Metabolic Effects of Cannabinoids
The fats you consume influence your endogenous cannabinoid system. The cannabinoids you consume influence whole-body metabolism.
Not medical advice.
To learn more about endocannabinoid biology and its relationship to feeding behavior and metabolism, try these M&M episodes:
M&M #123: Endocannabinoids, Stress, Exercise, Cortisol, Anxiety, Cannabis & Effects of Marijuana on Brain Development | Matthew Hill
M&M #134: Omega-6-9 Fats, Vegetable & Seed Oils, Sugar, Processed Food, Metabolic Health & Dietary Origins of Chronic Inflammatory Disease | Artemis Simopoulos
Cannabinoids Influence Whole-Body Metabolism
Cannabis is well-known for inducing a desire to eat palatable foods (“the munchies”). This effect is triggered when THC activates CB1 receptors in the brain, leading to increased food motivation—a phenomenon observed across many animal species. Our body's natural cannabinoids, endogenous cannabinoids (“endocannabinoids”), have a similar influence, with elevated endocannabinoid levels linked to higher food intake and weight gain. Elevating endocannabinoid levels, either systemically or within specific grain regions like the hypothalamus, can also increase food consumption.
The endocannabinoid system affects metabolism across the entire body, extending beyond just appetite regulation. When cannabinoids activate CB1 receptors (the same receptors that cause THC’s psychoactive effects), they influence several metabolic processes, including liver fat production, pancreatic insulin secretion, and glucose use in muscles. Overall, increased CB1 receptor stimulation promotes energy storage, effectively instructing the body to consume calories and save them for future use.
Fat cells contain CB1 receptors, enabling cannabinoids to impact fat storage directly. High endocannabinoid levels are associated with visceral fat accumulation and are linked to diet-induced obesity and poor metabolic health. CB1 receptors also appear in metabolic organs like the liver. Altering cannabinoid signaling, whether through THC consumption or dietary changes, can influence not only appetite regulation at the level of the brain, but how other organs of the body utilize what you consume.
Among other things, cannabinoids also play a role in gut-brain interactions via the microbiome, an exciting area of current research. (To learn more about this specific subject, see M&M 103 with Dr. Christoph Thaiss).
CB1 receptor activation by cannabinoids typically results in a variety of metabolic effects:
Increased food intake
Enhanced liver fat synthesis
Elevated insulin secretion
Greater nutrient absorption in the GI tract
Increased glucose metabolism in muscles
Accumulation of fat in adipose tissue
Dietary Influences on Endocannabinoids: Omega-3 vs. Omega-6 Fats
Endocannabinoid levels are affected by our diet. These molecules are derived from linoleic acid, an essential omega-6 fatty acid that must be obtained through food. As endocannabinoids are derived from omega-6 fats, a diet high in these fats tends to increase endocannabinoid levels. The typical Western diet is high in omega-6s, which are found in seed oils and other ultra-processed foods.
Modern diets have shifted significantly from the ancestral diets consumed by pre-modern humans. The last century has seen an increase in omega-6-rich oils, like those from seed oils (e.g. soybean oil), along with a decrease in animal fats like butter, which have a distinct fatty acid profile. This shift has contributed to the rise in obesity rates, with omega-6 intake now often twenty times higher than omega-3. This ratio was closer to one-to-one for much of human pre-history.
To learn more about related topics, check out these M&M articles:
A diet high in omega-6 fats and low in omega-3s is associated with inflammation, fat accumulation, obesity, and insulin resistance. Because endocannabinoids stimulate appetite, elevated levels from high omega-6 intake may prompt overeating, potentially creating a cycle of poor metabolic health.
Here’s a summary of the key points about how dietary fats influence endocannabinoid levels and metabolic health (I recommend this excellent review paper by Dr. Artemis Simopoulos, which covers topics we discussed on M&M #134.):
Endocannabinoids are produced from omega-6 fats. Diets high in omega-6 fatty acids increase endocannabinoid levels.
A diet high in omega-6 fats is characteristic of the modern Western diet. It is associated with higher endocannabinoid levels, weight gain, inflammation, and poor overall metabolic health.
Omega-3 fats are critical for endocannabinoid function in the brain. Diets deficient in omega-3s can lead to deficits in endocannabinoid-related brain function.
