Δ8-THC Induces Up-Regulation of Glutamatergic Pathway Genes in Differentiated SH-SY5Y: A Transcriptomic Study

Int J Mol Sci. 2023 May 30;24(11):9486. doi: 10.3390/ijms24119486.

Abstract

Cannabinoids, natural or synthetic, have antidepressant, anxiolytic, anticonvulsant, and anti-psychotic properties. Cannabidiol (CBD) and delta-9-tetrahydrocannabinol (Δ9-THC) are the most studied cannabinoids, but recently, attention has turned towards minor cannabinoids. Delta-8-tetrahydrocannabinol (Δ8-THC), an isomer of Δ9-THC, is a compound for which, to date, there is no evidence of its role in the modulation of synaptic pathways. The aim of our work was to evaluate the effects of Δ8-THC on differentiated SH-SY5Y human neuroblastoma cells. Using next generation sequencing (NGS), we investigated whether Δ8-THC could modify the transcriptomic profile of genes involved in synapse functions. Our results showed that Δ8-THC upregulates the expression of genes involved in the glutamatergic pathway and inhibits gene expression at cholinergic synapses. Conversely, Δ8-THC did not modify the transcriptomic profile of genes involved in the GABAergic and dopaminergic pathways.

Keywords: GABAergic synapses; SH-SY5Y cells; cholinergic synapses; delta-8-tetrahydrocannabinol; dopaminergic synapses; glutamatergic synapses; transcriptomic analysis.

MeSH terms

  • Cannabidiol* / pharmacology
  • Cannabinoids* / pharmacology
  • Dronabinol / pharmacology
  • Humans
  • Neuroblastoma* / genetics
  • Transcriptome
  • Up-Regulation

Substances

  • Dronabinol
  • Cannabinoids
  • Cannabidiol