March 11, 2016
Representative Matthew Baker and the Pennsylvania Legislature
213 Ryan Office Building
PO Box 202068
Harrisburg, PA 17120-2068
Dear Representative Baker,
On behalf of the American Epilepsy Society I am writing in opposition to Pennsylvania SB-3 and toshare the position of our organization and highlight some of the experience of our members in otherstates, especially those in Colorado who have seen the most epilepsy CBD cases in the U.S. We
applaud your measured approach and for giving this issue thoughtful consideration.
The American Epilepsy Society is the leading U.S. organization of clinical and research professionals
specializing in the diagnosis and treatment of people with epilepsy, with more than 3,800 members
engaged in all aspects of epilepsy. For nearly 85 years, the members of the American Epilepsy Society
have led nearly every medical and scientific advance in epilepsy. Each year, the American Epilepsy
Society hosts a scientific meeting on epilepsy more than 1,500 scientific studies are presented,
making this the world’s largest and most respected epilepsy meeting. This year’s meeting inPhiladelphia attracted over 5000 attendees from around the world.
Epilepsy is the most common and potentially devastating neurological disease that affects people
across the lifespan. In America, one in 26 people will be diagnosed with epilepsy at some time in thecourse of their life - more will experience an isolated seizure. Epilepsy is associated with significant
morbidity and mortality and carries an increased risk of many co-morbidities including depression,cognitive dysfunction, and autism. Today between 2.2 and 3 million Americans, including almost
400,000 children, live with epilepsy, with one third living with treatment-resistant seizures that do
not respond to current medications. The large number of treatment resistant cases emphasizes theurgency of bringing forth new treatments for epilepsy, but those treatments must be proven safe andeffective in order to be truly helpful to people with epilepsy.
Despite the pressure of anecdotal evidence prevalent in the popular press and social media, for thepast two years the American Epilepsy Society has been opposed to the expanded use of medical
marijuana and its derivative, cannabidiol or CBD, in the treatment of children with severe epilepsy. At
this time there is no evidence from controlled trials that strongly supports the use of marijuana fortreatment of epilepsy. Our position is informed by the lack of available research and supported by
the position statements from the American Academy of Neurology, the American Academy ofPediatrics, and the American Medical Association.
The American Epilepsy Society has consistently advised states against acting on anecdotal evidence
alone and has called for more research. The need for more research is a consistent theme from nearly
every medical society in the U.S. To help advance research, the American Epilepsy Society hasrequested that the Federal Drug Enforcement Agency reschedule marijuana to ease access for clinicalstudies.

The well intentioned law makers who have enacted laws in many states have done so without the benefit of any
scientific evidence for people with epilepsy. This has created an uneasy situation where the laws are ahead of thescience because we do not understand how and why various treatments work and for whom they are effective.
Research also helps us understand the correct dose, side effects, and potential interactions with other medications.
At present, the epilepsy community does not know if marijuana is a safe and effective treatment nor do we know thelong-term effects that marijuana will have on learning, memory and behavior, especially in infants and young
children.
AES has consistently been supportive of the compassionate use program of GW Pharmaceuticals, where a purified
and uniform preparation of cannabidiol (CBD) called Epidiolex is being administered under the guidance and closemonitoring of an appropriate medical professional.
The lead investigator for this clinical trial, AES member Dr. Orrin Devinsky, released results of a phase II study during
the December 2015 Annual Meeting of the American Epilepsy Society held in Philadelphia. While Dr. Devinsky called
the findings promising, he cautioned that “these results are from an uncontrolled study. Further study is needed
before results can be confirmed. Randomized controlled studies are now underway to help us better understand theeffectiveness of the drug.” The results of this phase II study have just been published in Lancet Neurology in theMarch 2016 issue.
Phase III of this study is now beginning and this is a placebo controlled study. AES supports this critical step to help
our whole community better understand the potential role of CBD in treatment of epilepsy. It is also important tonote that in these studies Epidiolex was added to current antiepileptic drug (AED) treatment regimes.
A pharmaceutical grade marijuana extract of purified cannabidiol, Epidiolex is being rigorously tested in several types
of epilepsy in FDA authorized trials that are ongoing at dozens of US epilepsy centers. Many have already been
completed or at least finished enrollment. Because the trials enrolled so quickly it is possible that an FDA approved
product could be on the market sometime in 2017. Once an FDA approved product is on the market and available topeople with epilepsy throughout the US, there is much less urgency for individual states to pass complex legislation
about regulation and distribution of medical marijuana.
It is also a very important distinction that the CBD oil Epidiolex used in the clinical trials is a vastly different substancethan the artisanal cannabis products that are being considered for use in Pennsylvania, and are being used in otherstates like Colorado. In states like Colorado where medical marijuana and its derivatives are legal the content of theseproducts is not regulated for purity or uniformity. Pharmacy-grade products like Epidiolex have followed Good
Manufacturing Processes, meaning that the CBD content is measured by rigorous standards, that it is carefully
monitored for additives or contaminants and that even the equipment used for manufacturing meets rigorousstandards. None of this is true for the artisanal products.
The artisanal products currently provided in Colorado do not meet the FDA definition of expanded or compassionate
use. The FDA requires compassionate use therapies to meet the same criteria as an investigational new drug which
require standard purity, content and content uniformity testing of the product and adherence to good manufacturing
processes. None of these criteria are met in the products being given to people with epilepsy in Colorado and we areseeing the distressing results noted below. And yet, these and other similar products are being considered for use in
several states.
An observational study by a team from Children’s Hospital Colorado that was published in the April 2015 issue of thejournal Epilepsy & Behavior found that artisanal “high CBD” oils resulted in no significant reduction in seizures in themajority of patients and in those for whom the parents reported improvements, these improvements were notassociated with improvement in electroencephalograms (EEGs), the gold standard monitoring test for people withepilepsy.
Additionally, in 13% of cases reviewed seizures worsened with use of cannabis and in some patients there weresignificant adverse events. These are not the stories that you have likely heard in your public hearings or have read in
popular press, but they are the reality of AES members who are practitioners at Children’s Hospital Colorado who
have cared for the largest number of cases of children with epilepsy treated with cannabis in the U.S.

