Cannabinoids and obesity: could cannabis help tackle a global health crisis?

In a new extract from the Principles of Cannabinology Handbook, Viola Brugnatelli and Fabio Turco, examine whether cannabis could play a role in tackling the global obesity crisis.

Obesity has evolved into a significant public health crisis, with alarming global prevalence rates and with profound health and economic implications. Aside from healthcare costs, lost productivity at work, an increase in mortality rates, and permanent disabilities are also consequences. Obesity demands innovative solutions, and the cannabis plant might hold a key to unlocking new treatment modalities.

In this article – an extract from the Handbook Principle of Cannabinology by Cannabiscientia SA- we embark on a journey to explore the potential of Tetrahydrocannabinolic Acid (THCA) and other cannabinoids in the context of obesity and its associated health concerns. 

Obesity in brief

With obesity’s prevalence tripling since 1975 and affecting over 1.9 billion adults, this condition is associated with cardiovascular diseases, diabetes, and other components of metabolic syndromes, making it a major public health concern. The pathophysiology of obesity involves an imbalance in energy intake and expenditure, leading to the accumulation of triglycerides in white adipose tissue. Hormonal dysregulation, such as leptin resistance and insulin resistance, contributes to the pathophysiological mechanism of obesity, while chronic inflammation is a key component, with proinflammatory factors produced in adipose tissue leading to systemic low-grade inflammation. Conventional approaches focus on caloric reduction and increased physical activity, but pharmacological interventions, with their limited and often short-lived effectiveness, have demonstrated unfavorable risk-benefit ratios and side effects. 

Additionally, obesity’s development is influenced by a multitude of factors, including genetics, biology, psychology, sociocultural aspects, and the environment, leading to significant variability in individual responses to treatment.

The role of thermogenesis

Thermogenesis also plays a pivotal role in controlling obesity. This metabolic process, responsible for heat production in the body, occurs predominantly in adipose (fat) and muscle tissue. Thermogenesis consumes a substantial portion of the energy produced by metabolism and, thus, holds the potential to aid in weight control.

Humans have two types of adipose tissue: 

• white adipose tissue (WAT),
• brown adipose tissue (BAT). 

The latter, known as the body’s major heat production center, contains a critical player called thermogenin, responsible for sparking thermogenesis. 

Recent discoveries have shown that we can transform white adipose tissue into brown through a process called browning, mediated partly by PPARγ receptors. These “brite” or “beige” adipocytes contribute to a decrease in body fat mass.

While lifestyle changes are the primary approach to mitigate obesity’s effects, pharmacological treatments are utilized when these efforts fall short, often accompanied by side effects and limited efficacy. As a promising alternative, Cannabis Sativa derivatives show potential as anti-inflammatory, antioxidant agents. Given the complexities and limitations of current treatments, these phytocannabinoids offer a novel approach to metabolic restoration in obesity, addressing an urgent need for more effective and safer therapeutic options.

Tetrahydrocannabinolic Acid (THCA) to treat obesity

THCA is a non-decarboxylated cannabinoid found in raw cannabis, precursor of THC. THCA doesn’t induce psychotropic effects and, instead, exhibits an affinity for PPARγ receptors (as a partial agonist), which are vital in regulating metabolic disorders, including lipid and glucose metabolism. 

Recent research highlights the potential role of THCA in addressing obesity and associated metabolic issues:

• THCA’s effectiveness was compared to traditional antidiabetic drugs like rosiglitazone (RGZ). It was found that THCA has a lower adipogenic capacity than RGZ and enhances the formation of bone-regenerating cells, offering a potential solution to RGZ’s side effects.
• THCA demonstrated several benefits in animal studies. In mice with a normal diet, it promoted thermogenesis and reduced fat mass. In mice on a high-fat diet, it not only stimulated thermogenesis but also significantly reduced fat mass, improved glucose tolerance, and prevented metabolic issues such as hepatic steatosis and adipogenesis.
• THCA induces the transformation of white adipose tissue into brown, through increased thermogenin expression, contributing to a decrease in body fat mass. It also exhibits anti-inflammatory properties, counteracting fat diet-induced inflammation.
• THCA’s partial agonist activity on PPARγ, its lower adipogenic effects, and benefits in improving bone density make it a potential candidate for managing obesity and related metabolic diseases.

Other phytocannabinoids against obesity

Apart from THCA, cannabidiol (CBD) and tetrahydrocannabivarin (THCV) hold promise in addressing obesity and metabolic concerns:

• CBD’s potential impacts include promoting the conversion of white adipose tissue into calorie-burning brown adipose tissue, reducing appetite, improving lipid metabolism, combating inflammation, enhancing insulin sensitivity, increasing thermogenesis, and influencing gut microbiota. These diverse mechanisms position CBD as a valuable candidate in obesity management.
• THCV offers a unique approach to obesity management especially because its lack of psychoactive effects. It regulates appetite, boosts energy expenditure and thermogenesis, and potentially limits fat storage. THCV is an inverse agonist/selective antagonist of the CB1 receptor, but its impact on CB1 receptors seems to vary with dosage. At lower doses, it reduces appetite, while at higher doses, it can stimulate appetite. Thus, further research are needed to fully establish its role in obesity

Addressing obesity with cannabinoids

Obesity is an escalating global health crisis, entailing significant health and economic repercussions. Its multifaceted nature, rooted in complex physiological and environmental factors, demands innovative solutions. Within this landscape, cannabis and its derivatives -mainly THCA, THCV and CBD- offer a promising avenue for exploring novel treatment modalities.

While the early findings surrounding cannabinoids and obesity management are undoubtedly promising, it’s essential to remember that this a brand-new field of study. In-depth, controlled clinical trials are required to establish the efficacy and safety of cannabinoid-based interventions.

Researchers need to delve deeper into topics such as optimal dosages, potential side effects, and the long-term impact of cannabinoids use. Furthermore, the interplay between THCA, THCV, CBD and other cannabinoids, as well as individual genetic variations, needs to be explored comprehensively.

Stay informed

To gain deeper insights into the role of cannabinoids in obesity and various other medical conditions, we encourage you to explore a comprehensive resource, the “Principles of Clinical Cannabinology.” This handbook, co-authored by Cannabiscientia SA and Prohibition Partners, is a valuable support for European healthcare professionals and anyone interested in understanding the medical applications of cannabis in Europe.

Within this single textbook, you’ll find an extensive overview of the science, regulations, medicine, and cannabis products available on the market. It covers topics ranging from the physiology of the endocannabinoid system to the pharmacology of cannabis and its clinical significance in addressing various pathologies. Practical evidence and case studies shared by experienced prescribers worldwide offer guidance in translating theory into real-world applications.

Moreover, the handbook provides a comprehensive guide to the diverse laws governing medical cannabis in 12 European countries, from Belgium to the United Kingdom. It also delves into the available products, requirements for prescribers and pharmacists, patient access pathways, and the availability of reimbursed medications.

For those seeking a deeper understanding of cannabinoids in the medical field, and especially their potential role in obesity management, the Principles of Clinical Cannabinology is an invaluable resource. By purchasing and exploring this handbook, you can stay at the forefront of the evolving landscape of medical cannabis in Europe and contribute to the ongoing advancements in healthcare.