What is it?

Diabetes mellitus is an autoimmune disease that causes an increase in blood glucose (sugar) levels. Type 1 diabetes is characterized by the body’s inability to produce insulin, while type 2 diabetes is characterized by the body’s inability to properly use insulin, known as insulin resistance.

What about Metabolic Syndrome?

Most commonly known as pre-diabetes, metabolic syndrome is a combination of conditions that increase the risk of heart disease, stroke, and type 2 diabetes. It is characterized by high blood pressure, high blood sugar levels, excess abdominal fat, abnormal cholesterol levels, and insulin resistance. The exact cause of metabolic syndrome is unknown, but it is believed to be related to a combination of genetic and environmental factors, including obesity, physical inactivity, and poor diet. Symptoms of metabolic syndrome may include increased waist circumference, high blood pressure, high blood sugar levels, high triglyceride levels, and low levels of HDL cholesterol.

The endocannabinoid system (ECS) plays an important role in metabolism, dysmetabolism, and the intestinal microbiome, making it a new and emerging target system in the treatment of metabolic syndrome and diabetes.

There are currently more than seventy studies examining the use of cannabis components for diabetes treatment. Collectively, the data suggest that there are several mechanisms by which modulation of the endocannabinoid system can produce relevant therapeutic effects, including:

• Improved metabolic function
• Reduction of insulin resistance
• Decreased obesity rates
• Improved lipid and glucose parameters
• Reduction of pancreatic inflammation
• Reduction of autoimmune dysfunction
• Antioxidant properties
• Reduction of diabetic comorbidities (such as heart disease, obesity, neuropathies)

Clinical trials in humans have focused on the effects of the phytocannabinoids CBD and THCV, as well as hemp protein consumption in diabetic patients.

The most promising data comes from a 2020 meta-analysis, suggesting that THCV is the best cannabinoid candidate for diabetes and may provide therapeutic benefits to patients. A double-blind study involving 62 individuals evaluated the effects of THCV and CBD in different ratios. The main findings were that compared to the placebo, THCV significantly reduced fasting plasma glucose and improved pancreatic beta cell function, although plasma HDL was not affected. Compared to the start of the study (but not the placebo), CBD reduced resistin and increased glucose-dependent insulinotropic peptide. THCV may represent a new therapeutic agent in glycemic control for individuals with type 2 diabetes, as it may aid in neuroprotection, appetite suppression, and glycemic control, with a low side effect profile.

Animal studies have shown the protective role of CBD in diabetes, metabolic syndrome, and comorbidities. A 2016 animal study demonstrated that experimental CBD treatment reduces early pancreatic inflammation in type 1 diabetes (reduction in inflammation markers in pancreatic microcirculation studied by intravital microscopy). Other preclinical studies indicate that CBD can reduce levels of aspartate transaminase (AST) and alanine transaminase (ALT); reduce cardiovascular response to stress models, playing a positive role in the heart, peripheral vasculature, and cerebral vasculature; improve parameters of anxiety and depression in diabetic animals. The results of a 2005 Israeli study indicate that CBD can inhibit and delay destructive insulitis and the production of inflammatory Th1-associated cytokines in mice, resulting in a reduced incidence of diabetes, possibly through an immunomodulatory mechanism shifting the immune response from Th1 to Th2 dominance.

Furthermore, in a clinical trial in humans, participants who consumed 40g of hemp protein per day showed a reduction in postprandial glucose and insulin concentrations (in a dose-dependent manner).

Evidence points to the enormous potential of medical cannabis in helping to treat and prevent metabolic syndrome, diabetes, and comorbidities. However, further research is needed to determine each case’s effectiveness, safety, and proper dosage. As of now, cannabis treatment does not replace conventional treatment. Moderation of lifestyle, adjustment of various nutritional factors, appropriate physical exercise, and also the use of adjunct cannabinoid-based therapies can be valuable strategies.

References:

• Abioye A, Ayodele O, Marinkovic A, Patidar R, Akinwekomi A, Sanyaolu A. Δ9-Tetrahydrocannabivarin (THCV): a commentary on potential therapeutic benefit for the management of obesity and diabetes. J Cannabis Res. 2020 Jan 31;2(1):6. doi: 10.1186/s42238-020-0016-7. PMID: 33526143; PMCID: PMC7819335.
• Chaves YC, Genaro K, Crippa JA, da Cunha JM, Zanoveli JM. Cannabidiol induces antidepressant and anxiolytic-like effects in experimental type-1 diabetic animals by multiple sites of action. Metab Brain Dis. 2021 Apr;36(4):639-652. doi: 10.1007/s11011-020-00667-3. Epub 2021 Jan 19. PMID: 33464458.
• Di Marzo V, Piscitelli F, Mechoulam R. Cannabinoids and endocannabinoids in metabolic disorders with focus on diabetes. Handb Exp Pharmacol. 2011;(203):75-104. doi: 10.1007/978-3-642-17214-4_4. PMID: 21484568.
• Jadoon KA, Ratcliffe SH, Barrett DA, Thomas EL, Stott C, Bell JD, O’Sullivan SE, Tan GD. Efficacy and Safety of Cannabidiol and Tetrahydrocannabivarin on Glycemic and Lipid Parameters in Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Pilot Study. Diabetes Care. 2016 Oct;39(10):1777-86. doi: 10.2337/dc16-0650. Epub 2016 Aug 29. PMID: 27573936.
• Lehmann C, Fisher NB, Tugwell B, Szczesniak A, Kelly M, Zhou J. Experimental cannabidiol treatment reduces early pancreatic inflammation in type 1 diabetes. Clin Hemorheol Microcirc. 2016;64(4):655-662. doi: 10.3233/CH-168021. PMID: 27767974.
• Mollard RC, Johnston A, Serrano Leon A, Wang H, Jones PJ, MacKay DS. Acute effects of hemp protein consumption on glycemic and satiety control: results of 2 randomized crossover trials. Appl Physiol Nutr Metab. 2021 Aug;46(8):887-896. doi: 10.1139/apnm-2020-0907. Epub 2021 Jan 25. PMID: 33493023.
• Weiss L, Zeira M, Reich S, Slavin S, Raz I, Mechoulam R, Gallily R. Cannabidiol arrests onset of autoimmune diabetes in NOD mice. Neuropharmacology. 2008 Jan;54(1):244-9. doi: 10.1016/j.neuropharm.2007.06.029. Epub 2007 Jul 17. PMID: 17714746; PMCID: PMC2270485.
• Zorzenon MRT, Santiago AN, Mori MA, Piovan S, Jansen CA, Perina Padilha ME, Ciotta SR, Cezar de Freitas Mathias P, Guimarães FS, Weffort de Oliveira RM, Milani PG, Mareze-Costa CE. Cannabidiol improves metabolic dysfunction in middle-aged diabetic rats submitted to a chronic cerebral hypoperfusion. Chem Biol Interact. 2019 Oct 1;312:108819. doi: 10.1016/j.cbi.2019.108819. Epub 2019 Sep 6. PMID: 31499052.