Exploring the Connection Between Cannabis and Diabetes
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Understanding the Role of the Endocannabinoid System
In the previous installment, I outlined how diabetes negatively impacts blood sugar regulation due to insulin resistance or insufficient production. In recent years, the endocannabinoid system (ECS) has been identified as a significant player in managing body weight and metabolism. This section of "Cannabis and Diabetes" will delve into the ECS's functions and its implications for diabetes management.
Balancing Energy Intake and Expenditure
Obesity is the primary risk factor for Type 2 diabetes, arising from a prolonged imbalance between energy intake and expenditure. In simple terms, energy balance refers to the calories consumed versus those burned. When calorie intake exceeds expenditure, the body stores the excess as fat. Although temporary fluctuations in energy balance are manageable, chronic imbalances can lead to severe health issues. Consequently, sustaining a healthy energy balance is crucial for overall well-being.
The ECS, composed of various signals and receptors, is integral to maintaining energy balance. Notably, it does not merely promote weight gain; rather, it plays a complex role in the process. Cannabinoid Receptor 1 (CB1), prevalent in brain regions that regulate food-seeking behaviors and reward, when activated, increases hunger-inducing hormones while suppressing satiety hormones. This activation also stimulates reward pathways, enhancing the pleasure associated with eating. These combined effects may contribute to what some researchers call the "thrifty genotype," where our bodies behave as if food scarcity is a constant threat.
Simultaneously, ECS activity outside the brain can diminish energy expenditure. CB1 promotes sugar absorption and storage in fat cells while inhibiting the formation of metabolically active "brown" fat. This mechanism leads to an accumulation of less active "white" fat, which not only decreases energy output but also raises endocannabinoid levels in the bloodstream. These endocannabinoids further activate CB1, perpetuating food-seeking behaviors and increasing fat storage. Thus, ECS activation can contribute to obesity and Type 2 diabetes.
The first video titled "Marijuana and Diabetes: What's All the High - Er, Hype - About?" explores the complex relationship between cannabis use and diabetes management. It offers insights into the potential benefits and risks associated with using cannabis for diabetic individuals.
Exploring Evidence from Research
A significant portion of our understanding regarding the ECS stems from animal studies, particularly with rodents. Although these findings are invaluable, they do not always translate directly to human biology. Fortunately, there is considerable human data available, particularly from studies of rimonabant, a now-discontinued medication intended for weight loss and diabetes management.
Rimonabant is a selective CB1 antagonist that binds to and inhibits this receptor. Approved in 2006 within the European Union, it was marketed as an appetite suppressant due to its effects on brain reward pathways. Early clinical trials indicated it was generally well-tolerated and effective in promoting weight loss while reversing some metabolic issues associated with obesity and Type 2 diabetes. Projections at its launch suggested it might eventually gain FDA approval in the US.
However, the effects of blocking the brain’s reward system led to severe side effects, including anxiety, depression, sleep disturbances, and suicidal ideation. Tragically, several patients who used rimonabant took their own lives, and numerous trial participants withdrew due to psychological distress, leading to the premature termination of studies for safety concerns. Consequently, rimonabant was never introduced to the American market and was withdrawn from European markets in 2008.
The second video, "What to Know About Cannabis Use and Type 1 Diabetes, with Halis Akturk, MD," provides valuable insights into how cannabis may impact individuals with Type 1 diabetes, discussing both potential advantages and challenges.
Understanding Diabetic Complications
This unfortunate situation highlights the ECS's crucial role in regulating both metabolic and mental health. Its influence extends beyond energy balance; components of the ECS are linked to various adverse health effects associated with both Type 1 and Type 2 diabetes. Below is a brief overview of these effects and the potential therapeutic benefits of modulating the ECS outside of the brain.
β-cell Viability
Research indicates that CB1 in the pancreas may contribute to β-cell death. The Zucker diabetic fatty rat serves as a prominent Type 2 diabetes model, demonstrating progressive β-cell loss and metabolic irregularities akin to human Type 2 diabetes. Administering CB1 antagonists to these rats has been shown to mitigate β-cell deterioration, although the underlying mechanisms remain partially understood. This approach is less likely to assist in preventing Type 1 diabetes, where β-cell loss is primarily driven by autoimmune responses.
Non-Alcoholic Fatty Liver Disease (NAFLD)
NAFLD, characterized by fat accumulation in the liver, often disrupts its normal functioning and correlates strongly with obesity and Type 2 diabetes. A recent meta-analysis found that approximately 54% of Type 2 diabetes patients also exhibit NAFLD. This condition arises when the liver's production of fatty acids outpaces its capacity to utilize them for energy. Evidence suggests that CB1 activation in the liver inhibits the genes responsible for fatty acid oxidation, while the absence of CB1 protects the liver from high-fat diet effects.
Diabetic Nephropathy
Diabetic nephropathy entails gradual kidney function deterioration due to diabetes, leading to severe complications. Both types of diabetes can elevate CB1 levels in the kidneys, resulting in inflammation and damage. This increased CB1 expression activates genes that control sugar absorption, eventually harming kidney cells. Interestingly, some studies in rodents indicate that stimulating CB2 may counteract these adverse effects.
Diabetic Neuropathy
Diabetic neuropathy, which affects a significant portion of individuals with either Type 1 or Type 2 diabetes, often manifests as painful sensations in the extremities. While ECS activation has shown promise in pain management, activating CB1 may exacerbate other diabetic complications, raising questions about the safety and efficacy of ECS modulation for pain relief.
Diabetic Retinopathy
Diabetic retinopathy affects over 80% of individuals who have had diabetes for two decades or more. Early stages may not present symptoms and can only be detected through eye examinations. As the condition progresses, it leads to blood vessel damage in the retina, resulting in serious vision issues. Activation of CB1 in the retina is associated with increased oxidative stress and inflammation, accelerating retinopathy's progression. Blocking CB1 can mitigate this damage and slow down the condition's advancement.
While much of this evidence originates from laboratory models, the ECS's involvement in diabetic complications is increasingly evident. Researchers are now focusing on developing new generations of CB1 blockers that retain the protective benefits of rimonabant without affecting the brain's reward centers. Although such therapies have not yet undergone clinical trials, their potential is promising.
In the next section, I will discuss natural ECS modulators, particularly plant-based cannabinoids, and their roles in managing energy balance and diabetic complications.
About the Author
- Brandon Lowry holds a PhD from the Institute of Molecular Biology at the University of Oregon. As a digital nomad and freelance writer, he explores topics related to cannabis, science, health, and travel. He also serves as the editor for Midnight Mosaic Fiction.