“Introduction: Diabetes mellitus (DM) is a common endocrinopathy in felines. Treatment is based on glycemic control and management of clinical signs by insulin administration coupled with a low-carbohydrate and high-protein content diet. However, achieving adequate remission or glycemia control is not always possible. Effects of cannabinoids on the regulation of glucose uptake and the incidence of diabetes have been observed in experimental models. Nevertheless, little is known about their possible relevance in controlling this condition in veterinary and human medicine.

Case presentation: This is a case study of an 18-year-old, neutered, mixed-breed female domestic longhair cat diagnosed with type 2 DM. She was treated with long-acting glargine (3-5 IU/12 h), and her diet changed to ultra-processed commercial food for diabetic cats. Three months after the start of the treatment with insulin, cannabidiol (CBD)-enriched extract in handmade olive oil, tetrahydrocannabinol: CBD ratio = 1:24, was incorporated. The route of administration was oromucosal. After 3 months, the glycemia was reduced. The patient decreased the polyuria/polydipsia, recovered sleep cycles, remained attentive to all movements, and increased her physical activity.

Conclusion: This report provides evidence that using a CBD-rich extract was effective as a co-adjuvant in alleviating clinical signs of DM and concurrent disorders, allowing for the reduction of insulin intake.”

https://pubmed.ncbi.nlm.nih.gov/39474238/

“This case report shows the beneficial effects of a CBD-enriched phytocannabinoid extract in a feline patient with type 2 DM. Added to glycemia control, indicators measured showed an improvement in the patient’s quality of life. Moreover, neurological and behavioral aspects associated with DM and aging improved. No secondary effects were observed.”

https://karger.com/mca/article/7/1/206/913300/Use-of-Cannabidiol-Dominant-Extract-as-Co-Adjuvant

“Cannabis is considered (Cannabis sativa L.) a sacred herb in many countries and is vastly employed in traditional medicine to remedy numerous diseases, such as diabetes.

This research investigates the chemical composition of the aqueous extracts from Cannabis sativa L. seeds. Furthermore, the impact of these extracts on pancreatic α-amylase and lipase, and intestinal α-glucosidase enzymes is evaluated, as well as their antihyperglycemic effect. Analysis of the chemical composition of the aqueous extract was conducted using high-performance liquid chromatography with a photodiode array detector (HPLC-DAD). In contrast, the ethanol, hexanic, dichloromethane, and aqueous extract compositions have been established. Additionally, the inhibitory effects of ethanolic, dichloromethane, and aqueous extracts on pancreatic α-amylase and lipase, and intestinal α-glucosidase activities were evaluated in vitro and in vivo.

The results of HPLC analysis indicate that the most abundant phenolic compound in the aqueous cannabis seed extract is 3-hydroxycinnamic acid, followed by 4-hydroxybenzoic acid and rutin acid. Moreover, administration of ethanolic and aqueous extracts at a dose of 150 mg/Kg significantly suppressed postprandial hyperglycemia compared to the control group; the ethanolic, dichloromethane, and aqueous extracts significantly inhibit pancreatic α-amylase and lipase, and intestinal α-glucosidase in vitro. The pancreatic α-amylase test exhibited an inhibition with IC₅₀ values of 16.36 ± 1.24 µg/mL, 19.33 ± 1.40 µg/mL, 23.53 ± 1.70 µg/mL, and 17.06 ± 9.91 µg/mL for EAq, EDm, EET, and EHx, respectively. EET has the highest inhibitory capacity for intestinal α-glucosidase activity, with an IC₅₀ of 32.23 ± 3.26 µg/mL. The extracts inhibit porcine pancreatic lipase activity, demonstrating their potential as lipase inhibitors. Specifically, at a concentration of 1 mg/mL, the highest inhibition rate (77%) was observed for EDm. To confirm these results, the inhibitory effect of these extracts on enzymes was tested in vivo. The oral intake of aqueous extract markedly reduced starch- and sucrose-induced hyperglycemia in healthy rats. Administration of the ethanolic extract at a specific dose of 150 mg/kg significantly reduced postprandial glycemia compared with the control group.

