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Cannabinoids and Epilepsy


Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome.

Devinsky O(1), Cross JH(1), Laux L(1), Marsh E(1), Miller I(1), Nabbout R(1),
Scheffer IE(1), Thiele EA(1), Wright S(1); Cannabidiol in Dravet Syndrome Study

Author information: 
(1)From the New York University Langone Comprehensive Epilepsy Center, New York
(O.D.); the University College London Great Ormond Street Institute of Child
Health (J.H.C.) and GW Pharmaceuticals (S.W.) - both in London; Lurie Children's 
Epilepsy Center, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago 
(L.L.); the Children's Hospital of Philadelphia, Philadelphia (E.M.); Miami
Children's Hospital, Miami (I.M.); Hôpital Necker-Enfants Malades, Paris (R.N.); 
Florey Institute, Austin Health and Royal Children's Hospital, University of
Melbourne, Melbourne, VIC, Australia (I.E.S.); and Massachusetts General
Hospital, Boston (E.A.T.).

BACKGROUND: The Dravet syndrome is a complex childhood epilepsy disorder that is 
associated with drug-resistant seizures and a high mortality rate. We studied
cannabidiol for the treatment of drug-resistant seizures in the Dravet syndrome.
METHODS: In this double-blind, placebo-controlled trial, we randomly assigned 120
children and young adults with the Dravet syndrome and drug-resistant seizures to
receive either cannabidiol oral solution at a dose of 20 mg per kilogram of body 
weight per day or placebo, in addition to standard antiepileptic treatment. The
primary end point was the change in convulsive-seizure frequency over a 14-week
treatment period, as compared with a 4-week baseline period.
RESULTS: The median frequency of convulsive seizures per month decreased from
12.4 to 5.9 with cannabidiol, as compared with a decrease from 14.9 to 14.1 with 
placebo (adjusted median difference between the cannabidiol group and the placebo
group in change in seizure frequency, -22.8 percentage points; 95% confidence
interval [CI], -41.1 to -5.4; P=0.01). The percentage of patients who had at
least a 50% reduction in convulsive-seizure frequency was 43% with cannabidiol
and 27% with placebo (odds ratio, 2.00; 95% CI, 0.93 to 4.30; P=0.08). 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
cannabidiol group as compared with 34% of the placebo group (P=0.02). The
frequency of total seizures of all types was significantly reduced with
cannabidiol (P=0.03), but there was no significant reduction in nonconvulsive
seizures. The percentage of patients who became seizure-free was 5% with
cannabidiol and 0% with placebo (P=0.08). Adverse events that occurred more
frequently in the cannabidiol group than in the placebo group included diarrhea, 
vomiting, fatigue, pyrexia, somnolence, and abnormal results on liver-function
tests. There were more withdrawals from the trial in the cannabidiol group.
CONCLUSIONS: Among patients with the Dravet syndrome, cannabidiol resulted in a
greater reduction in convulsive-seizure frequency than placebo and was associated
with higher rates of adverse events. (Funded by GW Pharmaceuticals; number, NCT02091375 .).

2. N Engl J Med. 2017 May 25;376(21):2075-2076. doi: 10.1056/NEJMe1702205.

Cannabinoids for Epilepsy - Real Data, at Last.

Berkovic SF(1).

Author information: 
(1)From the Epilepsy Research Centre, University of Melbourne at Austin Health,
Heidelberg, VIC, Australia.

Pharmacogenetics of Cannabinoids.

Hryhorowicz S(1), Walczak M(2), Zakerska-Banaszak O(2), Słomski R(2,)(3),
Skrzypczak-Zielińska M(2).

Author information: 
(1)Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32,
60-479, Poznan, Poland. Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder (2)Institute of Human 
Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479, Poznan, Poland.
(3)Department of Biochemistry and Biotechnology, University of Life Sciences,
Dojazd 11, 60-632, Poznan, Poland.

Although the application of medical marijuana and cannabinoid drugs is
controversial, it is a part of modern-day medicine. The list of diseases in which
cannabinoids are promoted as a treatment is constantly expanding. Cases of
significant improvement in patients with a very poor prognosis of glioma or
epilepsy have already been described. However, the occurrence of side effects is 
still difficult to estimate, and the current knowledge of the therapeutic effects
of cannabinoids is still insufficient. In our opinion, the answers to many
questions and concerns regarding the medical use of cannabis can be provided by
pharmacogenetics. Knowledge based on proteins and molecules involved in the
transport, action, and metabolism of cannabinoids in the human organism leads us 
to predict candidate genes which variations are responsible for the presence of
the therapeutic and side effects of medical marijuana and cannabinoid-based
drugs. We can divide them into: receptor genes-CNR1, CNR2, TRPV1, and GPR55,
transporters-ABCB1, ABCG2, SLC6A, biotransformation, biosynthesis, and
bioactivation proteins encoded by CYP3A4, CYP2C19, CYP2C9, CYP2A6, CYP1A1, COMT, 
FAAH, COX2, ABHD6, ABHD12 genes, and also MAPK14. This review organizes the
current knowledge in the context of cannabinoids pharmacogenetics according to
individualized medicine and cannabinoid drugs therapy.