Hoy falleció Raphael Mechoulam, el descubridor del THC. Su hallazgo en un laboratorio de Israel cambió para siempre la historia contemporánea del cannabis y el desarrollo científico.
Sin su invaluable aporte, que hizo junto a un puñado de colaboradores en plena prohibición, mucho de lo que hoy sabemos sobre el cannabis probablemente aún estaría en las sombras.
Años atrás, THC tuvo el placer de conversar con él. El resultado fue una extensa entrevista en la que hablamos de su trabajo y de la necesidad urgente de avanzar en más y mejores investigaciones científicas.
Aquí les dejamos el fruto de ese encuentro con alguien a quien vamos a extrañar y que, hasta sus últimos días, apostó a brindar herramientas para superar los prejuicios y mejorar la calidad de vida de las personas. Nada más y nada menos.
Una charla con el descubridor del THC
“Me cuesta decir que no”, admitió más de una vez Raphael Mechoulam. En general lo aclara con mucha amabilidad cada vez que es entrevistado.
Luego, poco a poco, cede a la tentación de sumergirse en el relato de cada una de sus experiencias que, juntas, componen una historia extraordinaria que empezó hace más de medio siglo.
Mechoulam nació en Sofía, Bulgaria, en 1930. Su familia fue una de las tantas que, muchas penurias mediante, escapó del Holocausto.
Finalizada la guerra, estudió Ingeniería química en su país. Pero, cuando en 1949 comenzó su vida en Israel, eligió abandonar la Ingeniería y sumergirse en los misterios químicos.
Durante el tiempo que pasó en el ejército israelí se dedicó a estudiar el uso de insecticidas. Sin embargo, su obsesión terminaría siendo investigar la relación entre los productos naturales y los problemas biológicos. Finalmente, su tesis doctoral fue sobre los esteroides.
Su carrera como investigador lo llevó primero a Estados Unidos. Allí trabajó en el Instituto Rockefeller, hasta su regreso a Israel donde ocuparía un lugar en el Instituto Weizmann.
En uno de esos laboratorios, Mechoulam haría su gran descubrimiento: el THC, uno de los compuestos activos del cannabis desconocido hasta entonces. Era 1964.
Mechoulam no se respaldó en la gloria de su hallazgo, de hecho los laureles que recibió fueron, en principio, muy pocos. Su logro se produjo en un contexto marcado por el desinterés y signado por los albores de la prohibición.
Sin embargo, a partir de aquel Big Bang Mechoulam y su trabajo se convirtieron en inspiración para toda una generación de científicos que son quienes, en las últimas décadas, han sumado sus esfuerzos para alcanzar una comprensión más ajustada del complejo y fascinante mundo del cannabis que, gracias a las evidencias provistas por sus investigaciones, podría ser la nave insignia de una nueva revolución médica, farmacológica y cientítica.
Nos separan varios miles de kilómetros y seis horas. En Buenos Aires acaba de salir el sol, en Jerusalén, donde Mechoulam se instaló en 1966, es pleno mediodía.
Cuando atiende el teléfono se lo escucha no solo más despierto: es la voz de un hombre joven que está atento porque, ante todo, no quiere perder el tiempo.
“Un placer hablar con ustedes, quizás podrían enviarme las preguntas por mail, pero bueno, también podemos probar a ver cómo sale a través del teléfono”.
Nosotros, de nuestro lado, deslizamos la primera pregunta. Y, pese a la resistencia que le impone ser quien comanda uno de los equipos científicos más atareados e influyentes del mundo, Mechoulam va a entregarse, una vez más y lentamente, al placer de la conversación.
¿Cuándo se descubrió el THC?
El primer compuesto del cannabis que Raphael Mechoulam descubrió y aisló en su laboratorio fue el cannabidiol (CBD), en el año 1964. Luego anunció el descubrimiento del tetrahidrocannabinol (THC), el principal compuesto activo presente en la planta de cannabis.
Primero que nada, ¿por qué decidió estudiar justamente el cannabis?
