It is well known that cannabis and its major active compound THC can increase appetite and cause “the munchies.”

But did you know that cannabis use might also contribute to a healthy body weight?

The role of cannabis and endocannabinoids in appetite regulation and body weight has been extensively studied for the past 15 years. Clinical research shows that cannabis, as well as THC and its analogues, can stimulate appetite and may improve body weight in patients with HIV/AIDS, hepatitis C, Alzheimer’s disease, anorexia nervosa, inflammatory bowel disease, and cancer.

Indeed, this is an important therapeutic benefit of THC — its ability to stimulate appetite and improve body weight in patients suffering from disease

Does long-term cannabis use increase the risk of obesity?

Contrary to what one might expect, researchers find the prevalence of obesity may be lower in cannabis users compared to non-users.

Studies suggest a lower prevalence of diabetes mellitus and metabolic syndrome in cannabis users compared with people who have never used cannabis. However, other studies have found no relationship between cannabis use and type 2 diabetes .

In a nationally representative survey of 4657 American adults, current use of cannabis was associated with 16% lower levels of fasting insulin, lower insulin resistance, and smaller waist circumference.

Despite its associations with increased appetite and caloric intake, cannabis use is associated with lower body mass index and lower insulin levels.

How can this be?

The endocannabinoid system

Our endocannabinoid system is an ancient system found throughout our body and is how we recognize and interact with the cannabis plant. It helps to regulate a wide variety of functions, including appetite, body weight, sleep, pain, inflammation, psychiatric diseases, stress, and emotional state.

It is also well established that the endocannabinoid system is involved in both the regulation of energy balance and the development of obesity.

Our endocannabinoid system includes the CB1 and CB2 cannabinoid receptors, which are found throughout the body, including the brain, nerves, muscles, immune cells, intestines and skin.

CB1 receptors are highly expressed in the hypothalamus, an area of the brain that plays a major role in controlling appetite and food intake.

Our endocannabinoid system also includes anandamide, which takes its name from the Sanskrit word ananda, meaning “bliss” or “delight.”  Anandamide is made from fatty acids in our body and has a similar effect to THC.

Both THC and anandamide are partial agonists of the CB1 receptor, meaning they can bind to CB1 receptors in the brain and activate them, which in turn can stimulate appetite.

Interestingly, blocking or suppressing CB1 receptors has the opposite effect, and can suppress appetite and lead to weight loss.

This finding led to the development of CB1 blockers as anti-obesity drugs.

Rimonabant – a cautionary weight loss tale

Rimonabant, also known as Acomplia, was a drug developed by Sanofi-Aventis as a CB1 receptor antagonist. It works by blocking CB1 receptors. In 2006, Rimonabant was approved in more than 30 countries for weight loss and appetite suppression, but was withdrawn several years later because it also induced severe symptoms of anxiety and depression.

Other anti-obesity drugs aimed at inhibiting or blocking the CB1 receptor, including Taranabant by Merck & Co, have been discontinued.  

Can cannabinoids inhibit the CB1 receptor?

Tetrahydrocannabivarin (THCV) is also found in cannabis and is structurally similar to THC, but has different effects on the body.

THCV is a high-affinity CB1 receptor antagonist and can inhibit the CB1 receptor. However, unlike Rimonabant, THCV does not fully block the CB1 receptor, and it’s also a partial agonist for the CB2 receptor. Because of this, THCV is not thought to cause the same harmful side effects as Rimonabant and Taranabant.  

THCV has been shown to suppress appetite and weight gain in mice and is being investigated as a novel anti-obesity treatment.  

In a randomized, double blind, placebo-controlled study, patients with non insulin-treated type 2 diabetes who consumed THCV (five milligrams, twice daily for 13 weeks) had significantly decreased fasting plasma glucose and improved pancreatic β-cell function. However at this dose, THCV treatment had no effect on appetite or body weight after 13 weeks.

What about cannabidiol?

In addition to THCV, cannabidiol (CBD) may also inhibit CB1 receptors and has been shown to suppress appetite in rats.

Interestingly, CBD may contribute to weight loss by promoting the browning of white adipocytes or fat cells. Brown fat is a specialized type of fat that can increase energy expenditure, produce heat, improve glucose metabolism and limit weight gain.  Compounds such as CBD that increase the browning of fat may promote healthy body weight, however more research is necessary.

Can THC both activate and block CB1 receptors?

Dr. Bernard Le Foll, a clinician scientist at the University of Toronto, believes that THC may actually be responsible for the anti-obesity effects of cannabis.

Dr. Le Foll hypothesizes that THC can act as a functional antagonist during situations of “high endocannabinoid tone”. This means that THC may have the opposite effect in long-term cannabis/THC users. Instead of stimulating the CB1 receptors, it may block or suppress CB1 receptors in the brain, leading to a suppressed appetite.

Another example of THC having opposite effects is with dopamine release in the brain. Short-term THC administration causes increased dopamine release and neuronal activity, whereas long-term use is associated with blunting of the dopamine system.

Preliminary research from Dr. Keith Sharkey’s group at the University of Calgary shows that long term THC use can suppress appetite and reduce body weight in obese rats, but has no effect on lean rats. Despite these interesting findings, more research is required in humans.

What about other cannabinoids?

Other cannabinoids including cannabinol (CBN) and cannabigerol (CBG) have been shown to increase food intake in preliminary animal trials.

CBN is a breakdown product of THC degradation, and occurs in higher amounts in old or aged cannabis. If using cannabis for weight loss, it may be best to choose fresher strains versus aged strains.

What about terpenes?

Cannabis flowers contain terpenes, including limonene and linalool, that give cannabis its characteristic smell.

D-limonene is a cyclic terpene with a sweet citrus odour, and is found in the peel of citrus fruits including orange, lemon, grapefruit and lime, as well as cannabis flowers and extracts.

The aroma of limonene has been shown to suppress appetite, at least in rats and insects, indicating that limonene in cannabis flowers may also help suppress hunger.  

Limonene is recognized as safe for consumption and can be absorbed into the body simply through inhalation (smelling), with a study showing 70 per cent human pulmonary uptake during exposure to different doses.

Limonene is metabolized quickly and can accumulate in fatty tissues, such as the breast. Interestingly, limonene has recently been shown to turn white fat into brown fat [39], which is more metabolically active and may lead to weight loss.  

On the other hand, there may also be certain terpenes that increase appetite.

Linalool is a terpene with a pleasant floral aroma found in lavender, as well as certain strains of cannabis. The aroma of lavender and linalool has been shown to increase appetite and body weight in rats. However, at this point it is unknown if one should avoid cannabis containing linalool for weight loss.  

Can other foods or herbs inhibit the CB1 receptor?

Falcarinol is found in carrots, parsley, celery, and in the medicinal plant Panax ginseng. Similar to the drug rimonabant, falcarinol has been shown to be a selective CB1 receptor antagonist in human skin cells, meaning that it can inhibit CB1 receptors. Further research will have to determine if falcarinol can be useful for weight loss.

Putting it all together

Cannabis is a diverse plant with many uses. Cannabinoids, and especially THC, can stimulate appetite and increase the desire to eat. However, some researchers suggest that long-term use of cannabis and or THC as well as higher dosages of THC may have the opposite effect and may inhibit the CB1 receptor and suppress appetite and potentially lead to weight loss.

In addition, other cannabinoids like THCV and CBD along with terpenes like limonene are also being studied for their appetite suppressing and fat burning effects. Given the early state of research in this area, it is premature to give specific recommendations on strain selection or dosage. That said, cannabis therapeutics for targeting obesity and weight-loss will be a topic of great interest going forward.