Unlike the product used in the GW Pharmaceutical study, the families and children moving to Colorado are receiving
unregulated, highly variable artisanal preparations of cannabis oil prescribed, in most cases, by physicians with notraining in pediatrics, neurology or epilepsy. As a result, the epilepsy specialists in Colorado have been at the bedside ofchildren having severe dystonic reactions and other movement disorders, developmental regression, intractable
vomiting and worsening seizures that can be so severe they have to put the child into a coma to get the seizures to stop.
Because these products are unregulated, it is impossible to know if these dangerous adverse reactions are due to theCBD or because of contaminants found in these artisanal preparations. The Colorado team has also seen families who
have gone into significant debt, paying hundreds of dollars a month for oils that do not appear to work for the vast
majority. For all these reasons not a single pediatric neurologist in Colorado recommends the use of artisanal cannabis
preparations. Possibly of most concern is that some families are now opting out of proven treatments, such as surgery
or the ketogenic diet, or newer antiseizure medications because they have put all their hope in CBD oils.
Epilepsy specialists in Colorado are now conducting a state-funded observational study to monitor children with CBD.
The study is going to consist of analyzing the results from 150 medical marijuana patients who consume cannabis
products regularly. This is just one of many studies now underway with CBD for people with epilepsy. There is greatinterest within the professional community to explore the potential of CBD but the research needs to be conducted
before new laws are enacted.
It is also worth noting that in February 2016 and February 2015, the FDA issued several warning letters to firms thatclaim their products contain CBD. The FDA has tested those products and, in some of them, did not detect any CBD as
claimed on the label. Because there is no standard for these products, the market is increasingly flooded with a wide
variety of products. Should Pennsylvania approve access to these preparations it will bear the burden of monitoring for
quality and controlling for the continuity of supply. This requires a level of new administrative oversight and theassociated budget impact.
The well-intentioned law makers in the states that have passed CBD laws are now coming to grips with the substantial
financial and administrative burdens of developing, maintain and running a CBD access program. In reality, theseprograms could be abandoned as quickly as they are established should an FDA approved drug be available within thenext 18-24 months.
The American Epilepsy Society is very sympathetic to the desperation of parents whose children have severe, treatmentresistant epilepsy. Our members, face these families daily at the clinic and at their bedside and are highly attuned to theneed for compassionate use of promising new therapies in appropriate and controlled circumstances. We are however,
opposed to the use of artisanal preparations of unregulated compounds of cannabis that contain unverified content andare produced by people with no experience in pharmaceutical production. That is what is currently happening in
Colorado and other states across the county as they legalize the use of medical marijuana products.
In sum, there simply is no clinical, controlled research to support the adoption of new CBD legislation for epilepsy suchas your state is considering. The anecdotal results of a few families in Colorado, shared in the media, should not be thebasis for law making.
The rush by states to pass CBD legislation has created an unusual situation where people with epilepsy and their families
are demanding access to a highly variable homegrown substance that may or may not be beneficial and the medical andscientific community lacks the necessary efficacy and safety data to make good treatment decisions regarding cannabis
for people with epilepsy, especially in children. It has also created a heavy financial and administrative burden on states.
Don’t let Pennsylvania move in this direction, vote no on SB-3.
Sincerely,

Michael D. Privitera, MD
President
American Epilepsy SocietyDirector, Epilepsy Center
University of Cincinnati Neuroscience Institute