Tobacco consumption is one of the main public health problems worldwide and is the leading cause of preventable premature mortality throughout the world. It is estimated that globally, 22.5% of adults (32% males, 7% females) currently smoke tobacco. Despite the known harms associated with tobacco, only 5% of smokers who try to quit on their own remain abstinent during the first six months and around 50-75% of “former smokers” relapse in the first week of trying.

It should be noted that giving up tobacco also produces numerous undesirable effects, including physical, affective and cognitive symptoms. The most common cognitive disorders include attention deficits and memory impairment. Several scientific studies suggest that related to nicotine withdrawal side effects partly promote relapse into the habit. In fact, varenicline, a drug used in quitting smoking, acts to improve mood and cognitive function during the early period of abstinence.

Until now the cause of cognitive disorders related to the nicotine withdrawal remained unknown. Now, a study led by Fernando Berrendero, principal investigator of the Neuropharmacology Laboratory at Pompeu Fabra University (NeuroPhar), has discovered the link between a specific neuronal receptor, CB1R, and the cognitive defects associated with tobacco withdrawal.

The endocannabinoid system consists of endogenous ligands capable of activating a network of neural receptors that regulate reward, learning and memory processes, among others. In addition, it has been observed that this system plays an important role in nicotine addiction. CB1Rs belong to the endocannabinoid system and, according to the results of this research, are mainly responsible for failures in memory and attention due to the nicotine withdrawal.

Morphological analysis of neurons has enabled the research team to observe a decrease in the number of mature dendritic spines (that is, the areas where the synapses take place) after four days without consuming nicotine. However, by eliminating CB1R receptors located in a particular area of the hippocampus, these structural changes in hippocampal neurons and memory deficits induced by nicotine withdrawal were not observed.

“The typical attention and memory alterations during the first days without smoking seem to be involved in relapse,” says leading researcher, Fernando Berrendero. “That's why drugs that improve these cognitive defects are a good strategy for treating nicotine withdrawal symptoms or could serve as an additional therapy for those smokers who are more prone to these problems.”

CB1R receptors located in the hippocampus are thus revealed in this research published in Biological Psychiatry as a possible pharmacological target to prevent smoking relapse by increasing cognitive function during the first days of abstinence.

Reference work: Rocio Saravia, África Flores, Ainhoa Plaza-Zabala, Arnau Busquets-García, Antoni Pastor, Rafael de la Torre, Vincenzo Di Marzo, Giovanni Marsicano, Andrés Ozaita, Rafael Maldonado, Fernando Berrendero. CB1 Cannabinoid Receptors Mediate Cognitive Deficits and Structural Plasticity Changes During Nicotine Withdrawal. Biological Psychiatry, Julio 2016. doi:10.1016/j.biopsych.2016.07.007