Lennox-Gastaut Syndrome – Medical Marijuana Research Overview

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Lennox-Gastaut syndrome is a type of severe epilepsy that develops during early childhood and is characterized by a high volume of seizures. Studies have shown marijuana is a potential treatment option for curtailing intractable seizures.

Overview of Lennox-Gastaut Syndrome

Lennox-Gastaut syndrome is a severe form of epilepsy that typically develops before the age of four. The syndrome typically causes impaired intellectual development and limits information processing, causing behavioral problems. While the cause of Lennox-Gastaut syndrome can’t always be determined, it many cases, it be attributed to either brain malformations, perinatal asphyxia, severe head injury, central nervous system infection and inherited degenerative or metabolic conditions.

The type of seizures caused by Lennox-Gastaut syndrome can include tonic (body stiffens, eyes deviate upward, pupils dilate, respiratory patterns become altered), atonic (brief loss of consciousness and muscle tone, abrupt falling), atypical absence (spell of staring), and myoclonic (sudden muscle jerks). The Epilepsy Foundation, however, notes that tonic and atonic seizures are most common in Lennox-Gastaut syndrome.

There is no cure for the disorder and complete recovery and freedom from seizures is unusual. It’s rare for anti-seizure medications to be effective in individuals with Lennox-Gastaut syndrome. In addition, the National Institute of Neurological Disorders and Stroke note that children that respond positively to a drug can later show tolerance and resume their uncontrollable seizures.

Findings: Effects of Cannabis on Lennox-Gastaut Syndrome

A number of scientific reviews have concluded that a major cannabinoid found in cannabis, cannabidiol (CBD) is a well-tolerated and promising therapeutic treatment that has demonstrated the ability to reduce or even eliminate seizures (Blair, Deshpande & DeLorenzo, 2015) (Rosenberg, Tsien, Whalley & Devinsky, 2015) (Szaflarski & Bebin, 2014) (Devinsky, et al., 2014). In a preclinical trial, the administration of cannabis provided significant anticonvulsant effects in mice and rats (Hill, et al., 2013).

The capability of CBD to reduce or eliminate seizures is due to its effects on the body’s endocannabinoid system. CBD activates cannabinoid receptor 1 (CB1); The CB1 receptor then dampens the release of neurotransmitter and produces an overall reduction in neuronal excitability (Wallace, Wiley, Martin & DeLorenzo, 2001) (Hoffman & Frazier, 2013).

Although double-blind randomized, placebo-controlled studies are currently lacking, early research suggests that cannabis is effective in the treatment of severe pediatric epilepsy disorders like Lennox-Gastaut syndrome. In one questionnaire study, 84% of parents reported a reduction in their child’s 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 children with Lennox-Gastaut syndrome, 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).

One case report analyzing a young girl with Dravet syndrome, another severe childhood epilepsy disorder, found that medical marijuana brought the child’s 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 antiepileptic drugs she had been taking (Maa & Figi, 2014).

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 Lennox-Gastaut Syndrome

Currently, just South Carolina has approved medical marijuana specifically for the treatment of Lennox-Gastaut Syndrome. However, 24 other states have approved medical marijuana specifically to treat epilepsy and other seizure disorders. These states include: Alabama (debilitating epileptic conditions), Connecticut, Delaware (intractable epilepsy), Florida, 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, 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, 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 epilepsy if it’s determined in writing by a qualifying patient’s 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 Cannabis’ Effect on Lennox-Gastaut Syndrome
  • CBD-enriched cannabis reduced seizure frequency in 85% of children and 14% reported complete seizure freedom. Children also saw improvements in sleep (53%), alertness (71%), and mood (63%).
    Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: A potential role for infantile spasms and Lennox-Gastaut syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/25935511)
  • Cannabis reduced seizure frequency in 84% of children, while 11% reported complete seizure freedom. Additional beneficial effects included increased alertness, better mood, and improved sleep.
    Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy.
    (http://www.ncbi.nlm.nih.gov/pubmed/24237632)
  • Cannabis provided significant anticonvulsant effects in mice and rats.
    Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism
    (http://www.ncbi.nlm.nih.gov/pubmed/23902406)

References

Blair, RE., Deshpande, LS., and  DeLorenzo, RJ. (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.

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.

Lennox-Gastaut Syndrome (LGS). (2014, March). Epilepsy Foundation. Retrieved from http://www.epilepsy.com/learn/types-epilepsy-syndromes/lennox-gastaut-syndrome-lgs.

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

NINDS Lennox-Gastaut Syndrome Information Page. (2015, July 17). National Institute of Neurological Disorders and Stroke. Retrieved from http://www.ninds.nih.gov/disorders/lennoxgastautsyndrome/lennoxgastautsyndrome.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 epilepsy–from 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.

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