Resumo da apresentação:

Synthetic Cannabinoids (SCs) comprise a diverse group of new psychoactive substances (NPS) that bind and activate cannabinoid receptors (e.g. CB1, CB2) with higher potency than tetrahydrocannabinol (THC, the main psychoactive element of cannabis). Despite being initially designed for therapeutic applications, SCs’ increased potency and longer‐lasting psychoactive effects compared to THC favored their recreational use. However, SCs also promote stronger adverse effects compared to THC. In fact, the recreational use of SCs has become a major challenge for public health and policy-makers due to the increasing number of SC-related acute intoxications and deaths. SC use by pregnant women and women of child-bearing age is especially alarming due to the potential onset of neurodevelopmental disorders in the offspring. Within the scope of the ongoing NeuroSCANN project, our team has assessed the neurotoxic potential of distinct SCs, particularly focusing on how they affect in vitro neurogenic processes in NG108-15 neuroblastoma x glioma cells, following exposure to SCs at non-toxic, biologically relevant concentrations (≤ 1 nM), either in acute or repeated exposure settings. We reported first-hand that two commonly reported SCs, THJ-2201 and 5F-PB22, enhanced differentiation ratios and total neurite length of NG108-15 cells near 2-fold compared to vehicle-treated cells, in a CB1R activation-dependent way, as CB1 receptor blockade with a specific antagonist abrogated SC-induced effects. Interestingly, at those same concentrations, the SCs tested increased mitochondrial membrane potential but did not affect other toxicological parameters like cell viability, proliferation or intracellular ATP levels. Nevertheless, further research is required to identify the action mechanisms involved in SC-mediated increase of neurodifferentiation.

Biography:
João Pedro Silva (JP Silva) graduated in Applied Biology (2002) at the University of Minho. He further holds an MSc in Molecular Genetics (2004) and a PhD in Biological Sciences (2009) from the same University (Biology Department), having assessed the pharmacological potential of de novo-synthesized antioxidants for oxidative stress-related pathologies. As a Post-Doctoral Researcher (2010-2016), whose work spanned the Centre of Biological Engineering (UMinho), the University Medical Centre Groningen (Netherlands) and University of California Riverside (USA), JP Silva tackled prevailing medical challenges related to wound healing and tuberculosis, having been awarded an Honor Mention in the Bluepharma/UCoimbra 2016 Innovation Award and filing an international patent. Since 2016, JP Silva is a Research Associate at the Toxicology Lab, Faculty of Pharmacy (Univ. Porto) focused on assessing the toxicity of new psychoactive substances (NPS), namely in understanding the role of synthetic cannabinoids in the onset of neurodevelopmental disorders and identify potential therapeutic targets for such pathologies.