The aim of these studies in healthy cats was 2-fold: first, to evaluate the postprandial time course of plasma CBD concentrations over 4 hours following ingestion of an initial dose, and also after 2 weeks of daily supplementation at 4mg/kg BW; and second to demonstrate tolerance of daily supplementation of 4mg/kg BW over a 26-week period.

Peak mean CBD concentration in plasma was found at 2 h post-dose at both d0 (251 ng/mL) and week 2 (431 ng/mL), and CBD absorption and clearance rates were higher at week 2 compared to the first dose. This conclusion was inferred from the significant increase in AUC coupled with the lack of differences between the postprandial concentrations of plasma CBD. 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). In our study, the 2 h data of 251 ng/mL (95% CI: 108.7, 393.4) from cats fed a meal with their CBD dose are more similar to those reported by Wang et al. (15) for the first dose in their study at 282 ng/mL (±149.4), where the meal was fed 1 h after the CBD/CBDA paste offering. We observed an AUC upon first dose of 621.7 ng/mL (95% CI: 387.5, 855.9) over our 4 h time course compared to 908.5 ng/mL (±528.1) over 24 h in the literature (15), indicating that there is potentially a higher presence of CBD in the plasma after a dose of CBD/CBDA paste when compared to CBD in sunflower oil and that there is circulating CBD beyond the 4 h mark. When comparing these AUC values, it should be noted that pharmacokinetic software packages have been used by the other groups, likely employing a linear-log trapezoidal method, while our analysis employed a linear trapezoidal method which may overestimate the AUC (26). Given the comparatively short time frame (4 h) of our postprandial sampling, any impact of this overestimate should be limited. When comparing the literature, it is important to understand the compositions of the treatments being used as inclusion of several phytocompounds has been shown to alter the observed effects when compared to single phytocompounds. This observation, named the “entourage effect” by several publications (27–29), describes the potential for other compounds found in hemp, such as THC or CBG, to interact and possibly increase absorption of CBD (30). Both the U.S. Food and Drug Administration (FDA) and European Food Safety Authority (EFSA) have expressed concerns over the limitations of the current literature when it comes to interpreting safety due to the different preparations and extracts, varying concentrations of CBD or other cannabinoids, small sample sizes, and quality of the data (31, 32).

This is the first study in cats to report data on fasted plasma CBD concentrations using uniform dosing over a period of more than a week and after a washout period. 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). Our BCS data were insufficiently broad to assess this. Moreover, due to the semi-qualitative nature of this measurement and potential for assessor bias, the ability to confirm this via BCS is limited and alternative methods of assessing fat content should be considered. Similar trends in plasma CBD concentrations were seen in a comparable study performed in dogs, and additionally the routes of excretion, i.e., via the feces rather than urine, also appear to be consistent (11).

To evaluate whether chronic daily feeding of CBD was safely tolerated by the cats, both groups received regular veterinary examinations, as well as routine assessment of hematology, clinical biochemistry, and urinalysis. With the exception of cholesterol, sodium:potassium ratio, mean platelet volume (MPV), and eosinophil count, all group means for biochemistry and hematology analytes remained within published reference ranges throughout the 26-week study. Differences between groups or over time were transient and not deemed to be of clinical significance during the weekly and fortnightly veterinary reviews.

Across both studies, three cats experienced high ALT with concurrent inappetence and/or general lethargy. These cats were subsequently diagnosed, via abdominal ultrasound as well as blood biochemistry and complete blood count information, with suspected ascending cholangitis (an inflammation of the gall bladder and liver). One cat was in the placebo group and two in the CBD group. It is unknown whether the incidence of cholangitis was higher in the CBD group coincidentally or if the supplement (and/or involvement in the study) contributed through added pressure on the hepatic (and any linked) system and metabolic processes in these cats. The clinical opinion, however, was that CBD itself was unlikely to have caused the infection directly. Literature suggests that the prevalence of cholangitis in cats worldwide is common and cited as the second most common hepatic disease (33) across the four distinct forms of the condition: neutrophilic, lymphocytic, destructive, and chronic (34). The asymptomatic cat from study one was followed beyond study completion, no further complications were noted, and a return to normal range for ALT and AST occurred within 3 weeks. The changes in liver enzymes observed in specific individuals in the present studies, considered together with the variability of plasma CBD measurements, suggest that there are likely to be individual differences in the response of cats to multiple doses of CBD. It is not known whether there is a genetic basis for susceptibility to high ALT (or hypertransaminasemia). When evaluating adverse observations such as hypertransaminasemia potential drug interactions are the focus (35), however, during these studies we controlled access to any potential medications that could interact with CBD to minimize this risk. It is known that cats have a low capacity for hepatic glucuronidation which reduces the capacity for metabolism and excretion of several compounds including non-steroidal anti-inflammatories and CBD (16, 36). This may be a contributing factor to the differences between dog and cat responses to CBD; however, future work to address individual susceptibility could explore metabolomics of CBD absorption and excretion.

In conclusion, THC-free CBD fed at a dose of 4 mg/kg BW was absorbed into plasma and well tolerated when supplemented over 26 weeks in cats. However, caution should be applied, and veterinary checks recommended, if any history of liver issues is known or in the event of suspected concurrent infection. There is also further need for determining efficacy of CBD doses to improve our understanding of CBD and its use in cats.