Medical Cannabis and Epilepsy: PowerPoint Presentation, PPT - DocSlides

Medical Cannabis and Epilepsy:Talking to your doctor, Safety and Update on Clinical Trials

Lubov

Romantseva

, MD

Child Neurology and Epilepsy

Rush University Medical Center

Nov 12, 2016

Disclosures

I have no financial interest in any pharmaceutical company mentioned in this presentation

I will discuss non-FDA approved use of medical cannabis in epilepsy

I am involved in clinical trials for patients with epilepsy

Background on Cannabis

1 Cannabis plant= 100+ bioactive

phytocannabinoids

Most understood are: CBD and THC

CBD=

Cannabidiol

: likely responsible for most of anti-seizure and anti-pain(analgesia) effects

THC=Tetra-hydro-

cannabinol

: responsible for psychoactive “high” effect, ?anti-seizure effect

Each Strain of Cannabis has a DIFFERENT ratio of CBD:THC

Within one strain, each individual Cannabis plant has a unique ratio of CBD:THC depending on climate and growing conditions

Artisanal Cannabis preparations are like growing Tomatoes

Variable CBD: THC ratio from batch to batch

Truthful labeling?

Quality control?

Contaminated with pesticides? heavy metals?

Unregulated industry WITHOUT a common standard

Vulnerable patients and caregivers at risk for misinformation and fraud

Evidence for Efficacy-1

162 patients, 1-30 years old

2

0% Lennox-

Gastaut

, 20%

Dravet

, 60% other epilepsies

Open label study, safety and efficacy assessed

Epidiolex

: purified grown cannabis, high CBD: low THC

Doses used: 2 mg/kg/day to 25-50 mg/kg/day

Efficacy: mean 36% reduction in monthly motor seizure count, 4% became seizure-free

Common side effects: somnolence, diarrhea, low appetite

Severe side effects: 1 death(SUDEP), status

epilepticus

6%

Reference: Orrin

Devinsky

et al.

Lancet Neurology

2016;15: 270–278

Evidence for Efficacy-2

Epidiolex

study in Lennox-

Gastaut

patients

Double blind, placebo controlled (gold standard)

2-55 years old, 171 patients

Patients: median baseline DROP seizure rate was 74/month

Epidiolex

dose 20 mg/day, added to current meds

Response rate: median

drop seizure reduction

44% in CBD group

vs

22% in placebo group, p=0.0135

Safety profile similar to open-label study

CBD: Safety and Monitoring

Mortality: likely low, most deaths appear due to SUDEP or status

epilepticus

Behavior effects: variable, most are tolerable

Interaction with standard seizure drugs**

CBD

raises

CLOBAZAM(

Onfi

)

level by 60-500%: need to track

Clobazam

levels and adjust doses or risk toxicity

CBD also likely

raises

Valproic

acid(

Depakote

)

level

Bottom line: CBD interacts with several liver enzymes used in drug metabolism(CYP3A4, CYP2C19) which may result in unexpected effects

Reference: A

Geffrey

et al.

Epilepsia

2015;56:1246–1251

Safety: what is NOT known

Longterm

cognitive effects: learning, attention, organization, memory

Longterm

psychiatric effects: impulse control, risk of mood disturbance or psychosis, risk of future addiction to “hard drugs” or alcohol

Longterm

seizure-control rates

CBD-Drug interactions?

What seizure types/epilepsies worsen with CBD?

Future Clinical Trials

Epidiolex

(purified plant CBD) study in refractory Infantile Spasms population (GW pharmaceuticals)

Pilot study for Infantile Spasms to start in 2017

Synthetic CBD: toxicity and safety studies complete (

Insys

pharmaceuticals)

Lennox-

Gastaut

efficacy trial: on hold

Infantile Spasms trial out of UCLA

Tuberous sclerosis trial

Medical Cannabis and FDA

Epidiolex

makers met with FDA in summer 2016

Plan to submit New Drug Application(NDA) with

clinicial

trial data in first half of 2017

Epidiolex

makers seek FDA approval for treatment of

refractory

Dravet

syndrome

refractory Lennox-

Gastaut

syndrome

Timeline to FDA decision?

Future Clinical Trials

Website: www.clinicaltrials.gov

Search: “

cannabidiol

and epilepsy”

31 trials registered now, in 2014 there were 4

Conditions addressed: Lennox-

Gastaut

,

Dravet

, Infantile Spasms, Tuberous Sclerosis, other refractory epilepsies

This is the BEST time to get involved in a clinical trial and help bring CBD therapy out of the shadows

Legal status of Medical Marijuana

Federal level

Classified as Schedule I substance (no accepted medical use)

In same category as heroine and cocaine

State level: extremely variable

Legal for recreational and medical use

Legal for medical use only(specific conditions)

Not legal for any use

Medical Cannabis Law in Illinois

IL Medical Cannabis Act of 2013

Legal for medical use in specific medical conditions, including refractory epilepsy in children under 18

yo

compassionate use for patients who have FAILED standard medical treatment, last resort option

Specific procedures to be followed

Patient and caregiver must register with the state, receive a registration card, then can obtain LEGAL medical cannabis from one of IL dispensaries

Website:

www.illinois.gov

, links to

Medical Cannabis Pilot Program webpage

Medical Cannabis in Illinois

Physician CANNOT prescribe dose/frequency

Not licensed by FDA, no standard dose yet

Physician CAN

certify

that the patient has a qualifying medical condition under IL law

Certifying Physician needs to have a bona fide(pre-existing) relationship with the patient

If patient is a minor, 2 physicians need to certify

Medical Cannabis in Illinois

Certification by MD is NOT a guarantee of treatment success

Certification states that “benefits from medical cannabis MAY outweigh the risks” for a particular patient

Talking to your doctor about Medical Cannabis

Ultimately, physicians want to do what is best for their patients

Safety is a huge concern: “first do no harm” is a basis of physician practice philosophy

Reasons for Provider hesitation:

Lack of knowledge of

longterm

safety/side effects

Inability to prescribe a specific dose

Lack of FDA approval

U

ncertain legal status/risk of litigation, loss of license

Lack of hospital policies regarding medical cannabis*

Talking to your doctor about medical cannabis

Be honest and direct

Find out your doctor’s comfort level and knowledge base

Remember: most MD’s have no formal training on the subject and are learning as we go

Discuss all other options, share what you know

Make a joint plan about other medications

Change only one thing at a time

Keep communication lines open

CBD in National Epilepsy News:The Latest from Child Neurology Society meeting-October 2016

Senior Child Neurologist Dr Elizabeth Thiele from Mass General hospital in Boston sums up the progress made

Video clip on Neurology Advisor website

http://www.neurologyadvisor.com/cns-2016-coverage/video-cannabidiol-and-our-progress-towards-a-treatment-for-refractory-epilepsy/article/569490/

Summary Points-1

Medical cannabis has some efficacy in treating refractory epilepsies in children and adults

Cannabis is a complex plant and its

longterm

effects on brain and body

are not yet known

Medical Cannabis has a

sensitive legal status

, with Federal and State regulations at odds with each other

Medical cannabis is NOT FDA approved at this point, but may become so in next 2 years

Summary points-2

Option of Medical Cannabis should be discussed openly and directly with the treating provider

Clobazam

and

Valproic

acid levels

need to be monitored if CBD is added to treatment regimen

FIRST, DO NO HARM

Knowledge is POWER=JOIN a Clinical trial

Thank you!

Questions?