La morfina ha sido aislada a partir del opio hace 100 años o más. La cocaína también ha sido aislada a partir de las hojas de coca, pero la química del cannabis no era para nada conocida desde un punto de vista científico ni médico, entonces nos parecía importante establecer las bases químicas de la acción del cannabis.
Además es una cuestión que hace al trabajo del científico: hay que elegir temas que uno considere relevantes, con potencial. Por otra parte, no podíamos ni siquiera pensar en competir con otros centros de investigación que venían estudiando otros temas. No teníamos suficiente presupuesto. Por todas esas razones el cannabis parecía una buena opción y así empezamos.
¿Cómo comenzó con esos estudios?, ¿alguna institución lo apoyó?
Al principio solo lo hizo el director del Instituto Weizmann donde yo trabajaba. A nadie le interesaba mucho el cannabis. Él fue el que me ayudó a conseguir el hachís con el que realizamos los primeros estudios. Era hachís que venía del Líbano y que secuestraba la policía para quemarlo. Nada de mucha importancia.
¿Es cierto que las primeras muestras con las que trabajó eran ilegales?
No totalmente. Hubo, digamos, solo algunos errores burocráticos. Por entonces, se necesitaba una autorización del Ministerio de Salud para que se me entregara el cannabis, ni el director del Instituto ni yo lo sabíamos. Simplemente nos manejamos en confianza. Fui a buscar el hachís en colectivo y me dieron 5 kilos sin preguntarme nada. Después me enteré del problema, hice los trámites correspondientes y continué recibiendo el hachís y transportándolo en mi bolso, siempre en transporte público, pero con autorización.
¿Cómo encontró el THC?, ¿sabía algo de antemano o se topó con él repentinamente?
Nosotros en principio sabíamos lo que buscábamos: los compuestos activos de la planta. Pero no sabíamos nada respecto a sus efectos y usos. En la literatura antigua se habla de variados usos y hoy se puede ver que tiene sentido. Pero nosotros empezamos por aislar una buena cantidad de componentes. Después los testeamos en monos y el THC fue el único que causó un efecto de sedación en ellos.
¿La prueba en humanos la hizo con amigos suyos?
Sí, y fue voluntario. Le pedí a mi esposa que hiciera una torta en casa. Calculamos unos 10 miligramos de THC por persona. Ninguno había usado cannabis antes y a todos les hizo efecto, por supuesto, pero lo interesante es que a todos los afectó de manera diferente. Algunos se reían, otros se relajaban, otros hablaban sin parar, hasta pude observar un caso de ansiedad. Fue muy interesante y me dio la pauta de que estábamos ante algo importante.
¿Y con esas evidencias logró que finalmente otras instituciones se interesaran por su trabajo y financiaran sus investigaciones?
No mucho. Ya habíamos pedido presupuesto al Instituto Nacional de Salud de Estados Unidos y nos lo habían negado. Pero seguimos avanzando sobre la química, la farmacología, la bioquímica… Hasta que recibí un llamado de un farmacólogo del Instituto Nacional de Salud Mental de ese país. Parecía que allá una persona importante estaba preocupada sobre los efectos del cannabis en el cerebro, dado que había encontrado a su hijo consumiéndolo.
El instituto no tenía una respuesta, así que me pidieron THC para hacer unos estudios ellos mismos y se los di, nosotros teníamos el único THC puro del mundo. Creo que lo ingresaron de contrabando y creo que la mayoría de las investigaciones que se hicieron durante esos años en Estados Unidos fueron con esos 10 gramos que se llevaron de nuestro laboratorio en Israel. Y desde entonces, por casi 50 años, hemos recibido apoyo económico del Instituto Nacional de Salud y nunca interfirieron en nuestros estudios.
¿Cómo se compone el cannabis?
“Hay esencialmente un componente principal, causante de la psicoactividad, que es el tetra-hidro-cannabinol [THC] y otros componentes con menor actividad, como el cannabidiol [CBD], que es otro componente importante con poca psicoactividad, pero que actúa generando cambios significativos sobre la acción del THC”, explica Mechoulam. “No hay que olvidar que hay una sinergia importante entre todos los componentes de la planta de cannabis”.
Usted trabajó mucho sobre las posibilidades terapéuticas del THC. A su entender, ¿cuáles son las aplicaciones médicas con mayor evidencia?
