While it is well known that cannabis can cause the munchies, researchers have now revealed a mechanism in the brain that promotes appetite in a set of animal studies at Washington State University.
The discovery, detailed in the journal Scientific Reports, could pave the way for refined therapeutics to treat appetite disorders faced by cancer patients as well as anorexia and potentially obesity.
After exposing mice to vaporized cannabis sativa, researchers used calcium imaging technology, which is similar to a brain MRI, to determine how their brain cells responded. They observed that cannabis activated a set of cells in the hypothalamus when the rodents anticipated and consumed palatable food that were not activated in unexposed mice.
When the mice are given cannabis, neurons come on that typically are not active. There is something important happening in the hypothalamus after vapor cannabis."
Jon Davis, assistant professor of neuroscience at WSU and corresponding author on the paper
Calcium imaging has been used to study the brain's reactions to food by other researchers, but this is the first known study to use it to understand those features following cannabis exposure.
As part of this research, the researchers also determined that the cannabinoid-1 receptor, a known cannabis target, controlled the activity of a well-known set of "feeding" cells in the hypothalamus, called Agouti Related Protein neurons. With this information, they used a "chemogenetic" technique, which acts like a molecular light switch, to home in on these neurons when animals were exposed to cannabis. When these neurons were turned off, cannabis no longer promoted appetite.
"We now know one of the ways that the brain responds to recreational-type cannabis to promote appetite," said Davis.
This work builds on previous research on cannabis and appetite from Davis' lab, which was among the first to use whole vaporized cannabis plant matter in animal studies instead of injected THC-;in an effort to better mimic how cannabis is used by humans. In the previous work, the researchers identified genetic changes in the hypothalamus in response to cannabis, so in this study, Davis and his colleagues focused on that area.
The current research received support from the Alcohol and Drug Abuse Research Program, the National Institute on Alcohol Abuse and Alcoholism, and the U.S. Department of Agriculture as well as by funds provided by the state of Washington Initiative Measure No. 171.
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Journal reference:
Wheeler, E. C., et al. (2023). Cannabis Sativa targets mediobasal hypothalamic neurons to stimulate appetite. Scientific Reports. doi.org/10.1038/s41598-023-50112-5.