Scott Perry, M.D., the Director of Neurology at Cook Children’s, has participated in multiple international studies, examining the effectiveness and safety of a nearly-pure CBD oil for treating patients with epilepsy. While the internet is full of testimonials for the effective use of CBD for other conditions, epilepsy remains one of the only disorders with strong data to support the benefit of CBD for medical treatment. He points out that lack of data does not mean CBD cannot be effective in other conditions, it simply means the research is not there yet to tell us how effective the drug may be, what doses might be needed, how it interacts with other drugs used in the condition, the safety of the drug used in specific patients, etc.

So as a scientist and physician, it’s difficult to blame him for being a little concerned at the number of medicinal CBD oil stores popping up around the area.

Dr. Perry has seen success in treating children with severe forms of epilepsy during the clinical trials he has overseen. But as far as day-to-day use such as treating anxiety or chronic pain, he says not enough research has been performed. He’s especially concerned about the use of CBD in children for common ailments and he says more and more Cook Children’s pediatricians are being asked about its use daily.

The trials Dr. Perry conducted used a form of CBD oil produced under strict guidelines to ensure the purity of the product – no different from how any FDA-approved pharmaceutical would be produced. The studies were rigorously designed to provide the data necessary to show the drug works and is safe to use. The studies are blinded and placebo-controlled which means neither the doctor nor the patient knows whether they are getting the real drug or a placebo during the study. This helps remove bias (people feeling like their seizures are better because they know they are taking the real drug). It also helps separate which side effects are due to the drug and which occur randomly in the course of life (for example fevers, rash, nausea which can occur commonly regardless).

While the studies showed CBD helped reduce seizures, the number of patients who became seizure free was small. Likewise, the drug was well tolerated, but not without side effects. In fact, the studies revealed that some patients taking CBD oil could get significant elevation of their liver enzymes which needs to be monitored. Without these studies, commenting on the safety and effectiveness of CBD for epilepsy would largely be a guessing game. The same now holds true for other conditions – recommending CBD oils for other ailments is still largely a guessing game, based on small reports or testimonials, but without the support needed to make an informed medical decision.

Dr. Perry points out that it is important to understand the CBD oil tested in these studies is but one version of CBD oil and the data cannot be applied to every other CBD oil. There are thousands of CBD oils being sold these days and all may be made in different ways, contain various amounts of CBD, have varied levels of purity, and may contain substances other than CBD where the safety and efficacy is even more unknown.

“When you walk into a CBD store, you don’t know exactly what you’re getting because it’s not regulated or monitored,” Dr. Perry said “I worry they haven’t been studied or proven effective, certainly not in most pediatric cases, for use. Many of the conditions that CBD is being used for have subjective symptoms, so assessing response is very difficult. Even when a store provides a lab analysis of the CBD oil they provide you, there is no regulation or true oversight to ensure the report is accurate. This is not to say that CBD retailers are trying to make a quick buck, it just means there are shortcomings to the products that must be taken into account.”

When people are treated with typical antiepileptic drugs, they are taking a single compound, like carbamazepine or levetiracetam for example. But when you get a CBD oil in a store, you get a substance that may have a high amount of CBD, but it also can contain varied amounts of the multiple other compounds from the plant.

“We don’t know how effective and safe those other compounds are, so we must be cautious to recommend it to treat a child,” Dr. Perry said “Currently, there are no testing standards to make sure the CBD oil you get from a company contains what the label says, thus the formulation may change some from month to month.”

While all CBD oils contain the similar CBD compound, they may be produced from different types of plant, using different growing techniques/conditions, and manufactured with different processes, creating different medications with different other compounds included.

Dr. Perry said it’s not that doctors are necessarily against using CBD oils, “we just have to be realistic about their limitations.”

Another concern is that many children for whom CBD oil might be tried are on other medications and “we don’t know enough to know how it might interact with those medicines or oils.”

“Cannabis and CBD have a long history of use for medical purposes,” Dr. Perry said. “But until recently, standardized studies gathering large amounts of data have been lacking. Now, with the change in social climate and attitude toward the potential of cannabis and CBD, we are gaining that data in the practical use of CBD in patients with seizures and epilepsy. But as far as general use in conditions such as anxiety or insomnia, I don’t believe we have enough research yet. Without more research and actual studies, we don’t know proper doses or side effects.”

