Epilepsia

 

La epilepsia se refiere a un grupo de trastornos caracterizados por crisis recurrentes, que pueden ir acompañadas de convulsiones. El cannabis y las terapias a base de cannabis han demostrado tener efectos beneficiosos en varios tipos de epilepsia, a través de diferentes mecanismos biológicos.

Anticonvulsivo

Cerca del 60% de todas las crisis epilépticas son convulsivas, lo que significa que van acompañadas de convulsiones que se caracterizan por las contracciones rápidas, e involuntarias, de los músculos que pueden hacer que todo el cuerpo sufra temblores o sacudidas sin control. El tipo más común es la convulsión tónico-clónica, que consiste en un corto período de inmovilidad seguido de un temblor incontrolable. Ambos ataques epilépticos, los acompañados por convulsiones, y los que no, son causados por una actividad excesiva en las neuronas del cerebro. Si la actividad es grave y prolongada, las convulsiones pueden ocasionar daños en el tejido cerebral, sobre todo en los niños pequeños, cuando el cerebro todavía está en desarrollo. El síndrome de Dravet es sólo uno de los tipos de epilepsia que aparecen durante la infancia y que pueden causar daños neurológicos.

 

Hace siglos, si no milenios, que los seres humanos conocen las propiedades anticonvulsivas del cannabis. En 1947, los investigadores analizaron las propiedades anticonvulsivantes de los cannabinoides. En un primer estudio, realizado en la Universidad de Sydney en 1974, se demostró que Δ⁹-THC administrado en dosis elevadas tenía un efecto anticonvulsivo en ratones, a los que se les había hecho sufrir convulsiones administrándoles descargas eléctricas y químicas. Se observó que el CBD aumentaba este efecto del Δ⁹-THC, aunque los investigadores no pudieron comprobar que el CBD fuese eficaz por si mismo.

Desde entonces, varios estudios han demostrado que, de hecho, el CBD posee propiedades anticonvulsivas importantes por si solo, además de potenciar los efectos de Δ⁹-THC. Un estudio, elaborado en 2001, demostró que Δ⁹-THC y el análogo sintético de Δ⁹ THC, WIN 55.212-2, ejercen un efecto al agonizar los receptores CB₁. El CBD ejerce sus efectos de una forma diferente, ya que no agoniza el receptor CB₁ sino que actúa como un antagonista débil.

Aún no se ha establecido el mecanismo exacto utilizado por el CBD para controlar las convulsiones, pero está más que demostrado que resulta muy eficaz en el tratamiento de diversos tipos de epilepsia, entre los que se incluye el síndrome de Dravet en los niños pequeños, y ha ganado terreno, rápidamente, como posible tratamiento debido a su falta de psicoactividad, dejando en claro que es el efecto sinérgico y en conjunto de los cannabinoides los que hacen de esta planta una medicina.

Neuroprotector

A medida que avanza la investigación del sistema endocannabinoide, queda claro que éste desempeña un papel importante en la regulación de la duración y frecuencia de las convulsiones, de hecho, algunos investigadores creen que la epilepsia podría ocurrir como resultado de un desequilibrio inherente del sistema endocannabinoide (una supuesta enfermedad conocida como deficiencia endocannabinoide clínica), que podría surgir debido a una lesión cerebral, infección o predisposición genética.

 

La epilepsia puede afectar a diferentes zonas del cerebro, como al lóbulo temporal (© mitopencourseware)

En 2008, un estudio publicado en la revista Nature indicó que los pacientes que sufren epilepsia del lóbulo temporal parecían tener sistemas endocannabinoides disfuncionales. Como su propio nombre indica, la epilepsia del lóbulo temporal afecta al lóbulo temporal del cerebro, y por lo general produce crisis sin convulsiones que implican algún grado de perturbación sensorial (visual, auditiva, olfativa o gustativa incluso), aunque también puede producir convulsiones tónico-clónicas en los casos graves.

