AXON STATIONS: Marijuanalike chemicals called cannabinoids seem to help guide the root-like feelers or axons [such as above] projecting from certain brain cells in fetal mice. The chemicals activate protein receptors peppering the axons (green).
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Natural marijuanalike chemicals may direct key brain cells to make proper connections while in the womb, according to a new study. Researchers report that the molecules, called cannabinoids, serve as guideposts for young cells in the attention and decision-making parts of fetal mouse brains.

The finding may help explain studies showing that the children of mothers who smoked marijuana during pregnancy are slower to process information than their peers (although they are just as intelligent overall). Tetrahydrocannabinol (THC), the active ingredient in marijuana, might knock the cell-guiding machinery off course by overstimulating the brain. Researchers, however, say they are still a long way from determining exactly what effects cannabinoids have on developing human brains.

"I would say yes there is human relevance," says study co-leader and neurobiologist Tibor Harkany of the Karolinska Institute in Stockholm, "but I cannot prove this, and these findings will not prove this."

Scientists know that particular receptor proteins on human and animal adult brain cells respond to THC-like chemicals, or cannabinoids, which prevent the cells from making strong connections to one another, Harkany says. But they were in the dark about the role of endocannabinoids—the kind made by the brain—during fetal development. So Harkany and his colleagues cultured mouse embryonic brain cells that expressed cannabinoid receptor proteins (CBRs) and exposed them to gradients of synthetic cannabinoids.

The cells withdrew their rootlike feelers, or axons, from the high concentration of cannabinoids; the axons, which seek out and communicate with neighboring cells, veered instead in other directions, the group reports in a paper published online today in Science. In effect, "if you activate the cannabinoid system" of these cells, Harkany says, "it will send a message to the cell that 'I don't want to grow there, I want to grow somewhere else'" and connect to another cell.

The researchers found two groups of brain cells in embryonic mice that carried the CBR proteins for several days during late development. (Mice gestate in 18 or 19 days.) The cells were located in the cortex, the brain region that controls attention and planning in humans and other mammals.

THC would likely affect very similar brain systems in human fetuses, says neuroscientist Yasmin Hurd of the Mount Sinai School of Medicine in New York City, who was not part of the research, but its concentration would be much higher than that of any endocannabinoid. "It would have an even more pronounced effect on axonal growth and guidance," she says.

Neuroscientist Ken Mackie of Indiana University, another co-leader of the new study, says that natural cannabinoids can reach very high concentrations but are secreted by the brain in precise locations. THC would activate CBRs indiscriminately, he says. "The effects of endocannabinoids released in a regulated fashion," he says, "will almost always be different from THC from smoked cannabis."