By Narda Robinson, DO, DVM Chances are, if you treat patients with seizures, you have encountered a certain percentage whose seizures you just can’t control, even with multiple medications. It is likely, too, that even if your clients caring for these patients haven’t already asked about medical marijuana (MMJ) as an adjunctive approach, they have seen reports of its success in children1,2 and wonder if it would work for their dog or other small animal. A One-Health Perspective Parents of severe seizure sufferers frequently feel frustrated. They dread the next seizure and the adverse effects of drugs on quality of life.3,4 Last-ditch options for pediatric patients with pharmacoresistant seizures include ketogenic diets, high-dose steroid treatment, and/or surgery, while choices for dogs with uncontrollable seizures may dwindle to euthanasia as one of the few alternatives available. Thus, when desperate caregivers for dogs hear promising reports of success with seizures from MMJ in children, hope turns to cannabis for help in controlling seizures in kids’ canine counterparts. With states easing restrictions and access increasing, veterinary clients, like parents of pediatric epileptics, are seeking guidance from their healthcare practitioners about MMJ’s risks, benefits, interactions with other medications and legal status. That said, however, many veterinarians assume, with good reason, that the proscription on veterinary prescriptions for cannabis prevents them from outright recommending cannabis for dogs and cats. Nonetheless, as with other herbal and nutritional supplements, the Internet affords several types of cannabis edibles directly targeted to the canine-loving consumer, no prescription required.5 Sellers may cite their source as “industrial hemp,” i.e., cannabis containing less than 0.3 percent delta-9-tetrahydrocannabinol (THC). A low concentration of THC reduces the compound’s psychoactive side effects and thereby elevates its safety profile. In contrast, the human-targeted, MMJ-infused edibles and oils that sicken dogs and cats have high levels of THC. Commercial cannabis operations have cultivated strains that have ever-greater concentrations of THC per plant in order to meet the humans’ hunger for a bigger buzz. Alternatively, growers with different aims may select strains with extremely low amounts of THC in their phytocannabinoid profile. (The term “phyto”-cannabinoid refers to cannabis agents derived from plants.) Due to the undesirable effects of THC in dogs, many of the canine cannabinoids sold today tout cannabidiol (CBD) as the main ingredient. In fact, the surge in popularity of cannabis for patients with pharmacoresistant epilepsy seems to stem from publicity surrounding MMJ for children, highlighting in particular oils made from strains with high CBD and low THC.6,7 Whereas THC is the main psychoactive chemical in cannabis, CBD is its major psycho-inactive component.8 Research suggests that CBD has low toxicity and high tolerability in humans and non-humans.9 This cannabinoid has come under intense scrutiny as a health-restoring component of cannabis unto itself, with or without THC. CBD reduces pain, inflammation, and anxiety10 as well as seizure activity. That said, some claim that satisfactory control of drug-resistant epilepsy may require carefully tailoring the ratio of THC to other cannabis constituents, according to anecdotal reports.11 Estimates suggest that up to 30 percent of human epileptics experience resistance to conventional anti-seizure medication.12 Decades of research indicate that CBD yields notable anticonvulsant effects with minimal neurotoxicity. It reliably reduces neuronal activity and seizure severity, whereas THC exhibits either pro- or anticonvulsant activity, depending on dose and seizure type.13 CBD affects several endogenous cannabinoid pathways simultaneously, demonstrating a multiplicity of neuropharmacologic mechanisms of action.14 It works additively and at times synergistically with other anti-epileptic drugs; this allows clinicians to more readily introduce CBD into a seizure patient’s drug regimen without reducing the effectiveness of pharmaceuticals already “on board.” The Endocannabinoid (eCB) System As it turns out, the nervous, lymphatic and possibly other systems within the body already house cannabinoid receptors, making them already prepared to respond to both phyto- and endo-cannabinoids.15 Perhaps unsurprisingly, given the observed benefits of MMJ for epilepsy, the eCB system regulates neuronal excitability. When it falters, an “eCB deficiency syndrome” may result, associated not only with seizures16,17 but also with the onset of fibromyalgia, irritable bowel syndrome, migraine and other maladaptive states.18 In other words, while a normally functioning eCB system dampens neuronal excitation, its downregulation fosters neuronal hyperexcitability and dysfunction.19 In fact, many integrative approaches for epilepsy also affect eCB states, including acupuncture along with certain nutritional supplements, herbal medicines, dietary changes, and, of course, cannabis.20 Wanted: Rigorous Research According to the authors of a recent parent survey of CBD-enriched cannabis for children with treatment-resistant epilepsy, “Parents report a high rate of success in reducing seizure frequency with this treatment. CBD-enriched cannabis appears to be behaviorally well tolerated with some positive side effects not commonly associated with other [anti-epileptic drugs].”21 However, these authors also caution, “The new trend of medical cannabis use in children poses risks because of a lack of standardization and regulation, imprecise dosing, and possible adverse side effects and medication interactions. A lack of regulation and