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  • The effect of synthetic cannabinoid ADB-FUBI-NACA on primary neuronal cultures ß-galacto-sidase activity: preliminary findings
    Publication . Roque-Bravo, Rita; Carmo, Helena; Silva, João Pedro; Carvalho, Félix; Silva, Diana Dias da; Dias da Silva, Diana Cristina
    ADB-FUBINACA (ADB-FUB) is a synthetic cannabinoid (SC) that has gained popularity among users as a new psychoactive substance. This stems from SC's pharmacological similarity to the active principle of cannabis, D9-tetrahydrocannabinol (THC). However, unlike THC, SCs demonstrate full agonism of cannabinoid receptors 1 and 2 [1]. Recent scientific developments have shown that can-nabis use may aggravate ageing-related parameters [2,3]. Moreover, a study using human fibroblasts re-vealed that 1 μM THC (2h-longexposure, for 15 days) can increase ß-galactosidase activity [3], which serves as a first-line marker for cellular senescence. This study was designed to investigate whether these biologically-relevant concentrations could accelerate neuronal ageing. PHC were isolated from Wistar rat day 18-19 embryos and cultured for up to 21 days-in-vitro (DIV). Exposure to 1 pM, 1 nM and 1 μM ADB-FUB (concentrations previously shown to be non-cytotoxic to PHC) started either on DIV3 or DIV7 and was maintained up to 21 DIV. At that final timepoint, ß-galactosidase activity was evaluated. DMSO at 0.02% was employed as solvent control. Under these experi-mental conditions, PHC exposed to 1 nM and 1 μM ADB-FUB in the DIV3-21 protocol had lower ß-galactosidase activity when compared to control conditions (p<0.05, 1 nM; p<0.001, 1 μM). No statisti-cally significant results were registered for PHC under the DIV7-21 exposure protocol. These findings are, to the best of our knowledge, the first evidence of a potential “anti-ageing” effect of ADB-FUB. Evaluation of other senescence-related endpoints will follow. Moreover, experiments using another in vitroneuronal model (human neuroblastoma cell line SH-SY5Y) are underway to compare the effects of the same drug in different models and further substantiate conclusions on ADB-FUB’s effect.
    2024-05-01Comunicação em conferência Acesso aberto Ver mais