How Cannabis Activates Hunger-Related Brain Cells in Mice
A 2023 study from Washington State University provides new detail on how cannabis can stimulate appetite. In experiments involving rats and mice, researchers found that vaporized cannabis increased food-seeking and feeding behavior and altered activity in hunger-related neurons in the hypothalamus.
The findings, published in Scientific Reports, point to a role for neurons that produce agouti-related peptide, or AgRP. These cells are located in the mediobasal hypothalamus, a brain region involved in regulating hunger and energy balance.
Researchers exposed rodents to vaporized whole-plant cannabis rather than administering isolated, injected THC. They then combined behavioral tests with calcium imaging, electrophysiology and chemogenetic techniques to examine how the animals’ brains and feeding behavior changed.
In mice exposed to cannabis, hypothalamic neurons showed activity when the animals anticipated and consumed palatable food. The researchers also found evidence that cannabinoid-1 receptors, or CB1 receptors, reduced inhibitory signals reaching AgRP neurons. When the team used chemogenetic methods to inhibit those neurons, cannabis no longer produced the same appetite-stimulating effect.
In rats, cannabis exposure increased meal frequency and motivation to obtain food. The effect was not simply explained by greater general movement: the study found increased food-seeking behavior without a corresponding increase in locomotor activity under some experimental conditions.
Using vaporized plant material was intended to make the animal model more comparable to the way many people consume cannabis than earlier experiments based only on injected THC. Even so, the work remains preclinical. The subjects were rodents, the cannabis exposure was controlled by researchers, and the findings do not establish that the same neural response occurs in humans or that cannabis is an effective treatment for appetite disorders.
The study was supported by the National Institute on Alcohol Abuse and Alcoholism, the U.S. Department of Agriculture’s National Institute of Food and Agriculture, Washington State University and funds from Washington state’s Initiative Measure No. 171, according to Washington State University.
The results help explain the biological basis of the familiar “munchies,” but they do not resolve cannabis’s broader relationship with weight and metabolism. Earlier observational and policy research has linked legalization with higher sales of some high-calorie snack foods, while other studies have reported associations between cannabis use and lower obesity or type 2 diabetes risk. Those studies examine different populations, exposures and outcomes, and they cannot by themselves show that cannabis prevents obesity or diabetes.
A 2023 meta-analysis, for example, reported a lower statistical odds of type 2 diabetes among cannabis users but also noted substantial differences among the studies it combined. Such findings are associations, not proof that cannabis protects against the disease. More rigorous human research would be needed before cannabis-based treatments could be evaluated for anorexia, treatment-related appetite loss or other disorders.
For now, the Washington State study offers a clearer picture of one pathway through which cannabis can promote feeding: activation of cannabinoid signaling that changes the activity of AgRP neurons in the hypothalamus. That insight may guide future research, but it is not yet a clinical recommendation.
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