Working memory (WM) depends on several neural networks and neurochemical systems. One of them is the endocannabinoid (eCB) system, which CB1 receptor (CB1R) is widely distributed all over the brain. The stimulation of CB1R by agonists reduces WM efficiency. The CNR1 human gene (6q14-15) encodes the CB1R. AATn polymorphism of the CNR1 gene has been related to psychiatric disorders, and to procedural learning and attention in healthy subjects. The aim of this exploratory research was to test whether AATn polymorphism of the CNR1 is related to the WM performance, by measuring n-back task. Mexican healthy young adults (n = 94) performed the WM n-back task. One of the most frequent AATn allele in our sample was the AAT12. We formed three groups, as a function of the AATn genotype: AAT ≤ 12/AAT≤12, AAT ≤ 12/AAT > 12 and AAT > 12/AAT > 12, and their accuracy on the n-back task was compared. WM accuracy differed among genotypes (P=0.03): AAT ≤ 12/AAT≤12 group had a higher performance than the AAT > 12/AAT > 12 group (statistical power: 0.65, f(2) = 0.20, P<0.05). These results suggest that the fewer AATn repeats of the CNR1 gene, the better WM performance, and sustain the idea that eCB system participates in the modulation of the human brain network involved in WM.
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