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PARIS: Researchers on Sunday said they had pinpointed the biochemical pathway by which cannabis causes memory loss in mice.

The discovery could help open the way to drugs that have marijuana's desired pain-killing properties but without its amnesia-related side effects, according to the paper, published in the journal Nature Neuroscience.

It has long been known that cannabis produces memory loss by acting on the hippocampus, the region in the brain that governs most of our cognitive functions. But whether that impact was long-term or lasted only during the drug's use, as well as how the drug acted biochemically, has been intensely debated.

"Heavy use of marijuana"

Rafael Maldonado and and Andres Ozaita at Pompeu Fabra University in Barcelona believe they can help answer both questions. The scientists first created a new model of cognitive impairment so that they could easily assess the impact of cannabis use on memory in normal mice.

Marijuana's active ingredient, THC, acts on cannabinoid receptor neurons called CB1. While found in several locations within the brain, there are two concentrations of CB1-type cells in the hippocampus.

To explore how each of these neural networks might affect memory loss, the researchers created two groups of genetically modified mice, each missing the CB1 receptors in either of the two regions. The rodents were then injected with doses of THC equivalent to "heavy use" of marijuana in humans.

Forgetful mice

One of the groups reacted in the well-known forgetful fashion when required to do memory tests. The other mouse group – whose CB1 receptors had been removed from the so-called GABAergic neurons – was unaffected by the drug.

"Not only were the behavioural effects abolished, the biochemical responses that are directly responsible for the amnesic-like effect were abolished too," Maldonado said.

This should make it possible to develop a molecule that will produce cannabis' positive effect without affecting the GABAergic brain cells that govern memory, he added.