Cannabinoids and Epilepsy ABRIL 2018

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Cannabinoids and Epilepsy

1.
Modulation of Astrocyte Activity by Cannabidiol, a Nonpsychoactive Cannabinoid.

Kozela E(1)(2), Juknat A(3)(4), Vogel Z(5)(6).

Author information: 
(1)The Dr Miriam and Sheldon G. Adelson Center for the Biology of Addictive
Diseases, Sackler Faculty of Medicine, Tel Aviv University, 6997801 Tel Aviv,
Israel. Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo..
(2)Neurobiology Department, Weizmann Institute of Science, 76100 Rehovot, Israel.
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(3)The Dr Miriam and Sheldon G. Adelson Center for the Biology of Addictive
Diseases, Sackler Faculty of Medicine, Tel Aviv University, 6997801 Tel Aviv,
Israel. Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo..
(4)Neurobiology Department, Weizmann Institute of Science, 76100 Rehovot, Israel.
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(5)The Dr Miriam and Sheldon G. Adelson Center for the Biology of Addictive
Diseases, Sackler Faculty of Medicine, Tel Aviv University, 6997801 Tel Aviv,
Israel. Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo..
(6)Neurobiology Department, Weizmann Institute of Science, 76100 Rehovot, Israel.
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The astrocytes have gained in recent decades an enormous interest as a potential 
target for neurotherapies, due to their essential and pleiotropic roles in brain 
physiology and pathology. Their precise regulation is still far from understood, 
although several candidate molecules/systems arise as promising targets for
astrocyte-mediated neuroregulation and/or neuroprotection. The cannabinoid system
and its ligands have been shown to interact and affect activities of astrocytes. 
Cannabidiol (CBD) is the main non-psychotomimetic cannabinoid derived from
Cannabis. CBD is devoid of direct CB1 and CB2 receptor activity, but exerts a
number of important effects in the brain. Here, we attempt to sum up the current 
findings on the effects of CBD on astrocyte activity, and in this way on central 
nervous system (CNS) functions, across various tested models and
neuropathologies. The collected data shows that increased astrocyte activity is
suppressed in the presence of CBD in models of ischemia, Alzheimer-like and
Multiple-Sclerosis-like neurodegenerations, sciatic nerve injury, epilepsy, and
schizophrenia. Moreover, CBD has been shown to decrease proinflammatory functions
and signaling in astrocytes.


2.
Evaluation of Cannabidiol in Animal Seizure Models by the Epilepsy Therapy
Screening Program (ETSP).

Klein BD(1), Jacobson CA(2), Metcalf CS(3), Smith MD(3)(4), Wilcox KS(3), Hampson
AJ(5), Kehne JH(6).

Author information: 
(1)National Institute of Neurological Disorders and Stroke, National Institutes
of Health, Rockville, MD, 20852, USA. Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo..
(2)Department of Neurology, UCSF, San Francisco, CA, 94143, USA.
(3)Anticonvulsant Drug Development Program, Department of Pharmacology and
Toxicology, University of Utah, Salt Lake City, UT, 84112, USA.
(4)School of Dentistry, University of Utah, Salt Lake City, UT, 84112, USA.
(5)National Institute on Drug Abuse, National Institutes of Health, Rockville,
MD, 20852, USA.
(6)National Institute of Neurological Disorders and Stroke, National Institutes
of Health, Rockville, MD, 20852, USA.

Cannabidiol (CBD) is a cannabinoid component of marijuana that has no significant
activity at cannabinoid receptors or psychoactive effects. There is considerable 
interest in CBD as a therapy for epilepsy. Almost a third of epilepsy patients
are not adequately controlled by clinically available anti-seizure drugs (ASDs). 
Initial studies appear to demonstrate that CBD preparations may be a useful
treatment for pharmacoresistant epilepsy. The National Institute of Neurological 
Disorders and Stroke (NINDS) funded Epilepsy Therapy Screening Program (ETSP)
investigated CBD in a battery of seizure models using a refocused screening
protocol aimed at identifying pharmacotherapies to address the unmet need in
pharmacoresistant epilepsy. Applying this new screening workflow, CBD was
investigated in mouse 6 Hz 44 mA, maximal electroshock (MES), corneal kindling
models and rat MES and lamotrigine-resistant amygdala kindling models. Following 
intraperitoneal (i.p.) pretreatment, CBD produced dose-dependent protection in
the acute seizure models; mouse 6 Hz 44 mA (ED50 164 mg/kg), mouse MES (ED50
83.5 mg/kg) and rat MES (ED50 88.9 mg/kg). In chronic models, CBD produced
dose-dependent protection in the corneal kindled mouse (ED50 119 mg/kg) but CBD
(up to 300 mg/kg) was not protective in the lamotrigine-resistant amygdala
kindled rat. Motor impairment assessed in conjunction with the acute seizure
models showed that CBD exerted seizure protection at non-impairing doses. The
ETSP investigation demonstrates that CBD exhibits anti-seizure properties in
acute seizure models and the corneal kindled mouse. However, further preclinical 
and clinical studies are needed to determine the potential for CBD to address the
unmet needs in pharmacoresistant epilepsy.


