Cannabidiol Medicine May Help Patients with Epilepsy Who Don’t Benefit from Standard Medications, Research Suggests

 

Cannabidiol Medicine May Help Patients with Epilepsy Who Don’t Benefit from Standard Medications, Research Suggests

HOUSTON – An oral formulation of Cannabidiol – or CBD, a purified molecule from the
cannabis plant that doesn't cause a "high" – may reduce the frequency of seizures in children
and adults with forms of epilepsy that are difficult to treat, suggest results of randomized,
double-blind, placebo-controlled trials being presented at the American Epilepsy Society 70th
Annual Meeting.

CBD also may reduce seizure severity in patients with treatment-resistant epilepsy no matter
the cause, suggest findings of an early open-label study also being presented at the meeting.
The CBD medicine is dispensed in the mouth two times a day and can be taken with or
without food. It is a purified and carefully manufactured product that has not been approved
by the Food and Drug Administration (FDA) and is not available at dispensaries, even in states
where medical marijuana is legal.

"For many children with treatment-resistant Dravet syndrome, Lennox-Gastaut syndrome and
other epilepsies, CBD appears to be an effective – sometimes extremely effective – treatment
that is safe and well-tolerated overall," said Elizabeth A. Thiele, M.D. Ph.D., a study author,
director of the Pediatric Epilepsy Program at Massachusetts General Hospital, Boston, and
professor of neurology at Harvard Medical School. "It is not a silver bullet, but there are
children who benefit from this more than they have from other treatments."
The findings suggest CBD may provide hope for patients at risk for catastrophic problems such
as intellectual disability due to uncontrolled seizures and who don't benefit from standard
anti-epileptic drugs (AEDs), she said.

Randomized trials show CBD may reduces seizures in those with challenging forms of
epilepsy

Researchers presented randomized controlled trial results of patients with forms of epilepsy
that are difficult-to-treat: Dravet syndrome, a rare genetic disorder that causes severe
seizures in infants, and Lennox-Gastaut syndrome (LGS), responsible for 2 to 5 percent of
childhood seizures and which causes various types of seizures. Both forms are difficult to
treat, and seizures may persist for many years.
In both studies, the treatment group received 20 mg/kg (of weight) per day of CBD and
patients or their parents called a dedicated phone number every night to report seizure
activity.

Dravet syndrome: In this randomized study of 120 children (average 10 years old) with
Dravet syndrome, 61 received CBD and 59 received a placebo. Patients were included
if they experienced at least four seizures in the 28-day baseline period before
treatment began. Participants previously had tried a median of four AEDs and
currently were taking a median of three AEDs. Nine CBD and three placebo patients
withdrew early for various reasons, ranging from side effects to inability to make
regular doctor visits.

After 14 weeks, CBD patients experienced a 39 percent overall reduction in seizure
frequency compared to a 13 percent reduction among placebo patients. Seizures
stopped completely in three CBD patients. Adverse events occurred in 93 percent of
CBD patients and 75 percent of placebo patients, and included drowsiness, diarrhea,
decreased appetite, fatigue, fever, vomiting, lethargy, upper respiratory tract
infection and convulsion. Serious adverse events – including liver function levels,
drowsiness and loss of appetite – were reported in 16 percent of those taking CBD (8
percent considered treatment-related) and 5 percent of placebo patients.

In a separate study on the safety of CBD, 34 Dravet syndrome patients (4 to 10 years
old) were randomized to receive CBD (5, 10 or 20 mg/kg/day) or a placebo. The most
common side effects in CBD vs. placebo patients were: drowsiness (19 percent versus
14 percent); fever (22 percent vs. 0 percent); decreased appetite (19 percent vs. 0
percent); and increased sedation (15 percent vs. 0 percent). "We learned that CBD is a
safe therapy, but as is often the case with treatments, there can be interactions with
other anti-epileptic drugs," said Dr. Thiele. "We're still learning how to use CBD along
with other medications." For example, patients should be monitored closely, including
having routine liver tests, with other medications adjusted as necessary, she said.

Lennox-Gastaut syndrome (LGS): In this randomized study of 171 children and adults
(2-55 years old) with LGS, 86 received CBD and 85 received a placebo. Fourteen CBD
and one placebo patients withdrew early for various reasons, from side effects to
inability to keep doctor visits. Patients were eligible if they experienced at least two
"drop" seizures in which they went limp and fell to the ground during the baseline
week before the study started. Patients had been treated with an average of six AEDs
before the trial and continued taking an average of three AEDs during the study.