For now if you are thinking about using CBD or allowing your child to use it, Dr. Perry asks parents to please talk to their pediatrician first.

Greenwich Biosciences (GW Pharma) received the approval for Epidiolex, an oil-based purified cannabidiol (CBD), studied specifically in two rare epilepsy syndromes - Lennox Gastaut and Dravet Syndrome.

Cook Children’s participated in several of GW Pharmaceutical’s clinical trials of Epidiolex used to treat children over the age of 2 with Lennox Gastaut and Dravet and continues to enroll children in a trial of the drug for treatment of seizures in Tuberous Sclerosis Syndrome.

The trials were the largest of their kind in the world and have provided the gold-standard evidence needed to prove cannabidiol can be effective as a treatment for epilepsy,” said M. Scott Perry MD, Medical Director of Neurology and principle investigator for the trials performed at Cook Children’s.

The Drug Enforcement Agency (DEA) now has 90 days to schedule epidiolex and it is expected to be available to the public by fall 2018.

Dr. Perry said with the FDA’s approval there now is a standardized, reliable, safe and effective form of CBD oil available for people with epilepsy.

“It means the door is opening for more treatments from the cannabis plant, not just for epilepsy,” Dr. Perry said. “The company (GW Pharma) has shown how quality research, using cannabis can be done safely, scientifically and legally to achieve a result that will prove beneficial to many.”

Dr. Perry explains that Epidiolex is an essentially pure CBD substance produced under strict standards to ensure the drug is the same with every batch. With its approval, the drug will be obtained from a pharmacy, prescribed by a doctor and more likely to be covered by insurance.

Scott Gottlieb, M.D., Commissioner of Food and Drugs, said the FDA will continue to support rigorous scientific research on the potential medical uses of “marijuana-derived product and work with product developers who are in interested in bringing patients safe and effective, high quality products.”

"This approval serves as a reminder that advancing sound development programs that properly evaluate active ingredients contained in marijuana can lead to important medical therapies,” Dr. Gottlieb said.

Previous Articles On This Topic:

• 9 Facts about Cannabidiol (CBD) Oild and The Texas Compassionate Use Act
• Texas legalizes non-euphoric cannabdiol for seizures in epileptic patients
• Success in CBD study: Cook Children's researchers play a vital role
• Cannabis oil trial ongoing at Cook Children's
• Study: Cannabis Oil Can Dramatically Decrease Epileptic Seizures

The bill required DPS to license at least three dispensing organizations by Sept. 1, 2017, should they meet requirements.

On Feb. 8, 2018, the first medical dispensary in the state of Texas will open.

What does all of this mean for children with epilepsy?

1. What is it in the cannabis plant that helps treat epilepsy?

The truth is we don’t yet really know. There are over 500 chemical compounds in the cannabis plant and over 100 of them are plant-based cannabinoids (phytocannabinoids) which may interact with the endocannabinoid system of the human body and treat disease. Cannabidiol (CBD) is a non-psychoactive component (i.e. does not produce a “high” feeling) and has been most widely studied so far for epilepsy. It does not interact with either of the two known cannabinoid receptors in the brain and its mechanism is still unclear. Tetrahydrocannabidiol (THC) is the component in the plant that produces a high and does interact with the cannabinoid receptors, but for many reasons, is not likely to be a good choice as an antiepileptic compound.

2. What is CBD oil and what types of CBD oil are now legal in Texas?

A CBD oil is an oil made from a cannabis plant that is high in CBD and typically lower in THC. The oil may contain amounts of multiple other compounds found in the plant as well. The 2015 Texas Compassionate Use Act allows for “high” CBD (more than 10 percent by weight)/”low” THC ( less than 0.5 percent by weight). This is slightly higher than the amount of THC (less than 0.3 percent) allowed in a plant to be considered hemp. Hemp oils are produced from these lower THC plants and are often a poor source of CBD but have been legal and widely available.

3. People on the Internet already say CBD oil works, so why aren’t all doctors OK with using it over typical medications prescribed for seizures?

All FDA approved antiepileptic medications have gone through rigorous studies to prove they work and they are safe to use. The studies are blinded and placebo-controlled which means neither the doctor nor the patient knows whether they are getting the real drug or a placebo until the study is complete. This helps remove bias (i.e. people feeling like their seizures are better because they know they are taking the real drug). It also helps separate which side effects are due to the drug and which occur randomly in the course of life (for example fevers, rash, nausea which can occur commonly regardless). CBD has only recently been tested in this type of rigorous study – more on this later – and the other components of the plant lack this type of research so far.

