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Review
. 2020 Apr;94(4):1085-1133.
doi: 10.1007/s00204-020-02693-7. Epub 2020 Apr 6.

Designer drugs: mechanism of action and adverse effects

Dino Luethi  1   2   3 , Matthias E Liechti  4
Affiliations
Review

Designer drugs: mechanism of action and adverse effects

Dino Luethi et al. Arch Toxicol. 2020 Apr.

Erratum in

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 (GABAA) or GABAB 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 (CB1) 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-HT2A) 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.

Keywords: Designer drug; New psychoactive substance; Psychedelic; Stimulant; Synthetic cannabinoid; Synthetic opioid.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
DAT vs. SERT selectivity of a variety of stimulants. Stimulants with low (< 0.1) DAT/SERT ratios are likely to induce entactogenic MDMA-like effects, while substances with a high (> 10) DAT/SERT ratio are associated with distinct psychostimulant effects and a high abuse potential. The DAT/SERT ratio is expressed as 1/DAT IC50: 1/SERT IC50. Full names of the substances and source of pharmacological data are provided in the supplementary information
Fig. 2
Fig. 2
Correlation between reported clinical potencies and in vitro monoamine transporter inhibition of a variety of stimulants. Figure modified from (Luethi and Liechti 2018). Full names of the substances and source of pharmacological data are provided in the supplementary information
Fig. 3
Fig. 3
Examples of amphetamine, cathinone, and pyrovalerone derivatives. Full names of the substances are provided in the supplementary information
Fig. 4
Fig. 4
Examples of stimulant designer drugs and reference substances. Full names of the substances are provided in the supplementary information
Fig. 5
Fig. 5
Examples of sedative designer drugs and reference substances for comparison. Full names of the substances are provided in the supplementary information
Fig. 6
Fig. 6
Examples of dissociative designer drugs and reference substances for comparison. Full names of the substances are provided in the supplementary information
Fig. 7
Fig. 7
Structures of Δ9-THC and a selection of cannabinoid designer drugs. Full names of the substances are provided in the supplementary information
Fig. 8
Fig. 8
Correlation between reported clinical potencies and in vitro human 5-HT2A receptor affinities of a variety of psychedelics. Figure modified from (Luethi and Liechti 2018). Full names of the substances and source of pharmacological data are provided in the supplementary information
Fig. 9
Fig. 9
Examples of psychedelic phenethylamines, tryptamines, and lysergamides. Full names of the substances are provided in the supplementary information
See this image and copyright information in PMC

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