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Molecular and clinical aspects of potential neurotoxicity induced by new psychoactive stimulants and psychedelics

Rudin, Deborah and Liechti, Matthias E. and Luethi, Dino. (2021) Molecular and clinical aspects of potential neurotoxicity induced by new psychoactive stimulants and psychedelics. Experimental neurology, 343. p. 113778.

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Official URL: https://edoc.unibas.ch/84425/

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Abstract

New psychoactive stimulants and psychedelics continue to play an important role on the illicit new psychoactive substance (NPS) market. Designer stimulants and psychedelics both affect monoaminergic systems, although by different mechanisms. Stimulant NPS primarily interact with monoamine transporters, either as inhibitors or as substrates. Psychedelic NPS most potently interact with serotonergic receptors and mediate their mind-altering effects mainly through agonism at serotonin 5-hydroxytryptamine-2A (5-HT; 2A; ) receptors. Rarely, designer stimulants and psychedelics are associated with potentially severe adverse effects. However, due to the high number of emerging NPS, it is not possible to investigate the toxicity of each individual substance in detail. The brain is an organ particularly sensitive to substance-induced toxicity due to its high metabolic activity. In fact, stimulant and psychedelic NPS have been linked to neurological and cognitive impairments. Furthermore, studies using in vitro cell models or rodents indicate a variety of mechanisms that could potentially lead to neurotoxic damage in NPS users. Cytotoxicity, mitochondrial dysfunction, and oxidative stress may potentially contribute to neurotoxicity of stimulant NPS in addition to altered neurochemistry. Serotonin 5-HT; 2A; receptor-mediated toxicity, oxidative stress, and activation of mitochondrial apoptosis pathways could contribute to neurotoxicity of some psychedelic NPS. However, it remains unclear how well the current preclinical data of NPS-induced neurotoxicity translate to humans.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Psychopharmacology Research (Liechti)
05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Molecular and Systems Toxicology (Odermatt)
UniBasel Contributors:Liechti, Matthias Emanuel
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier
ISSN:1090-2430
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:27 Jan 2022 15:49
Deposited On:27 Jan 2022 15:49

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