Designer drugs: mechanism of action and adverse effects

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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.

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Author and article information

Contributors

Dino Luethi:

ORCID: http://orcid.org/0000-0003-0874-4875

dino.luethi@meduniwien.ac.at

Matthias E. Liechti:

ORCID: http://orcid.org/0000-0002-1765-9659

matthias.liechti@usb.ch

Journal

Journal ID (nlm-ta): Arch Toxicol

Journal ID (iso-abbrev): Arch. Toxicol

Title: Archives of Toxicology

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 0340-5761

ISSN (Electronic): 1432-0738

Publication date (Electronic): 6 April 2020

Publication date PMC-release: 6 April 2020

Publication date (Print): 2020

Volume: 94

Issue: 4

Pages: 1085-1133

Affiliations

[1 ]GRID grid.22937.3d, ISNI 0000 0000 9259 8492, Center for Physiology and Pharmacology, Institute of Pharmacology, , Medical University of Vienna, ; Währinger Strasse 13a, 1090 Vienna, Austria

[2 ]GRID grid.5329.d, ISNI 0000 0001 2348 4034, Institute of Applied Physics, , Vienna University of Technology, ; Getreidemarkt 9, 1060 Vienna, Austria

[3 ]GRID grid.410567.1, Division of Clinical Pharmacology and Toxicology, , University Hospital Basel and University of Basel, ; Schanzenstrasse 55, 4056 Basel, Switzerland

Author information

Dino Luethi http://orcid.org/0000-0003-0874-4875

Matthias E. Liechti http://orcid.org/0000-0002-1765-9659

Article

Publisher ID: 2693

DOI: 10.1007/s00204-020-02693-7

PMC ID: 7225206

PubMed ID: 32249347

SO-VID: 88430058-00d3-40d4-bd75-b019401f2f91

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 14 February 2020

Date accepted : 25 February 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001711, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung;

Award ID: P2BSP3_181809

Award Recipient : Dino Luethi

Funded by: FundRef http://dx.doi.org/10.13039/501100002329, Bundesamt für Gesundheit;

Award ID: 16.921318

Award Recipient : Matthias E. Liechti

Custom metadata

ScienceOpen disciplines: Toxicology

Keywords: designer drug,new psychoactive substance,stimulant,synthetic opioid,synthetic cannabinoid,psychedelic

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ScienceOpen disciplines: Toxicology

Keywords: designer drug, new psychoactive substance, stimulant, synthetic opioid, synthetic cannabinoid, psychedelic

Designer drugs: mechanism of action and adverse effects

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Journal of the Netherlands Society of Toxicology

Most cited references 631

Endocannabinoid-mediated control of synaptic transmission.

Endocannabinoid signaling and synaptic function.

Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action.

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