La causa común de las crisis convulsivas, y no convulsivas, es la excitación excesiva de las neuronas del cerebro, y la zona del cerebro que se ve afectada varía según el tipo de epilepsia. En pacientes sanos, se cree que los cannabinoides endógenos anandamida y 2-AG desempeñan un papel fundamental en la regulación del nivel de excitación neuronal, reduciendo así la probabilidad de que se desencadene un ataque. De este modo, en los pacientes que poseen un sistema endocannabinoide disfuncional, el cannabis y las terapias a base de cannabis pueden dirigirse, realmente, a la causa de la epilepsia y proporcionar un efecto neuroprotector que reduce la gravedad y la frecuencia de los síntomas.

El estado epiléptico

En casos muy graves de epilepsia, se puede producir una enfermedad conocida como status epilepticus o estado epiléptico. El estado epiléptico puede implicar crisis convulsivas, o no convulsivas, que o bien duran un período de más de cinco minutos cada una, o se producen con una frecuencia de más de un ataque cada cinco minutos sin recuperar la plena conciencia entre los mismos. Si al paciente no se le proporciona atención médica inmediata, durante un episodio de estado epiléptico, la pérdida prolongada de la función normal del cerebro puede ocasionar daño cerebral, o incluso la muerte. Si se proporciona una atención médica adecuada, los pacientes epilépticos suelen sobrevivir a un episodio de estado epiléptico sin mayores complicaciones.

El estado epiléptico suele tratarse con benzodiazepinas o barbitúricos. Ambas clases de fármacos son conocidos porque suelen producir una gran debilidad como efecto secundario, y están lejos de ser efectivos en general. Sin embargo, hay pruebas de que los cannabinoides, concretamente los agonistas de los receptores CB₁, como la anandamida, Δ⁹-THC, y el análogo sintético WIN 55.212-2, pueden proporcionar una mayor protección contra el estado epiléptico. En un estudio de 2006 publicado en el Journal of Pharmacology, WIN 55.212-2 demostró la capacidad de suprimir completamente todos los ataques, incluyendo los episodios prolongados asociados al estado epiléptico. El estudio también señaló que WIN 55.212-2 superaba con creces a la fenitoína y al fenobarbital a la hora de suprimir el estado epiléptico.

 

El fenobarbital suele utilizarse para tratar el estado epiléptico, aunque sin éxito total (Nottingham Vet School)

A partir de éste y otros estudios afines, realizados durante la última década aproximadamente, se ha demostrado que los agonistas de los receptores CB₁ son de fundamental importancia para suprimir las convulsiones, y prevenir la aparición de un estado epiléptico. Asimismo, se ha constatado que en los pacientes epilépticos, el que exista un desequilibrio en el sistema endocannabinoide aumenta la frecuencia y la gravedad de las convulsiones. En un artículo de 2007, se observó que si, a las neuronas epilépticas, se les administraba antagonistas de los receptores CB₁, se producía una actividad epiléptica continua, como la que se produce en los pacientes con estado epiléptico. Sin embargo, si se las trataba con agonistas de los receptores CB₁, la actividad excesiva se detenía. Por el contrario, cuando las neuronas no epilépticas recibieron tratamiento con antagonistas de los receptores CB₁, no se produjo ningún tipo de actividad excesiva parecida al estado epiléptico.

Por lo tanto, es evidente que tanto Δ⁹-THC como el CBD desempeñan un papel importante en el control de los ataques de la epilepsia. Sin embargo, aún no se entienden completamente los respectivos mecanismos de acción, en particular en el caso del CBD.

 

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CB1 agonists, locally applied to the cortico-thalamic circuit of rats with genetic absence

epilepsy, reduce epileptic manifestations. (abst – 2013)

http://www.ncbi.nlm.nih.gov/pubmed/23860329

 

The secret “spice”: an undetectable toxic cause of seizure. (abst – 2013)

http://www.ncbi.nlm.nih.gov/pubmed/23983854

 

Effects of WIN 55,212-2 mesylate on the anticonvulsant action of lamotrigine,

oxcarbazepine, pregabalin and topiramate against maximal electroshock-induced seizures

in mice. (abst – 2013) http://www.ncbi.nlm.nih.gov/pubmed/24161913

 

