Giovanni Marsicano: “The endocannabinoid system has not yet yielded up all its secrets”

Taking its name from the product by which it was identified, the endocannabinoid system is a group of cellular and molecular receptors, the natural role of which is being gradually unravelled. It is over 15 years since Giovanni Marsicano, leader of a team at Neurocentre Magendie (Bordeaux), devoted himself to its study. In 2010, he obtained funding from the European Research Council (ERC Starting Grant) to find out about its role in food intake. This starting point took him far beyond that...

What led you to become interested in the endocannabinoid system?

© Inserm, L. Prat

I have had a somewhat atypical career: I trained as a vet, and started research in Italy in 1992 – first in the university, and then in the private sector. But that was mainly applied research. Since I wanted to focus on unexplored phenomena and because I was fascinated by the neurosciences, I decided to return to university in 1997, at the Max Planck Institute: three years of a PhD in neurosciences, followed by three years’ post-doctoral work, enabled me to focus on the endocannabinoid system. Having specialised in this way, I was able to join Neurocentre Magendie, where I obtained this ERC grant in 2010.

How does this system control food intake? 

We have been able to demonstrate that hunger stimulates the endocannabinoid receptors, which in turn activate smell. Our sense of smell is then heightened, making food more attractive, which increases our desire to eat. But this is one property of the endocannabinoid system, among so many others! Its receptors increasingly seem to be regulators involved in many areas of brain activity. In my laboratory, I wanted our research to start from the bottom, from one molecule, so that we could follow it through all the biological mechanisms in which it is involved. This approach is particularly well suited to the endocannabinoid system, which plays a transversal role. The ERC funding allows us to advance in several directions at a time. 

What have you been able to find out? 

We have demonstrated two major phenomena: in the first place, we showed that endocannabinoid receptors, present on the surface of brain cells, are also present on the inside, bound to the mitochondrial surface. The activity of these organelles, the “power plants” of the cells, might therefore be disrupted in cannabis users, which would explain the problems they can have with memory retention. Another discovery: we have found that pregnenolone, a natural precursor of several of our hormones, can inhibit some harmful effects associated with cannabis use. This discovery could lead to the development of a product for weaning users off cannabis. According to data obtained in animal models, it might also protect them from its psychotic effect and reduce the psychiatric disorders experienced by many users. These discoveries could have therapeutic implications in the coming years: we have just won an ERC Proof of Concept grant to conduct feasibility studies testing this latter hypothesis... 

Find out more about Giovanni Marsicano and his work
Giovanni Marsicano leads the Endocannabinoids and Neuroadaptation team at Inserm Unit 1215, Neurocentre Magendie, Bordeaux.

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