Hormone hampers effects of marijuana

Study in rodents could lead to new treatments for cannabis addiction

A nondescript hormone that moonlights as a potent pot blocker in the brain may lead to drugs that help people curb cannabis dependence. The hormone pregnenolone blunts marijuana’s effects in rats and mice, scientists report in the Jan. 3 Science.

The results are “incredibly exciting, both at a scientific level and at the level of public health,” says Margaret Haney of Columbia University Medical Center. Recent laws that legalize medical marijuana will expand the already-popular drug’s reach, leading to more people who struggle with cannabis addiction, she says. “We have no options to help the substantial number of people who are seeking treatment for that disorder,” Haney says. “This looks like a very exciting potential tool for that.”

Pregnenolone was thought to be an inert building block for other flashier hormones, such as testosterone, progesterone and estrogen, says study coauthor Pier Vincenzo Piazza of INSERM, the National Institute of Health and Medical Research in France. Instead, the hormone has the unexpected ability to curb marijuana’s effects in the brain. “It was really a big surprise,” Piazza says.

Pregnenolone is normally present in the rodent brain. But in response to a big dose of THC, the active ingredient in marijuana, pregnenolone levels temporarily soared, increasing in some cases by 3,000 percent above baseline levels.  When researchers injected large amounts of the hormone into rodents, the animals became immune to several effects of THC. Mice and rats that received pregnenolone minutes before receiving THC didn’t get the munchies that come with marijuana use, and mice were better able to remember objects. The hormone also seemed to curb mice’s craving for a THC-like molecule. After receiving pregnenolone, the animals were less likely to self-administer the drug.

The results at this early stage have little to do with people who struggle with drug abuse or dependence, cautions neuroscientist Carl Hart of Columbia University. Studies on rodents can’t model the complexities of human addiction, he says. “We as thinking humans have to be careful to understand that what they’re doing is a nice first step, but the relevance to the human model is at best unclear.”

Pregnenolone itself isn’t a viable treatment to curb the effects of marijuana, Piazza says. When taken orally, the hormone isn’t easily absorbed by the body and is converted into other hormones within minutes. (Those facts might discourage people from buying pregnenolone supplements, which are marketed as an aid for a host of ailments including fatigue, psoriasis, PMS, Alzheimer’s and aging.) Piazza and his colleagues are working to develop a family of compounds that work similarly to pregnenolone without these metabolic problems. 

Laura Sanders is the neuroscience writer. She holds a Ph.D. in molecular biology from the University of Southern California.

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