08:28pm Monday 11 November 2019

Revealed – how marihuana alters memory

It has been known for some time that cannabis can cause memory loss. Research work, published in the prestigious Cell journal, has managed to uncover the mechanism whereby the chronic, on-going and excessive consumption of marihuana causes alterations in what is known as working memory – that which retains and processes information over short periods of time. Collaborating in the study with doctors Juan Mendizabal and Pedro Grandes, lecturers at the Department of Neurosciences at the UPV/EHU’s Faculty of Medicine and Odontology, were researchers from France, Canada, China and the United States. Moreover, this research, led by Xia Zhang of the University of Ottawa in Canada and Giovanni Marsicano at the University of Bordeaux in France, is the first confirmation of the role of the astrocytes, cells of the nervous system, in a cognitive function such as memory, given that to date they had been assigned a secondary task of support, nutrition and protection of the neurones.

Tetrahydrocannabinol (THC) is the principal psychoactive component of marihuana. As with any other pharmaceutical drug, the THC acts on certain proteins, which act as receptors. In this case, according to what the research has revealed, the proteins on which the THC acts in the astrocytes are the CB1 receptors. These receptors, on being activated in the hippocampus, trigger the secretion of glutamate, an amino acid that has an excitant function on the central nervous system. Then there is a chain process. The glutamate secreted from the astrocytes causes the triggering of the NMDA receptors in the neurones and this has the consequence of other glutamate receptors – known as AMPAs – disappearing form the neuronal surface. On the AMPA disappearing, communication between the neurones of the hippocampus falls and, as a result, memory suffers impairment.

The contribution of the UPV/EHU neuroscientists to the research has been in localising the CB1 receptor in the astrocytes. To this end, they used wild mice, which have the CB1 protein, and genetically modified mice, which lack it. They were able to confirm that, in the latter, THC did not have an effect on the synapsis of the neurones in the hippocampus.

These results highlight the fundamental role of CB1 receptors, located in the astrocytes, in the cognitive deterioration induced by cannabinoids. The question is whether the marihuana triggers a similar mechanism in the human brain. It is expected to do so, given that this drug alters short-term memory both in humans and in rodents. Moreover, the potential therapeutic applications of marihuana derivatives, presently limited by their adverse effects, “may benefit from these results, on helping researchers to generate new pharmaceutical drugs with the same therapeutic benefits as cannabis, but with fewer side-effects”, concluded doctor Grandes.

Biokimika, Medikuntza

Internet reference
Reference to the Cell journal article: Jing Han, Philip Kesner, Mathilde Metna-Laurent, Tingting Duan, Lin Xu, Francois Georges, Muriel Koehl, Djoher Nora Abrous, Juan Mendizabal-Zubiaga, Pedro Grandes, Qingsong Liu, Guang Bai, Wei Wang, Lize Xiong, Wei Ren, Giovanni Marsicano and Xia Zhang. Acute Cannabinoids Impair Working Memory through Astroglial CB1 Receptor Modulation of Hippocampal LTD (DOI 10.1016/j.cell.2012.01.037)
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