Researchers at Washington State University have identified specific neurons in the brain that are activated by cannabis which stimulate appetite, providing an explanation for the well-known “munchies” effect of marijuana.
Key Findings of the Research
The study, published this week01693-7) in the journal Cell Reports, found that cannabinoids in cannabis activate a newly discovered set of neurons in the amygdala that drive eating behaviors. Specifically:
- A new subpopulation of neurons that express the neurotensin neuropeptide (NTS neurons) was identified in the basolateral amygdala, a region involved in motivation and reward-driven behaviors
- Activation of the NTS neurons by cannabinoids administered to mice led to voracious food intake, even in sated mice
- Blocking the NTS neurons prevented cannabinoid-induced eating
- The number of NTS neurons correlated with the amount of food consumption
- Activating around 500 NTS neurons led mice to double their normal food intake
- Mice with ~1,500 NTS neurons activated ate up to 10 times more food when given THC
Senior author Marco Pravetoni said “This suggests that the basolateral amygdala is the region where cannabis acts to enhance food intake in mammals”. Pravetoni notes that the endocannabinoid system, which is activated by cannabis use, is known to modulate appetite, but the neural circuits involved were poorly understood. “This circuit that we discovered is a key gateway through which cannabinoids can impact eating behaviors.”
The identification of a specific neuronal pathway through which cannabis impacts appetite has broader implications:
- It substantiates the phenomenon of “munchies” that generations of cannabis users have experienced
- It provides a strong lead for developing appetite-stimulating pharmaceuticals, which could benefit patients with wasting syndromes or diseases impairing appetite like cancer or HIV
- Blocking this pathway might offer treatment approaches for compulsive overeating disorders
Co-author Olivia Vollmer said: “Enhancing appetite can have medical benefits, but excessive appetite obviously contributes to the epidemic of obesity and metabolic disorders plaguing our country. Hopefully our work will equip clinicians with better tools to help patients who struggle with appetite and weight regulation.”
History of Investigating the “Munchies”
The munchies phenomenon has been fodder for jokes and an accepted truth amongst cannabis users for decades. But clinically investigating the underlying pathways involved has been hindered legally and politically.
Plant biochemist Raphael Mechoulam kickstarted scientific research into cannabis in 1964 when he isolated and structurally characterized tetrahydrocannabinol (THC), identifying it as the primary psychoactive component. Mechoulam noted early on that while euphoria was the most common subjective effect of THC administration in humans, it reliably caused hyperphagia – excessive eating beyond metabolic needs.
However, the Schedule 1 classification of cannabis in the Controlled Substances Act of 1970 placed stringent restrictions on research. Only recently have scientists begun elucidating the physiological basis of precisely how cannabis triggers hunger signals and food-seeking behaviors.
Researchers will build upon these seminal findings in the basolateral amygdala to expand knowledge of how cannabinoids like THC interface with appetite regulation throughout the body and brain.
Pravetoni says “We have for the first time identified a neural mechanism through which cannabis causes the munchies in animals. There is still much work to do – does this same circuitry explain the munchies in humans? Are the mechanisms identical for endocannabinoids produced naturally in the body and phytocannabinoids from cannabis? Do other regions also contribute? But we finally have a foothold in unpacking this phenomenon.”
Understanding these pathways may lead to appetite-stimulating medicines derived from cannabis to help wasting disease patients, while new modes of treatment could target overeating driven by excessive endocannabinoid signaling. Unravelling the intricate science behind the ubiquitous munchies may lead to a feast of new breakthroughs in treating appetitive disorders.
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