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The use of illicit drugs places a large burden on the American healthcare system due to their detrimental effects on patients and their families. Network pharmacology is a novel approach to investigate drug actions. This study seeks to investigate illicit drugs and their targets in the context of a drug-protein network to elucidate the molecular mechanisms of abused drugs. We extracted 188 illicit substances from the DrugBank database. Among them, 86 drugs had 74 unique human targets, which formed a drug-target network specific for illicit drugs. We then analyzed the network by superimposing enriched pathways of these targets, drug categories, and network clusters. We found that four sub-networks corresponded to three major medication categories: depressants, stimulants, and narcotics & analgesics. The results not only provide novel insights on illicit drug actions but also illustrate that the methods utilized here can identify important drugs and targets. This study represents the first systematic investigation of drug-target interactions in drug addiction.