How Cannabis Influences Appetite

Many people are familiar with the sensation of getting the “munchies” after using cannabis. You find yourself staring into the fridge, wondering which food will taste best. But why does this happen? What is the evolutionary purpose behind it? Let’s take a closer look.

The Role of Cannabinoids

The psychoactive compounds in cannabis—cannabinoids—are responsible for this effect. The most active and well-studied cannabinoid is delta-9-tetrahydrocannabinol, or THC. Dronabinol, a synthetic cannabinoid, is approved for medical use in the United States, Canada, and some European countries. However, since its advantages over other antiemetic and pain-relief medications are questionable, dronabinol is usually prescribed only when standard therapies are not tolerated.

It’s been known for thousands of years that cannabis increases appetite, likely since humans first encountered the plant. Cannabis enhances taste sensations and increases the pleasure derived from eating (though it can also intensify unpleasant flavors). However, the specific mechanisms by which cannabinoids affect feeding behavior in animals had not been thoroughly described until recently.

Scientific Findings on Appetite Stimulation

A 2015 study by Yale University scientists shed light on the biochemical mechanisms triggered when cannabinoids enter the brain. Researchers examined functional changes in mouse brain tissue after administering synthetic cannabinoids. They found that activation of CB1 receptors in the endocannabinoid system within a group of POMC neurons (which normally suppress appetite and are located in the hypothalamus) by exogenous cannabinoids causes hyperpolarization of these receptors. This leads to changes in mitochondrial metabolism, increased cellular respiration (producing reactive oxygen species), synthesis of mitochondrial uncoupling protein 2 (UCP2), and production of β-endorphin—all of which stimulate and reinforce feeding behavior.

Essentially, brain cells that usually control and suppress appetite start working in reverse under the influence of cannabinoids: they produce neurotransmitters that make animals eat more.

Previously, scientists believed that cannabis-induced overeating worked differently, assuming that cannabis temporarily shut off receptors signaling satiety. The discovery that the same neurons can suppress appetite in a normal state but trigger intense hunger under the influence of cannabis was unexpected. This finding could form the basis for therapies for people suffering from appetite loss, such as cancer or HIV patients.

The Endocannabinoid System and Feeding Behavior

Evidence of the endocannabinoid system’s influence on feeding behavior includes the presence of endocannabinoids in cow’s milk and soft cheeses. Other studies confirm the presence of endocannabinoids in human breast milk. The survival of offspring in many mammal species, which largely depends on their appetite for breast milk, is well studied.

Recent research has also identified the role of the endocannabinoid system in newborns:

• Lower levels of the endocannabinoid anandamide in embryos affect their ability to implant in the uterus.
• Increased levels of the enzyme that breaks down anandamide in mothers raise the risk of miscarriage.
• CB1 receptors are temporarily present in the white matter of the fetal and newborn brain, indicating a role in brain development.
• Endocannabinoids are found in maternal milk, and activation of CB1 receptors appears critical for newborn mice to suckle, as it activates oral-motor muscles.
• Anandamide has neuroprotective properties in the developing postnatal brain.
• Prenatal exposure to THC (the active component of cannabis) affects prefrontal cortex functions, memory, as well as motor and addictive behaviors, highlighting the role of the CB1 endocannabinoid system in brain structures that control these functions.

Further observations suggest that children may be less susceptible to the psychoactive side effects of THC or endocannabinoids than adults. The medical implications of these findings are significant and suggest a promising future for cannabinoids in pediatric medicine for conditions such as “non-organic failure to thrive” and cystic fibrosis.

Why Cannabis Makes You Hungry

Understanding how the endocannabinoid system works in mammals is key to explaining why cannabis use increases appetite. Scientists have discovered a new pathway for cannabinoid interaction with CB1 receptors in the brain. Cannabinoids stimulate mitochondrial respiration, leading to the production of reactive oxygen species, increased expression of mitochondrial uncoupling protein (which regulates feeding behavior), and increased synthesis of β-endorphin, which stimulates eating.