Medical Marijuana at Forefront in Drug-Resistant Epilepsy  News Author: Sue HughesStudy of Dr Friedman and his coauthor, Orrin Devinsky, MD

Epilepsy

Defined as recurrent and ongoing seizures caused by changes in neuronal firing in the brain.

synchronized excitation of large groups of brain cells.

Pharmacotherapy aims to restore normal neuronal function and decreases seizure frequency.

History

Earliest: 2,700 bc in China for variety of medical ailments, including gout, malaria, constipation, menstrual disorders and absentmindness.

Western medicine in 19th century: Analgesic It was available as an OTC in US until the

1937 Marijuana Tax Act. Passed the Controlled substances Act in 1970

as Schedule I classification.

Clinical context

Estimated 30% of people with epilepsy continue to have seizures.

Adverse central nervous system effects of antiepileptic agents may affect quality of life.

Study synopsis and perspective

The rise of medical marijuana as a treatment for epilepsy is due to sharing of personal stories on the Internet and social media.

The idea that marijuana may be useful for epilepsy has been around for centuries.

It is of the utmost importance that the double-blind, randomized studies now underway are completed.

Why marijuana is being studied and legalized?

This has come about because individuals have shared anecdotal experiences about its effectiveness in children with severe intractable epilepsy on the Internet and these have spread across the globe.

"The use of medical cannabis for the treatment of epilepsy could go the way of vitamin and nutritional supplements, for which the science never caught up to the hype and was drowned out by unverified claims, sensational testimonials, and clever marketing,"

Two cannabinoid pharmaceutical products are under study in randomized trials:-Purified cannabis extract containing 99% cannabidiol (the constituent believed to have the antiseizure effect).-a synthetic cannabinoid of less than 0.10% tetrahydrocannabinol (the psychoactive component).

Cannabis contains two main component

1. Delta-9-tetrahydrocannabinol (THC)-the psychoactive portion of marijuana-Partial agonist at cannabinoid type 1 receptors in the hippocampus and amygdala.

2. Cannabidiol (CBD)-Nonpsychoactive portion-has gained interest as possible agent for epileps.y-Recent trials have shown more consistent anticonvulsant properties.-Common route: Inhalation

Dr Friedman and Dr Devinsky are both involved in a double-blind, phase 2/3 trial with the purified cannabinoid product in children with Dravet syndrome-- from which initial results are expected within the next year.

“There is emerging evidence on efficacy. The preclinical evidence is reasonably strong for cannabidiol” -The clinical data are still early. So far the studies have been small and methodologically flawed, but results are encouraging.-A recent study showed that 40% of patients with severe epilepsy refractory to therapy had a 50% reduction in seizures with cannabinoid pure extract.

Difficulties:

regulatory issues issue of public perception high expectations

Dr Friedman said he does not disagree with the legalization per se. "Families with children with severe drug-resistant epilepsy are looking for options and I don't oppose them trying medical marijuana under the care of a physician, but they need counseling that there is not a good level of scientific evidence yet."

Variability in regulation

In some states there is a high degree of regulation with external testing of products to verify the cannabidiol/THC [tetrahydrocannabinol] content.

In other states, it is left to the individual dispensaries to stipulate the content and there is no external validation.

Other products derived from hemp are legally available on the Internet.

Recommendations:

If there are no exhausted proven effective therapies, they pursue agents that are known to work and have a well-understood benefit/risk profile.

But for patients who have exhausted such therapeutic options and can access cannabinoids, have a discussion with your physician about such approach.

Medical marijuana is now available in 23 US states and patients can now avail them from the internet.

Only double-blind, placebo-controlled, randomized clinical trials in which consistent preparations of one or more cannabinoids are used can provide reliable information on safety and efficacy.

Study highlights

Preclinical evidence and preliminary data from human studies suggest that cannabidiol and Δ9-THC may be effective in the treatment of some patients with epilepsy.

No conclusions can be drawn.

In the preliminary results of an open-label study of the use of cannabidiol oral solution for severe, refractory, childhood-onset epilepsy, the most common adverse effects were: 1. somnolence (21%)2. diarrhea (17%)3. fatigue (17%)4. reduced appetite (16%)

High levels of Δ9-THC are linked to:1. Psychosis2. Increased risk for motor vehicle crashes3. Addiction in approximately 9% of long-term

users.Little is known about the effects of fetal exposure to cannabinoids.

Members of the healthcare team should be aware that cannabis-based treatment with Δ9-THC may have:

1. irreversible effects on brain development2. long-term use of cannabis in childhood may

be associated with lower-than-expected IQ scores.

Study highlights:

Some positive anecdotal reports and legalization of medical cannabis in many states do not obviate the need for double-blind, placebo-controlled, randomized clinical trials.

Only such trials using consistent preparations of 1 or more cannabinoids can provide reliable information on safety and efficacy.

A case-control study of illicit drug use and new-onset seizures in Harlem, New York, showed that men who used cannabis within 90 days before hospital admission had a significantly lower risk of presenting with new-onset seizures than men who did not use cannabis (odds ratio, 0.36; 95% confidence interval, 0.18-0.74).

Surveys of caregivers suggest that children given cannabinoids for epilepsy have a lower frequency of seizures, but electroencephalograms obtained before and after cannabis administration did not show improvement in background activity.

Case reports and surveys have shown conflicting effects of cannabinoids on seizure control.

2 studies showed a reduction in the number of seizures in patients treated with cannabidiol, whereas the other 2 studies showed no effect.

A preliminary report from this open-label study showed a median reduction in the number of seizures of 54%, after 12 weeks of treatment

Conclusion

Insufficient evidence regarding the efficacy as an antiepileptic agent.

Limited clinical studies and were inadequately powered, lacked complete information and used small sample sizes.

Cannot be determined at this time, more large scale studies are needed.