Summary of several recently published veterinary cannabinoid studies:
Since 2018, there has been a sharp increase in veterinary clinical studies on cannabinoids. In the US, due to the legal hurdles surrounding the schedule 1 status of THC, studies are performed using hemp-based products. Fortunately, we are seeing more trials using THC in companion animals originating from other countries.
-In one study published in 2018,8 dogs were used to determine the pharmacokinetics of a full spectrum CBD/CBDA dominant, hemp-based oil infused formula. The elimination half-life was 4.2 hours at both the 2mg/kg and 8 mg/kg dose, with no observable side effects. Then, a randomized, placebo-controlled, double blinded, cross-over study was conducted using the same formula at 2 mg/kg BID for 4 weeks. The results were positive showing efficacy for pain associated with osteoarthritis with no adverse side effects, although 9 out of 16 of the dogs did develop rises in ALP values on serum chemistry analysis.
-Another paper, also published in 2018,9 studied the pharmacokinetic profile of 3 different formulas given to healthy research dogs at doses of approximately 10 mg/kg and 20 mg/kg. Of the 3 different formulations, oral microencapsulated oil beads, oral CBD-infused oil, or CBD-infused transdermal cream, the infused oil had the greatest absorption and bioavailability, with a half-life of 3.33 +/- 0.9 hours for the 10 mg/kg dose and a half-life of 2.13 +/- 0.54 hours for 20 mg/kg dose.
-In this study completed at CSU in 2018,10 a randomized, blinded, placebo controlled clinical trial of 26 client-owned dogs with intractable epilepsy, a CBD-infused oil was given at 2.5 mg/kg po BID for 12 weeks, in addition to existing anti-epileptic medications (AEDs). 17 dogs completed the study, 9 in the CBD group and 7 in placebo group. Those in the treatment group had a significant reduction in seizure frequency (33% median reduction in mean monthly seizure frequency), with no significant difference in serum phenobarbital or bromide concentrations. 3 of the 12 dogs assigned to the CBD group had to be removed, 1 due to worsening condition and 2 that developed ataxia. Study dogs also developed increases in ALP, with unknown clinical significance, but no adverse behavioral effects were seen.
-Another recent study published in 201911 looked at single dose PK and safety of a hemp-based CBD product in healthy dogs and cats for 12 weeks. Both species were given 2 mg/kg BID, in either an oral canine whole-plant CBD-infused soft chew or an oral feline CBD-infused fish oil. Both had CBD and CBDA in a 1:1 ratio. It showed short pharmacokinetic half-lives of CBD in dogs (T ½ life mean was 1 h) and cats (T ½ life mean was 1.5 h), with cats showing far lower oral absorption kinetics or rapid elimination suggesting dosing may differ between the two species. Safety testing revealed no significant serum chemistry evaluations in dogs, and in the feline subjects, values were not observed to be outside of the normal ranges at any time point for the cats other than a single cat with elevated ALT level during treatment. Adverse effects in dogs were minimal, loose stool being the most common at 3.3%. In cats, the most common adverse effects were licking and head shaking after administration of the oil. The study concluded that overall, hemp-based CBD appears to be relatively safe in healthy populations of dogs and cats, and dogs appear to absorb CBD better than cats.
-An exciting, recently published study12 looked at the safety and tolerability of escalating doses of 3 different cannabis formulations: CBD, THC, and a ratio product containing both CBD and THC in a 1.5:1 ratio. This randomized, placebo controlled, blinded, parallel study tested the above formulas against 2 placebos in healthy dogs, and evaluated the occurrence and severity of adverse events (AEs) during a series of up to 10 increasing doses. The highest dose achieved in each category was ~62 mg/kg CBD in the 10th dose, ~49 mg/kg THC in the 10th dose, and ~12mg/kg CBD + 8 mg/kg THC in the ratio product in the 5th dose. The doses were increased by 2-2.5 times following the initial dose, and thereafter, serial doses increased by 1.2-2-fold. The escalation interval was every 3 days. The results also showed that AEs were reported in all groups, including placebo groups, with 94.9% being mild. In the CBD group, there were only mild AEs and the dose escalation was tolerated as well as placebo, with completion of all 10 doses. In the THC group, the majority of AEs were mild, with 2 reported moderate and 1 reported as severe, also with completion of all 10 doses. The CBD:THC ratio group had the highest percentage of AEs rated as severe and necessitated the discontinuation of dose escalation after the 5 doses. Only 2 dogs developed ALP elevations during this study, both deemed not clinically significant.