Abstract
BackgroundDrug addiction is a complex and chronic mental disease, which places a large burden on the American healthcare system due to its negative effects on patients and their families. Recently, network pharmacology is emerging as a promising approach to drug discovery by integrating network biology and polypharmacology, allowing for a deeper understanding of molecular mechanisms of drug actions at the systems level. This study seeks to apply this approach for investigation of illicit drugs and their targets in order to elucidate their interaction patterns and potential secondary drugs that can aid future research and clinical care.ResultsIn this study, we extracted 188 illicit substances and their related information from the DrugBank database. The data process revealed 86 illicit drugs targeting a total of 73 unique human genes, which forms an illicit drug-target network. Compared to the full drug-target network from DrugBank, illicit drugs and their target genes tend to cluster together and form four subnetworks, corresponding to four major medication categories: depressants, stimulants, analgesics, and steroids. External analysis of Anatomical Therapeutic Chemical (ATC) second sublevel classifications confirmed that the illicit drugs have neurological functions or act via mechanisms of stimulants, opioids, and steroids. To further explore other drugs potentially having associations with illicit drugs, we constructed an illicit-extended drug-target network by adding the drugs that have the same target(s) as illicit drugs to the illicit drug-target network. After analyzing the degree and betweenness of the network, we identified hubs and bridge nodes, which might play important roles in the development and treatment of drug addiction. Among them, 49 non-illicit drugs might have potential to be used to treat addiction or have addictive effects, including some results that are supported by previous studies.ConclusionsThis study presents the first systematic review of the network characteristics of illicit drugs, their targets, and other drugs that share the targets of these illicit drugs. The results, though preliminary, provide some novel insights into the molecular mechanisms of drug addiction. The observation of illicit-related drugs, with partial verification from previous studies, demonstrated that the network-assisted approach is promising for the identification of drug repositioning.
Highlights
Drug addiction is a complex and chronic mental disease, which places a large burden on the American healthcare system due to its negative effects on patients and their families
We extended our previous, preliminary work [24] and applied network pharmacology approaches for analysis of illicit drugs and their targets to further understand the relationships between the various addictive substances and their targets
The networks were visualized by the software Cytoscape, an open source network analysis platform [33]. Illicit drugs and their targets We obtained 188 illicit drugs according to the “illicit” status annotated by DrugBank
Summary
Drug addiction is a complex and chronic mental disease, which places a large burden on the American healthcare system due to its negative effects on patients and their families. Drug addiction is a complex and chronic mental disease characterized by compulsive drug seeking and use despite its harmful consequences. It places a large burden on the American healthcare system due to the detrimental. Twin and familial studies have suggested that the genetic factors account for 30-60% of the overall risk for the development of drug addiction [5]. This genetic involvement has been shown to be polygenic, which involves multiple genes that might cooperate through numerous pathways [6]. Due to the genetic complexity of addiction and the numerous types of addictive substances, we hypothesize that a large-scale analysis of multiple illicit drugs and their target genes can provide a broader understanding of substance abuse
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