3.
Neurological Aspects of Medical Use of Cannabidiol.

Mannucci C(1), Navarra M(2), Calapai F(1), Spagnolo EV(3), Busardò FP(4), Cas
RD(5), Ippolito FM(5), Calapai G(6).

Author information: 
(1)Department of Biomedical and Dental Sciences and Morphofunctional Imaging,
University of Messina, Messina, Italy.
(2)Department of Chemical, Biological, Pharmaceutical and Environmental Sciences,
University of Messina, Messina, Italy.
(3)Department of Biotechnology and Legal Medicine, University of Palermo,
Palermo, Italy.
(4)Unit of Forensic Toxicology, Department of Anatomical, Histological, Forensic 
and Orthopedic Sciences, Sapienza University of Rome, Rome, Italy.
(5)National Center of Epidemiology, National Institute of Health, Rome, Italy.
(6)Department of Biomedical and Dental Sciences and Morphofunctional Imaging,
University of Messina, Messina, Italy. Via Consolare Valeria 1, 98125 Messina,
Italy.

BACKGROUND: Cannabidiol (CBD) is among the major secondary metabolites of
Cannabis devoid of the delta-9-tetra-hydrocannabinol psychoactive effects. It is 
a resorcinol-based compound with a broad spectrum of potential therapeutic
properties, including neuroprotective effects in numerous pathological
conditions. CBD neuroprotection is due to its antioxidant and antiinflammatory
activities and the modulation of a large number of brain biological targets
(receptors, channels) involved in the development and maintenance of
neurodegenerative diseases.
OBJECTIVE: The aim of the present review was to describe the state of art about
the pre-clinical research, the potential use and, when existing, the clinical
evidence related to CBD in the neurological field.
METHOD: Collection of all the pre-clinical and clinical findings carried out
investigating the effects of CBD alone, not in combination with other substances,
in the neurological arena with the exclusion of studies on neuropsychiatric
disorders.
RESULTS: Laboratory and clinical studies on the potential role of CBD in
Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS),
Huntington's disease (HD), amyotrophic lateral sclerosis ALS), cerebral ischemia,
were examined.
CONCLUSION: Pre-clinical evidence largely shows that CBD can produce beneficial
effects in AD, PD and MS patients, but its employment for these disorders needs
further confirmation from well designed clinical studies. CBD pre-clinical
demonstration of antiepileptic activity is supported by recent clinical studies
in human epileptic subjects resistant to standard antiepileptic drugs showing its
potential use in children and young adults affected by refractory epilepsy.
Evidence for use of CBD in PD is still not supported by sufficient data whereas
only a few studies including a small number of patients are available.

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4.
Cannabidiol as potential treatment in refractory pediatric epilepsy.

Paolino MC(1), Ferretti A(1), Papetti L(2), Villa MP(1), Parisi P(1).

Author information: 
(1)a Child Neurology, Headache Paediatric Center, Paediatric Sleep Disorders,
NESMOS Department, Chair of Pediatrics, Faculty of Medicine and Psychology ,
Sapienza University, c/o Sant'Andrea Hospital , Rome , Italy.
(2)b Department of Pediatrics, Child Neurology Division , Sapienza University of 
Rome , Rome , Italy.

In recent years there has been great scientific and public interest focused on
the therapeutic potential of compounds derived from cannabis for the treatment of
refractory epilepsy in children. From in vitro and in vivo studies on animal
models, cannabidiol (CBD) appears to be a promising anticonvulsant drug with a
favorable side-effect profile. In humans, CBD efficacy and safety is not
supported by well-designed trials and its use has been described by anecdotal
reports. It will be necessary to investigate CBD safety, pharmacokinetics and
interaction with other anti-epileptic drugs (AEDs) alongside performing
double-blinded placebo-controlled trials in order to obtain conclusive data on
its efficacy and safety in children.