The Latest Application in Cannabidiol (CBD) Science: A Promising Weight Management Tool
Cannabis and weight management – but wait, what about those “munchies”? Doesn’t Cannabis stimulate appetite?
It may seem counterintuitive, but several large epidemiological studies show an inverse relationship between Cannabis use and BMI.1-4 National Health and Nutrition Examination Survey (NHANES) data showed a lower risk of metabolic syndrome in Cannabis users, with males showing a statistically significant smaller waist circumference.4,5 Research shows that a major Cannabis constituent, cannabidiol (CBD), has a favorable effect on metabolic health.
Obesity and the Endocannabinoid Control Center
Obesity has reached epidemic proportions affecting over 1 billion people worldwide. It’s associated with type 2 diabetes (T2D), metabolic-dysfunction associated steatotic liver disease (MASLD), cardiovascular diseases (CVDs), chronic kidney diseases (CKDs), and cancers.6 Because of these associations, treatments targeting obesity are imperative.
Cellular mechanisms like inflammation, lipid metabolism, and insulin resistance involved in disease development are therapeutic targets that happen to be regulated in part by the endocannabinoid system (ECS).2 Endocannabinoid receptors and their endogenous ligands are dysregulated in patients with obesity, cardiovascular disease, hypertension, and diabetes.1,7-9
The body’s endogenous endocannabinoid system via the cannabinoid receptor type 1 (CB1) regulates energy homeostasis and appetite behavior in the brain. Downregulation of the CB1 receptor is associated with better metabolic health, yet CB1 receptors are overactive in obesity.1,9,10 The CB1 receptor is mainly concentrated in the brain, but also present in tissues such as adipose, liver, skeletal muscle, GI tract, and pancreas.2
The CB2 receptor is also involved, but stimulation of this receptor is associated with reduced food intake and weight loss. The CB2 receptor is expressed mainly on immune cells, playing a role in inflammation. Pro-inflammatory cytokine secretion promotes obesity and metabolic disorders, and CB2 stimulation has anti-inflammatory effects.11,12
Synthetic therapies and phytocannabinoids that influence cannabinoid receptors have been studied for their potential as weight loss agents.
CBD May Promote Weight Loss
Cannabidiol (CBD) is a prominent, nonpsychotropic phytocannabinoid of the Cannabis sativa plant that has numerous therapeutic applications. It is a CB1 negative allosteric modulator, making it an ideal potential weight management therapy.1 It also indirectly stimulates CB2 receptors.13
Human studies using the synthetic CB1 blocker Rimonabant were successful for weight loss, decreasing waist circumference, and improving other metabolic parameters, but had serious psychiatric side effects and was withdrawn from the market. Therefore, naturally acting phytocannabinoids such as CBD or tetrahydrocannabivarin (THCV) may be a better solution without serious side effects. Rodent studies using CBD and/or THCV show promise for weight loss.2,7
A systematic review of human clinical trials investigating whether CBD decreases appetite and body weight showed mixed results. Participants with a higher BMI at baseline seemed to benefit the most and had a greater decrease in body weight. The authors suggested that the range of dosing regimens may account for the mixed effects, with doses ranging from 5 mg/kg/day up to 750 mg BID.14
A recent study on 56 obese individuals showed that taking a combination product including THCV and CBD resulted in statistically significant weight loss, decreased abdominal girth, systolic blood pressure, and total and LDL cholesterol. The trial lasted 90 days and included 2 mucoadhesive strip dosages, with the higher dosage (16 mg THCV/20 mg CBD) having the most efficacy.12
CBD Reduces Appetite
Cannabis is made up of numerous constituents with opposing effects.15 Studies using CBD at higher doses to reduce seizures in childhood epilepsy noted loss of appetite as a common side effect.14,16 Dronabinol (Marinol®), a synthetic form of tetrahydrocannabinol (THC), stimulates appetite and is FDA-approved to promote weight gain in cancer and AIDS patients.17
Rat studies show that THC stimulates the CB1 receptor, while CBD antagonizes it, making CBD a better therapeutic option for weight loss.15,18 Antagonizing the CB1 receptor, and stimulating the CB2 receptor appears to reduce appetite and control obesity.11 CBD also acts through other systems involved in regulating food intake by regulating receptors in the serotonin (5-HT1A) and other systems.7,15,18,19
CBD Promotes Brown Fat Metabolism
All mammals have both white adipose tissue (WAT) and brown adipose tissue (BAT), each with opposing actions. WAT stores fat, and BAT increases fat metabolism by inducing thermogenesis, or burning energy as heat. White fat can convert to beige or brown fat.
In a cell study, CBD-treated white adipocytes expressed a brown phenotype, evidenced by upregulated brown fat-specific genes and proteins. CBD upregulated lipolysis, fatty acid oxidation, and mitochondrial biogenesis, while downregulating lipogenesis in adipocytes.20 CBD may be a helpful adjunct in obesity treatment to induce fat browning, although human studies are needed to confirm this effect.
Decreased Risk of Metabolic Disorders
NHANES data shows us that Cannabis users have a lower risk of metabolic syndrome.4 Researchers suggest CBD as an adjuvant therapy for treating metabolic syndrome and complications including strokes.8,21 In vitro and rodent studies exhibit CBD’s numerous beneficial metabolic effects including decreased liver enzymes, steatosis, adipocyte formation, pro-inflammatory cytokines, platelet aggregation, and fibrosis, and increased insulin sensitivity, anti-inflammatory cytokines, lipolysis, and thermogenesis.2,10
A randomized, double-blind, placebo-controlled, parallel group pilot study observed the effects of CBD and THCV on lipid and glucose metabolism in 62 type 2 diabetics. Treatment lasted 13 weeks and was well tolerated. THCV alone significantly reduced fasting glycemia, improved pancreatic β-cell function, increased apolipoprotein A, and adiponectin in comparison to placebo. Compared with baseline (but not placebo), CBD alone decreased resistin and increased glucose-dependent insulinotropic peptide.22 High levels of resistin are associated with obesity.14
CBD: A Promising Weight Loss Adjunct
CBD acts via multiple mechanisms to regulate energy homeostasis through the body’s natural endocannabinoid system. CBD also influences mood and pain, which can both be contributing factors in obesity.2 In combination with nutrition and lifestyle adjustments, CBD may help patients lose weight, suppress appetite, improve fat metabolism, and lower the risk of metabolic disorders.
References:
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