Diabetes has two major forms: Type 1 diabetes is an auto-immune disorder where insulin-producing β-cells in the pancreatic Islets of Langerhans are attacked by the body's immune system resulting in reduced insulin production. Type 2 diabetes results from increased tolerance of cells to insulin resulting in a reduced effect of insulin.
Either type of diabetes is a metabolic disorder where blood-glucose/energy levels are poorly maintained. As the endocannabinoid system is involved in maintaining energy homeostasis/balance, it has great potential in the prevention and/or treatment of diabetes type 2. Several components of the endocannabinoid system, such as Anandamide and CB1, CB2 and GPR55 receptors, are already implicated in (the treatment of) diabetes and more are likely to follow.
Similarly, plant cannabinoids THC and CBD have reported potential in the treatment of diabetes and more (such as THCV) are likely to follow. Apart from regulating blood-glucose levels, the endocannabinoid system is also involved in regulating the immune system, more particularly in suppressing auto-immune responses. Therefore, in theory cannabinoids have excellent potential not just to prevent, but also to slow down or even cure both type 1 and type 2 diabetes. More research is required to discover the true potential of cannabinoids in the treatment of diabetes.
DAGL inhibitors have been proposed to treat metabolic disorders due to their effects on the CB1 receptor through 2-AG (Janssen & van der Stelt, 2016).
So far, Anandamide and CB1, CB2 and GPR55 receptors are implicated in the pathophysiology of diabetes type 2 (Jenkin et al., 2014; Jourdan et al., 2014; Troy-Fioramonti et al., 2014). This suggests the endocannabinoid system is a valid target for the treatment of diabetes type 2.
In line with this, CBD and THC were found to help maintain healthy blood-glucose levels and counteract diabetic oxidative stress (Coskun and Bolkent, 2014; Wheal et al., 2014) In mice, CBD was found to prevent β-cell degeneration and insulitis and thus to reduce the incidence and slow-down the development of type 1 diabetes (Weiss et al., 2006, 2008). Similar results were obtained with THC (Li et al., 2001).
Janssen, F. J., & van der Stelt, M. (2016). Inhibitors of diacylglycerol lipases in neurodegenerative and metabolic disorders. Bioorganic & Medicinal Chemistry Letters, 26(16), 3831-3837. https://doi.org/10.1016/j.bmcl.2016.06.076
Jenkin, K.A., McAinch, A.J., Zhang, Y., Kelly, D.J., and Hryciw, D.H. (2014). Elevated CB1 and GPR55 receptor expression in proximal tubule cells and whole kidney exposed to diabetic conditions. Clin. Exp. Pharmacol. Physiol.
Jourdan, T., Szanda, G., Rosenberg, A.Z., Tam, J., Earley, B.J., Godlewski, G., Cinar, R., Liu, Z., Liu, J., Ju, C., et al. (2014). Overactive cannabinoid 1 receptor in podocytes drives type 2 diabetic nephropathy. Proc. Natl. Acad. Sci. U. S. A. 111, E5420–E5428.
Li, X., Kaminski, N.E., and Fischer, L.J. (2001). Examination of the immunosuppressive effect of delta9-tetrahydrocannabinol in streptozotocin-induced autoimmune diabetes. Int. Immunopharmacol. 1, 699–712.
Troy-Fioramonti, S., Demizieux, L., Gresti, J., Muller, T., Vergès, B., and Degrace, P. (2014). Acute Activation of cannabinoid Receptors by Anandamide Reduces Gastro-Intestinal Motility and Improves Postprandial Glycemia in Mice. Diabetes.
Weiss, L., Zeira, M., Reich, S., Har-Noy, M., Mechoulam, R., Slavin, S., and Gallily, R. (2006). Cannabidiol lowers incidence of diabetes in non-obese diabetic mice. Autoimmunity 39, 143–151.
Weiss, L., Zeira, M., Reich, S., Slavin, S., Raz, I., Mechoulam, R., and Gallily, R. (2008). Cannabidiol arrests onset of autoimmune diabetes in NOD mice. Neuropharmacology 54, 244–249.
Wheal, A.J., Cipriano, M., Fowler, C.J., Randall, M.D., and O’Sullivan, S.E. (2014). Cannabidiol improves vasorelaxation in Zucker diabetic fatty rats through cyclooxygenase activation. J. Pharmacol. Exp. Ther. 351, 457–466.
Several clinical trials have shown the potentially therapeutic effects of cannabinoids in the treatment of diabetes. Not only do cannabinoids promote weight loss, but they also help maintain healthy blood-glucose levels (Hollander, 2007; Hollander et al., 2010; Scheen et al., 2006). However, these trials used the synthetic cannabinoid Rimonabant, which is much more potent than natural cannabinoids and consequently produces many adverse effects (nausea, dizzyness, depression).
In one 16-patient trial, inhaled THC lowered the pain associated with diabetic peripheral neuropathy. Low (1%), medium (4%) and high (7%) doses all reduced perceived pain and while higher doses were more effective, they also reduced cognitive testing scores as THC does impair short-term memory (Wallace et al., 2015).
Hollander, P. (2007). endocannabinoid blockade for improving glycemic control and lipids in patients with type 2 diabetes mellitus. Am. J. Med. 120, S18–S28; discussion S29–S32.
Hollander, P.A., Amod, A., Litwak, L.E., Chaudhari, U., and ARPEGGIO Study Group (2010). Effect of rimonabant on glycemic control in insulin-treated type 2 diabetes: the ARPEGGIO trial. Diabetes Care 33, 605–607.
Scheen, A.J., Finer, N., Hollander, P., Jensen, M.D., Van Gaal, L.F., and RIO-Diabetes Study Group (2006). Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet 368, 1660–1672.