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P03-10 Synthetic cannabinoids & neuronal senescence: distinctive responses of in vitro models to AMB-FUBINACA
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Abstract(s)
Among the array of new psychoactive substances, synthetic cannabinoids (SC) stand out as highly popular among consumers. These substances closely resemble, in terms of their pharmacology, Δ9-tetrahydrocannabinol (THC), cannabis’ main active principle, albeit exhibiting full agonism at the cannabinoid receptors 1 and 2. In light of recent scientific findings suggesting that cannabis use can exacerbate ageing-related parameters, the present work was designed to explore whether SC share similar potential effects. For this purpose, we employed two distinct in vitro models. The first model involved primary hippocampal cultures (PHC), isolated from Wistar rat embryos at embryonic day 18–19; after seeding, cells were kept in culture and exposed to the popular SC AMB-FUBINACA (AMB-FUB) at 1 pM, 1 nM and 1 µM, starting at day-in-vitro (DIV) 3 or DIV7, and perpetuated until DIV21. DMSO at 0.02% was used as the solvent control. At the end of the exposure, ß-galactosidase activity (a common first-line cell senescence biomarker) was assessed using a commercially-available kit. Our findings under these experimental conditions, revealed that PHC exposed to all AMB-FUB concentrations had less ß-galactosidase activity than the control condition (p<0.01, 1 pM; p<0.001, 1 nM and 1 µM). The other in vitro model used herein was the human neuroblastoma cell line SH-SY5Y. Beginning at passage 24, cells were seeded and exposed to 1 nM and 1 µM AMB-FUB. At passages 24 (48h after drug exposure) and 28, samples were collected for the analysis of several senescence-related endpoints, namely ß-galactosidase activity, cell cycle analysis (via flow cytometry, following DNA staining with propidium iodide) and relative telomere length measurement (using qPCR). Surprisingly, no discernible effect of AMB-FUBINACA was observed for any of the endpoints examined. The apparent observed “anti-ageing” effect of AMB-FUB on PHC warrants further investigation. Moreover, the differential reponse observed between the two in vitro models also requires scrutiny, particularly in light of recent published findings suggesting that THC has the potential to increase ß-galactosidase activity. Further experiments will ensue to hopefully shed some light on these interesting results.
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Pedagogical Context
Citation
Bravo, R. R., Carmo, H., Silva, J. P., Carvalho, F., & da Silva, D. D. (2024). P03-10 Synthetic cannabinoids & neuronal senescence: Distinctive responses of in vitro models to AMB-FUBINACA. Toxicology Letters, 399, S126. https://doi.org/10.1016/j.toxlet.2024.07.324
Publisher
Elsevier