In the first publication of its kind, a recently published study examines CBD and CBDA’s metabolism and potential drug-drug interactions involving canine cytochrome P-450 metabolism, UDP-glucuronosyltransferase conjugation and P-glycoprotein drug efflux influences.
The publication led by Dr. Michael H. Court of Washington State University utilized dog liver microsomes to better characterize how the liver metabolizes CBD+CBDA. “The way in which the liver handles CBD and CBDA has long been a question since dogs do not make the typical metabolites that rats and humans make,” said paper co-author Dr. Joseph J. Wakshlag, chief veterinary medical officer, ElleVet Sciences.
The publication suggests that CBD+CBDA are each metabolized differently in dogs, with P450 enzymes, particularly CYP1A2 and CYP2C21, playing a major role with CYP1A2 being the likely primary metabolizer of CBD. The factors influencing the activity of these enzymes, such as co-administration of drugs that are enzyme inducers or inhibitors, or genetic polymorphisms, could alter the bioavailability and biological effects of these phytocannabinoids. CBDA appears to skip the first step of the biotransformation and is directly glucuronidated (the glucose-like molecule) on the carboxylic acid, which makes CBD different from CBDA.
“This publication is emblematic of ElleVet’s mission to improve the lives of animals through science,” said, ElleVet Sciences CEO and Co-Founder Christian Kjaer. “Furthering our understanding of how CBD and CBDA is uniquely metabolized in dogs enables us to continuously innovate and develop CBDA-based products that improve the quality of life for dogs and their owners.”
“We are all excited about the profound differences in the acidic molecules and how we can tailor our products to best support different species, different situations, and to deepen our understanding of the acidics in relation to the whole endocannabinoidome,” said ElleVet Sciences CCO and Co-Founder Amanda Howland.
“We now know that the CYP1 system is heavily involved in CBD metabolism and based on physiological concentrations of CBD and CBDA observed in dogs. Pharmacodynamic modeling suggests minimal risk of significant interactions with other concomitantly used drugs at current dosing recommendations. Most importantly, CBD and CBDA does not alter activity of the multi-drug resistant transporter showing that it should be safe for all dogs,” claims Dr. Wakshlag.