Dravet Syndrome and Cannabidiol


Dravet Syndrome Ė Medical Marijuana Research Overview

6 October, 2015
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Dravet syndrome is a type of severe epilepsy that develops during the first year of childhood and is characterized by frequent febrile seizures. Studies have shown marijuana has the capability of reducing, and in some cases eliminating, seizures.

Overview of Dravet Syndrome

Dravet syndrome, which is also referred to as severe myoclonic epilepsy of infancy (SMEI), is a severe form of epilepsy that typically develops during the first year of life. The high frequency of seizures caused by the syndrome commonly causes children to experience difficulty developing language and motor skills. In addition, they often experience hyperactivity and have problems relating to others.

Dravet syndrome typically causes febrile seizures, which are fever-related (associated with a high body temperature but without any attributing health issue). Seizures can be triggered by slight body temperature changes, flashing lights, emotional stress or excitement. In addition, myoclonic seizures, characterized by involuntary muscle spasms, and status epilepticus, a state of continuous seizure that lasts longer than 30 minutes and requires emergency care, can arise.

According to the National Institute of Neurological Disorders and Stroke, 30 to 80% of Dravet syndrome cases are caused by defects in the SCN1A gene, which are essential for the brain cells to properly function.

There is no cure for Dravet syndrome, but in some cases medications can help control seizures. In addition, adjusting the diet so that itís high in fats and low in carbohydrates may be beneficial. While itís a lifelong condition, itís not uncommon for children with Dravet syndrome to experience improvements and better cognitive function with age.

Findings: Effects of Cannabis on Dravet Syndrome

One of the major cannabinoids found in cannabis, cannabidiol (CBD), has been determined to be a well-tolerated therapeutic treatment that can reduce or even eliminate seizures in a variety of childhood epilepsy disorders (Blair, Deshpande & DeLorenzo, 2015) (Rosenberg, Tsien, Whalley & Devinsky, 2015) (Szaflarski & Bebin, 2014) (Devinsky, et al., 2014). Preclinical trials have found that cannabis causes significant anticonvulsant effects in mice and rats (Hill, et al., 2013) (Hill, Williams, Whalley & Stephens, 2012).

CBD is able to reduce or eliminate seizures because it activates the cannabinoid receptor 1 (CB1) of the bodyís endocannabinoid system. The CB1 receptor, once activated, inhibits the release of a particular neurotransmitter and reduces overall neuronal excitability, thus silencing the triggers of seizures (Wallace, Wiley, Martin & DeLorenzo, 2001) (Hoffman & Frazier, 2013).

One case report analyzing a young girl with Dravet syndrome found that medical marijuana brought the childís seizure frequency from nearly 50 convulsive seizures per day to 2-3 nocturnal convulsions per month. In addition, the child was able to wean from the additional anti-epileptic drugs she had been taking (Maa & Figi, 2014).

Double-blind randomized, placebo-controlled studies are currently lacking, but early research suggests that cannabis may be effective in treating a variety of of severe pediatric epilepsy disorders like Dravet syndrome. In one questionnaire study, 84% of parents reported a reduction in their childís seizure frequency following cannabis treatment. Out of those parents, 11% of them responded that their child has reached complete seizure freedom, while 42% reported a greater than 80% reduction in seizure frequency. The parents also reported additional beneficial effects, such as increased alertness, better mood and improved sleep (Porter & Jacobson, 2013). Another similar survey found that CBD-enriched cannabis brought about a reduction in seizure frequency in 85% of epileptic children, while 14% experienced complete seizure freedom. The children also reported an improvement in sleep (53%), alertness (71%), and mood (63%) while being treated with CBD (Hussain, et al., 2015).

Traditional medicines used to treat epilepsy are not just ineffective for most; they often come with a number of adverse side effects. Cannabinoids found in cannabis, however, have shown to produce anticonvulsant effects in preclinical and preliminary human studies while producing fewer adverse effects that other antiepileptic drugs (dos Santos, et al., 2015). A questionnaire study found that parents tried an average of 12 different antiepileptic drugs, due to ineffectiveness or unacceptable side effects, before finding gentle effectiveness with cannabis (Porter & Jacobson, 2013).

