California’s legalization spurred Dr. Geoffrey Guy and Dr. Brian Whittle to found GW Pharmaceuticals, a company that would utilize clinical trials to unpack various cannabinoid formulations as potential therapies with the overriding focus of developing what would later be known as Sativex (Nabiximols). This oral mucosal spray was made up of CBD and THC in a 1:1 ratio and successfully combated neuropathic pain, spasticity, overactive bladder, and symptoms of multiple sclerosis.
To make matters more confusing, nine states (including California, Washington, and Colorado) let residents buy cannabis-based products with or without THC. Nearly two dozen other “medical marijuana states” allow the sale of cannabis, including capsules, tinctures, and other items containing CBD or THC, at licensed dispensaries to people whose doctors have certified that they have an approved condition (the list varies by state but includes chronic pain, PTSD, cancer, autism, Crohn’s disease, and multiple sclerosis). Sixteen more states legalized CBD for certain diseases. But because all these products are illegal according to the federal government, cannabis advocates are cautious. “By and large, the federal government is looking the other way,” says Paul Armentano, deputy director of the Washington, DC–based National Organization for the Reform of Marijuana Laws (NORML), but until federal laws are changed, “this administration or a future one could crack down on people who produce, manufacture, or use CBD, and the law would be on its side.”
Así, en la periferia, cuando el nociceptor se activa en respuesta a un estímulo nocivo, se inicia la síntesis de anandamida y 2-AG, los cuales son liberados en el espacio extracelular. Allí, estas dos moléculas pueden unirse a células del sistema inmune y a keratinocitos. La unión a linfocitos y macrófagos conduce a la inhibición de la liberación de sustancias proinflamatorias y pronociceptivas. Por su parte, la unión de endocannabinoides a los keratinocitos aumenta la liberación de betaendorfinas, que se unirán a la membrana del nociceptor, contribuyendo con la disminución de la transmisión de la señal nociceptiva.