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 and observational studies indicate that the administration of cannabinoids is inversely associated with diabetes,[1] may modify disease progression, and may provide symptomatic relief to those suffering from the disease.[2-3] 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 genetically modified to possess the disease. Investigators reported that 86 percent of untreated control mice in the study developed diabetes. By contrast, only 30 percent of CBD-treated mice developed the disease.[4] In a separate experiment by this same research team, 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.[5] 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.”[6]
Other preclinical studies report that cannabinoids may mitigate various symptoms of the disease. For example, 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[7] — one of the leading causes of blindness in working-age adults. Other preclinical studies show that cannabinoid administration reduces diabetic-related tactile allodynia (pain resulting from non-injurious stimulus to the skin)[8-9] and symptoms of diabetic cardiomyopathy (weakening of the heart muscle). Experts have 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.”[10]
Randomized placebo-controlled clinical data has replicated some of these preclinical results. For example, a 2015 study published in The Journal of Pain reported that vaporized, whole-plant cannabis significantly reduces diabetic neuropathy in subjects resistant to other analgesics. Authors reported: “This small, short-term, placebo-controlled trial of inhaled cannabis demonstrated a dose-dependent reduction in diabetic peripheral neuropathy pain in patients with treatment-refractory pain. … Overall, our finding of an analgesic effect of cannabis is consistent with other trials of cannabis in diverse neuropathic pain syndromes.”[11] A 2017 placebo-controlled clinical trial published in the journal Diabetes Care reported that the administration of THCV “significantly decreased fasting plasma glucose” levels and improved pancreatic cell function in type 2 diabetics.[12]
Numerous observational trials have reported that those with a history of cannabis use possess a lower risk of type 2 diabetes than do those with no history of use. For example, 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, myocardial 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.”[13]
In 2013, 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.”[14]
In 2015, investigators from the Conference of Quebec University Health Centers assessed cannabis use patterns and body mass index (BMI) in a cohort of 786 Inuit (Arctic aboriginal) adults ages 18 to 74. Researchers reported that subjects who consumed cannabis in the past year were more likely to possess a lower BMI, lower fasting insulin, and lower HOMA-IR (insulin resistance) as compared to those who did not use the substance.[15] Their findings are consistent with previous research showing an inverse relationship between cannabis use and diabetic markers and are supportive of previous population data showing that those who consume cannabis, typically possess lower BMI,[16] lower odds of metabolic syndrome[17-18] and non-alcoholic fatty liver disease,[19] and are less likely to be obese as compared to those who do not.[20-21]
More recent studies have continued to reaffirm these trends. For instance, a 2018 Canadian study assessed the association between cannabis use and diabetes in a nationally representative sample, while accounting for a range of potential confounders – including lifestyle behaviors, socio-demographics, and mental health disorders. Compared to nonusers, subjects with a history of cannabis use possessed an approximately 20 percent decreased likelihood of diabetes. Those subjects with past-year marijuana use possessed an approximately 50 percent decreased risk. Authors concluded: “In sum, a decreased likelihood of diabetes for both lifetime and 12-month cannabis users versus nonusers was found after accounting for a range of potential confounders, including mental health disorders.”[22]
Another observational study published in the year 2020 assessed the relationship between cannabis consumption and fasting insulin levels and insulin resistance in a nationally representative sample of over 129,000 adults. Investigators reported that both current and past cannabis use was associated with significant and persistent changes in insulin levels in obese subjects compared to nonusers. However, these changes were only evident in overweight subjects. “[W]e found that lifetime marijuana use is significantly associated with lower fasting insulin and HOMA-IR (a measure of insulin resistance) in obese individuals,” authors concluded. “We also found that, a long time (> 10 years) after cessation, former users showed significant lower levels of fasting insulin and HOMA-IR scores than did never users, independent of their frequency of use in the past.”[23]
Hepatitis C-infected patients who use cannabis have also been documented to possess a lower risk of diabetes as compared to never-users. Researchers in 2020 reported that subjects who acknowledged current marijuana use were approximately half (OR: 0.49) as likely to have diabetes than were nonusers. Those who formerly consumed marijuana also possessed a reduced risk of diabetes as compared to never-users, but their reduced risk was not as significant (OR: 0.81).[24]
Experts in the field have called for additional clinical trials to assess the use of cannabinoids in diabetes patients under controlled conditions,[25] and observational research assessing the relationship between cannabinoids and diabetes remains ongoing.