Therapeutic potential of cannabinoid medicines. (abst – 2013)

http://www.ncbi.nlm.nih.gov/pubmed/24006213

 

Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1

receptor-independent mechanism. (abst – 2013)

http://www.ncbi.nlm.nih.gov/pubmed/23902406

 

Epidiolex – GW Pharmaceuticals (drug development page – 2013)

http://www.gwpharm.com/Epidiolex.aspx

 

Science/Animal: CBD inhibits the activity of a certain liver enzyme (news – 2013)

http://www.cannabismed.

org/english/bulletin/ww_en_db_cannabis_artikel.php?id=391&search_pattern=2013#10

 

Cannabis Anti-Convulsant Shakes up Epilepsy Treatment (news – 2013)

http://www.thecompassionchronicles.com/2013/01/26/cannabis-anti-convulsant-shakes-up-epilepsytreatment/

 

New cannabis discovery could lead to better treatments for epilepsy (news – 2013)

http://www.reading.ac.uk/news-and-events/releases/PR464765.aspx

 

Parents of epileptic N.J. tot lament medical marijuana delays (news – 2013)

http://articles.philly.com/2013-06-24/news/40148313_1_marijuana-law-marijuana-card-dispensary

 

Medical Marijuana for Kids? Some Praise Results While Others Worry About Risks

(news – 2013) http://www.cnbc.com/id/100876423

 

New therapy for fragile X chromosome syndrome discovered (news – 2013)

http://www.sciencecodex.com/new_therapy_for_fragile_x_chromosome_syndrome_discovered-110170

 

Charlotte’s Web Of Suffering: Six-Year-Old Colorado Girl With Dravet Syndrome Finds

Relief From Marijuana High In CBD (news – 2013)

http://www.marijuana.com/news/2013/06/charlottes-web-of-suffering-six-year-old-colorado-girl-withdravet-

syndrome-finds-relief-from-marijuana-high-in-cbd/

 

Toronto family hopes for access to controversial treatment to cure baby’s rare epilepsy

(news – 2013)

http://globalnews.ca/news/714104/toronto-family-hopes-for-access-to-controversial-treatment-to-curebabys-

rare-epilepsy/

 

New Study: Cannabinoids Protect the Brain and Heart From Injury (news – 2013)

http://www.science20.com/news_articles/thc_can_prevent_brain_damage_study-113512

 

Families of children with epilepsy moving to Colorado, drawn by success of marijuana

oil (news – 2013)

http://gazette.com/families-of-children-with-epilepsy-moving-to-colorado-drawn-by-success-of-marijuanaoil/

article/1507895#AZpGzkjtp6Hzx785.99

 

Families migrate to Colorado for marijuana miracle (news – 2013)

http://www.denverpost.com/fitness/ci_24498723/families-migrate-colorado-marijuana-miracle?source=rss

 

Comes Now Epidiolex (FDA approves IND studies of CBD) (news – 2013)

http://www.beyondthc.com/comes-now-epidiolex-fda-approves-ind-studies-of-cbd/

 

Pharmaceuticals Provides Update on Orphan Program in Childhood Epilepsy for

Epidiolex® (news – 2013)

http://www.gwpharm.com/GW%20Pharmaceuticals%20Provides%20Update%20on%20Orphan%20Progra

m%20in%20Childhood%20Epilepsy%20for%20Epidiolex.aspx

 

Cannabis-Based Epilepsy Drug Approved For Clinical Trials (news – 2013)

http://www.medicaljane.com/2013/10/23/cannabis-based-epilepsy-drug-approved-for-clinical-trials/

 

OBTAINING EPIDIOLEX™ IN THE U.S. (news – 2013)

http://www.dravetfoundation.org/dravet-syndrome/consider-dravet/obtaining-epidiolex

 

Endogenous Signaling by Omega-3 Docosahexaenoic Acid-derived Mediators Sustains

Homeostatic Synaptic and Circuitry Integrity. (abst – 2014)

http://www.bioportfolio.com/resources/pmarticle/229933/Endogenous-Signaling-By-Omega-3-

Docosahexaenoic-Acid-derived-Mediators-Sustains-Homeostatic-Synaptic.html