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In the context of use and misuse of drugs and forensic toxicology, new psychoactive substances have arguably had more impact on toxicology than anything in the last five decades. This chapter describes the background to these substances, along with the analytical considerations. Whilst many may be detectable during routine analysis using modern techniques, the large number of possible substances presents a challenge to the analytical toxicologist, particularly as some are unstable and occur at very low concentrations in biological fluid. Common classes of new psychoactive substances based around certain chemical frameworks are discussed, with particular emphasis on dose, formulation, route of administration, effects and toxicity/safety. These include amphetamines (phenylethylamines), piperazines, tryptamines, cathinones, aminoindanes and synthetic cannabinoids. Toxicologically, the various types of new psychoactive substances can be summarised as being stimulant, hallucinogenic or sedative in nature, with some overlap in action. The typical signs and symptoms with such actions can be used to identify potential cases, especially in the absence of scene evidence, no specific drug history or no immediate indication of new psychoactive drug use. Even if there is some initial evidence, due to the wide range of possible new psychoactive substances and various factors involved, the investigation of these cases is a challenging aspect of forensic toxicology. For example, it should not be assumed that a particular brand or product is associated with a particular substance. Ideally any actual seized products should be analysed to determine the true contents and prospective substances to aid analytical strategies. These issues are also risks to users and the ingestion by whatever route of an unexpected substance may have adverse dose outcomes. The chapter outlines the various issues and considerations associated with the investigation of new psychoactive substances in casework.

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