Epileptologist Northeast Regional Epilepsy Group Marijuana QuotesReferences A harmless giggle John Lennon When I was a kid I inhaled frequently That was the point Barack Obama ID: 777365
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Marijuana in Epilepsy
Philippe Douyon, MDEpileptologistNortheast Regional Epilepsy Group
Slide2Marijuana Quotes/References
“A harmless giggle” ~ John Lennon“When I was a kid I inhaled frequently. That was the point.” ~ Barack Obama“That is not a drug. It’s a leaf.” ~ Arnold Schwarzenegger“Casual drug users should be taken out and shot.” ~ Chief of LAPD“Music and herb go together. It’s been a long time now I smoked herb. From 1960s when I first start singing.” ~Bob Marley“I enjoy smoking cannabis and see no harm in it.” ~ Jennifer Aniston“Not the quality of life we want.” ~ Chris Christy
“You bet I did and I enjoyed it” ~ Michael Bloomberg
“The Grass Makes the Other Side of the Hill Look Greener” ~ Lecture Title
Slide3“If we think them not enlightened enough to exercise their control with wholesome discretion, the remedy is not to take it away from them but to inform their discretion by education.” ~
Thomas Jefferson
Slide4Cannabis Genus
Cannabis Sativa and Indica speciesRope, clothing, paper, livestock feeds, recreation, religious ceremonies, and medicineMedicinal preparations – China (~2,700 BC)Gout, rheumatism, malaria, constipation, menstrual pain Medieval Time: n/v, epilepsy, inflammationWestern Medicine: 1800s – most common analgesicMarijuana Tax Act of 1937 – limited its access
Slide5Slide6Slide7Slide8Endocannabinoid System
Slide9Endocannabinoid System
EndocannabinoidsProduced on demandDampens excessive neuronal stimulationFound on both (GABA)ergic and glutamatergic neuronsUnpredictable
Slide10Endocannabinoid System
CB1 receptors are concentrated in the hippocampus, association cortices, basal ganglia, cerebellum, spinal cords, and peripheral nerves
CB1 receptors are notably absent from the thalamus and brainstem
Slide11Slide12Marijuana and the munchies
Giovanni Marsicano, Univ of Bordeaux THC binds into receptors in the brains olfactory bulbsSmell and taste food more acutelyHypothalamusGhrelinStimulates hunger
Slide13Marijuana and Pleasure
Nucleus accumbensIncreasing the release dopamine pleasureTHC is manipulating pathways that already exist our brains
Slide14Marijuana and Apathy
Cerebral CortexPrefrontal CortexLoss of interestApathyInability to complete tasksPoor planning and decision making
Slide15Slide16Slide17Cannabidiol (CBD)Cannabidiol (CBD)
Does not activate CB1 and CB2 receptorsLikely accounts for its lack of psychotropic activityInteracts with many other, non-endocannabinoid signalling systemsInhibitsEquibilibrative nucleoside transporter (ENT)Organophosphate G protein coupled receptor GPR55Transient receptor potential of melastin type 8 (TRPM8)Enhances 5-HT glycine receptorsCBD has bi-directional effect on intracellular calcium
CBD is multitarget drug
Slide18Cannabidiol (CBD)Cannabidiol (CBD)
Exerts influence on THCMay potentiate some of the beneficial effects of THCReduces the psychoactivity of THCCounters the functional consequence of CB1 activationWidens the therapeutic windowNambiximols – Used in Multiple Sclerosis ( Equal amount of CBD : THC)Ratio of CBD : THC that mattersHigh CBD : THC ratios are less likely to develop psychotic symptomsLow CBD : THC ratios are more likely to develop psychotic symptoms
Slide19Entourage Effect
Slide20Howard 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"
Slide21Seizure
A sudden surge of electrical activity in the brain
Slide22Epilepsy: 2 or more unprovoked seizures
Epilepsy is the fourth most common neurological disorder and affects people of all agesEpilepsy 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
Slide23Slide24Slide25Slide26Slide27Slide28Medically Intractable Epilepsy
No single step in treatment defines intractabilityAfter each drug failure, the statistical probability of seizure control by the next drug becomes lower, but it never approaches zero
Slide29Slide30Epileptic Encephalopathies
Dravet SyndromeLennox-Gastaut SyndromeWest SyndromeLandau-Kleffner Syndrome
Slide31Slide32Endocannabinoid System
Theory: Endogenous cannabinoids are produced on demand in periods of excessive neuronal excitationCB1 receptors mediates neuronal inhibition by decreasing the calcium influx and increasing potassium efflux
Slide33Endocannabinoid System