A diet with balanced levels of omega-6 and omega-3 fatty acids seems to be desirable for overall health.
Omega-3 Fatty Acids, Brain Function & Mental Health
Many people (including me) would say that reducing omega-6 intake would be beneficial for metabolic health, especially for the majority of Americans currently consuming an enormous amount of these fatty acids. Omega-6 fats are abundant in processed foods and oils like grapeseed, sunflower, and other seed oils.
Sufficient omega-3 levels, found in foods like salmon, oysters, and other seafoods, seem to be necessary for endocannabinoid function in the brain. Omega-3 deficiency can abolish forms of endocannabinoid-mediated neuroplasticity, and low omega-3 levels are associated with mental health disorders.
Why Doesn’t Chronic THC Use Lead to Weight Gain?
While THC temporarily boosts appetite, national surveys have observed a negative correlation between obesity rates and cananbis consumption. Why would chronic cannabis use be associated with lower rates of obesity if cannabinoids like THC stimulate eating?
One possibility: the association between cannabis use and lower obesity rates is not real, perhaps because the self-reported data captured by surveys is not reliable. An alternative explanation is that while THC my drive a short-term increase in food intake, there may be compensatory changes in feeding or metabolism that counteract the acute effects of “the munchies” over longer intervals.
To assess whether such correlations might represent a real relationship, we can look to cause-and-effect experiments in animals to see if results are consistent. Cause-and-effect experiments in rodents, which control for diet and THC consumption, have found that that chronic THC consumption seems to protect against weight gain. In rodents with diet-induced obesity, chronic THC exposure leads to less weight and fat mass gain, as well as lower energy intake. This effect may come, in part, from alterations to the gut microbiome.
Other animal research indicates that although THC drives an acute increase in food intake, this is compensated for by a reduction in subsequent intake, such that it does not promote overall weight gain. The acute increase in food intake happens to some extent whether animals are already hungry or satiated. This work has also shown that THC can acutely shift the preference for high-fat vs. high-carbohydrate food depending on the animal’s initial hunger state, as well as sex differences in the details of the effects between males and females. Overall, cause-and-effects animal research looks consistent with the human correlational data—there is no overall weight gain in response to THC consumption, despite “the munchies” in the short-term, due to a compensatory decrease in food intake over longer periods.
Cannabinoid-Based Pharmaceuticals vs. Diet for Weight Loss & Metabolic Health
If activating CB1 receptors tends to promote weight gain, then blocking these receptors should theoretically have the opposite effect. This was the basis for Rimonabant, an anti-obesity drug developed in the 2000s that blocked CB1 receptors. While effective at inducing weight loss, Rimonabant was withdrawn due to severe psychiatric side effects like depression and suicidal thoughts. This outcome should not be surprising: the endocannabinoid system operates across the body, so blocking CB1 receptors systemically will naturally disrupt a wide range of bodily functions.
An alternative approach to pharmaceuticals is proactive management of your diet. Food is not simply calories. The nutrients we consume as fuel can also act as signaling molecules that influence cell function. Similar to endogenous cannabinoids, macronutrients like fat can serve as precursors to critical messengers in the body which orchestrate how we process what we consume—a gram of fat from one food source can have very different metabolic effects than a gram from another. In addition, many drugs and foods affect key liver enzymes responsible for metabolizing many other substances.
Actively managing your metabolic health by tracking nutrients takes time, effort, and willpower. Processed foods, such as omega-6-rich seed oils, are cheap and easy to acquire. They’re often engineered to have properties that interfere with the body’s natural satiety mechanisms. It’s in the food processor’s economic interest for you to finish your bag of chips quickly, stay hungry, and then buy another.
Food scientists have worked for years to hack our biology by artificially boosting the palatability of junk foods and short-circuiting our natural satiety mechanisms. This can lead to eating foods that disrupt metabolism, costing you not only your health but an enormous amount of lifetime dollars. Besides more costly grocery runs, people with obesity have significantly higher medical costs.
What you consume, including both food and pharmaceuticals, influences who you become. This is not just flowery language: you are physically built from what you consume, and what you consume influences how your body uses the building blocks you provide to it.
Choose wisely.
To learn more about the topics covered in this essay, try these episodes of the Mind & Matter podcast: