Novel synthetic opioids (NSOs) consist of a series of abused substances, which are posing a serious threat to the health of consumers. Among them: pain relievers available legally by prescription, such as oxycodone, hydrocodone, hydromorphone, but diverted in the illegal market; compounds synthetized by pharmaceutical companies in the last decades of past century and never commercialized such as the benzamide derivatives U-47700 and U-49900 and finally various legal and illegal analogs of fentanyl. Due to the low cost of the required materials and equipment for producing these compounds in clandestine laboratories, NSOs are used as stand-alone products, as adulterants in heroin, or as constituents of counterfeit prescription medications. All these drugs are causing a recent rise in acute intoxication and overdose deaths inducing a classic opioid toxidrome, which can be reversed with the competitive antagonist naloxone. However, due to the putative high potency of NSOs, to be effective naloxone doses have to be empirically increased. Because NSOs offer enormous profit potential, and there is strong demand for their use, these drugs are being trafficked by organized crime and present major challenges for medical professionals, law enforcement agencies, and policymakers. Information regarding pharmacology and toxicology of these substances in abuse settings is still lacking. This research topic seeks to provide updated studies, reviews, minireviews and case reports concerning pharmacotoxicology of NSOs as an eye opener of this incoming hazard to scientists and health professionals operating in the field of drugs of abuse.

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