Theory: Seizures: associated with sustained sustained neuronal activation and elevated intracellular calciumNeuronal hyperexcitability that accompanies seizures activity may stimulate endogenous cannabinoid synthesis resulting in activation of CB1 receptor, which can influence seizure activity
Slide34Entourage Effect
Slide35The Pursuit of Charlotte’s Web
Slide36Endogenous
cannabinoidsCB1 regulates neuronal excitabilityNeuronal hyperexcitability is associated with seizures
No studies –endogenous
cannabinoid
system in an intact model of epilepsy
Slide37Systematic 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, PhD, Sarah Youssof, MD, Gary Gronseth, MD, FAAN and David Gloss, MD
Slide38Spasticity in patients with MS
Central pain and painful spasms in MSBladder dysfunction in MSInvoluntary movements, including tremor, in MSDyskinesias of Huntington disease, levodopa induced dyskinesias in PD, cervical dystonia, and tics of Tourette syndromeSeizure frequency in epilepsy
Slide39Analytic Process
Searched Medline, EMBASE, PsychINFO, Web of Science, and Scopus1,729 abstractsSurveys, case reports/series, non placebo-controlled trials were excludedReviewed the full text of 63 articles33 articles met inclusion criteria
Slide40Do cannabinoids decrease seizure frequency?
No Class I-III studies2 Class IV studies that did not demonstrate a significant benefit and did not show adverse effects over 3-18 weeks of treatmentConclusion: “data is insufficient to supports or refute the efficacy of cannabinoids for reducing frequency”
Slide41The 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
Slide42There 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.
Slide43American 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.”
Slide44American 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.”
Slide45The 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.
Slide46Marijuana Resource Center: State Laws Related to
MarijuanaSince 1996, 20 states and Washington, DC have passed laws allowing smoked marijuana to be used for a variety of medical conditions. It is important to recognize that these state marijuana laws do not change the fact that using marijuana continues to be an offense under Federal law. Nor do these state laws change the criteria or process for FDA approval of safe and effective medications.“www.whitehouse.gov”
Slide47Slide48Marijuana: Class I Scheduled Drug
Slide49Medical 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 22nd 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
Slide50Compassionate Care Act (07/2014)
Allows doctors to prescribe nonsmokable forms of marijuana23rd state to permit the use of medical marijuanaSigned by Andrew Cuomo
Slide51New York State Medical Marijuana Program
The Medical Marijuana Program will make medical marijuana accessible to patients with conditions including cancer, HIV/AIDS, Lou Gehrig's disease (ALS), Parkinson's disease, multiple sclerosis, damage to the nervous tissue of the spinal cord with objective neurological indication of intractable spasticity, epilepsy, inflammatory bowel disease, neuropathies and Huntington's disease. The law includes these conditions when there is a clinical association with or complication of the condition resulting in cachexia or wasting syndrome, severe or chronic pain, severe nausea, seizures; or severe or persistent muscle spasms. Acting State Health Commissioner Dr. Howard Zucker is also exploring mechanisms that may accelerate access to medical marijuana for children suffering from epilepsy. The Health Commissioner may expand the list of eligible conditions for which medical marijuana certifications may be issued by practitioners.
http://
www.health.ny.gov/regulations/medical_marijuana
/
Slide52NJ Senate Bill 2842
Prohibits limitations on number of strains of medical marijuana cultivated, and expands available means of packaging and distribution thereof.**Approved September 10th 2013
Slide53N.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-not-yet-sold.html?_r=0
Slide54Slide5523 Legal Medical Marijuana States and DC
AlaskaArizonaCalifornia
Colorado
Connecticut
DC
Delaware
Hawaii
Illinois
(2013)
Maine
Maryland (2014)
Massachusettes
Michigan
Minnesota
(2014)
Montana
Nevada
New Hampshire
(2013)
New Jersey (2010)
New York (2014)
New Mexico
Rhode Island
Vermont
Washington
Oregon
Slide56Slide57Slide58Slide591969 – Gallop Poll : 12% of Americans favored marijuana legalization
2012 – 2013 support for legalization grew 10 %
Slide60Slide61Slide62Slide63Is Marijuana Addictive?
