Although the phenomenon of cannabis-induced “munchies,” or a temporary surge in appetite, is widely recognized, scientists have recently uncovered the brain mechanism responsible for this effect. The researchers discovered that when they inhibited the activity of agouti-related peptide (AgRP) neurons — often referred to as “hunger neurons” — the effects of cannabis vapor on these behaviors were negated. Their findings have been published in Scientific Reports.
Agouti-related protein neurons (AgRP neurons) are a group of neurons located in the arcuate nucleus of the hypothalamus region in the brain. They are known to play a crucial role in regulating appetite and energy balance by releasing specific neuropeptides that promote feeding behavior and reduce energy expenditure.
AgRP neurons are naturally activated in response to energy deficiency or fasting, leading to increased hunger and food-seeking behavior. They are part of a complex neural circuit that interacts with other hypothalamic neurons to maintain energy homeostasis in the body. Artificially activating these neurons in rats makes them start looking for food and eat if food is available.
Cannabis sativa, commonly known as marijuana, , is recognized for enhancing appetite in humans, leading to its use in treating anorexia—an eating disorder marked by an intense fear of weight gain that results in restricted food intake, a distorted body image, and significantly low body weight. However, the precise neural mechanism through which cannabis enhances appetite remained unclear until now.
Study author Emma C. Wheeler and her colleagues hypothesized that specific chemicals in cannabis known as cannabinoids might be triggering specific receptors in the hunger neurons (the cannabinoid type-1 receptors), increasing their activity and, in turn, increasing appetite. They conducted a study on rodents to test whether this is the case.
The research involved male Long-Evans rats and two genetic strains of mice, which were housed in enclosures with unrestricted access to food and water and subjected to a 12-hour light-dark cycle. One rat was excluded due to its size.
During the experiments, rats were divided randomly into experimental and control groups. On test days, the experimental group was placed in a chamber filled with cannabis vapor for 10 minutes, ensuring they received a specific dose (800 mg) known to stimulate food intake. The control group was placed in an identical chamber without cannabis vapor. The researchers then performed various behavioral tests on the subjects.
The procedure for mice was similar, except that they were exposed to 100 mg of cannabis vapor over a 5-minute period, with some mice receiving higher doses for further observation. Following exposure, the researchers conducted biochemical tests and neural activity imaging on the mice.
The results confirmed cannabis’s appetite-stimulating effects. Both rats and mice exposed to cannabis showed an increase in food consumption 2-3 hours post-exposure compared to the control group. They also exhibited increased metabolic activity. Rats’ motivation to obtain food increased just one hour after exposure, although this effect dissipated after two hours.
Contrary to the researchers’ initial assumptions, the movement of rats exposed to cannabis did not change. The activity of AgRP neurons in mice exposed to cannabis increased both when anticipating food and while eating.
Further analysis indicated that cannabis vapor activates the cannabinoid type-1 receptors in these neurons, leading to their disinhibition and heightened activity. This resulted in increased food-seeking behavior and consumption. By using chemogenetics to inhibit AgRP neuron activity, the researchers were able to diminish the appetite-stimulating effects of cannabis vapor, confirming the role of AgRP neurons in this process.
“Based on these results, we conclude that MBH [mediobasal hypothalamus] neurons contribute to the appetite stimulatory properties of inhaled cannabis,” the study authors concluded.
The study makes an important contribution to the scientific understanding of the neural mechanisms behind psychological effects of cannabis sativa components. However, it should be noted that the study was done on rodents. Although rodents and humans share many physiological similarities, they are still very different species. Effects on humans might not be equal.
The paper, “Cannabis Sativa targets mediobasal hypothalamic neurons to stimulate appetite,” was authored by Emma C. Wheeler, Pique Choi, Joanne De Howitt, Sumeen Gill, Shane Watson, Sue Yu, Peyton Wahl, Cecilia Diaz, Claudia Mohr, Amy Zinski, Zhihua Jiang, David Rossi, and Jon F. Davis.
