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Synthetic cannabinoids, cathinones, and piperazines are sought by users for their psychoactive effects, perceived safety profile, minimal legal regulations, and lack of detection on routine urine drug screening. However, these drugs are beginning to be recognized by the medical community for their toxic effects. The neuropsychiatric and cardiovascular toxicities are among the most common reasons for emergency medical treatment, which in some cases, can be severe and even life-threatening. Management strategies are often limited to supportive and symptomatic care due to the limited published data on alternative treatment approaches. The purpose of this article is to offer health care providers, emergency medical personnel in particular, an awareness and understanding of the dangers related to some of the new psychoactive drugs of abuse. 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