Podríamos decir que el THC ayuda sobre todo en lo que conocemos como post-trauma. Ayuda con el sueño, el apetito y en trastornos de la alimentación. Colabora con algunos efectos fisiológicos en relación a temblores y también, aunque aún no está debidamente comprobado, en Parkinson y cáncer, pero no hay ensayos clínicos concluyentes al respecto todavía.
¿Y qué ocurre con el CBD?
El CBD es un componente antiinflamatorio y se ha descubierto que, en el ser humano, ayuda en pacientes con esquizofrenia. Se ha comprobado que el CBD reduce la ansiedad, la depresión y que sirve para contrarrestrar enfermedades autoinmunes, aunque solamente en animales porque no fue testeado en humanos.
Para enfermedades autoinmunes como diabetes tipo 1 o artritis reumatoidea se demostró que funciona muy bien en animales y hay reportes individuales de que también colabora en humanos, aunque no hay ensayos clínicos que lo comprueben definitivamente. Y ambos, tanto el THC como el CBD, son agentes anticancerígenos en animales, pero tampoco hay ensayos clínicos en humanos con ninguno de los dos casos.
Pero si hablamos de algo tan delicado como la posibilidad de tratar el cáncer, ¿por qué no se avanza con mayor firmeza?
Como científico mi obligación es destacar que los cannabinoides han logrado reducir las células cancerígenas en probeta y en ratones, sin embargo hasta el momento no hemos podido avanzar en ensayos clínicos en humanos.
Respecto al cáncer, ¿hay indicios que permitan pensar que el cannabis pueda ser una herramienta para curarlo?
Sabemos que ayuda mucho con los síntomas adversos del tratamiento, tal vez en algunas personas pueda llegar a curarlo, tal vez en algunos tipos de cáncer sea más útil que en otros, pero ¿eso significa, por extensión, que su acción química cura el cáncer? No. No podemos saberlo, pues no hay suficientes ensayos clínicos, no todos los que necesitamos para hacer una afirmación semejante. La gente pagaría con gusto para que avancemos en nuestras investigaciones, pero los gobiernos no, los Estados no financian esta clase de ensayos clínicos.
Sin embargo, según contó, usted mismo encaró por su cuenta un ensayo clínico con niños en un hospital público de Jerusalén.
Sí, en 1995. Lo hicimos junto a Ayra Avramov, por entonces directora del departamento de oncología pediátrica de un establecimiento. Los niños, lamentablemente, también pueden contraer cáncer y los tratamientos son verdaderamente muy difíciles de sobrellevar. Vómitos, nauseas. Aplicamos THC sublingual durante el tratamiento. Queríamos hacer un doble ciego al comienzo, una parte de ellos recibiendo aceite con THC y otros solo aceite. A la semana ella me dijo que no iba a seguir con ese método, porque ya podía diferenciar quién había usado THC y quién no. A partir de ahí, todos recibieron su aceite de cannabis. Se detuvieron en su totalidad las nauseas y los vómitos con dosis muy bajas de THC.
¿También realizó estudios clínicos con pacientes con epilepsia?, ¿cuáles fueron los resultados que obtuvo?
Sí, es correcto. Fue un trabajo en conjunto con un grupo de científicos brasileños. Obtuvimos grandes cantidades de cannabidiol, extraído del hachís, y luego les dimos dosis altas a pacientes epilépticos, 200 miligramos por persona. Y funcionó. Lamentablemente este trabajo no se utilizó y tomó muchos años hasta que la gente se diera cuenta de que el cannabidiol es un buen agente antiepiléptico y ahora se usa ampliamente en el tratamiento de niños con epilepsia.
El cannabis en el cuerpo humano y el “efecto séquito”
Luego de que en Estados Unidos un grupo de investigación descubriera la existencia en el cuerpo humano del receptor CB1, sobre el que actúa el THC, Mechoulam y su equipo se preguntaron por qué el cuerpo tendría ese receptor, ya que no tenía sentido que existiera sólo para que el cannabis hiciera efectos al ser consumido. A comienzos de los 90, Mechoulam y sus colaboradores anunciaron el descubrimiento de la anandamida, un endocannabinoide que el cuerpo produce y al actuar sobre el receptor CB1 produce los mismos efectos que el THC.
