Medical Marijuana May Help Treat Drug-Resistant Epilepsy
1. Medical Marijuana at
Forefront in Drug-Resistant
Epilepsy
News Author: Sue Hughes
Study of Dr Friedman and his coauthor, Orrin Devinsky, MD
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. "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,"
8. 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).
9. 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
10. 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.
11. “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.
13. 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."
14. 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.
15. 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.
16. 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.
17. 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.
18. 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%)
19. High levels of Δ9-THC are linked to:
1. Psychosis
2. Increased risk for motor vehicle crashes
3. Addiction in approximately 9% of long-term
users.
Little is known about the effects of fetal exposure to
cannabinoids.
20. Members of the healthcare team should be aware
that cannabis-based treatment with Δ9-THC may
have:
1. irreversible effects on brain development
2. long-term use of cannabis in childhood may be
associated with lower-than-expected IQ scores.
21. 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.
22. 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.
23. 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
24. 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.
Editor's Notes
30 million people worldwide.
characterized by recurrent sudden attacks of altered consciousness, convulsions, or other motor activity. A seizure is the synchronized excitation of large groups of brain cells.
The Marijuana Tax act limited its accessibility.
Controlled substances act in 1970- making it use illegal.
Since 1970, there has been increasing interested in the use of Marijuana for its possible antiepileptic properties.
-although they receive appropriate treatment and more than 20 different antiseizure drugs are available.
-The media have highlighted recent use of cannabis-based treatment of epilepsy, now that many states have legalized cannabis for the treatment of epilepsy and other medical conditions in children and adults.
-Two years ago the epilepsy community wasn't really seriously considering this as an option. But it has now really taken off.
-It was used medicinally in ancient China and by Victorian neurologists for seizures, but it has never been properly scientifically studied.
"Once it became 'out there,' families have been clamoring for access to the product and we have had to pay attention. That is why medical marijuana is being legalized and studies are finally being done."
Cannabis sativa- more psychotropic and stimulating effects.
Cannabis indica- causing more sedation.
-what makes cannabis an attractive agent for epilepsy its because of its cannabinoid type 1 receptors in the hippocampus and amygdala, both of which are associated with partial seizures.
-CBD interacts with other nonendocannabinoid signaling systems, reducing the psychotropic activity of THC while increasing tolerance.
Dravet syndrome- - a treatment-resistant form of childhood epilepsy
-The most recent study -- presented at this year's American Academy of Neurology meeting.
-"But this was an open study, so not as scientifically rigorous as we would like," Dr Friedman cautioned.
"There are regulatory issues because these are all schedule I compounds [that] have many restrictions, so clinical trials have too many additional layers of regulatory bureaucracy,"
-Then there is the issue of public perception: there is a disconnect between what we know about efficacy from scientific literature and what the public perceive the evidence to be. Many states have legalized medical marijuana for several conditions, including e- this could confound clinical trial results by leading to a very high placebo response.
pilepsy, so there is the perception that it has been proven to work, but this is not the case.
-
-so you can't be sure what you're getting," he said. "It's a bit like health supplements -- a product may say it contains 1000 units of vitamin C, but when tested, it often has nowhere near this amount in it."
-Internet and are touted as having a high cannabinoid content, "but a recent FDA [US Food and Drug Administration] analysis of some of these products found big discrepancies in this, and some contained no cannabinoids at all."
-those preparations should be approved and made readily available
but no conclusions can be drawn, because currently available data from human studies are extremely limited.
