The effects of Synthetic Cannabinoids ADB-FUBINACA, AMB-FUBINACA, AB-CHMINACA and HU-308 on Differentiation and Proliferation of Brain NG108-15 Cells
Synthetic Cannabinoids (SCs) are the largest group of new psychoactive substances monitored by the EMCDDA through the EU Early Warning System, with a recent report released by the drugs agency disclosing that 209 SCs were detected between 2008 and 2020. The abuse of these substances embodies major public health and social risks as they have been responsible by numerous intoxications and deaths. Phytocannabinoids, the drugs of abuse most frequently consumed by adolescents and young adults (including pregnant women and women of childbearing age), have been linked to neurodevelopmental disorders. Thus, this work hypothesises that the abuse of SCs may also exert profound negative effects during neurogenesis.
To test this hypothesis, a neuroblastoma x glioma hybrid cell line NG108-15 was exposed to 4 SCs, ADB-FUBINACA, AMB-FUBINACA, AB-CHMINACA and HU-308, at concentrations considered biologically relevant (1pM, 1nM and 1µM). Cell differentiation was assessed by measuring the differentiation ratios (i.e., the percentage of primary neurites per cell) and the total length of neurites, after 72-h incubations in differentiation medium. Cell proliferation was also evaluated by using the sulforhodamine B assay (SRB) after 24-h, 48-h, and 72-h incubations.
Both ADB-FUBINACA (p<0.01, at all concentrations) and AMB-FUBINACA (p<0.01, at 1pM and 1µM) increased the neuronal differentiation ratios and the total length of primary neurites (p<0.05, at 1nM for both drugs). On the other hand, neither AB-CHMINACA or HU-308 affected overall differentiation. Of note, none of the drugs affected cell proliferation of NG108-15 at the concentrations tested.
These results show, for the first time, that two of the worldwide most consumed SCs (ADB-FUBINACA and AMB-FUBINACA) impact in vitro neuronal differentiation, suggesting that significant post-exposure effects may also occur during neurodevelopment.