Más tarde, tras descubrir el receptor CB1 y los endocannabinoides anandamida y 2-AG, se concluyó que en el cuerpo existe un sistema endocannabinoide que regula un conjunto de funciones biológicas de suma importancia como el sueño, el apetito, el dolor y el estado de ánimo, entre otras.
Finalmente, en 1999, Mechoulam y el Dr. Ben Shabat presentan la teoría del “efecto séquito” que indica que si bien los cannabinoides de la planta tienen efectos individuales, cuando se usan en conjunto consumiendo la planta en lugar de aislarlos, interactúan entre ellos y producen un efecto más completo y eficaz.
¿Puede afirmar que es un hecho científicamente probado que existe un sistema completo de cannabinoides adentro del cuerpo humano?
Bueno, en principio debería aclarar que no es solo adentro del cuerpo humano, sino de la mayoría de los mamíferos. Lo que llamamos sistema endocannabinoide es un sistema de orden mayor que está involucrado en una gigantesca cantidad de procesos biológicos y se ha publicado que es probable que tenga participación en la mayoría de las enfermedades humanas. Es verdaderamente muy importante.
¿Cómo llegó a ese descubrimiento?, ¿lo sospechaba desde el comienzo?
Ya en los años 80 habíamos logrado aprender mucho sobre los cannabinoindes en la planta. Los habíamos evaluado en animales y personas, pero lo cierto es que entendíamos bastante poco sobre sus mecanismos de acción. Fue en ese momento cuando la profesora Allyn Howlett, una investigadora norteamericana, encontró un receptor específico para el THC. Lo llamó receptor CB1. Fue muy importante, porque fue la primera prueba de que en nuestro cerebro existe un receptor específico para los compuestos activos del cannabis. La gran pregunta que surgió luego es por qué tenemos esos receptores, por qué hay componentes en nuestro cuerpo que imitan la acción del cannabis.
¿Fue cuando comenzaron a indagar sobre los cannabinoides endógenos?
Sí, hicimos ese trabajo con un gran equipo: los doctores Lumir Hanus, Bill Devane y Aviva Broier. Empezamos trabajando con cerebros de cerdo dado su parecido con el de los humanos. Así que todas las semanas viajábamos desde Jerusalén hasta Tel Aviv para comprarlos. Y, finalmente, encontramos la sustancia del cerebro que actúa sobre los receptores cannabinoides.
¿Se refiere al compuesto que usted bautizó como anandamida?
Sí, aunque el nombre original era araquidonoiletanolamida, pero nos parecía una denominación un poco compleja. Así que tratamos de darle un nombre relacionado a sus funciones que tienen que ver con los cambios en el ánimo, con las emociones. Pensamos que quizás estas alteraciones vinculadas a estos receptores se producen en busca de la dicha, una dicha interna. Así que, en base a una idea de Bill Devane, fuimos por el sánscrito. En esa lengua, alegría es “ananda” y pensando en las particularidades químicas llegamos a anandamida.
¿Por qué cree que la investigación sobre el sistema endocannabinoide tiene tanta importancia para la ciencia y la medicina?
En mamíferos, los receptores CB1 y CB2 cubren casi todo el organismo, se trata de algo esencial en nuestra vida como especie. Las investigaciones científicas indican que su funcionamiento podría estar vinculado a todas las enfermedades humanas.
El cannabis medicinal y la investigación científica
Muchos médicos, en coincidencia con el discurso de los laboratorios, sostienen que para que el cannabis tenga un uso medicinal efectivo el único camino es crear formas sintéticas, ¿cuál es su opinión?
El THC está presente en la planta, también el CBD. Nosotros hemos publicado un grupo de componentes que son más activos que el CBD, derivados del CBD. El THC es un componente bastante activo y si resulta ser un agente anticancerígeno, probablemente la gente lo usaría. Pero en definitiva que se haga uso de un compuesto aislado o no, va a depender siempre de la enfermedad. En algunos casos de epilepsia el CBD puede ser suficiente por sí solo, pero no en todos. En otras enfermedades, como puede ser el cáncer, tal vez es mejor tener ambos, THC y CBD. El problema es que actualmente no tenemos todavía suficiente información, es decir, hasta que no sea testeado en humanos no lo sabremos a ciencia cierta.