standardization in the medical cannabis industry results in products that are of questionable quality and composition. “Most parents reported using cannabis extracts, purchased either from a dispensary or directly from a medical cannabis grower. Cannabis extracts are often inaccurately labeled and can contain highly variable levels of CBD and THC. These extracts could also contain contaminants, such as fungus and pesticides, which may cause long-term organ damage. “Because parents are increasingly using artisanal preparations of CBD-enriched cannabis in an attempt to reduce their child’s seizure burden, it is critical to obtain more data about the safety and efficacy of CBD. … Formal studies to determine safety, optimal dosing, tolerability, and efficacy of a standardized CBD preparation in different populations of children and adults with epilepsy will provide the data necessary to determine whether CBD has a place in epilepsy treatment.”22 The admonitions listed above similarly apply to dogs, cats and other animals afflicted with this stressful and potentially brain-damaging condition. Delist the Drug What would dramatically aid in the effort for university researchers to engage in high quality research is the delisting of cannabis as a Schedule I drug by the federal government—something a bipartisan group from the U.S. Congress is asking President Obama to do.23 This would open the door to what nearly everyone wants—rigorous research and large-scale, well-controlled, double-blind randomized trials24 that would benefit humans and animals alike. With the stroke of a pen signing an executive order,25 President Obama could pave the way for researchers to improve medical marijuana safety for all. References 1 Gupta S. Why I changed my mind on weed. CNN Health. August 8, 2013. Accessed at http://www.cnn.com/2013/08/08/health/gupta-changed-mind-marijuana/ on 042314. 2 Bernard-Kuhn L. Families move to secure medical marijuana for kids. USA Today. The Cincinnati Enquirer. March 23, 2014. Accessed at http://www.usatoday.com/story/news/nation/2014/03/23/families-move-to-secure-medical-marijuana-for-kids-/6755071/ on 042314. 3 Porter BE and Jacobson C. Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy & Behavior. 2013;29:574-577. 4 Wessmann A, Volk HA, Parkin T, et al. Evaluation of quality of life in dogs with idiopathic epilepsy. J Vet Intern Med. 2014;28:510-514. 5 Canna-Pet website. “The Medical Cannabis for Pets”. Accessed at http://www.canna-pet.com/index.html#assets on 04-20-14. 6 Cortesi M and Fusar-Poli P. Potential therapeutical effects of cannabidiol in children with pharmacoresistant epilepsy. Med Hypotheses. 2007; 68(4):920-921. 7 Porter BE and Jacobson C. Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy & Behavior. 2013;29:574-577. 8 Costa B, Trovato AE, Comelli F, et al. The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain. European Journal of Pharmacology. 2007;556:75-83. 9 Jones NA, Glyn SE, Akiyama S, et al. Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures. Seizure. 2012;21:344-352. 10 Schier AR, Ribeiro NP, Silva AC, et al. Cannabidiol, a Cannabis sativa constituent, as an anxiolytic drug. Rev Bras Psiquiatr. 2012;34(Supl 1):S104-S110. 11 Robinson NG. Personal communication with cannabis dispensers who treat patients with pharmacoresistant epilepsy. April, 2014. 12 Ben Amar M. Cannabinoids in medicine: a review of their therapeutic potential. J Ethnopharmacology. 2006;105:1-25. 13 Hegde M, Santos-Sanchez C, Hess CP, et al. Seizure exacerbation in two patients with focal epilepsy following marijuana cessation. Epilepsy & Behavior. 2012;25:563-566. 14 Jones NA, Glyn SE, Akiyama S, et al. Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures. Seizure. 2012;21:344-352. 15 Izzo AA, Borrelli F, Capasso R, et al. Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends in Pharmacological Sciences. 2009; 30(10):515-527. 16 Hofmann ME and Frazier CJ. Marijuana, endocannabinoids, and epilepsy: Potential and challenges for improved therapeutic intervention. Experimental Neurology. 2013;244:43-50. 17 Hofmann ME and Frazier CJ. Marijuana, endocannabinoids, and epilepsy: Potential and challenges for improved therapeutic intervention. Experimental Neurology. 2013;244:43-50. 18 McPartland JM, Guy GW, and Di Marzo V. Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system. PLoS ONE. 9(3):e89566. Doi:10/1371/journal.pone.0089566. 19 Hegde M, Santos-Sanchez C, Hess CP, et al. Seizure exacerbation in two patients with focal epilepsy following marijuana cessation. Epilepsy & Behavior. 2012;25:563-566. 20 McPartland JM, Guy GW, and Di Marzo V. Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system. PLoS ONE. 9(3):e89566. Doi:10/1371/journal.pone.0089566. 21 Porter BE and Jacobson C. Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy & Behavior. 2013;29:574-577. 22 Porter BE and Jacobson C. Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy & Behavior. 2013;29:574-577. 23 Nelson S. 18 congressmen ask Obama to reschedule marijuana. US News. February 12, 2014. Accessed at http://www.usnews.com/news/articles/2014/02/12/18-congressmen-ask-obama-to-reschedule-marijuana on 04-21-14. 24 Hofmann ME and Frazier CJ. Marijuana, endocannabinoids, and epilepsy: Potential and challenges for improved therapeutic intervention. Experimental Neurology. 2013;244:43-50. 25 Sullum J. Obama, who evidently has not read the controlled substances act, denies that he has the power to reclassify marijuana. Forbes. January 31, 2014. Accessed at http://www.forbes.com/sites/jacobsullum/2014/01/31/obama-who-evidently-has-not-read-the-controlled-substances-act-denies-that-he-has-the-power-to-reclassify-marijuana/ Originally published in the June 2014 issue of Veterinary Practice News
