CRx MAGAZINE

Winter 2020

In the Lab: Cannabis and Metabolic Health and Disease

Little research exists on the long-term effects of cannabis exposure on health and disease in humans, including type 2 diabetes. However, efforts are underway to expand the pool of knowledge in this area, as researchers at the University of California, Riverside (UCR) School of Medicine are beginning to study how cannabis affects the stable equilibrium of glucose in the blood, which is a marker of type 2 diabetes.

“We plan to investigate the impact of specific chemical constituents of the cannabis plant—under conditions of short-term exposure and long-term exposure—on glucose homeostatic mechanisms using a mouse model of obesity, which displays several important characteristics like those found in human type 2 diabetes,” says Nicholas DiPatrizio, PhD, an assistant professor of biomedical sciences at the UCR School of Medicine. “Characteristics of type 2 diabetes include hyperglycemia and impaired glucose clearance.”

“Moreover,” he adds, “we will examine the impact of cannabis exposure on the expression and function of the endocannabinoid system in organs throughout the body that control glucose homeostasis and become dysregulated in type 2 diabetes.”

DiPatrizio was awarded a three-year, $744,000 grant from the Tobacco-Related Disease Research Program, administered by the University of California Office of the President, to conduct the study. This is the first cannabis-related grant awarded to any group at the Riverside campus. In another first for UCR, DiPatrizio was required to acquire a DEA Schedule 1 license in order to obtain the cannabis and THC necessary to conduct the study.

The hypothesis of the study, in its early stages, is that chronic cannabis exposure may lead to improvements in metabolic function and glucose homeostasis in obese mice. Good metabolic health is associated with ideal levels of blood sugar, triglycerides, cholesterol, blood pressure, and waist circumference. Characteristics of poor metabolic health often include high triglyceride levels, high blood pressure, and a larger waist circumference than average. People with poor metabolic health may find that their bodies can no longer naturally maintain normal blood sugar levels.

“This hypothesis is paradoxical given the widespread reports of increased eating during cannabis intoxication, such as the ‘munchies,’ which would lead to the belief that cannabis may drive overeating and deleterious effects on metabolism,” DiPatrizio says. “In 2005, however, we reported that this munchies effect in rats lasted only for two days following administration of THC. By the third day, rats failed to have the munchies. In addition, other groups reported that diet-induced obesity was blocked in mice chronically treated with THC. Moreover, humans that chronically consumed cannabis are reported to have improvements in a variety of metabolic parameters and have a decreased prevalence of type 2 diabetes.”

DiPatrizio adds that the research team will also be testing the impact of THC alone and whole cannabis extracts matched for THC in parallel groups of mice in order to identify whether THC, or possibly other chemicals, are the main players in the context of this study.

“We do not know if THC will be the most important chemical in the cannabis plant when it comes to effects of cannabis on metabolic health and disease,” he says.

As DiPatrizio explains, type 2 diabetes is characterized by a dysregulation of the processing of glucose levels in blood and its utilization by tissues. Cannabinoid receptors on the surface of cells throughout the body—including, but not limited to, cells in the pancreas that produce and secrete insulin—control the release of insulin and are involved in the regulation of glucose levels in the body.

“Our bodies also produce chemicals called the endocannabinoids, which bind and activate these receptors and control their function,” he adds. “In contrast to the endocannabinoids that are produced in our bodies, the major psychoactive chemical in the cannabis plant, known as delta-9-THC, also binds and activates these same receptors and is thought to hijack this natural signaling system. Thus, we think of the endocannabinoids as our body’s own cannabislike molecules.”

DiPatrizio says several labs, including that at UCR, are examining roles for the endocannabinoid system in glucose homeostasis. The endocannabinoid system is the collective term for the cannabinoid receptors, the endocannabinoids, and their biosynthetic and degradative enzymes.

According to the UCR website, the DiPatrizio laboratory is dedicated to examining the integrative neurobiology and physiology that controls food reward, sensory processing, and energy homeostasis. The lab’s research emphasis is on investigating the endocannabinoid system and its lipid-derived signaling molecules, the endocannabinoids, which naturally drive the seeking and sensing of calorie-dense foods, and the storage of their energy content for future use. Endocannabinoids are thought of as the ”body’s natural cannabis,” which bind and activate the same cannabinoid receptor signaling pathways throughout the body as do chemicals found in the cannabis plant.

DiPatrizio has an extensive background in the study of the endocannabinoid system. In addition to the cannabis-related grant, he received a five-year grant from the National Institutes of Health to identify endocannabinoid signaling pathways that control feeding behavior and become impaired in obesity. The focus of this study, also conducted on a mouse model, is on developing therapeutic strategies to safely treat obesity and related metabolic disorders.

When it comes to cannabis and its effects on metabolic health and disease, DiPatrizio says there needs to be a lot more research before making any concrete conclusions on the effect of cannabis exposure in people with type 2 diabetes.

“It is indeed an exciting time for cannabinoid research,” he says. “A challenge is, of course, available funding, as well as limited access to test compounds, given that THC and cannabis are tightly controlled DEA [Drug Enforcement Agency] Schedule 1 drugs.”

— Kathy Hardy is a freelance writer based in Phoenixville, Pennsylvania.

References

1. Földy C, Malenka RC, Südhof TC. Autism-associated neuroligin-3 mutations commonly disrupt tonic endocannabinoid signaling. Neuron. 2013;78(3):498-509.

2. Bar-Lev Schleider L, Mechoulam R, Saban N, Meiri G, Novack V. Real life experience of medical cannabis treatment in autism: analysis of safety and efficacy. Sci Rep. 2019;9(1):200.

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