Fumar marihuana se suele asociar exclusivamente a su empleo con fines recreativos. Sin embargo, en muchos hospitales de Israel podemos ver que el cannabis se fuma con fines medicinales, ¿por qué?
Bueno, hay una diferencia entre fumar cannabis e ingerirlo como extracto en un aceite. En forma de extracto en aceite, ingiriéndolo de cualquier manera, los efectos puros se sienten a la hora y media, y son efectos relativamente bajos. Y fumándolo, inmediatamente ingresa una enorme cantidad de THC en el torrente sanguíneo. A todo esto se le llama farmacocinética, entonces la farmacocinética del THC es distinta si es fumado o ingerido. Y el efecto del THC, al fumarlo, es inmediato.
Si mira a su alrededor, luego de todos estos años, ¿qué le parece hoy lo más remarcable en estudios sobre el cannabis?
Hay un montón de estudios hoy en día, pero lamentablemente no hay suficientes ensayos clínicos, me importa insistir con este punto. Se han hecho un montón de trabajos con animales, en bioquímica, muchos trabajos sobre farmacología y más… pero debido a problemas legales no hay trabajo suficiente en el aspecto clínico, generando ensayos clínicos con cannabinoides. Eso se ha dejado casi totalmente de lado. Es decir, no hay ni una sola publicación de trabajos clínicos relevantes sobre cannabinoides, por ejemplo, aplicados en cáncer de humanos.
En ese sentido, ¿cuán necesario es, para la comunidad científica, un cambio en los aspectos legales para poder trabajar apropiadamente en la investigación sobre el cannabis?
Es muy complicado. Cada Estado tiene su propio armado legal, sus propias regulaciones, sus propias leyes. Cada país es diferente. En Israel tenemos un Ministerio de Salud que se encarga del cannabis y es relativamente fácil ocuparse de realizar investigaciones. En otros países es muchísimo más difícil. Por ejemplo, en Estados Unidos vemos esencialmente que no hay estudios clínicos que sean considerados una prioridad, salvo en el caso del tratamiento de epilepsia con cannabidiol. Aquí, en Israel, es un poquito menos difícil, aunque de todas maneras hay problemas legales. Y no sé cómo es en Sudamérica, realmente no lo sé.
En la medicina y en la ciencia se suelen introducir prejuicios que no pertenecen a esos campos, ¿por qué cree que ocurre esto y cómo podrían los médicos relacionarse con el cannabis con menos preconceptos?
Hay una completa escisión entre el uso de cannabis y cannabinoides como agentes medicinales y el uso recreativo del cannabis. Son dos cosas completamente diferentes. El uso recreativo es claramente un tema social, mientras que el uso científico es un asunto médico. Son dos cosas muy distintas y a veces se mezclan demasiado. El médico, por su parte, debería poder ver los cannabinoides como drogas, igual que como ve la penicilina y tantas otras sustancias. Así de simple. Si tenemos suficiente información sobre los cannabinoides, entonces los médicos deberían poder ver los endocannabinoides, los cannabinoides y las distintas combinaciones de cannabinoides como drogas bien definidas y usarlas, en consecuencia, como drogas bien definidas. Esa no es siempre la situación, porque no siempre tenemos suficiente información médica y, por lo tanto, es una cuestión natural que el médico no sepa qué hacer con el cannabis.
Con todo esto en mente, ¿cuáles son sus expectativas en relación a los beneficios que puede traernos el cannabis?
Creo que los cannabinoides pueden resultar en una gran cantidad de nuevas formas de medicación, en nuevos tratamientos para enfermedades muy extendidas, pero aún nos falta recorrer un largo camino a todos los investigadores. Necesitamos avanzar en más y más ensayos clínicos con personas; si eso no ocurre, nada va a pasar. Ratas… ratas hay un montón, ¡pero las ratas no son humanos!
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