The Journal of the Arkansas Medical Society Med Journal June 2019 Final | Page 15

mechanisms of action. Preclinical data have
shown cannabidiol to have activity against sei-
zures in in-vitro and in-vivo models.
A Cochrane review in 2012 assessed the
safety and efficacy of cannabinoid use in pa-
tients with epilepsy. 3 A total of four studies
(blinded and unblinded randomized clinical
trials) were included in the review; however,
all these trials were of low quality with small
sample sizes and variations in product, dose,
frequency, and duration of treatment. It was de-
termined that the efficacy of CBD in the treat-
ment of epilepsy could not be confirmed, but a
dose of 200-300 mg daily can be administered
safely over a short period. Two of these stud-
ies were subsequently included in a systematic
review by the American Academy of Neurology
in 2014 to assess the role of medical marijuana
in various neurologic diseases such as multiple
sclerosis, epilepsy, and movement disorders. 4 It
was concluded that the data were insufficient
to support or refute the efficacy of cannabi-
noids for reducing seizure frequency. However,
the use of cannabinoids, specifically CBD, has
increased in response to several anecdotal re-
ports of remarkable response in epilepsy, and
the perception that a substance or medicine
derived from a natural source would be safer.
One such report was broadcasted on a CNN
special documentary, “Weed.” This special
presented a girl named Charlotte Figi, who has
Dravet syndrome, a rare and intractable genetic
epileptic encephalopathy syndrome associated
most commonly with SCN1A mutation. At five
years of age, her mother started giving her an
oral liquid, high-CBD, low-THC extract (later
called Charlotte’s Web) made by the Stanley
brothers in Colorado. Charlotte had suffered
from very frequent seizures and experienced
significant developmental delays and cognitive
compromise. She had been treated with several
antiepileptic drugs, with little or no improve-
ment. In response to treatment with CBD oil,
she experienced a >90% reduction in seizure
frequency within three months and a remark-
able improvement in cognition. 5 This and other
similar reports prompted many parents to move
their families across the country to gain access
to CBD products.
Up to 85% reduction in the seizure frequen-
cy and increased alertness, better mood, and
improved sleep were reported in several papers
derived from online surveys and retrospective
chart reviews. However, several confounders
were present in these open-label retrospective
studies; there were high expectations and mo-
tivations leading to reporting bias and acting as
obstacles to determine the actual efficacy of oral
cannabis extracts. Subsequently, the recent in-
terest in research in this sphere has led to the
completion of several well-controlled studies in
epilepsy, using a liquid proprietary oral formula-
tion of CBD. Devinski et al. conducted a double-
blind, placebo-controlled trial at 23 centers in
the U.S. and Europe, with random assignment of
120 children and young adults with the Dravet
syndrome and drug-resistant seizures to receive
placebo vs. 20 mg/kg/day of CBD. 6 The median
frequency of convulsive seizures per month de-
creased from 12.4 to 5.9 in response to CBD,
compared to a decrease from 14.9 to 14.1 with
placebo. A > 50% reduction in convulsive sei-
zure frequency was achieved in 43% of the CBD
CBD is far from a miracle
cure, and it is of paramount
importance to have a
reasonable expectation of its
usefulness as an antiepileptic
medication.
treated group vs. 27% in the placebo group. The
patient’s overall condition improved by at least
one category on the seven-category Caregiver
Global Impression of Change scale in 62% of the
CBD-treated subjects compared to 34% in the
placebo group. The frequency of total seizures of
all types was significantly reduced in response
to CBD (P=0.03), but there was no significant
reduction in nonconvulsive seizures. CBD ther-
apy rendered seizure freedom in 5% compared
to 0% in the placebo group (P=0.08). A major
weakness of the trial was the failure to report
changes in the plasma concentration of cloba-
zam and N-desmethylclobazam (level can in-
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