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Lennox-Gastaut Syndrome – Medical Marijuana Research Overview

The following information is presented for educational purposes only. Medical Marijuana Inc. provides this information to provide an understanding of the potential applications of cannabidiol. Links to third party websites do not constitute an endorsement of these organizations by Medical Marijuana Inc. and none should be inferred.

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) (Cunha, et al., 1980) (Filloux, 2015) (Hosseinzadeh, et al., 2016) (Rosenberg, Tsien, Whalley & Devinsky, 2015) (Szaflarski & Bebin, 2014) (Devinsky, et al., 2014) (Jones, et al., 2010) (Jones, et al., 2012) (Detyniecki & Hirsch, 2015) (Cilio, Thiele & Devinsky, 2014). Tetrahydrocannabinol (THC) has also demonstrated efficacy at reducing seizures in children with epilepsy (Lorenz, 2004). Another cannabinoid found in cannabis, cannabidivarin (CBDV) has also shown to have non-psychoactive anticonvulsant effects (Amada, Yamasaki, Williams & Whalley, 2013) (Hill, et al., 2012). 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 (Wallace, et al., 2003). CBD activates cannabinoid receptor 1 (CB1); The CB1 receptor then dampens the release of neurotransmitter and produces an overall reduction in neuronal excitability (Blair, et al., 2006) (Wallace, Wiley, Martin & DeLorenzo, 2001) (Hoffman & Frazier, 2013) (Wallace, Martin & DeLorenzo, 2002) (Karlócai, 2011).

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).

Another study examining the effect of CBD-enriched medical cannabis on children with epilepsy found that 89 percent of children reported a reduction in seizure frequency with CBD treatment. The children also reportedly saw improvements in behavior and alertness, language, communication,motor skills and sleep (Tzadok, et al., 2016).

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, several 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), West Virginia, 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, Washington, and West Virginia.

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.epilepsybehavior.com/article/S1525-5050(15)00157-2/fulltext
    )
  • 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.
    (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157067/)
  • 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:

Amada, N., Yamasaki, Y., Williams, C.M., and Whalley, B.J. (2013, November 21). Cannabidivarin (CBDV) suppresses pentylenentetrazole (PTZ)-induced increases in epilepsy-related gene expression. Peer J, 1:e214; doi 10.7717/peerj.214. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3840466/.

Blair, R.E., Deshpande, L.S., Sombati, S., Falenski, K.W., Martin, B.R., and DeLorenzo, R.J. (2006, June). Activation of the cannabinoid type-1 receptor mediates the anticonvulsant properties of cannabinoids in the hippocampal neuronal culture models of acquired epilepsy and status epilepticus. The Journal of Pharmacology and Experimental Therapeutics, 317(3), 1072-1078. Retrieved from http://jpet.aspetjournals.org/content/317/3/1072.long.

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. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845642/.

Cilio, M.R., Thiele, E.A., and Devinsky, O. (2014, June). The case for assessing cannabidiol in epilepsy. Epilepsia, 55(6), 787-90. Retrieved from http://onlinelibrary.wiley.com/doi/10.1111/epi.12635/full.

Cunha, J.M., Carlini, E.A., Pereira, A.E., Ramos, O.L., Pimentel, C., Gagliardi, R., Sanvito, W.L., Lander, N., and Mechoulam, R. (1980). Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology, 21(3), 175-85. Retrieved from https://goo.gl/JKQU41.

Detyniecki, K., and Hirsch, L. (2015, October). Marijuana use in epilepsy: The myth and the reality. Current Neurology and Neuroscience Reports, 15(10), 65. Retrieved from http://link.springer.com/article/10.1007%2Fs11910-015-0586-5.

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. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4707667/.

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. Retrieved from http://onlinelibrary.wiley.com/doi/10.1111/jcpt.12235/full.

Filloux, F. M. (2015). Cannabinoids for pediatric epilepsy? Up in smoke or real science? Translational Pediatrics, 4(4), 271–282. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4729003/.

Friedman, D. and Devinsky, O. (2015, September 10). Cannabinoids in the Treatment of Epilepsy. The New England Journal of Medicine, 373(11), 1048-58. Retrieved from http://www.nejm.org/doi/full/10.1056/NEJMra1407304.

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. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3792005/.

Hill, A., Mercier, M., Hill, T., Glyn, S., Jones, N., Yamasaki, Y., Futamura, T., Duncan, M., Stott, C.G., Stephens, G.J., Williams, C.M., and Whalley, B. (2012). Cannabidivarin is anticonvulsant in mouse and rat. British Journal of Pharmacology, 167(8), 1629–1642. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525866/.

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. Retrieved from http://www.sciencedirect.com/science/article/pii/S016372581100180X.

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. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3332149/.

Hosseinzadeh, M., Nikseresht, S., Khodagholi, F., Naderi, N., and Maghsoudi, N. (2016, April). Cannabidiol Post-Treatment Alleviates Rat Epileptic-Related Behaviors and Activates Hippocampal Cell Autophagy Pathway Along with Antioxidant Defense in Chronic Phase of Pilocarpine-Induced Seizure. Journal of Molecular Neuroscience, 58(4), 432-40. Retrieved from http://link.springer.com/article/10.1007%2Fs12031-015-0703-6.

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. Retrieved from http://www.epilepsybehavior.com/article/S1525-5050(15)00157-2/fulltext.

Jones, N. A., Hill, A. J., Smith, I., Bevan, S. A., Williams, C. M., Whalley, B. J., and Stephens, G. J. (2010). Cannabidiol Displays Antiepileptiform and Antiseizure Properties In Vitro and In Vivo. The Journal of Pharmacology and Experimental Therapeutics, 332(2), 569–577. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819831/.

Jones, N.A., Glyn, S.E., Akiyama, S., Hill, T.D., Hill, A.J., Weston, S.E., Burnett, M.D., Yamasaki, Y, Stephens, G.J., Whalley, B.J., and Williams, C.M. (2012, June). Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures. Seizure, 21(5), 344-52. Retrieved from http://www.seizure-journal.com/article/S1059-1311(12)00057-X/fulltext.

Karlócai, M. R., Tóth, K., Watanabe, M., Ledent, C., Juhász, G., Freund, T. F., & Maglóczky, Z. (2011). Redistribution of CB1 Cannabinoid Receptors in the Acute and Chronic Phases of Pilocarpine-Induced Epilepsy. PLoS ONE, 6(11), e27196. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3208595/.

Lorenz, R. (2004, February-April). On the application of cannabis in paediatrics and epileptology. Neuroendocrinology Letters, 25(1-2), 40-4. Retrieved from http://www.nel.edu/pdf_/25_12/NEL251204A02_Lorenz_.pdf.

Maa, E., and Figi, P. (2014, June). The case for medical marijuana in epilepsy. Epilepsia, 55(6), 783-6. Retrieved from http://onlinelibrary.wiley.com/doi/10.1111/epi.12610/full.

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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. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157067/.

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  • October 6, 2015