A team of researchers from the Neuropharmacology Unit of the Department of Experimental and Health Sciences at Universitat Pompeu Fabra has identified the mechanisms involved in the amnesic effects of the cannabinoids. The work was supervised by Rafael Maldonado, a Pharmacology professor at the UPF and director of the Unit.

This study was the subject for the doctoral thesis by Emma Puighermanal, which was supervised by Andrés Ozaita and Rafael Maldonado, and one of the research areas of Arnau Busquets, a pre-doctoral researcher at the Unit and the head of the behavioural studies. They were all co-authors of the article "Cannabinoid modulation of hippocampal long-term memory is mediated by mTOR signaling", which was published in the online edition of the journal Nature Neuroscience on 2 August.

Identified: the precise point where cannabinoids generate their amnesic effects

CB1 cannabinoid receptors, whether stimulated by endogenous neurotransmitters or substances exogenous to the organism, are responsible for the various pharmacological and physiological effects on the human body. For example, cognitive impairment due to cannabis consumption is one of the negative consequences associated with the recreational drug.

This study shows that an intracellular signalling pathway known as mTOR, which affects the brain at the hippocampus level, the region associated with control of cognitive responses, is involved in the amnesic effects caused by the cannabinoids when they activate the CB1 receptors.

Using genetically modified (knockout) mice, the UPF researchers' study showed that the cognitive deficiency caused by administration of D9-tetrahydrocannabinol (THC), the main psychoactive ingredient of marijuana, is measured by the CB1 receptors and occurs specifically in the gabaergic interneurons. This system of neurons is characterised by the presence of gamma-aminobutyric acid or GABA, probably due to an imbalance in the activity taking place in the neurotransmitter. The study also shows that these amnesic effects lead to a synthesis of new proteins at hippocampus level.

This is the first evidence for the functional role of CB1 receptors in GABA neurones, and the involvement of the mTOR signalling pathway in the effects of the central nervous system on the cannabinoid agonists. These results identify the specific target on which the cannabinoids act, as well as the mechanism by which they create their amnesic effects. They therefore provide the basis for developing new therapeutic strategies for preventing some of the most harmful effects of cannabis consumption.

For further reference, see:

Emma Puighermanal, Giovanni Marsicano, Arnau Busquets, Beat Lutz, Rafael Maldonado, Andrés Ozaita (2009), "Cannabinoid modulation of hippocampal long-term memory is mediated by mTOR signaling". Nature Neuroscience. (2/8/2009).