States That Have Approved Medical Marijuana for Dravet Syndrome

Currently, just South Carolina has approved medical marijuana specifically for the treatment of Dravet syndrome. However, 23 states have approved medical marijuana specifically to treat epilepsy and other seizure disorders. These states include: Alabama (debilitating epileptic conditions), Connecticut, Delaware (intractable epilepsy), Georgia (seizure disorder), Iowa (intractable epilepsy), Louisiana, Maine, Mississippi (intractable epilepsy), Missouri (intractable epilepsy), New Hampshire, New Jersey (seizure disorders), New Mexico, New York, North Carolina (intractable epilepsy), North Dakota, Ohio, Oklahoma (pediatric epilepsy), Pennsylvania, South Carolina (Dravet syndrome, Lennox-Gastaut syndrome, Refractory epilepsy), Texas (intractable epilepsy), Utah (intractable epilepsy), Virginia (intractable epilepsy), Wisconsin (seizure disorders), and Wyoming (intractable epilepsy).

In addition, several states approve medical marijuana to specifically treat seizures. These states include: Alaska, Arizona, Arkansas, California, Colorado, Delaware, Florida, Hawaii, Louisiana, Maryland, Michigan, Minnesota, Montana, Nevada, New Hampshire, North Dakota, Ohio, Oregon, Pennsylvania (intractable seizures), Rhode Island, Tennessee (intractable seizures), Vermont and Washington.

The state of Massachusetts will consider allowing medical marijuana to be used for the treatment of Dravet syndrome if itís determined in writing by a qualifying patientís physician.

In Washington D.C., any condition can be approved for medical marijuana as long as a DC-licensed physician recommends the treatment.

Recent Studies on Cannabisí Effect on Dravet Syndrome

References

Blair, RE., Deshpande, L.S., and  DeLorenzo, R.J. (2015, September). Cannabinoids: is there a potential treatment role in epilepsy? Expert Opinion on Pharmacology, 16(13), 1911-4.

Devinsky, O., Cilio, M.R., Cross, H., Fernandez-Ruiz, J., French, J., Hill, C., Katz, R., Di Marzo, V., Jutras-Aswad, D., Notcutt, W.G., Martinez-Orgado, J., Robson, P.J., Rohrback, B.G., Thiele, E., Whalley, B., and Friedman, D. (2014, June). Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia, 55(6), 791-802.

dos Santos, R.G., Hallak, J.E., Leite, J.P., Zuardi, A.W., and Crippa, J.A. (2015, April). Phytocannabinoids and epilepsy. Journal of Clinical Pharmacology and Therapeutics, 40(2), 135-43.

Friedman, D. and Devinsky, O. (2015, September 10). Cannabinoids in the Treatment of Epilepsy. The New England Journal of Medicine, 373(11), 1048-58.

Hill, T.D., Cascio, M.G., Romano, B., Duncan, M., Pertwee, R.G., Williams, C.M., Whalley, B.J., and Hill, A.J. (2013, October). Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism. British Journal of Pharmacology, 170(3), 679-92.

Hill, A.J., Williams, C.M., Whalley, B.J., and Stephens, G.J. (2012, January). Phytocannabinoids as novel therapeutic agents in CNS disorders. Pharmacology & Therapeutics, 133(1), 79-97.

Hoffman, M.E. and Frazier, C.J. (2013, June). Marijuana, endocannabinoids, and epilepsy: potential and challenges for improved therapeutic intervention. Experimental Neurology, 244, 43-50.

Hussain, S.A., Zhou, R., Jacobson, C., Weng, J., Cheng, E., Lay, J., Hung, P., Lerner, J.T., and Sankar, R. (2015, June). Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: A potential role for infantile spasms and Lennox-Gastaut syndrome. Epilepsy & Behavior, 47, 138-41.

Maa, E. and Figi, P. (2014, June). The case for medical marijuana in epilepsy. Epilepsia, 55(6), 783-6.

NINDS Dravet Syndrome Information Page. (2001, September 29). National Institute of Neurological Disorders and Stroke. Retrieved from http://www.ninds.nih.gov/disorders/dravet_syndrome/dravet_syndrome.htm.

Porter, B.E., and Jacobson, C. (2013, December). Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy & Behavior, 29(3), 574-7.

Rosenberg, E.C., Tsien, R.W., Whalley, B.J., and Devinsky, O. (2015, August 18). Cannabinoids and Epilepsy. Neurotherapeutics, Epub ahead of print. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/26282273.

Szaflarski, J.P., and Bebin, E.M. (2014, December). Cannabis, cannabidiol, and epilepsyĖfrom receptors to clinical response. Epilepsy & Behavior, 41, 277-82.

Wallace, M.J., Wiley, J.L., Martin, B.R., and DeLorenzo, R.J. (2001, September 28). Assessment of the role of CB1 receptors in cannabinoid anticonvulsant effects. European Journal of Pharmacology, 428(1), 51-7.

What is Dravet syndrome? (2014, March). Epilepsy Foundation. Retrieved from http://www.epilepsy.com/learn/types-epilepsy-syndromes/dravet-syndrome.

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