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Diabetes Mellitus

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Diabetes mellitus is a group of autoimmune diseases characterized by defects in insulin secretion resulting in hyperglycemia (an abnormally high concentration of glucose in the blood). There are two primary types of diabetes. Individuals diagnosed with type 1 diabetes (also known as juvenile diabetes) are incapable of producing pancreatic insulin and must rely on insulin medication for survival. Individuals diagnosed with type 2 diabetes (also known as adult onset diabetes) produce inadequate amounts of insulin. Type 2 diabetes is a less serious condition that typically is controlled by diet. Over time, diabetes can lead to blindness, kidney failure, nerve damage, hardening of the arteries and death. The disease is the third leading cause of death in the United States after heart disease and cancer.

Preclinical studies indicate that cannabinoids may modify diabetes progression and that they also may provide symptomatic relief to those suffering from it.[1-2] A 2006 study published in the journal Autoimmunity reported that injections of 5 mg per day of the non-psychoactive cannabinoid CBD significantly reduced the incidence of diabetes in mice. Investigators reported that 86% of untreated control mice in the study developed diabetes. By contrast, only 30% of CBD-treated mice developed the disease.[3] In a separate experiment, investigators reported that control mice all developed diabetes at a median of 17 weeks (range 15-20 weeks), while a majority (60 percent) of CBD-treated mice remained diabetes-free at 26 weeks.[4] A 2013 study assessing the effect of THCV (tetrahydrocannabivarin) in genetically modified obese mice reported that the cannabinoid's administration produced several metabolically beneficial effects relative to diabetes, including reduced glucose intolerance, improved glucose tolerance, improved liver triglyceride levels, and increased insulin sensitivity. Authors concluded, "Based on these data, it can be suggested that THCV may be useful for the treatment of the metabolic syndrome and/or type 2 diabetes (adult onset diabetes), either alone or in combination with existing treatments."[5]

Other preclinical trials report that cannabinoids may mitigate various symptoms of the disease. Writing in the March 2006 issue of the American Journal of Pathology, researchers at the Medical College of Virginia reported that rats treated with CBD for periods of one to four weeks experienced significant protection from diabetic retinopathy[6] -- one the leading cause of blindness in working-age adults.

Cannabinoids have also been shown to alleviate neuropathic pain associated with the disease in animal models. A pair of studies published in the journal Neuroscience Letters in 2004 reported that mice administered a cannabis receptor agonist experienced a reduction in diabetic-related tactile allodynia (pain resulting from non-injurious stimulus to the skin) compared to non-treated controls.[7-8] The findings suggest that "cannabinoids have a potential beneficial effect on experimental diabetic neuropathic pain." More recently, researchers from the United States, Switzerland and Israel reported in the Journal of the American College of Cardiology that the administration of CBD reduces various symptoms of diabetic cardiomyopathy (weakening of the heart muscle) in a mouse model of type 1 diabetes. Authors concluded, "[T]hese results coupled with the excellent safety and tolerability profile of CBD in humans, strongly suggest that it may have great therapeutic potential in the treatment of diabetic complications."[9]

In recent years, observational trials have reported that those who consume cannabis possess a lower risk of contracting type 2 diabetes than do nonusers. Researchers at the University of California, Los Angeles assessed the association between diabetes mellitus and marijuana use among adults aged 20 to 59 in a nationally representative sample of the US population of 10,896 adults. They reported that past and present cannabis consumers possessed a lower prevalence of adult onset diabetes, even after authors adjusted for social variables (ethnicity, level of physical activity, etc.), despite all groups possessing a similar family history of diabetes. Researchers did not find an association between cannabis use and other chronic diseases, including hypertension, stroke, myocradial infarction, or heart failure compared to nonusers. Authors concluded, "Our analysis ... showed that participants who used marijuana had a lower prevalence of DM and lower odds of DM relative to non-marijuana users."[10]

A separate observational trial published in the American Journal of Medicine in 2013 reported that cannabis consuming subjects possess favorable indices related to diabetic control compared to those without a history of marijuana use. Researchers at Harvard Medical School and the Beth Israel Deaconess Medical Center in Boston assessed the relationship between marijuana use and fasting insulin, glucose, and insulin resistance in a sample of 4,657 male subjects. They concluded, "[S]ubjects who reported using marijuana in the past month had lower levels of fasting insulin and HOMA-IR [insulin resistance], as well as smaller waist circumference and higher levels of HDL-C [high-density lipoprotein or 'good' cholesterol]. These associations were attenuated among those who reported using marijuana at least once, but not in the past 30 days, suggesting that the impact of marijuana use on insulin and insulin resistance exists during periods of recent use."[11-12]

Commenting on the 2013 American Journal of Medicine study, the journal's Editor-in-Chief wrote in an accompanying commentary: "These are indeed remarkable observations that are supported, as the authors note, by basic science experiments that came to similar conclusions. ... We desperately need a great deal more basic and clinical research into the short- and long-term effects of marijuana in a variety of clinical settings such as cancer, diabetes, and frailty of the elderly. I would like to call on the NIH and the DEA to collaborate in developing policies to implement solid scientific investigations that would lead to information assisting physicians in the proper use and prescription of THC in its synthetic or herbal form."[13]

REFERENCES

[1] Croxford and Yamamura. 2005. Cannabinoids and the immune system: Potential for the treatment of inflammatory diseases. Journal of Neuroimmunology 166: 3-18.

[2] Lu et al. 2006. The cannabinergic system as a target for anti-inflammatory therapies. Current Topics in Medicinal Chemistry 13: 1401-1426.

[3] Weiss et al. 2006. Cannabidiol lowers incidence of diabetes in non-obese diabetic mice. Autoimmunity 39: 143-151.

[4] Ibid

[5] Wargent et al. 2013. The cannabinoid Δ9-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity. Nutrition & Diabetes 3 [online ahead of print]

[6] El-Remessy et al. 2006. Neuroprotective and blood-retinal barrier preserving effects of cannabidiol in experimental diabetes. American Journal of Pathology 168: 235-244.

[7] Dogrul et al. 2004. Cannabinoids block tactile allodynia in diabetic mice without attenuation of its antinociceptive effect. Neuroscience Letters 368: 82-86.

[8] Ulugol et al. 2004. The effect of WIN 55,212-2, a cannabinoid agonist, on tactile allodynia in diabetic rats. Neuroscience Letters 71: 167-170.

[9] Rajesh et al. 2010. Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, and inflammatory and cell death signaling pathways in diabetic cardiomyopathy. Journal of the American College of Cardiology 56: 2115-2125.

[10] Rajavashisth et al. 2012. Decreased prevalence of diabetes in marijuana users. BMJ Open 2

[11] Penner et al. 2013. Marijuana use on glucose, insulin, and insulin resistance among US adults. American Journal of Medicine 126: 583-589. Previous observational data has similarly reported that the prevalence of obesity in the general population is sharply lower among marijuana consumers than it is among nonusers.

[12] Strat and Foll. 2011. American Journal of Epidemiology 174: 929-933.

[13] Science Daily. May 15, 2013 "Marijuana users have better blood sugar control."






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