Combined Addiction and Neurobiological Targets: An In Silico Analysis of Areca Nut and Areca Nut with Tobacco Biomolecules.

Background: The addictive potential of areca nut (AN) and tobacco is well-documented, but their combined neurobiological effects in AN-containing tobacco products (ANTP) remain obscure. This study employed a three-stage in silico approach to investigate the potential targets and pathways associated with the addictive properties of AN alone and in ANTP.

Materials and methods: Bioactive molecules were retrieved for AN and tobacco, followed by target prediction and pathway enrichment analysis. The identified biomolecules were categorized into AN and ANTP groups.

Results: A total of 195 bioactive molecules were identifid (38 to AN, 157 to tobacco). Absorption, distribution, metabolism, and excretion (ADME) details were retrieved. Predicted bioactivity (gene/protein interaction probability ≥80%) was analysed, revealing 13 shared targets between AN and tobacco, 12 exclusive to AN, and 33 exclusive to tobacco. AN and ANTP influenced 21 and 27 pathways (FDR ≤ 0.05), respectively, with distinct footprints. Notably, GABAergic and cholinergic synapses, nicotine addiction, calcium signaling, and morphine addiction pathways were differentially enriched between AN and ANTP.

Discussion: This study highlights the distinct and synergistic neurobiological effects of AN and tobacco in ANTP. The identified differences in target genes and pathways underscore the need for tailored interventions and cessation strategies for users of AN and ANTP products. Further research is warranted to validate these findings, explore interplay between diverse addiction factors, and develop effective prevention and treatment programs. (Neuropsychopharmacol Hung 2024; 26(3): 133-143)