Designer drugs: mechanism of action and adverse effects

Designer drugs, which are chemically or pharmacologically similar to traditional drugs of abuse, continue to appear on the recreational market, often sold by internet vendors without legal restrictions. Their mechanisms of action and adverse effects generally mirror those of traditional drugs: stimulants like amphetamines and cathinones affect monoamine transporters and cause sympathomimetic effects; sedatives act on μ-opioid and GABA receptors, potentially leading to cardiorespiratory depression; dissociative drugs block NMDA receptors, similar to ketamine; synthetic cannabinoids target CB1 receptors, producing more severe adverse effects than cannabis; and serotonergic psychedelics act on 5-HT2A receptors to alter perception and...

Study at a glance

Abstract

Abstract Psychoactive substances with chemical structures or pharmacological profiles that are similar to traditional drugs of abuse continue to emerge on the recreational drug market. 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 μ-opioid receptors and γ-aminobutyric acid-A (GABA A ) or GABA B receptors mediates the pharmacological effects of sedatives, which may induce cardiorespiratory depression. Dissociative designer drugs primarily act as N -methyl- d -aspartate receptor antagonists and pose similar health risks as the medically approved dissociative anesthetic ketamine. The cannabinoid type 1 (CB 1 ) 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 2A ) 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.