Background: Drug addiction is a complex and chronic mental disease, which places a large burden on the\r\nAmerican healthcare system due to its negative effects on patients and their families. Recently, network\r\npharmacology is emerging as a promising approach to drug discovery by integrating network biology and\r\npolypharmacology, allowing for a deeper understanding of molecular mechanisms of drug actions at the systems\r\nlevel. This study seeks to apply this approach for investigation of illicit drugs and their targets in order to elucidate\r\ntheir interaction patterns and potential secondary drugs that can aid future research and clinical care.\r\nResults: In this study, we extracted 188 illicit substances and their related information from the DrugBank\r\ndatabase. The data process revealed 86 illicit drugs targeting a total of 73 unique human genes, which forms an\r\nillicit drug-target network. Compared to the full drug-target network from DrugBank, illicit drugs and their target\r\ngenes tend to cluster together and form four subnetworks, corresponding to four major medication categories:\r\ndepressants, stimulants, analgesics, and steroids. External analysis of Anatomical Therapeutic Chemical (ATC) second\r\nsublevel classifications confirmed that the illicit drugs have neurological functions or act via mechanisms of\r\nstimulants, opioids, and steroids. To further explore other drugs potentially having associations with illicit drugs, we\r\nconstructed an illicit-extended drug-target network by adding the drugs that have the same target(s) as illicit drugs\r\nto the illicit drug-target network. After analyzing the degree and betweenness of the network, we identified hubs\r\nand bridge nodes, which might play important roles in the development and treatment of drug addiction. Among\r\nthem, 49 non-illicit drugs might have potential to be used to treat addiction or have addictive effects, including\r\nsome results that are supported by previous studies.\r\nConclusions: This study presents the first systematic review of the network characteristics of illicit drugs, their\r\ntargets, and other drugs that share the targets of these illicit drugs. The results, though preliminary, provide some\r\nnovel insights into the molecular mechanisms of drug addiction. The observation of illicit-related drugs, with partial\r\nverification from previous studies, demonstrated that the network-assisted approach is promising for the\r\nidentification of drug repositioning.
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