Pharmacokinetics of escalating single‐dose administration of cannabidiol to cats

Abstract

Cannabis sativa is the most well-known plant containing phytocannabinoids. The two most intensely studied phytocannabinoids from this plant are delta-9-tetrahydrocannabidiol (THC) and cannabidiol (CBD). CBD lacks the psychotropic effects of THC and has been a prominent subject of research for medical uses (Brenneisen, 2007). Hemp products (cannabis plant certified to contain less than 0.3% THC by dry weight) have exploded in popularity in recent years largely due to the 2018 Farm Bill (Congress. gov, 2017-2018) which descheduled hemp and hemp seeds and declared hemp an eligible crop under the federal crop insurance program.Cannabidiol has demonstrated interaction with a wide range of receptors in humans and pre-clinical models, including CB1, CB2, GPR3, GPR6, GPR 12, GPR55, TRPV1, 5HT1, PPARγ, D2 high, mu, and delta (Peres et al., 2018). There is also evidence that CBD inhibits certain subunits of the cytochrome P450 system (CYP450) of the liver (Yamaori et al., 2011) and may interact with the orexin/hypocretin system (Murillo-Rodríguez et al., 2019). Given its purported widespread biological activity, CBD has received attention as a potential therapeutic for numerous disease processes.

Healthy cats tolerate long-term daily feeding of Cannabidiol

“…Data were highly variable between individuals but showed overall increase in circulating concentrations up to week 18. This high variability between individual cats has been noted in the literature previously ( 14 , 25 ). A recent theory describes body fat as a contributing factor, suggesting that with increased BCS there is a higher potential for CBD to be held in reservoir within the body ( 25 ).…”

“…This high variability between individual cats has been noted in the literature previously ( 14 , 25 ). A recent theory describes body fat as a contributing factor, suggesting that with increased BCS there is a higher potential for CBD to be held in reservoir within the body ( 25 ). Our BCS data were insufficiently broad to assess this.…”

“…This timing broadly agrees with recent literature ( 14 , 15 ). Deabold et al ( 14 ) dosed six fasted cats with 2 mg/kg BW of a 50:50 CBD/CBDA mix in fish oil and reported a maximum concentration of 43 ng/mL at 2 h. Rozental et al ( 25 ) also used a fasted protocol to evaluate a CBD isolate in sunflower oil, observing a maximum concentration at 2 h of 17.8 and 61.1 ng/mL for 2.5 and 5.0 mg/kg BW, respectively. Dosing of Epidiolex ® at 5 mg/kg BW to fed cats was found to increase the maximum concentration (465.3 ng/mL) and area under the curve (2650.0 h × ng/mL) data when compared to fasted dosing (269.0 ng/mL and 921.0 h × ng/mL, respectively) ( 18 ).…”

Pharmacokinetics of cannabidiol-/cannabidiolic acid-rich hemp oil in juvenile cynomolgus macaques (Macaca fascicularis)

“…In addition to NHP, PK studies of CBD or CBDA have been conducted in dogs ( 28 , 55 , 70 , 71 ), cats ( 55 , 61 , 83 ), humans ( 84–86 ), horses ( 87 , 88 ), cows ( 89–91 ), rabbits ( 92 ), guinea pigs ( 93 ), rats ( 94 ), mice ( 51 ), and parrots ( 95 ). The CBD doses examined have been highly variable, ranging from 0.5–300 mg/kg in humans ( 96 ).…”

“…Cats have a lower serum concentration of cannabinoids compared to dogs but varied by study. The C max of an orally administered pure CBD isolate in oil was 17.8 ng/mL at 2.5 mg/kg, 61.1 ng/mL at 5 mg/kg, and 132.6 ng/mL at 10 mg/kg ( 83 ). In another study administering CBD/ArHO at 2 mg/kg, the C max of CBD was 43 ng/mL in cats, 6 times lower than dogs in the same study ( 55 ); however, this C max was twice that of the C max in our subjects at 8 mg/kg.…”