Marijuana's major psychoactive ingredient (THC) affects memory independent of its direct effect on neurons, say researchers.
According to the researchers of the study, marijuana's major psychoactive ingredient (THC) impairs memory independently of its direct effects on neurons.
The side effects stem instead from the drug's action on astroglia, passive support cells long believed to play second fiddle to active neurons.
The researchers claim that the findings offer important new insight into the brain and raise the possibility that marijuana's benefits for the treatment of pain, seizures and other ailments might some day be attained without hurting memory.
Giovanni Marsicano of INSERM in France said that with these experiments in mice, "we have found that the starting point for this phenomenon - the effect of marijuana on working memory - is the astroglial cells".
"This is the first direct evidence that astrocytes modulate working memory," Xia Zhang from the University of Ottawa in Canada, said.
The new findings aren't the first to suggest astroglia had been given short shrift. Astroglial cells - also known as astrocytes -k have been viewed as cells that support, protect and feed neurons for the last 100 to 150 years, Marsicano explained.
Over the last decade, evidence has accumulated that these cells play a more active role in forging the connections from one neuron to another.
The researchers didn't set out to discover how marijuana causes its cognitive side effects. Rather, they wanted to learn why receptors that respond to both THC and signals naturally produced in the brain are found on astroglial cells.
These cannabinoid type-1 (CB1R) receptors are very abundant in the brain, primarily on neurons of various types.
Zhang and Marsicano have now shown that mice lacking CB1Rs only on astroglial cells of the brain are protected from the impairments to spatial working memory that usually follow a dose of THC.
In contrast, animals lacking CB1Rs in neurons still suffer the usual lapses. Given that different cell types express different variants of CB1Rs, there might be a way to therapeutically activate the receptors on neurons while leaving the astroglial cells out, Marsicano said.
"The study shows that one of the most common effects of cannabinoid intoxication is due to activation of astroglial CB1Rs," the researchers said.
Zhang said that the findings further suggest that astrocytes might be playing unexpected roles in other forms of memory in addition to spatial working memory.
The study has been recently published in the journal Cell.