A study published in this week's issue of Nature sheds new light on why pot makes you really really hungry – even when you should feel full.

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In a study led by Yale neurobiologist Tamas Horvath, researchers injected cannabinoids into the brains of lab mice, activating a cannabinoid receptor called CB1R. Previous studies have shown that activation of CB1R increases the desire to eat, and Horvath's investigation confirmed this. "We show that chemical promotion of CB1R activity increases feeding," the researchers write in this week's issue of Nature. Makes sense. This is what they were expecting. So far, so stoned.

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But then the researchers noticed something they hadn't expected. CB1R activity, in addition to promoting hunger, had also boosted activity in a group of nerve cells called hypothalamic pro-opiomelanocortin (POMC) neurons, a tongue-twisting class of brain cells that, under normal circumstances, works to suppress appetite. The observation posed a mechanistic paradox: why were POMC neurons being activated in the brains of hungry mice?

It's not like CB1R's hunger-boosting activity was somehow overpowering the hunger-suppressing properties of POMC neurons, either. When Horvath and his colleagues artificially suppressed POMC neuron activity, it diminished CB1R-driven feeding. When they increased POMC neuron activity, feeding was enhanced. The "paradoxical increase in POMC activity," write the researchers, "is indispensable for appropriate promotion of feeding triggered by CB1R activity in the state of satiety." In other words, POMC activity was crucial for promoting cannabinoid-induced feeding in mice that had no business feeling hungry to begin with.

"It's like pressing a car's brakes and accelerating instead," said Horvath, in a press release. He and his team were surprised, he said, "to find that the neurons we thought were responsible for shutting down eating, were suddenly being activated and promoting hunger, even when you are full. It fools the brain's central feeding system."

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So how does cannabis dupe the system? Further investigation suggests the answer hinges on the POMC neuron's ability to release either α-Melanocyte-stimulating hormone (a peptide known to suppress appetite) or β-Endorphin (a peptide perhaps best known known for its role in "runner's high"). Horvath and his colleagues show that CB1R activity flips the peptide-producing switch on POMC neurons, causing them to release the appetite-boosting β-Endorphin instead of α-MSH, by way of a mitochondiral protein called UCP2. Instead of signaling that you're full, in other words, your POMC neurons signal to keep eating.

As Horvath told NPR: "Even if you just had dinner and you smoke the pot, all of a sudden these neurons that told you to stop eating become the drivers of hunger."

Read the full scientific study in the latest issue of Nature.

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