Previous epidemiological studies have suggested that marijuana use leads to a lower prevalence of obesity and diabetes vs. rates among those who have never used marijuana. In a recent study, researchers found that marijuana users displayed lower fasting insulin levels, insulin resistance and smaller waist circumference compared with those who did not use marijuana.

“It is possible that the inverse association in fasting insulin levels and insulin resistance seen among current marijuana users could be in part due to changes in usage patterns among those with a diagnosis of diabetes (ie, those with diabetes may have been told to cease smoking). However, after we excluded those subjects with a diagnosis of diabetes mellitus, the associations between marijuana use and insulin levels, [homeostasis model assessment of insulin resistance], waist circumference and HDL-C were similar and remained statistically significant,” study researcher, Elizabeth Penner, MD, MPH, said in a press release.

In a cross-sectional study, the researchers examined data from 4,657 adults from the National Health and Nutrition Examination Survey (2005-2010). Patients aged 20 to 59 years completed self-report assessments of marijuana use, and fasting insulin and glucose were measured after a 9-hour fast.

According to study data, 579 patients were current marijuana users and 1,975 were past users. Researchers found that current marijuana use was associated with 16% lower fasting insulin levels (95% CI, −26 to −6) and 17% lower HOMA-IR (95% CI, −27 to −6), and 1.63 mg/dL higher HDL levels (95% CI, 0.23-3.04) in multivariable adjusted models. Additionally, the researchers reported significant associations between marijuana use and smaller waist circumference despite higher caloric intake.

In an accompanying editorial, Joseph S. Alpert, MD,professor of medicine at the University of Arizona College of Medicine in Tucson, said the data were impressive.

“Is it possible that THC will be commonly prescribed in the future for patients with diabetes or metabolic syndrome alongside antidiabetic oral agents or insulin for improved management of this chronic illness? Only time will answer this question for us,” Alpert, editor-in-chief of The American Journal of Medicine, wrote. “Nevertheless, what is very clear is that we desperately need a great deal more basic and clinical research into the short- and long-term effects of this agent in a variety of clinical settings, such as cancer, diabetes and frailty of the elderly. I would like to call on the National Institutes of Health and the Drug Enforcement Administration 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.”

Source: healio.com/endocrinology

Discussion

In this large, cross-sectional study, we found that subjects who reported using marijuana in the past month had lower levels of fasting insulin and HOMA-IR, as well as smaller waist circumference and higher levels of HDL-C. 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.

There have been discrepant findings on the relationship between marijuana use and BMI. A study of young adults examining associations between marijuana use and cardiovascular risk factors reported no significant trend between marijuana use and BMI,⁵ whereas analyses of 2 large nationally representative surveys found lower BMI and decreased prevalence of obesity.⁴, ⁶ Few studies have explored possible underlying explanations for these associations. However, a recent analysis using NHANES III data showed that marijuana users had a lower prevalence of diabetes mellitus compared with nonusers;⁷similar results have been found with administration of cannabidiol in a mouse model.¹¹ In the present study, we demonstrate a significant association between current marijuana use and lower levels of fasting insulin and insulin resistance in multivariable adjusted analyses even after excluding participants with prevalent diabetes mellitus.

Particular focus has been given to the plant cannabinoid (-)-trans-Δ⁹-tetrahydrocannabinol, which acts as a partial agonist at both the cannabinoid type 1 and 2 receptors, and cannabidiol, which has lower affinity for the cannabinoid receptors but appears to antagonize both cannabinoid type 1 and 2.¹², ¹³ In addition, it has been found that repeated administration of cannabinoids reduces cannabinoid type 1 receptor density, producing a tolerance to its physiologic effects.¹², ¹⁴ Thus, a dose-response relationship may be expected; however, we did not find any evidence of this in the present study.

Although not completely elucidated, the mechanisms by which cannabinoids affect peripheral metabolism via these receptors have been studied extensively; the cannabinoid type 1 receptor antagonist, rimonabant, was found to improve insulin sensitivity in wild-type mice, but not in adiponectin knockout mice, suggesting that adiponectin at least partially mediates the improvement in insulin sensitivity;¹⁵ adiponectin has been reported to improve insulin sensitivity.¹⁶ This rimonabant-induced improvement in insulin resistance has been confirmed in human studies.¹⁷ Furthermore, in a randomized clinical trial, rimonabant was significantly associated with an increase in plasma adiponectin levels, as well as weight loss and a reduction in waist circumference.¹⁸ Cannabis itself, when administered to obese rats, was associated with weight reduction and an increase in the weight of pancreata, implying beta-cell protection.¹⁹ In addition, cannabinoid type 1 knockout mice are resistant to diet-induced obesity, suggesting that the role of this receptor is central in the metabolic processes leading to obesity.²⁰ Given that 2 of the main active phytocannabinoids in marijuana, (-)-trans-Δ⁹-tetrahydrocannabinol and cannabidiol, are classified as partial agonists and antagonists, respectively, and are thus capable of producing antagonistic effects at the cannabinoid receptors, it is possible that the associations observed in the aforementioned studies, as well as in the present study, are due at least in part to this adiponectin-mediated mechanism.

In our analyses, we presented alternative models, controlling for BMI as a potential confounder of the relationship between marijuana use and the remainder of the cardiometabolic parameters. We generated this model because of the potential for BMI to affect marijuana use and independently affect the cardiometabolic parameters. On the other hand, BMI may be a mediator of the association between marijuana use and the cardiometabolic outcomes, and thus was excluded from our primary multivariable model.