Designer drugs: mechanism of action and adverse effects

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 l-opioid receptors and c-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.

Acute DOB and PMA Administration Impairs Motor and Sensorimotor Responses in Mice and Causes Hallucinogenic Effects in Adult Zebrafish

“…It has been reported that synthetic analogous of mescaline, including DOB, are more potent to induce hallucinations than those of many naturally occurring hallucinogens [ 6 ]. DOB interacts with serotonergic receptors, with the highest affinity for 5-HT2A receptors [ 7 , 8 ]. Studies in vivo revealed that DOB is 10 times more potent than 4-bromo-2, 5-dimethoxyphenethylamine (2C-B) in humans [ 9 ] and double/triple to the phenethylamine analogous (2C-B) in mice [ 10 ].…”

New psychoactive substances: a review and updates

“…New psychoactive substances (NPS) are a complex and diverse group of substances often known as either designer or synthetic drugs, or by the more popular but misleading colloquial term of ‘ legal highs ’. 1 , 2 They tend to be either analogues of existing controlled drugs and pharmaceutical products or newly synthesised chemicals, created to mimic the actions and psychoactive effects of licensed medicines and other controlled substances. 3 – 5 By their number, nature and composition, NPS pose significant challenges for drug consumers, clinicians – both in drug services and, more broadly, researchers, forensic toxicologists, healthcare systems and drug control policy globally – and have been described as a ‘growing worldwide epidemic’.…”

Flakka: New Dangerous Synthetic Cathinone on the Drug Scene

“…Synthetic cathinone abuse mainly leads to sympathomimetic toxicity, which is mostly manifested as mania, tachycardia, high blood pressure, and occasionally hallucinations, hyponatremia, chest pain, and nausea. In severe cases it may cause epilepsy, severe peripheral organ damage, and rhabdomyolysis [9]. Data are only available from users who experience these possible hazardous consequences [10].…”