As one of the first two states in the United States to legalize cannabis, Colorado has been at the forefront of research. The Institute of Cannabis Research at Colorado State University Pueblo has just kicked off a series of virtual events during which researchers discuss their work, and where research is headed.
The first such webinar featured Stephanie McGrath, an associate professor of neurology and neurosurgery at the College of Veterinary Medicine and Biomedical Science at Colorado State University in Fort Collins. She focused her presentation on her work covering the use of cannabidiol (CBD) for dogs that have seizure disorders, and how glioma cancer cells in dogs respond to CBD treatment.
The next CU Pueblo research webinar will feature David Shurtleff, deputy director of the National Center of Complementary and Integrative Health, and will focus on the National Institute of Health’s “interest in cannabis research.”
(Read Cannabis Wire’s previous coverage of research out of Baylor College of Medicine, within the Texas Medical Center, on the therapeutic potential of CBD for dogs experiencing pain from arthritis.)
Like many medical professionals, McGrath didn’t enter medical school with a decision on which path she’d like to pursue, but she eventually settled on neurology. McGrath referred to epilepsy in dogs, the most common neurologic disorder in canines, as an “eye opener” that hit home, because existing treatments seemed inadequate, she said.
“Until you witness this, it’s really hard to appreciate what owners are going through,” McGrath said, referencing dogs undergoing grand mal seizures. “But when you’re looking at this dog’s eyes and you’re looking into the eyes of this family that are going through this very emotional, very traumatic and violent disease,” she said, you connect to the “real emotional aspect of it like this.”
While McGrath completed her residency in Colorado, legal adult use cannabis sales were taking off. McGrath referenced Charlotte Figi, a young girl whose family moved her to Colorado for access to CBD to treat her seizures. (Figi, who became internationally known for helping to catalyze the CBD-as-medicine movement, died in April). Watching the Sanjay Gupta special on Figi and CBD on CNN, McGrath wondered if CBD might have the same seizure-reducing effects on dogs.
“I went through school knowing marijuana is toxic for dogs. ‘It’s terrible. Don’t use it. Stay away from it.’ We see marijuana toxicosis in our emergency rooms,” McGrath said.
McGrath began her research on CBD at CSU under the 2014 Farm Bill, which allowed for states to launch hemp pilot programs. Hemp is abundant in CBD. But, she said, her work became easier when lawmakers passed the 2018 Farm Bill, which removed hemp, defined as cannabis plants containing .3% THC or less, from the list of controlled substances.
“I think it’s made it a lot easier for collaborators and other researchers and scientists to start exploring cannabis at their institutions as well, which is great,” McGrath said. She added that her own research began, in some senses at ground zero, because there were so few studies on dogs and CBD that could serve as a starting point for additional work.
“We had essentially no foundation for using this drug despite it being around forever. And so we had a lot of questions about bioavailability, whether this drug would even be absorbed,” she said.
McGrath started with a pharmacokinetic study during which 30 dogs were given three different CBD formulations. The dogs received a six-week course of two doses daily. The beagles used for the study were research animals that were “purpose-bred” for pharmacokinetic studies and that are adopted out once they reach middle age. Researchers looked for safety, drug tolerance, and any major adverse effects.
“It was very encouraging that at least we had a foundation, somewhere to go with this,” McGrath said, referencing that the oral preparations were at least measurable in the dogs’ blood streams. “Fortunately for adverse events, those were also fairly well-tolerated,” she said. The only major side effect was diarrhea, “which was transient, but it did occur in all dogs at all dosages at various time points.” There also was an elevation in one of the liver enzymes, alkaline phosphatase, and while the researchers didn’t have concerns related to short-term liver toxicity concerns, “that was definitely something we noted and wanted to continue to monitor.”
Overall, McGrath said, she felt that this study’s results would allow her to proceed to clinical trials in client-owned animals, starting with epilepsy. Her first effort was on the short-term effect of CBD on seizure frequency in dogs suffering from poorly-controlled idiopathic epilepsy. A total of sixteen dogs participated in this study, a limitation with such a small cohort, with nine in the treatment group and seven in the control group. All of these dogs had a confirmed diagnosis of idiopathic epilepsy, and they all had to remain on their standard anticonvulsant treatment during the three-month study. Researchers then added either CBD to the treatment regimen, or a placebo.
“We did see a significant reduction in seizure frequency in the treatment group as compared with the control group,” McGrath said. But, she added, when they looked at “responders,” a common way of recording antiepileptic drug efficacy, they wanted the dogs to have at least a 50 percent reduction in seizure activity, which didn’t happen.
“We concluded from this study that, although we did get some encouraging results, there’s still a lot more work to be done,” she said.
McGrath said the most interesting part of the study, to her, was that she saw a “significant correlation” between plasma level and seizure change.
“As the dogs, that for whatever reason, metabolize the drug in such a way that they reached higher plasma levels, they actually had a further decrease in seizure activity than dogs that never reach that level. And so seeing that correlation really gave me a lot of hope that if we can get more dogs sort of across the … arbitrary threshold, that we may be able to see better, more positive results,” McGrath said.
McGrath’s next clinical study was funded by the American Kennel Club Canine Health Foundation, and was much larger, with 60 dogs. It was a prospective double blind, placebo-controlled crossover study. The dogs in the study received either CBD or placebo in the first phase, and then CBD or placebo for the second phase.
“It gives us a bit more of a powerful study because each dog is able to be compared to itself as well as the treatment group and the control group,” she said. For this study, CBG was also added, and doses were increased in an effort to get more dogs into a higher-level plasma range. During the course of this study, Epidiolex, a CBD-based cannabis plant extract, was approved by the Food and Drug Administration, which McGrath and her team started using as part of the study.
“Spoiler alert: I do not have results of the study yet,” McGrath said. She and her team wrapped up enrollment last month, and the last dog is expected to finish in March, allowing them to publish results sometime next year.
“Overall, we didn’t see any clinical signs that were of concern. We are also measuring antiepileptic drug levels throughout the studies. So we are going to also assess whether CBD has any effect on raising or lowering the antiepileptic drug levels as well,” she said.
