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Cytotoxic, genotoxic, and oxidative stress-related effects of lysergic acid diethylamide (LSD) and phencyclidine (PCP) in the human neuroblastoma SH-SY5Y cell line

Jurič Andreja, Zandona Antonio, Lovaković Blanka Tariba, Rašić Dubravka, Pizent Alica, Kozina Goran, Katalinić Maja, Vrdoljak Ana Lucić, Karačonji Irena Brčić

Arhiv za Higijenu Rada i Toksikologiju April 1, 2022 DOI: 10.2478/aiht-2021-72-3604 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics In vitro experimental study Peer reviewed
Population Human neuroblastoma SH-SY5Y cell line
Interventions LSD PCP
Dose LSD 6.25 μmol/L, PCP 3.13 μmol/L
Duration 24-hour exposure
Topics LSD
Keywords Antioxidant enzymes Cell viability Dna damage Gsh Hallucinogenic drugs Psychoactive substances Ros Toxicity Antioksidacijski enzimi Halucinogene droge Oštećenje dna Pcp Psihoaktivne tvari Toksičnost Vijabilnost stanica
Citations 6
Key findings LSD has greater DNA damaging potential and stronger oxidative activity than PCP in SH-SY5Y cells.

Abstract

Lysergic acid diethylamide (LSD) is a classic hallucinogen, widely abused for decades, while phencyclidine (PCP) has increased in popularity in recent years, especially among the adolescents. Very little is known about the general toxicity of these compounds, especially about their possible neurotoxic effects at the cell level. The aim of this study was to address these gaps by assessing the toxic effects of 24-hour exposure to LSD and PCP in the concentration range of 0.39–100 μmol/L in the human neuroblastoma SH-SY5Y cell line. After cell viability was established, cells treated with concentrations that reduced their viability up to 30 % were further subjected to the alkaline comet assay and biochemical assays that enable estimation of oxidative stress-related effects. Treatment with LSD at 6.25 μmol/L and with PCP at 3.13 μmol/L resulted with 88.06±2.05 and 84.17±3.19 % of viable cells, respectively, and led to a significant increase in primary DNA damage compared to negative control. LSD also caused a significant increase in malondialdehyde level, reactive oxygen species (ROS) production, and glutathione (GSH) level, PCP significantly increased ROS but lowered GSH compared to control. Treatment with LSD significantly increased the activities of all antioxidant enzymes, while PCP treatment significantly increased superoxide dismutase (SOD) and glutathione peroxidase (GPx) but decreased catalase (CAT) activity compared to control. Our findings suggest that LSD has a greater DNA damaging potential and stronger oxidative activity than PCP in SH-SY5Y cells.

Comparable studies

Other preclinical and animal studies on LSD, most cited first.

Study Year Design Participants
Transcriptome Fingerprints Distinguish Hallucinogenic and Nonhallucinogenic 5-Hydroxytryptamine 2A Receptor Agonist Effects in Mouse Somatosensory Cortex Human embryonic kidney 293 cells stably expressing 5-HT2ARs; wild-type and 5-HT2AR... 2003 Experimental study
Evidence for a central 5‐hydroxytryptamine receptor stimulation by lysergic acid diethylamide Rats 1968 Experimental study
Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats 2020 Preclinical study
Lysergic acid diethylamide (LSD) promotes social behavior through mTORC1 in the excitatory neurotransmission Male mice 2021 Multidisciplinary experimental study with in vivo electrophysiology, optogenetics, behavioral paradigms, molecular biology, and conditional knockout mice
A non-hallucinogenic LSD analog with therapeutic potential for mood disorders. Mice and cultured rat cortical neurons 2023 Preclinical study

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