Drug-drug interactions and cannabidiol Following the approval of Epidiolex for the treatment of Epilepsy in 2018, modern medicine has received...Read more
In 2017, the global weight management and diet market was valued at $214.7 billion (USD), and it shows no signs of slowing, thanks to a CAGR of around 8.3%. Growth in the industry is being driven by increased awareness programs advocating wellness and fitness, improved diagnosis of chronic diseases such as diabetes, and extensive distribution channels in new markets.
In recent times, the industry’s diet and drug segments have witnessed the introduction of new products. New diet combinations have been formulated with new natural products tested for their potential to help with weight loss. Over the years, studies have investigated and supported the finding of some plant-derived products as worthy additions to the weight management industry’s organic product catalog—one of those additions: cannabidiol, or CBD.
The endocannabinoid system and weight control
An efficient weight control program involves a systematic study of the cellular and molecular circuitry playing important roles in feeding behavior, satiety, and weight control. The therapeutic exploitation of this circuitry holds therapeutic benefits in weight management. The endocannabinoid system is an intricate network of receptors, endogenous cannabinoids, and enzymes that have been characterized, studied, and confirmed to be responsible for principal roles in metabolic process control, glucose metabolism, and cell-to-cell signaling.
An early study investigating the connection between weight control and the endocannabinoid system in animal models confirmed that significant food intake levels, increased body weight, and fat accumulation were noticed in male mice pups treated orally with AEA, an endogenous cannabinoid. In other studies, mice treated with endogenous cannabinoids also show increased adipose tissue expression in adult life with an altered cannabinoid receptor (CB1) signaling in the hypothalamus.
In 2004, The International Journal of Obesity and Related Metabolic Disorders published the results of breakthrough research examining the incidence of weight control in CB1-deficient mice. In this research, the incidence of diet-induced obesity in wild type mice with a normal function of the CB1 receptors were compared. Results documented suggested that CB1-deficient mice are lean with their body weight, and adiposity reduced significantly when compared with the wild-type mice. Interestingly, mice from both groups have similar relative energy intake levels.
These studies confirmed that the CB1 receptor is a principal component in the regulation of body weight, diet-induced obesity, feeding behavior, and adiposity. The accumulated evidence confirming a link between weight control and the CBR1 receptor led to Rimonabant’s development and approval in 2006. As a potent CBR1 antagonist, several clinical trials and eventual mass use confirmed that Rimonabant effectively treated obesity. However, the drug was withdrawn in 2008 after reports of psychiatric side effects leading to increased suicidal ideation and actual suicide in users.
How does cannabidiol help with weight loss?
- Cannabidiol as a hunger suppressant
Regulation of the innate feeding behavior and the brain’s reward system is principal to appetite regulation. The initial reports of increased appetite stimulation in a consistent user of cannabis have largely been attributed to the psychoactive effects of delta-9-tetrahydrocannabinol (THC), a cannabinoid derived from the cannabis plant.
Pure extracts of cannabidiol are expected to act differently and suppress appetite based on earlier studies establishing a link between CBR1 antagonism and appetite suppression. The cannabinoid is an inverse agonist of the CBR1 receptors and, as such, does not directly deactivate these receptors. CBD instead can facilitate the deactivation of these receptors by other signaling molecules in the body. Despite the theory supporting CBD’s benefits in weight reduction, there are no clinical trials or studies confirming this claim.
- CBD and the conversion of white fat to brown fat
Research into the causes of obesity and undue weight gain in humans have suggested that in obese patients, the physiology of fat storage is distorted. An increased intake of energy and a low level of energy expenditure creates an excess energy balance in these individuals. This excess energy is stored as triglycerides (fat) in the white adipose tissues. This white adipose tissue fat—also called white fat—is prominently expressed in obese and overweight people and has been linked with increased risk of chronic complications, including diabetes and heart disease, and is characterized as “bad fat”.
Obesity studies in animal models suggest that mice with increased brown adipose tissue activity and increased brown-like adipocytes within the white adipose tissues are lean and protected from obesity, thereby characterizing brown fat as “good fat”. The research focus has since shifted towards recruitment of the brown-like phenotypes in white adipocytes (called browning) and activation of brown adipocytes in the fight against obesity.
In 2016, the peer-reviewed journal Molecular and Cellular Biochemistry published a report of research investigating the effect of cannabidiol on the induction of browning 3T3-L1 adipocytes. Results published confirmed that CBD enhanced the expression of brown fat-specific marker genes and increased the browning of 3T3-L1 adipocytes. This result indicated that CBD is potentially beneficial in weight reduction programs as it induces browning of white adipocytes, increases lipolysis, and reduces lipogenesis.
- Cannabidiol and the rate of fat expenditure
There anecdotal reports suggesting that CBD melts excess fats and break down fat storage to be dissipated as heat. Fat elimination in the form of heat burns excess calories and can be helpful in weight reduction. In contrast to fats in white adipose tissues, the primary function of the brown adipose tissues is to dissipate excess energy as heat. This process is considered important for weight loss and reducing the risk of chronic diseases. Since cannabidiol has been shown to increase the expression of brown fats, increase brown adipose tissue activity and also convert white fats to brown fats, it is logical to expect to suggest that CBD increases the rate of energy expenditure as heat dissipation in obese patients.
Numerous research has supported the use of cannabidiol and cannabis-derived products in weight training and recovery programs. However, extensive studies and clinical trials are needed to examine the safety profile and adverse effects of cannabinoids in humans. This is necessary as components of the endocannabinoid system are extensively distributed in the central nervous system and peripheral tissues.