-body convulsions. People with medication-resistant (also called intractable) epilepsy suffer from consequences of recurrent seizures, which could damage the brain and adversely impact their quality of life. This is commonly observed in children with certain types of devastating pediatric epilepsy, such as Lennox-Gastaut, Doose and Dravet syndromes.
Stories about desperate parents seeking anything to relieve their children’s seizures abound, but how much scientific evidence is there for cannabis’ effectiveness?
D. Samba Reddy, Ph.D., R.Ph., professor in the Department of Neuroscience and Experimental Therapeutics at the Texas A&M Health Science Center College of Medicine, studies novel therapies for epilepsy. He recently published an article, with co-author Victoria Golub, in the Journal of Pharmacology and Experimental Therapeutics about the current state of research into medical marijuana for treating epilepsy.
“There was a lot of media attention about how medical marijuana is good for epilepsy,” said Reddy, who is a fellow of both the American Association of Pharmaceutical Scientists (AAPS) and the American Association for the Advancement of Science (AAAS). “We became interested in finding out whether there was scientific evidence in the literature to support the claims of these people who have seen great benefits.”
There are at least 85 active components of the plant colloquially known as marijuana, but two major ones of have been the focus of study: delta 9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the psychoactive component of the plant, while CBD doesn’t cause any sort of a “high” and isn’t thought to be addictive. Preliminary studies—largely in animal models—have shown CBD might have some anti-seizure potential.
Derivatives of marijuana high in CBD (but with negligible amount of THC) might offer some benefit for intractable epilepsy. CBD-enriched products, like Epidiolex and Realm Oil, exist, but their efficacy hasn’t been proven and they exist in a sort of legal grey area. Homemade compounds exist, but since they don’t go through rigorous best practice manufacturing procedures and haven’t been approved by the FDA, it can be difficult for consumers to know exactly what they’re getting.
Although THC is known to share the actions of anandamide (from the Indian Sanskrit word “anand” for bliss or happiness), a naturally occurring compound in the brain, the exact mode of anti-seizure action of CBD is unclear. “It is critical to know how CBD controls seizures, so pharmaceutical companies can design novel synthetic compounds for epilepsy that could surpass the hurdles of mixed CBD extracts,” said Reddy, who directs an epilepsy research lab at Texas A&M. These compounds might provide the benefits without some of the risks—or the legal issues—associated with the marijuana plant.
A standard manufacturing process and clinical trials might help answer some of these questions, but conducting one isn’t easy, and there are currently only 19 clinical trials going on to test the use of cannabinoids for epilepsy. For one thing, cannabis is still listed as a Schedule I substance by the federal government, meaning gaining permission to use it in research on human participants is extremely difficult.
Still, change is occurring at the state level. Recreational marijuana use is legal for adults in four states (Alaska, Colorado, Oregon and Washington) and in 23 states and Washington, DC, medical marijuana is allowed. Texas, in a law passed during the last legislative session in 2015, legalized low-THC cannabis oils for people with intractable epilepsy while still prohibiting medical marijuana more broadly.
A new study at the University of Colorado Anschutz Medical Campus is enrolling Dravet epilepsy patients who have tried Charlotte’s Web, a specific strain of medical marijuana that is low in THC and high in CBD. The researchers will compare the genetics of those who have seen seizure activity decreased dramatically (at least 50 percent) in response to the drug versus those who did not. Although this research could yield useful information about how CBD and genetic factors interact in a Dravet population, it is not the gold standard of scientific drug trials: the randomized, placebo-controlled, double-blinded clinical trial in which patients were randomly assigned to either CBD or a placebo.
As for experts like Reddy, who is a Texas board-certified pharmacist, most are taking a cautious wait-and-see approach.
The American Epilepsy Society (AES) has released a statement on the use of medical marijuana in the treatment of epilepsy stating that due to the lack of data, no conclusion can be drawn at present. The Epilepsy Foundation doesn’t specifically discourage cannabis use, but urges anyone exploring treatment for epilepsy to work with their treating physician to make the best decisions for their own care and to follow applicable laws.
“Despite all of the controversy about medical marijuana as a potential therapy for epilepsy,” Reddy said, “most people agree that what we need is greater rigorous scientific study into cannabinoids to prove or disprove their safety and efficacy.”
About this psychology research
Funding: Gina Rippon has previously received funding from the Medical Research Council and the Wellcome Trust.
Source: Holly Shive – Texas A&M Image Source: Image is in the public domain. Original Research:Abstract for “The Pharmacological Basis of Cannabis Therapy for Epilepsy” by Doodipala Samba Reddy and Victoria Golub in Journal of Pharmacology and Experimental Therapeutics. Published online January 19 2016 doi:10.1124/jpet.115.230151
The Pharmacological Basis of Cannabis Therapy for Epilepsy
Recently, cannabis has been suggested as a potential alternative therapy for refractory epilepsy, which affects 30% of epilepsy patients including children who do not respond to current medications. There is a large unmet medical need for new antiepileptics for refractory epilepsy and conditions associated with refractory seizures that would not interfere with normal function. The two chief cannabinoids are delta-9-tetrahyrdrocannabinol, the major psychoactive component of marijuana, and cannabidiol (CBD), the major non-psychoactive component of marijuana. There are claims of clinical efficacy of CBD-predominant cannabis or medical marijuana for epilepsy, mostly from limited studies, surveys or case reports. However, the mechanisms underlying the antiepileptic efficacy of cannabis remain unclear. This article highlights the pharmacological basis of cannabis therapy, with an emphasis on the endocannabinoid mechanisms underlying the emerging neurotherapeutics of CBD in epilepsy. CBD is anticonvulsant, but it has a low affinity for the cannabinoid CB1 and CB2 receptors; therefore the exact mechanism by which it affects seizures remains poorly understood. A rigorous clinical evaluation of pharmaceutical CBD products is needed to establish the safety and efficacy for the treatment of epilepsy. Identification of mechanisms underlying the anticonvulsant efficacy of CBD is additionally critical to identify other potential treatment options.
“The Pharmacological Basis of Cannabis Therapy for Epilepsy” by Doodipala Samba Reddy and Victoria Golub in Journal of Pharmacology and Experimental Therapeutics. Published online January 19 2016 doi:10.1124/jpet.115.230151