POMC and the Marijuana Munchies
Ingestion of marijuana is known to cause an uncontrollable urge to eat, known as ‘the munchies’. A recent study by Koch and co-workers demonstrates that this drive is controlled by pro-opiomelanocortin (POMC)-producing neurons found in the hypothalamus. All previous evidence, based on examination of the functions of these neurons, has been consistent with their involvement in appetite suppression. However, this new study calls that function into questions.
When in the fed-state, POMC neurons are activated to produce a-melanocyte stimulating hormone (aMSH), which in turn promotes feelings of satiety. However, when POMC or aMSH synthesis or action is inhibited in mice, there is a significant increase in hyperphagia, or over-eating, and resultant morbid obesity.
Koch and colleagues took this one step further. They examined the effects of the cannabinoid mimic arachidonyl-2’-chloroethylamide (ACEA), which prompts overeating, in mice. Animals given ACEA over-ate, with this hyperphagia associated with POMC neuron activation. When POMC neuron activity was experimentally inhibited, the animals no longer exhibited ACEA-induced overeating, which confirmed the cells were essential for the behaviour.
The key finding came when treating POMC neurons with ACEA in culture. Instead of producing and secreting α-MSH, the neurons secreted β-endorphin—a hormone that when administered pharmacologically, increases appetite. It remains to be determined whether this mechanism is also the key to getting ‘high’ on cannabis.
Read the full article in Nature 2015;519: