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”), an effect triggered when THC activates CB1 receptors in the brain. This leads to increased food motivation, a phenomenon observed across animal species. Our body's natural, 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 brain regions like the hypothalamus, can also increase food intake.
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 are also expressed in 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.
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, especially with a low overall PUFA load.
Omega-3 Fatty Acids, Brain Function & Mental Health
Many people (including me) think that reducing omega-6 intake is beneficial for metabolic health, especially for the typical person consuming an enormous amount of this stuff. These 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, seems 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 cannabis 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: THC drives a short-term increase in food intake, but 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 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 changes in 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. THC can also acutely shift the preference for high-fat vs. high-carbohydrate food depending on the animal’s initial hunger state (there are also 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—no overall weight gain in response to THC, short-term “munchies,” due to a compensatory decrease in food intake over longer periods.
Cannabinoid-Based Pharmaceuticals vs. Diet for Weight Loss & Metabolic Health
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