Role of a Cannabis Extract in 2-Arachidonoylglycerol Metabolism Regulation During Physiological Aging

SALAS, SABRINA ROSICLER; MILANO, P. G.; MUSSO, FLORENCIA; PASCUAL, A.C.; PASQUARE, S.J

New York

Congreso; Meeting ISN-ASN 2025; 2025

International Society for Neurochemistry

The availability of the main neuroprotective endocannabinoid (EC), 2-arachidonoylglycerol (2-AG), was found to decrease in rat cerebral cortex (CC) synaptosomes (syn) during aging. It was alsodemonstrated that 2-AG metabolism can be modulated by its own receptors. Moreover, phytocannabinoids present in Cannabis sp. extracts (CE), capable of binding to cannabinoid receptors, are being used in several studies to treat neurodegenerative processes.The aim of the present work was to evaluate if a CE couldmodulate 2-AG metabolism and thus attenuate its deficit in aging. To this end, delta-9-tetrahydrocannabinol (THC) enriched CE were obtained from descarboxilated female flowers with ethanol as extraction solvent. The THC-freefraction (CE F/THC) was isolated from the CE using thin-layer chromatography. CC syn fromadult (4–6 months) and aged (24–26 months) rats were obtained by differential centrifugation and purified in ficoll gradients, and then used to test the synthesis (diacylglycerol lipase [DAGL] andlysophosphatidate phosphohydrolase [LPAase] and hydrolysis [monoacylglycerol lipase, MAGL]) of 2-AG. The syn were coincubated with THC enriched CE (1 μM THC), CE F/THC or 1 μM pure THC, and the respective radiolabeled substrate, simultaneously.Results showed that, none of the treatments modified the 2-AG metabolism in adult syn (p ≥ 0.05). However, in aged syn, CE F/THC caused a decrease in the MAGL (8%) and DAGL (84%) activities(p < 0.05). Additionally, THC-enriched CE reduced MAGL activity (7%), and pure THC caused a decline in DAGL activity (56%) (p < 0.05). These results demonstrate that the CE is capable of increasing the 2-AG availability in aged syn, possibly attenuating the deregulation of this EC observed in aging.This effect is observed only in the presence of the complete CE, demonstrating the synergy between the different components of the plant. These findings highlight the importance of using the entire CE in the success of Medicinal Cannabis.