This case report shows the beneficial effects of a CBD-dominant extract in a feline patient with type 2 DM. As described before, age, overweight, and genetics associated with cat breeds are comorbidity factors [4]. Tonkinese, Norwegian Forest, and Burmese cats had increased odds of DM compared to crossbred cats [16]. In this case, being overweight, neutering, and aging were relevant to developing type 2 DM in this cat. CBD-dominant extract, administered as a co-adjuvant treatment to insulin application, showed improved glycemia accompanied by reduced polyuria/polydipsia and glycosuria.

There is little information from studies in animal models about the use of full-spectrum preparations for treating insulin resistance and diabetes progression. In obese rats, cannabis extracts showed protective effects on β-cell survival and function, probably due to the control of pro-inflammatory pathways [17]. Other reports indicated that CBD improved metabolic dysfunction by incrementing insulin levels and reducing glycemia, fructosamine lipid, and total cholesterol [18]. Researchers showed that, CBD and Δ 9-tetrahydrocannabivarin (Δ9-THCV), both non-psychotropic cannabinoids, contributed to regulating glucose and lipid metabolism [14].

Despite this evidence in animal models, there is little information about the clinical impact of cannabinoids in diabetic cats. This case report constitutes a precedent of the use of CBD-enriched extract as a co-adjuvant to insulin treatment. Doses, frequency, and the way of administration of CBD or CBD-enriched extracts are relevant issues that need to be considered for medical use. For example, the administration of 100 mg twice daily of CBD in patients with type 2 DM had no effect compared with placebo, only a decreased polypeptidic hormone resistin and increased glucose-dependent insulinotropic peptide have been detected [19]. In humans, 0.18 mg/kg/day of CBD oil did not affect glycemia [20]. Herein, the dose of CBD, the main cannabinoid, was 0.49 mg/kg/day, administered twice a day (BID), transmucosal. This dose, smaller than other reports, was enough to control glycemia. A probable cause of the effectiveness might be the combination of an adequate dose of CBD with other cannabinoids and terpenes in this full-spectrum preparation. The protective impact of α-humulene on the function and survival of β-cells in diabetic rats has been reported [21]. β-caryophyllene, in conjunction with glibenclamide, a standard hypoglycemic drug, significantly reduced glycemia in rats with induced type 2 DM [22].

Another aspect to consider is the occurrence of adverse effects of cannabis administration. Although animals may well tolerate CBD, and it may have few side effects, we need to be careful with products with excess THC or toxins, such as heavy metals or pesticides that may cause harm. The most common signs of side effects are neurological, gastrointestinal, heart rate variation, and temperature control [15].

In the context of type 2 DM, information about side effects related to cannabinoid consumption is diverse. A report on a human diabetic patient shows that the replacement of insulin degludec for CBD oil did not produce secondary effects [20]. Contrarily, rimonabant, a synthetic CB1R inverse agonist, has effectively reduced food intake and body weight, two factors associated with type 2 DM. Although rimonabant was also effective in improving glucose homeostasis, it was not considered a plausible treatment due to numerous side effects [23]. In contrast, CBD and tetrahydrocannabivarin (THCV) act as antagonistic of CB1R and do not present adverse side effects such as psychoactive effects, depression, or anxiety [6]. On the other hand, the phytocannabinoid Δ9-THC is a stimulant of appetite and increases food intake, added to the psychotropic effect, not resulting in an indicated compound to treat diabetes [24]. Natural full-spectrum oil with 24:1 CBD:THC ratio used here shows positive results without secondary effects.

Herein, hepatic enzymes remain unaltered. Only the ALP exhibited a slight increment among the analyzed parameters, although it remained below the reference level. A study about the effects of long-term oral supplementation of healthy cats with 4 mg/kg of CBD extract did not show variation in hepatic parameters. They found an alanine aminotransferase increment 4 weeks after starting the study. In the long term, values did not show statistical differences compared with the placebo group [25]. It has been observed that the consumption of high therapeutic doses of CBD (more than 20 mg/kg/day) in both human patients and animal models increases the probability of hepatotoxicity, even more so when combined with other drugs, as in the case of certain antiepileptics. However, there is a lower risk of adverse hepatic effects at lower concentrations of cannabinoids contained in homemade extracts, dietary supplements, and food products [26]. More studies are needed to determine the doses at which hepatotoxic effects occur. In the same way, glucose exhibited a slight increment in the patient, which was not statistically significant compared to the treatment before CBD-enriched extract. As reported, glucose levels in cats present high variability under multiple situations. Stress hyperglycemia is frequent in sick cats or cats displaying signs of fear, including the stress of visits to medical facilities. Ambiental factors are challenging for managing DM [27].

Finally, a cannabinoid extract was conducted to reduce neuropathic pain, possibly associated with the control of oxidative stress [28, 29]. Such could explain why sleep regulation and activity state during wakefulness improved in this patient. The question remains about the effects of other compounds in extracts obtained from Cannabis sp that could potentiate the effect of cannabinoids. As we mentioned before, terpenes and flavonoids, among others, constitute a therapeutic potential in complications associated with DM [6, 30].

In summary, the present report constitutes a precedent showing that treatment with a CBD-rich extract improved the clinical condition of this feline patient with type 2 DM. However, further studies will be necessary to determine the mechanisms of action of phytocannabinoids. For example, other cannabinoid receptors beyond CB1R and CB2R are involved in the pathogenesis of DM, such as PPARs [31]. Further studies are needed to elucidate the mechanisms of action of cannabinoids on ECS and their role in DM.

Our results contribute to evaluating the relevance of the ECS in the development and progression of diabetes and the potential use of phytocannabinoids as part of the treatment. This case report constitutes a precedent for the medical use of phytocannabinoids in veterinary medicine. Information about the ECS and the potential of cannabinoids as contributors to DM treatment should be explored deeply.