Marijuana in Epilepsy Philippe Douyon MD Epileptologist Northeast

Marijuana in Epilepsy Philippe Douyon, MD Epileptologist Northeast Regional Epilepsy Group

• Objectives: • Brief overview of seizures/epilepsy • Endocannabinoid System • Mechanism of Action • Impact on the Brain/Theoretical role in Epilepsy • Politics of Marijuana

Seizure A sudden surge of electrical activity in the brain

Epilepsy: 2 or more unprovoked seizures Epilepsy is the fourth most common neurological disorder and affects people of all ages Epilepsy means the same thing as "seizure disorders" Epilepsy is characterized by unpredictable seizures and can cause other health problems Epilepsy is a spectrum condition with a wide range of seizure types and control varying from person-to-person

Medically Intractable Epilepsy • No single step in treatment defines intractability • After each drug failure, the statistical probability of seizure control by the next drug becomes lower, but it never approaches zero

Epileptic Encephalopathies • Dravet Syndrome • Lennox-Gastaut Syndrome • West Syndrome • Landau-Kleffner Syndrome

Howard compares his seizures to electricity and lightning. He asks, "What is it like to be split open from the inside by lightning? ” He provides one answer: "The actual seizure was when the bolt touched flesh, and in an instant so atomic, so nearly immaterial, nearly incorporeal, that there was almost no before and after. . . and Howard became pure, unconscious energy"

• Endogenous cannabinoids • CB 1 regulates neuronal excitability • Neuronal hyperexcitability is associated with seizures • No studies –endogenous cannabinoid system in an intact model of epilepsy

• CB 1 receptors are concentrated in the hippocampus, association cortices, basal ganglia, cerebellum, spinal cords, and peripheral nerves • CB 1 receptors are notably absent from the thalamus and brainstem

• Systematic review: Efficacy and safety of medical marijuana in selected neurologic disorders: Report of the Guideline Development Subcommittee of the American Academy of Neurology • Barbara S. Koppel, MD, FAAN, John C. M. Brust, MD, FAAN, Terry Fife, MD, FAAN, Jeff Bronstein, MD, Ph. D, Sarah Youssof, MD, Gary Gronseth, MD, FAAN and David Gloss, MD

• Spasticity in patients with MS • Central pain and painful spasms in MS • Bladder dysfunction in MS • Involuntary movements, including tremor, in MS • Dyskinesias of Huntington disease, levodopa induced dyskinesias in PD, cervical dystonia, and tics of Tourette syndrome • Seizure frequency in epilepsy

• Analytic Process • Searched Medline, EMBASE, Psych. INFO, Web of Science, and Scopus • 1, 729 abstracts • Surveys, case reports/series, non placebocontrolled trials were excluded • Reviewed the full text of 63 articles • 33 articles met inclusion criteria

• Do cannabinoids decrease seizure frequency? • No Class I-III studies • 2 Class IV studies that did not demonstrate a significant benefit and did not show adverse effects over 3 -18 weeks of treatment • Conclusion: “data is insufficient to supports or refute the efficacy of cannabinoids for reducing frequency”

• The AAN review also concluded that there is not enough information to show if medical marijuana, including smoked medical marijuana, is safe or effective in these neurologic diseases: • Motor symptoms in Huntington’s disease • Tics in Tourette syndrome • Cervical dystonia (abnormal neck movements) • Seizures in epilepsy

• There are safety concerns with medical marijuana use. Side effects reported in at least two studies were nausea, increased weakness, behavioral or mood changes, suicidal thoughts or hallucinations, dizziness or fainting symptoms, fatigue, and feelings of intoxication. There was one report of a seizure. Mood changes and suicidal thoughts are of special concern for people with MS, who are at an increased risk for depression or suicide. The studies showed the risk of serious psychological effects is about 1 percent, or one in every 100 people. In general, medical marijuana is prescribed as a treatment for use only when standard treatment has not helped.

“Don’t let my daughter die”

• NJ Senate Bill 2842 • Prohibits limitations on number of strains of medical marijuana cultivated, and expands available means of packaging and distribution therof. ** • Approved September 10 th 2013

• http: //www. state. nj. us/health/medicalmarijuana/index. shtml

Alternative Treatment Centers (ATC) NJ Compassionate Care Foundation 100 Century Drive Egg Harbor Twp, NJ Operational (609) 277 -7547 Greenleaf Compassionate Center 395 Bloomfield Ave Montclair, NJ Operational (973) 337 -5670 Garden State Dispensary U. S. Highway 1 North Woodbridge NJ (848)999 -2005 Operational

Alternative Treatment Centers (ATC) NJ Breakwater Alternative Treatment Center Location Pending Operations Pending (732) 703 -7300 Foundation Harmony Location Pending Operations Pending (201) 840 -5800 Compassionate Sciences, Inc. 111 Coolidge Avenue Bellmawr, NJ (856) 933 -8700 Operations Pending

• N. Y. / Region |NYT Now Connecticut Allows Medical Marijuana, but Sellers Encounter Hurdles By JOSEPH BERGERMAY 1, 2014 http: //www. nytimes. com/2014/05/02/nyregion/medical-marijuana-is-legal-in-connecticut-but-notyet-sold. html? _r=0

• Medical marijuana could be legalized in New York this spring: advocates “Proponents of medical pot say newly revised legislation could be approved in Albany this year, which would make New York the 22 nd state to legalize medical marijuana. Gov. Cuomo has hinted at his support, but opposition remains in the state Senate. ” BY GLENN BLAIN NEW YORK DAILY NEWS Published: Sunday, April 27, 2014, 7: 44 PM

• Medical Marijuana Refugees

• American Academy of Neurology (April 2014) “…. . scientific research on the use of medical marijuana in brain diseases finds certain forms of medical marijuana can help treat some symptoms of multiple sclerosis (MS), but do not appear to be helpful in treating drug-induced (levodopa) movements in Parkinson’s disease. Not enough evidence was found to show if medical marijuana is helpful in treating motor problems in Huntington’s disease, tics in Tourette syndrome, cervical dystonia and seizures in epilepsy. ”

• American Epilepsy Society (February 2014) “The recent anecdotal reports of positive effects of the marijuana derivative cannabidiol for some individuals with treatment-resistant epilepsy give reason for hope. However, we must remember that these are only anecdotal reports, and robust scientific evidence for the use of marijuana is lacking. The lack of information does not mean that marijuana is ineffective for epilepsy. It merely means that we do not know if marijuana is a safe and effective treatment for epilepsy, which is why it should be studied using the well-founded research methods that all other effective treatments for epilepsy have undergone. ”

• The Epilepsy Foundation supports the rights of patients and families living with seizures and epilepsy to access physician directed care, including medical marijuana. • The Epilepsy Foundation calls for an end to Drug Enforcement Administration (DEA) restrictions that limit clinical trails and research into medical marijuana for epilepsy. • The Epilepsy Foundation believes that an end to seizures should not be determined by one’s zip code.