Question: In today’s day and age, it seems that alternative, natural medicine is becoming highly sought after in America. On June 8th 2016, Ohio Governor John Kasich signed a bill allowing the use of medical marijuana or cannabis, making Ohio the 25th state with medical cannabis access. Medical cannabis can treat a wide variety of symptoms, ranging from arthritis to cancer and PTST. One disorder that cannabis effectively treats is epilepsy. Hundreds of Americans have moved to states like Colorado and Washington so they can legally get the treatment they need. Many of them claim that medical cannabis treats their symptoms much better than commercial pharmaceuticals do. My questions are what active ingredient in medical cannabis that treats epilepsy, and what makes it so effective.
Answer: There are about 113 active chemical compounds known as cannabinoids in cannabis. Cannabinoids bind to cannabinoid receptors in the brain (Aizpurua-Olaizola et al.). The most common cannabinoids are Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN). Cannabis is best known for the psychoactive compound, THC. THC mimics the anandamide neurotransmitter, known as the bliss molecule, meaning that THC is responsible for getting you “high” (Breene). Unlike THC, CBD and CBN are non-psychoactive. In a case out of Colorado, a three-year-old girl suffering from Dravet Syndrome (DS) was orally dosed with three milligrams of CBD oil per pound of body weight. This dosage decreased the amount of seizures she had from 300 per week to only two per month (Young). Due to the legality of cannabis, there are few studies available regarding CBD interactions with humans. CBD is highly hydrophobic and can interact with many non-endocannabinoid signaling systems (Devinsky et al.). CBD can be rapidly distributed to the brain, adipose tissue and other organs (Devinsky et al.). Dr. Orrin Devinsky studied the effects of CBD in mice and found that CBD, as well as THC, blocked Maximal Electroshock (MES) and Pentylenetetrazole (PTZ) induced seizures. MES and PTZ induced seizures mimic tonic seizures and are ways to test how well compounds work at treating seizures. Moreover, he found that CBD has anti-epileptiform and anticonvulsant effect in vitro and in vivo (Devinsky et al.). A study conducted by Dr. Duncan Ryan, from the University of Aberdeen, found that CBD targets the mitochondria of the cell to regulate intracellular calcium. Most seizures occur due to high Ca2+ oscillations when potassium levels are too high in the hippocampus, caused by some sort of inhibitor. To test CBD’s effect on Ca2+ oscillations, Dr. Ryan exposed hippocampal cultures to 4-aminopyridine (4AP) (50 uM), a K+ channel re-uptake blocker, to induce seizure-like conditions. Using Fura-2 AM Ca2+ imaging, Dr. Ryan observed under normal conditions, the cultures induced a sustained rise Ca2+ levels, leading to a lot more Ca2+ oscillations. However, when exposed to CBD (1 uM), Dr. Ryan observed that CBD lowers Ca2+ levels and oscillations when cultures were exposed to seizure like conditions (Ryan et al.). Although the exact mechanism is still unknown, these results suggest that CBD could prevent the initiation of epileptiform activity caused by 4AP (Ryan et al.). All in all, there is very little still known about medicinal cannabis, its medicinal properties, and its mechanisms of action. Medical cannabis has many non-psychoactive compounds with the potential to be very effective medicines. There are currently methods out there that can purify CBD to 99.99% purity. However, because cannabis is a schedule I narcotic, only certain government-sponsored agencies can research cannabis, and clinical trials on humans are not yet allowed (Throckmorton).
- Scott I.
- Aizpurua-Olizola, O., Soydaner, U., Öztürk, E., Schibano, D., Simsir, Y., Navarro, P., Etxebarria, N., & Usobiaga A. “Evolution of the Cannabinoid and Terpene Content during the Growth of Cannabis sativa Plants from Different Chemotypes”. Journal of Natural Products, 79(2): 324-31. (2016).
- Breene, Sophia. “How You Get High: What Marijuana Does to Your Brain”. Greatist, Web. (2015).
- Devinsky, O., Cilio, M., Cross, H., Fernandez-Ruiz, J., French, J., Hill, C., Katz, R., Di Marzo, V., Jutras-Aswad, D., Notcutt, W., Martinez-Orgado, J., Robson, P., Rohrback, B., Thiele, E., Whalley, B., & Friedman, D. “Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders”. Epilepsia, 55(6): 791-802. (2014).
- Ryan, D., Drysdale, A., Lafourcade, C., Pertwee, R., & Platt, B. “Cannabidiol Targets Mitochondria to Regulate Intracellular Ca2+ Levels”. The Journal of Neuroscience, 29(7): 2053-63. (2013).
- Throckmorton, Douglas. “FDA Work on Medical Products Containing Marijuana”. Food and Drug Administration, Web. (2015).
- Young, Sandra. “Marijuana stops child’s severe seizures”. CNN News, Web. (2013).