After 14 weeks, CBD patients experienced a 44 percent reduction overall in drop
seizure frequency compared to 22 percent in placebo patients. Drop seizures stopped
completely in three CBD patients. Adverse events occurred in 86 percent of CBD
patients (78 percent of which were mild or moderate) and 69 percent of placebo
patients, and included diarrhea, drowsiness, fever, decreased appetite and vomiting.
Serious adverse events – abnormal liver function levels, drowsiness and loss of appetite
– were reported in 23 percent of those taking CBD and 5 percent of placebo patients
(10 percent in the CBD and less than 1 percent in the placebo groups were considered
treatment-related). One patient in the CBD group died, considered unrelated to
treatment.

Early research suggests CBD reduces seizure severity
Separately, early research found CBD provided a 30 percent to 50 percent reduction in
frequency of seizures and a 50 percent reduction in severity in the majority of patients in the
study, researchers found. Adults and children with epilepsy were eligible to participate in the
study if they had not benefitted from at least four of the more than two dozen available
AEDs.

The results were based on an open-label study of 81 patients (42 children and 39 adults) who
experienced four or more seizures per month. Some of the children were having hundreds of
seizures each day. Patients were given an initial dose of 5 mg/kg/day, adding 5 mg/kg per
dose at each visit until a beneficial effect was reached, up to a maximum of 50 mg/kg/day.
During the course of the study, researchers determined the optimal CBD dose was between 20
and 25 mg/kg/day. In an open-label study, all patients receive the therapy and there is no
control group receiving a placebo for comparison's sake.

"It's encouraging that both frequency and severity of seizures appear to improve in the
majority of patients in our study with limited treatment options," said Jerzy P. Szaflarski,
M.D., Ph.D., one of the researchers and director of the University of Alabama at Birmingham
Epilepsy Center. "Our research adds to the evidence that CBD may reduce frequency of
seizures, but we also found that it appears to decrease the severity of seizures, which is a
new finding."

Not all patients benefited from CBD and a few worsened, said Dr. Szaflarski, who noted more
research is needed, including determining why and how CBD helps some people with epilepsy.

Researchers measured:
Reduction in seizure frequency: Patients kept a seizure journal and visited the
doctor every two weeks. After one month, 68 percent experienced a greater than 25
percent reduction in seizure frequency; 58 percent had a greater than 50 percent
reduction; 36 percent had a greater than 75 percent reduction and 9 percent were
seizure-free. Those results were maintained at three and six months. Twenty-three
percent stopped taking CBD: 14 because they didn't benefit, three because of severe
diarrhea and one because the seizures worsened. One adult patient died during the
course of this study of SUDEP (sudden unexpected death in epilepsy) unrelated to
treatment, researchers said.
Reduction in seizure severity: To assess decrease in seizure severity, researchers
used a questionnaire called a Chalfont Seizure Severity Scale, given before treatment
was started and at every two-week visit. Fifty-seven patients were followed for three
months: 67 percent experienced a more than 50 percent decrease in seizure severity,
while 33 percent did not. Of 47 patients followed for six months, 64 percent had a
greater than 50 percent decrease in seizure severity and 36 percent did not.
Interaction with AEDs: Because patients often take more than one medication to
treat seizures, researchers assessed interactions between CBD and 19 different AEDs
using a patient questionnaire and blood tests. They determined interactions ranging
from sedation to a decrease in liver function occurred when CBD was taken with
common AEDs: valproate, clobazam, rufinamide, topiramiate, zonisamide and
eslicarbazepine. In most cases, patients benefited by a decreased dose of the AED or
being taken off the AED entirely while continuing to take CBD, researchers said.

CBD is one of 500 compounds in cannabis, the marijuana plant. Another compound in
cannabis, tetrahydrocannabinol (THC), is the psychoactive component that produces a "high."
The pharmaceutical-grade product used in the study is processed so that it contains almost
pure CBD and less than 1 percent THC.

The product is expected to be submitted to the FDA for approval as a prescription medicine in
2017.

Dr. Thiele received a research grant from and both she and Dr. Szaflarski are consultants to
GW Pharmaceuticals, the manufacturer of the pharmaceutical-grade CBD used in the studies.

About the American Epilepsy Society
Founded in 1946, the American Epilepsy Society (AES) is a medical and scientific society
whose members are dedicated to advancing research and education for preventing, treating
and curing epilepsy. AES is an inclusive global forum where professionals from academia,
private practice, not-for-profit, government, and industry can learn, share and grow to
eradicate epilepsy and its consequences.

For more information, visit the American Epilepsy Society online at aesnet.org. Join the AES
Annual Meeting social conversation today by following @AmEpilepsySoc on Twitter and use
the hashtag #AES2016.