Diabetes is a chronic condition, characterised by high blood glucose levels. This can stem from either insulin resistance or the inability of the pancreas to produce the necessary amount of insulin to control glucose levels. As of 2023, 5% of Australians suffer from diabetes and the latest figures show these numbers are increasing. Diabetes is a manageable condition and patients can live an almost normal life; however various secondary symptoms stemming from diabetes can substantially lessen quality of life.
Neuropathy means nerve damage. Diabetic neuropathy is the most common form of neuropathy in humans. In the absence of insulin, high glucose and lipid levels in the blood stream are metabolised into toxic byproducts. These metabolites are thought to be the main cause of diabetic neuropathy, which cause oxidative stress and inflammation, which in turn can cause pain and numbness in extremities.
Diabetics generally exhibit varying levels of painful neuropathy caused by oxidative stress. Cannabidiol is a potent antioxidant capable of reducing oxidative stress and may help to prevent further nerve damage. Additionally cannabinoid receptors are densely populated through the CNS and have been shown to produce analgesia in many studies.
Causes of Diabetic Neuropathy
When glucose activates the Polyol pathway, one of the effects is decreased levels of glutathione in its reduced and oxidised states (GSH & GSSG, respectively). Glutathione is an important antioxidant in humans, preventing damage to important cellular components caused by free radicals. The reduction of GSH and GSSG levels, as well as the ratio of GSH to GSSG, in diabetics has been shown to create oxidative stress and cell damage. This is further reinforced by the increase of malondialdehyde (MDA), a marker for oxidative stress.
Possible Benefits of Endocannabinoid Activation with Cannabidiol
Studies have shown that the activation of the endocannabinoid system in diabetics results in increased levels of GSH, GSSG and the ratio of GSH to GSSG, while lowering MDA levels. This suggests that activation of the cannabinoid receptors may provide possible protection against one cause of diabetic neuropathy.
Neural Growth Factor (NGF) is an endogenous protein that plays an important role in the growth and maintenance of certain neurons. Diabetics show decreased levels of NGF in the sciatic nerve, among others. A recent study of diabetic rats treated with cannabinoids has shown their levels of NGF to be the same as healthy controls and significantly higher than the untreated diabetic animals.
A common symptom of diabetic neuropathy is pain. Studies show that the activation of the endocannabinoid system reduces pain by dulling the incoming pain signals from the peripheral nerves as well as activating the body’s endogenous pain modulatory path way. In human studies, measurements of pain are subjective with patients commenting on a reduction in pain, better sleep (due to less pain-related disturbances) and an overall better quality of life.
Night time can be particularly difficult for diabetics. A syndrome known as “restless leg syndrome” (RLS) is common. In rat models, CBD has been shown to increase mean sleep time as well as sleep latency, suggesting improvements in sleep quantity and quality.
Di Marzo, V., Piscitelli, F., & Mechoulam, R. (2011). Cannabinoids and endocannabinoids in metabolic disorders with focus on diabetes. In Diabetes-Perspectives in Drug Therapy (pp. 75-104). Springer Berlin Heidelberg.
Weiss, L., Zeira, M., Reich, S., Har-Noy, M., Mechoulam, R., Slavin, S., & Gallily, R. (2006). Cannabidiol lowers incidence of diabetes in non-obese diabetic mice. Autoimmunity, 39(2), 143-151.
Weiss, L., Zeira, M., Reich, S., Slavin, S., Raz, I., Mechoulam, R., & Gallily, R. (2008). Cannabidiol arrests onset of autoimmune diabetes in NOD mice.Neuropharmacology, 54(1), 244-249.