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Molecular Pharmacology of Synthetic Cannabinoids: Delineating CB1 Receptor-Mediated Cell Signaling
Open AccessArticle

The Synthetic Cannabinoids THJ-2201 and 5F-PB22 Enhance In Vitro CB1 Receptor-Mediated Neuronal Differentiation at Biologically Relevant Concentrations

UCIBIO, REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
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Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(17), 6277; https://doi.org/10.3390/ijms21176277
Received: 24 July 2020 / Revised: 25 August 2020 / Accepted: 28 August 2020 / Published: 30 August 2020
(This article belongs to the Special Issue Psychoactive Substances in Neuronal Development)
Recreational use of synthetic cannabinoids (SCs) before and during pregnancy poses a major public health risk, due to the potential onset of neurodevelopmental disorders in the offspring. Herein, we report the assessment of the neurotoxic potential of two commonly abused SCs, THJ-2201 and 5F-PB22, particularly focusing on how they affect neuronal differentiation in vitro. Differentiation ratios, total neurite length, and neuronal marker expression were assessed in NG108-15 neuroblastoma x glioma cells exposed to the SCs at non-toxic, biologically relevant concentrations (≤1 μM), either in acute or repeated exposure settings. Both SCs enhanced differentiation ratios and total neurite length of NG108-15 cells near two-fold compared to vehicle-treated cells, in a CB1R activation-dependent way, as the CB1R blockade with a specific antagonist (SR141718) abrogated SC-induced effects. Interestingly, repeated 5F-PB22 exposure was required to reach effects similar to a single THJ-2201 dose. Cell viability and proliferation, mitochondrial membrane potential, and intracellular ATP levels were also determined. The tested SCs increased mitochondrial tetramethyl rhodamine ethyl ester (TMRE) accumulation after 24 h at biologically relevant concentrations but did not affect any of the other toxicological parameters. Overall, we report firsthand the CB1R-mediated enhancement of neurodifferentiation by 5F-PB22 and THJ-2201 at biologically relevant concentrations. View Full-Text
Keywords: developmental neurotoxicity; endocannabinoid system; neurogenesis; new psychoactive substances; substances of abuse developmental neurotoxicity; endocannabinoid system; neurogenesis; new psychoactive substances; substances of abuse
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MDPI and ACS Style

Alexandre, J.; Malheiro, R.; Dias da Silva, D.; Carmo, H.; Carvalho, F.; Silva, J.P. The Synthetic Cannabinoids THJ-2201 and 5F-PB22 Enhance In Vitro CB1 Receptor-Mediated Neuronal Differentiation at Biologically Relevant Concentrations. Int. J. Mol. Sci. 2020, 21, 6277. https://doi.org/10.3390/ijms21176277

AMA Style

Alexandre J, Malheiro R, Dias da Silva D, Carmo H, Carvalho F, Silva JP. The Synthetic Cannabinoids THJ-2201 and 5F-PB22 Enhance In Vitro CB1 Receptor-Mediated Neuronal Differentiation at Biologically Relevant Concentrations. International Journal of Molecular Sciences. 2020; 21(17):6277. https://doi.org/10.3390/ijms21176277

Chicago/Turabian Style

Alexandre, João; Malheiro, Rui; Dias da Silva, Diana; Carmo, Helena; Carvalho, Félix; Silva, João P. 2020. "The Synthetic Cannabinoids THJ-2201 and 5F-PB22 Enhance In Vitro CB1 Receptor-Mediated Neuronal Differentiation at Biologically Relevant Concentrations" Int. J. Mol. Sci. 21, no. 17: 6277. https://doi.org/10.3390/ijms21176277

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