Getting “the munchies” is a famous side effect of marijuana—and for many consumers, that just means grabbing an extra bag of potato chips or making a pizza run. But the boost in appetite that comes from consuming cannabis is the product of a complex interplay of cannabinoids, neurotransmitters and hormones in the brain. Now, recent discoveries about those relationships reveal how cannabis can stimulate the appetite—and that has profound benefits for people with health conditions like cancer, HIV/AIDS and dementia for which low appetite and nausea are part of the illness.
The brain’s central hunger switch is the hypothalamus, a small area in the forebrain that’s responsible for managing the activity of the autonomic nervous system, the pituitary gland and a variety of other homeostatic functions such as body temperature, thirst and appetite.
The hypothalamus is ultimately responsible for regulating feelings of hunger and satiation. But in order to do that, it responds to signaling from ghrelin and leptin, two hormones that are produced elsewhere in the body.
Ghrelin is a hormone secreted primarily from cells in the stomach, but also in smaller amounts from the pancreas, intestines and brain. Ghrelin levels in the blood are determined by food intake.
Levels of ghrelin secreted by the stomach typically rise just before eating or during fasting. This accounts largely for the hunger pangs that tell us it’s time to eat something. Eating lowers the levels of ghrelin in the bloodstream—and certain foods, such as those containing carbohydrates and proteins, are more effective at lowering those levels than fats are. Ghrelin also plays a role in regulating insulin, an important factor in managing diabetes.
Ghrelin in the bloodstream circulates to the hypothalamus, which responds with signals to stop eating—or to eat more. This essential hormone also acts on the amygdala, an area of the brain related to the pleasure-reward-learning circuit, which helps to explain some eating disorders and the love of comfort foods during times of stress.
Balancing the activity of ghrelin is leptin—a hormone secreted by the fat cells throughout the body that’s responsible for balancing fuel and energy expenditure. Leptin signals the hypothalamus to alter food intake by encouraging the release of neurotransmitters that reduce appetite and suppressing those that stimulate it.
Because leptin is released from fat cells, the amount of leptin in the body depends on the amount of body fat a person has—more fat means higher levels of leptin. As a person loses weight, levels of leptin fall, triggering the hypothalamus to send signals that stimulate the appetite so that the body doesn’t starve.
Many things can affect the cycle of ghrelin/leptin release and hypothalamic signaling. But new research reveals that the most potent influences on this appetite regulating cycle may come from cannabinoids, both the natural versions produced by the body’s own endocannabinoid system (ECS) and the compounds in cannabis, specifically its psychoactive ingredient tetrahydrocannabinol (THC).
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The ECS is one of the largest signaling systems in the body. Receptors for the naturally produced cannabinoids anandamide and 2-arachidonoyl glycerol (2-AG) are found in many organs and tissues, and they’re especially plentiful in many areas of the brain, including the hypothalamus.
Cannabinoids such as cannabidiol (CBD) and THC are so similar to those natural cannabinoids that they can bind to the same receptors and affect the outcome of neurological signaling through the ECS in the brain and other parts of the body. That explains why cannabis compounds can affect the expression of appetite-related signals from the hypothalamus.
So far, research has discovered two cannabinoid receptors, called CB1 and CB2. The hypothalamus contains numerous CB1 receptors that can bind both with the natural 2AG and anandamide as well as with cannabinoids from cannabis. Recent studies show that when THC binds to these receptors, it can stimulate the release of ghrelin to cause feelings of hunger.
Cannabinoids can also affect the production of leptin thanks to their effects on an enzyme called AMP-activated Kinase, or AMPK. In the hypothalamus, AMPK helps link the appetite-stimulating effects of cannabinoids and ghrelin, and that combination appears to affect the production of leptin in adipose, or fatty, tissue.
What’s more, THC and other cannabinoids may also stimulate the olfactory bulb, so that food tastes and smells better. Along with those effects, cannabinoids also encourage the release of dopamine, the feel-good chemical at the center of the pleasure-reward circuit, so that eating is a pleasant experience.
The effects of cannabis on appetite and hunger can help people who experience a loss of appetite due to circumstances such as chemotherapy for cancer, or those with illnesses such as HIV/AIDS. Cannabis in all its forms can help stimulate feelings of hunger and make food taste better, so that patients eat more, improve nutrition and gain back lost weight. Gaining weight also means a higher percentage of fat cells, which encourages the production of leptin.
Research on the effects of cannabis on appetite has also explored the uses of cannabis for weight loss. That led to the production in the early 2000s of a few drugs such as rimonabant and taranabent that target the brain’s CB1 receptors to reduce appetite rather than increase it.
But these drugs had a number of undesirable side effects such as depression and anxiety, so they were taken off the market for retooling. Still, this line of research points to the fact that cannabinoids can play a major role in appetite and hunger responses.
Cannabis can affect people very differently—and some may get the munchies more than others do, or not at all. But because THC and other cannabinoids can boost hunger messages to the brain, cannabis products can stimulate the appetite—and help people with low appetite and weight loss from a variety of conditions to eat more, gain weight and feel better.
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