REFERENCES
[1] Alshaaraway and Anthony. 2015. Cannabis Smoking and Diabetes Mellitus: Results from Meta-Analysis with Eight Independent Replication Samples. Epidemiology 26: 597-600.
[2] Croxford and Yamamura. 2005. Cannabinoids and the immune system: Potential for the treatment of inflammatory diseases. Journal of Neuroimmunology 166: 3-18.
[3] Lu et al. 2006. The cannabinergic system as a target for anti-inflammatory therapies. Current Topics in Medicinal Chemistry 13: 1401-1426.
[4] Weiss et al. 2006. Cannabidiol lowers incidence of diabetes in non-obese diabetic mice. Autoimmunity 39: 143-151.
[5] Ibid.
[6] Wargent et al. 2013. The cannabinoid Δ9-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity. Nutrition & Diabetes 3 [open access journal]
[7] El-Remessy et al. 2006. Neuroprotective and blood-retinal barrier preserving effects of cannabidiol in experimental diabetes. American Journal of Pathology 168: 235-244.
[8] Dogrul et al. 2004. Cannabinoids block tactile allodynia in diabetic mice without attenuation of its antinociceptive effect. Neuroscience Letters 368: 82-86.
[9] 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.
[10] 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.
[11] Wallace et al. 2015. Efficacy of inhaled cannabis on painful diabetic neuropathy. The Journal of Pain 16: 616-627.
[12] Jadoon et al. 2017. 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 39: 1777-1786.
[13] Rajavashisth et al. 2012. Decreased prevalence of diabetes in marijuana users. BMJ Open 2.
[14] Penner et al. 2013. Marijuana use on glucose, insulin, and insulin resistance among US adults. American Journal of Medicine 126: 583-589.
[15] Ngueta et al. 2015. Cannabis use in relation to obesity and insulin resistance in the inuit population. Obesity 23: 290-295.
[16] Beulaygue and French. 2016. Estimating the Relationship between Marijuana Use and Body Mass Index. The Journal of Mental Health Policy and Economics.
[17] Vidot et al. 2016. Metabolic Syndrome Among Marijuana Users in the United States: An Analysis of National Health and Nutrition Examination Survey Data. The American Journal of Medicine 129: 173-179.
[18] Waterreus et al. 2016. Metabolic syndrome in people with a psychotic illness: is cannabis protective? Psychological Medicine 46: 1651-1662.
[19] Adejumo et al. 2017. Cannabis use is associated with reduced prevalence of non-alcoholic fatty liver disease: A cross-sectional study. PLOS ONE [open access journal].
[20] Le Strat and Le Foll. 2011. Obesity and cannabis use: results from 2 representative national surveys. American Journal of Epidemiology 174: 929-933
[21] Li et al. 2016. Associations Between Body Weight Status and Substance Use Among African American Women in Baltimore, Maryland: The CHAT Study. Substance Use & Misuse.
[22] Imtiaz and Rehm. 2018. The relationship between cannabis use and diabetes: Results from the National Epidemiologic Survey on Alcohol and Related Conditions III. Drug & Alcohol Review 37: 897-902.
[23] Ngueta and Ndjaboue. 2020. Lifetime use of marijuana use in relation to insulin resistance in lean, overweight, and obese US adults. The Journal of Diabetes 12 [open access journal].
[24] Barre et al. 2020. Cannabis use is associated with a lower risk of diabetes in chronic hepatitis C-infected patients. Journal of Viral Hepatitis 27: 1473-1483.
[25] Science Daily. May 15, 2013 “Marijuana users have better blood sugar control.“