Recreational MDMA doses do not elicit hepatotoxicity in HepG2 spheroids under normo- and hyperthermia.
Arthur L. De Oliveira, Raul G Miranda, Daniel J Dorta
Toxicology March 1, 2024 DOI: 10.1016/j.tox.2024.153761 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro experimental study Peer reviewed |
|---|---|
| Population | HepG2 spheroids (human liver cell line) |
| Intervention | MDMA |
| Dose | recreational doses |
| Topics | MDMA |
| Keywords | Tridimensional cell culture Drug research MDMA/Ecstasy/Molly/E Liver toxicity/hepatotoxicity/citotoxicity |
| Citations | 1 |
| Key findings | MDMA at recreational doses did not induce hepatotoxicity in HepG2 spheroids under normothermia or hyperthermia. |
Abstract
MDMA (3,4-methylenedioxymethamphetamine), an entactogen with empathogenic and prosocial effects, is widely used in music festivals and other festive settings. High MDMA doses have been associated with drug-induced liver injury and cases of hyperthermia. Although the latter condition is thought to increase MDMA hepatotoxicity, this correlation remains poorly explored for recreational MDMA doses. On the other hand, the fact that MDMA acts to extinguish fear and to reconsolidate memory could be explored as an adjunct to psychotherapy during treatment of neuropsychiatric disorders such as post-traumatic stress disorder. In this context, assessing MDMA toxicity is relevant, and tridimensional cell culture has emerged as an alternative to animal models in toxicity assessment. Herein, we have used HepG2 spheroids to evaluate MDMA-induced hepatotoxicity at recreational doses, under normo- or hyperthermia. The MTT reduction assay did not evidence significantly reduced cell viability. Moreover, MDMA did not increase reactive oxygen species production, deplete the mitochondrial membrane potential, arrest the cell cycle, or induce apoptotic cell death. These findings support further pre-clinical investigation of MDMA safety from the perspective of both harm reduction and therapy given that non-abusive recreational and therapeutic doses overlap.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cites 36
- MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine June 1, 2021
- Gender differences in the subjective effects of MDMA Psychopharmacology March 5, 2001
- Human psychobiology of MDMA or ‘Ecstasy’: an overview of 25 years of empirical research Human Psychopharmacology: Clinical and Experimental July 1, 2013
- Safety pharmacology of acute MDMA administration in healthy subjects Journal of Psychopharmacology February 21, 2017
- 3,4-Methylenedioxymethamphetamine facilitates fear extinction learning Translational Psychiatry September 15, 2015
and 31 more in the library