4. If CBD has already been studied, why are some doctors still hesitant to recommend CBD oil?

When people are treated with typical antiepileptic drugs, they are taking a single compound, like carbamazepine or levetiracetam for example. When you get a CBD oil, you get a substance that may have a high amount of CBD, but it also can contain varied amounts of the multiple other compounds from the plant. We do not know how effective and safe those other compounds are, so we must be cautious to recommend it to treat your child. Currently, there are no testing standards to make sure the CBD oil you get from a company contains what the label says, thus the formulation may change some from month to month – something akin to getting a different generic antiepileptic medication each month. While all CBD oils contain the similar CBD compound, they may be produced from different types of plant, using different growing techniques/conditions, and manufactured with different processes – thus creating different medications with different other compounds included. Think of it as being prescribed a sodium-channel drug like carbamazepine, but potentially getting one of multiple other sodium channel drugs such as oxcarbazepine, phenytoin, rufinamide, lamotrigine, etc. So doctors aren’t necessarily averse to CBD oils, we just have to be realistic about their limitations.

5.What did the studies of CBD show?

First, understand that the Greenwich Biosciences CBD compound Epidiolex is not the same as the CBD oil you get from a dispensary. It is a nearly pure CBD substance produced under strict standards to ensure the drug is the same with every batch. In 120 patients with Dravet syndrome, 43 percent on CBD had more than 50 percent reduction of convulsive seizures versus 27 percent on placebo. This was actually not a statistically significant difference. In 171 patients with Lennox-Gastaut syndrome, 44 percent on CBD had more than 50 percent reduction of drop seizures versus 23.5 percent on placebo and this was significant. From these results we can conclude that CBD does appear to have some antiseizure effect, but it is not necessarily any better than most other available drugs. It is also not without side effect, as diarrhea (19%), sleepiness (15%), fever (13%), decreased appetite (13%), and vomiting (11%) were reported. So CBD is an option for epilepsy treatment, but is not likely to cure every patient.

6. How does the Texas Compassionate Use Act work?

Under this law, doctors can register to recommend CBD oils only to patients with intractable epilepsy. To register, a doctor must be board certified in Neurology or Child Neurology and must also be certified in Epilepsy/Neurophysiology or spend more than 50 percent of their practice treating patients with epilepsy. If a registered doctor feels CBD oil is appropriate for their patient because the patient has tried all reasonable, better-studied and available treatment alternatives, the doctor can recommend an amount of CBD to be taken. This recommendation must be approved by a second registered doctor who reviews the case and agrees with the decision. Registered patients can then go to one of three dispensaries in the state to get a CBD oil.

7 .Will the CBD oil be covered by insurance?

No. As this is not an FDA approved treatment, it is unlikely any insurance company will cover the cost. The price is typically several hundred dollars per month depending on the amount of CBD recommended.

8. Now that we have this law, it is legal right?

The cannabis plant and all the components of the plant remain a schedule 1 substance on the Drug Enforcement Agency’s list- meaning it has no medicinal value and is illegal. CBD is part of the plant and still falls under this category for federal law despite what a state law may say. While the 2013 directive from the Department of Justice indicated they had better things to do than prosecute people following the laws of their state, Jeff Sessions reversed this opinion several weeks ago – thus it is unclear how the federal government will choose to deal with CBD oils now.

9. When will a pharmaceutical grade CBD oil be available?

Greenwich Biosciences has submitted their drug, Epidiolex, to the FDA for approval December 2017. While the FDA could take years to rule, they have indicated their plan is to rule on approval by summer 2018. Once approved, this drug would be obtained from a pharmacy, prescribed by a doctor, and more likely to be covered by insurance.

Previously on this topic:

• Texas legalizes non-euphoric cannabdiol for seizures in epileptic patients
• Drug in Cook Children's epilepsy trial shows positive results in separate trial
• Success in CBD study: Cook Children's researchers play a vital role
• Cannabis oil trial ongoing at Cook Children's
• Study: Cannabis Oil Can Dramatically Decrease Epileptic Seizures