To study exactly how cannabis affects working memory in such a fashion, Giovanni Marsicano of the University of Bordeaux in France, Xia Zhang of the University of Ottawa Institute of Mental Health Research and their colleagues removed cannabinoid receptors from neurons in mice, reports Ruth Williams at Scientific American. These receptors are proteins that respond to marijuana’s chief psychoactive ingredient, THC (tetrahydrocannabinol).
Using microelectrodes implanted into the brains of rats, the researchers found that THC weakens the connections (synapses) between neurons in the hippocampus, an area of the brain crucial for memory formation.
The mice whose cannabinoid receptors had been removed from their neurons were just as forgetful as regular mice when given THC; that is to say, they were just as bad at memorizing the position of a hidden platform in a water pool. But when the cannabinoid receptors were removed from astrocytes, a type of glial cells, the mice could find the platform just fine while on THC.
The research reveals that the star-shaped astrocytes have a major role in working memory, with the results suggesting that the role of glia in mental activity has been overlooked. Glial cells were previously viewed as little more than the “glue” which supports neurons.
Although recent research has shown that glia are involved in many unconscious processes and diseases, this is one of the first studies to suggest that glia play a major role in conscious thought.
“Our study provides compelling evidence that astrocytes control neurons and memory,” Zhang said, reports Mo Costandi at Nature. “The supporting actor has become the leading actor.”
“It’s very likely that astrocytes have many more functions than we thought,” Marsicano said. “Certainly their role in cognition is now being revealed.”“It’s always difficult to extrapolate from rodents to humans, but marijuana impairs working memory in both species, so I expect that similar mechanisms are involved,” Marsicano said.
The study shows an exciting link between astrocyte signaling and cognitive function, according to Ben Whalley, a pharmacologist at the University of Reading, UK. “It’ll be fascinating to investigate their consequences for endogenous cannabinoid signaling in normal brain function and in pathological states,” Whalley said.
Since THC’s pain-relieving property appears to work through neurons — unlike its effect on working memory — in theory, it might be possible to design THC-type drugs that target neurons, but not glia, thus offering pain relief without forgetfulness to patients who wish to maintain their cognitive capacity.
“But we still haven’t separated out the different effects of neuronal and astrocyte CB1 receptors, so the jury’s still out on the potential therapeutic effects of targeting the neuronal receptors,” Whalley said.
In the meantime, studies have shown that patients who use strains of marijuana containing high concentrations of the non-psychoactive but medicinal cannabinoid called cannabidiol (CBD) do not experience memory impairment, according to Nature. These strains are increasingly being used for medicinal purposes, especially with children; for example, the high-CBD strain Charlotte’s Web is being used by more and more families to stop the severe epileptic seizures associated with Dravet’s syndrome.