It is, therefore, undeniable that cannabis extracts represent a promising option as a potentially effective treatment for type 2 diabetes.”

https://pubmed.ncbi.nlm.nih.gov/38202676/

“The cultivation of cannabis seeds in Morocco has sparked interest in exploring their potential applications. Our research has revealed their ability, both in vitro and in vivo, to inhibit the activity of ⍺-amylase, pancreatic lipase, and intestinal ⍺-glucosidase. These enzymes play a crucial role in sugar digestion, and the observed hypoglycemic effects suggest the potential of our hemp seed extract in diabetes prevention. This effect can be explained by the presence of phenolic compounds as well as the notable antioxidant potency of the extracts, as substantiated by our prior investigations.The results of this study show interesting anti-diabetic activity, suggesting its application in the medical field and food industry. “

https://www.mdpi.com/1420-3049/29/1/93

“Ethnopharmacological relevance: In recent times the decriminalisation of cannabis globally has increased its use as an alternative medication. Where it has been used in modern medicinal practises since the 1800s, there is limited scientific investigation to understand the biological activities of this plant.

Aim of the study: Dipeptidyl peptidase IV (DPP-IV) plays a key role in regulating glucose homeostasis, and inhibition of this enzyme has been used as a therapeutic approach to treat type 2 diabetes. However, some of the synthetic inhibitors for this enzyme available on the market may cause undesirable side effects. Therefore, it is important to identify new inhibitors of DPP-IV and to understand their interaction with this enzyme.

Methods: In this study, four cannabinoids (cannabidiol, cannabigerol, cannabinol and Δ⁹-tetrahydrocannabinol) were evaluated for their inhibitory effects against recombinant human DPP-IV and their potential inhibition mechanism was explored using both in vitro and in silico approaches.

Results: All four cannabinoids resulted in a dose-dependent response with IC₅₀ values of between 4.0 and 6.9 μg/mL. Kinetic analysis revealed a mixed mode of inhibition. CD spectra indicated that binding of cannabinoids results in structural and conformational changes in the secondary structure of the enzyme. These findings were supported by molecular docking studies which revealed best docking scores at both active and allosteric sites for all tested inhibitors. Furthermore, molecular dynamics simulations showed that cannabinoids formed a stable complex with DPP-IV protein via hydrogen bonds at an allosteric site, suggesting that cannabinoids act by either inducing conformational changes or blocking the active site of the enzyme.

Conclusion: These results demonstrated that cannabinoids may modulate DPP-IV activity and thereby potentially assist in improving glycaemic regulation in type 2 diabetes.”

https://pubmed.ncbi.nlm.nih.gov/38169946/

https://www.cell.com/heliyon/fulltext/S2405-8440(23)10497-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS240584402310497X%3Fshowall%3Dtrue

“In recent years, cannabidiol (CBD), a non-psychotropic cannabinoid, has garnered substantial interest in drug development due to its broad pharmacological activity and multi-target effects. Diabetes is a chronic metabolic disease that can damage multiple organs in the body, leading to the development of complications such as abnormal kidney function, vision loss, neuropathy, and cardiovascular disease. CBD has demonstrated significant therapeutic potential in treating diabetes mellitus and its complications owing to its various pharmacological effects. This work summarizes the role of CBD in diabetes and its impact on complications such as cardiovascular dysfunction, nephropathy, retinopathy, and neuropathy. Strategies for discovering molecular targets for CBD in the treatment of diabetes and its complications are also proposed. Moreover, ways to optimize the structure of CBD based on known targets to generate new CBD analogues are explored.”

https://pubmed.ncbi.nlm.nih.gov/37933286/

“CBD is a non-psychoactive cannabinoid, which has demonstrated great translational potential. According to the current experimental results, CBD is of great value in the treatment of diabetes and its complications. CBD can improve pancreatic islet function, reduce pancreatic inflammation and improve insulin resistance. For diabetic complications, CBD not only has a preventive effect but also has a therapeutic value for existing diabetic complications and improves the function of target organs.”

https://onlinelibrary.wiley.com/doi/10.1002/EXP.20230047