Slide64Slide65Slide66Is Marijuana Addictive?
Columbia’s Marijuana Research LaboratoryMargaret Haney, PhD1999 – Chronic marijuana usersAlternating course of active marijuana versus placebo (21 days)Monitored behavior on closed circuit TVMonitored Sleep patterns, food intake, shift in moodsDisturbances in sleepMood DisturbancesChange in appetite
Criterion 2 – withdrawal symptoms
Slide67Slide68Is Marijuana Addictive?
Abstinence??? Chronic Users: 15 - 37% are able to maintain abstinence (cocaine)Physical Withdrawal Symptoms (i.e., insomnia, suppressed appetite, etc)Psychological Withdrawal Symptoms (i.e., anxiety, craving)Drives relapseThe withdrawal symptoms from marijuana play a role in the inability to maintain abstinenceCriterion 4 – unsuccessful efforts to cut down
Slide69Is Marijuana Addictive?
Alcohol – get into fights; criminal activity, blackouts, seizures, overdoseHeroin – overdose; get hepatitis or HIVCrack – seizure or heart attackCrystal Meth – psychoticMarijuana – disorder about the absence of thingsUnmotivatedCognitively slowerCriterion 6 – importance of activities reduced
Slide70Is Marijuana Addictive?
Is Marijuana Addictive: Yes/No/ProbablyMost people using marijuana probably don’t experience significant problemsBut there is a subset of people who doAmerican Psychiatric Association – “ “cannabis use disorder” includes standard addiction signs like a failure to fulfill major roles at work, school, or home; important activities ….. are reduced or given up and afflicts 9% of pot smokers.”
Slide71Adolescents and Marijuana
Opinions versus TrendsAs the majority of Americans see marijuana as less risky, the use of marijuana increasesNot every user is harmed, but harm from Marijuana does occur.
Slide72Slide73Adolescents and Marijuana
Clinical EEG and Neuroscience“use of marijuana during the teen years negatively impacted : brain structure volume, quality of white matter, and ability to perform cognitive function.”
Slide74Slide75Center for Injury Epidemiology and Prevention
Alcohol: 13 fold increase risk of a MVAMarijuana: doubles the risk of a MVAMarijuana + Alcohol: 24 fold risk of a MVAFrom 1999 – 2010 involvement in traffic fatalities: Alcohol: stable at 40%Marijuana: tripled from 4-12%
Slide76Risks and Benefits
Slide77Are We At A Place of No Return?
More usersPotentially more treatmentsPotentially more help for people who really need itPotentially more addictsPotentially more cognitive dysfunctionPROGNOSISMore questionsMore Research
Slide78INTERMEDIATE SIZE PATIENT IND
PROTOCOL TITLE: An Open Label Prospective Study of Cannabidiol as an Adjunctive
Treatment for Drug Resistant Epilepsy in the Pediatric Population
PRINCIPAL INVESTIGATOR:
Evan Fertig, MD
Northeast Regional Epilepsy Group
20 Prospect Avenue, Suite 800
Hackensack, NJ 07601
(201)343-6676
Slide79PROTOCOL TITLE:
A Prospective Observational Study of the Cognitive and Behavioral Effects of Medical Marijuana as Adjunctive Therapy in Adult Patients with Drug-Resistant EpilepsyPRINCIPAL INVESTIGATOR: Evan Fertig, MDNortheast Regional Epilepsy Group
20 Prospect Avenue, Suite 800
Hackensack, NJ 07601
(201)343-6676
Slide80www.mpp.org/states/
new-york/
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