ENDOCANNABINOID GENETIC VARIATION LINKS COGNITIVE PERFORMANCE, EMPATHY, AND STRESS REGULATION IN OLDER ADULTHOOD

The endocannabinoid system is essential in the regulation of stress and cognitive processes, both of which are susceptible to age-related decline. Genetic variations in the CNR1 gene, which encodes the cannabinoid receptor type 1, may influence these mechanisms through modulation of neural and neuroendocrine pathways. This study aimed to investigate whether genetic variation in the CNR1 gene, specifically the promoter polymorphism rs806371 (T/G), is associated with cognitive performance, empathy, and HPA axis activity in older adults.
A total of 189 adults aged over 60 years were genotyped for the CNR1 rs806371 polymorphism. Participants were anssesed for executive function, memory, attention, and processing speed, as well as the Pictorial Empathy Test (PET). Salivary cortisol samples were collected at six time points throughout the day to derive three indices of diurnal cortisol secretion: cortisol awakening response (AUCiCAR), total daily cortisol output (AUCtotal), and diurnal cortisol slope.
Carriers of the G allele demonstrated significantly poorer performance in executive function and memory compared with TT homozygotes, alongside higher empathy scores on the PET. In addition, G allele carriers exhibited lower cortisol secretion, as reflected by reduced AUCiCAR and AUCtotal values, indicating a blunted HPA axis response.
These findings suggest that the CNR1 rs806371 polymorphism contributes to individual differences in cognitive, socioemotional, and neuroendocrine functioning in later life. Overall, the results support the role of the endocannabinoid system as a pathway linking genetic susceptibility to stress regulation, empathy, and cognitive aging.
Supported by MCIN (PID2021-125945OB-I00; PID2024-160587OB-I00), EU/AEI (RED2022-134191-T; 10.13039/501100011033), Comunidad de Madrid predoctoral contract (59/000982.9/23).