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Internet vendors may at least temporarily sell these so-called designer drugs without adhering to legal statutes or facing legal consequences. Overall, the mechanism of action and adverse effects of designer drugs are similar to traditional drugs of abuse. Stimulants, such as amphetamines and cathinones, primarily interact with monoamine transporters and mostly induce sympathomimetic adverse effects. Agonism at \u03bc-opioid receptors and \u03b3-aminobutyric acid-A (GABA\n A<\/jats:sub>\n ) or GABA\n B<\/jats:sub>\n receptors mediates the pharmacological effects of sedatives, which may induce cardiorespiratory depression. Dissociative designer drugs primarily act as\n N<\/jats:italic>\n -methyl-\n d<\/jats:sc>\n -aspartate receptor antagonists and pose similar health risks as the medically approved dissociative anesthetic ketamine. The cannabinoid type 1 (CB\n 1<\/jats:sub>\n ) receptor is thought to drive the psychoactive effects of synthetic cannabinoids, which are associated with a less desirable effect profile and more severe adverse effects compared with cannabis. Serotonergic 5-hydroxytryptamine-2A (5-HT\n 2A<\/jats:sub>\n ) receptors mediate alterations of perception and cognition that are induced by serotonergic psychedelics. Because of their novelty, designer drugs may remain undetected by routine drug screening, thus hampering evaluations of adverse effects. Intoxication reports suggest that several designer drugs are used concurrently, posing a high risk for severe adverse effects and even death.\n <\/jats:p>","DOI":"10.1007\/s00204-020-02693-7","type":"journal-article","created":{"date-parts":[[2020,4,5]],"date-time":"2020-04-05T23:25:19Z","timestamp":1586129119000},"page":"1085-1133","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":237,"title":["Designer drugs: mechanism of action and adverse effects"],"prefix":"10.1007","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0874-4875","authenticated-orcid":false,"given":"Dino","family":"Luethi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1765-9659","authenticated-orcid":false,"given":"Matthias E.","family":"Liechti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,6]]},"reference":[{"key":"2693_CR1","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1007\/7854_2016_54","volume":"32","author":"SM Aarde","year":"2017","unstructured":"Aarde SM, Taffe MA (2017) Predicting the abuse liability of entactogen-class, new and emerging psychoactive substances via preclinical models of drug self-administration. 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