(CORDIS) — The medicinal properties of marijuana have long been a contentious issue, with those denouncing its use citing its negative effects on working memory and the ability to retain information for short periods of time as reasons for not prescribing the drug. While these side-effects have been known to scientists for some time, now international researchers have pushed forward knowledge of how the drug works by getting to grips with the neurobiology behind these well known side-effects.
Writing in the journal Cell, the team, from Canada, China, France, Spain and the United States, present their findings on the source of memory lapses. They found that 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 be less important than active neurons. By working out how to separate these two parts of the drug, the team says that one day marijuana’s benefits for the treatment of pain, seizures and other ailments might be attained without hurting memory. Astroglial cells have long been viewed as cells that support, protect and feed neurons, but it is only in the last decade that scientists have started to find evidence supporting the idea that these cells play a more active role in forging the connections from one neuron to another.
‘We have found that the starting point for this phenomenon, the effect of marijuana on working memory, is the astroglial cells,’ comments one of the study authors Giovanni Marsicano from INSERM in France. Xia Zhang from the University of Ottawa in Canada adds that ‘this is the first direct evidence that astrocytes modulate working memory.’
However, the researchers stumbled upon this finding by accident as they had originally set out to learn why receptors that respond to both THC and signals naturally produced in the brain are found on astroglial cells. These CB1R receptors are very abundant in the brain, primarily on neurons of various types. In their experiments the team showed 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. They also observed that those who lacked CB1Rs in neurons still suffer the usual lapses.
Thus they concluded that if 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.
‘The study shows that one of the most common effects of cannabinoid intoxication is due to activation of astroglial CB1Rs. The findings further suggest that astrocytes might be playing unexpected roles in other forms of memory in addition to spatial working memory,’ continues Xia Zhang.
Now the team hope to look into the activities of endogenous endocannabinoids, which naturally trigger CB1Rs, on astroglial and other cells. The endocannabinoid system is involved in appetite, pain, mood, memory and many other functions. Giovanni Marsicano states that for ‘just about any physiological function you can think of in the body, it’s likely at some point endocannabinoids are involved.’
Understanding how these molecules work could lead to future discoveries in Alzheimer’s, for example.