N,N-Dimethyltryptamine (DMT) is a naturally occurring substituted tryptamine used as a psychedelic drug for ritual purposes by various cultures. Derivatives were already found on the drug of abuse market, such as N1-tert-butoxycarbonyl-N,N-dimethyltryptamine (DMT-Boc). The aim of the current study was to investigate the toxicokinetics of DMT-Boc and three related DMT derivatives, by name...
Archives of ToxicologyJuly 1, 2026Kamil Jurowski, Alicja Krośniak, Damian Kobylarz et al.
Lysergamide analogs such as ALD-52, 1P-LSD, 1B-LSD, 1 V-LSD, and 1cP-LSD have emerged as new psychoactive substances (NPS) with hallucinogenic potential, yet their toxicological profiles remain largely unexplored. In this study, a comprehensive in silico assessment was conducted using multiple platforms (e.g., ADMETlab 3.0, Percepta, STopTox, ProTox 3.0, VEGA, TEST 5.1.2) to predict critical...
Abstract Designer benzodiazepines (DBZDs) are a class of new psychoactive substances (NPS) designed as legal alternatives to prescription BZDs. Bromazolam has been the most prevalent DBZD detected on the recreational market around the world; however, a new DBZD, ethylbromazolam (8-bromo-1-ethyl-6-phenyl-4 H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine; also known as bromoethylazolam) has recently...
Understanding the toxicity of serotonergic tryptamines is becoming increasingly important from both clinical and forensic perspectives, yet experimental data for these compounds remain extremely limited. Despite their growing medical relevance and widespread non-medical use, there is still no systematic evaluation of their toxicological risks. This study presents the first comprehensive in...
Phencyclidine (PCP), historically known as "angel dust," and its analogues (3-HO-PCP, 3-MeO-PCP, 4-MeO-PCP, 3-HO-PCE, 3-MeO-PCE, 4-MeO-PCE) are dissociative new psychoactive substances with high abuse potential and limited experimental safety data. An integrated in silico workflow (STopTox, admetSAR 3.0, ADMETlab 3.0, ACD/Labs Percepta, Toxtree, ProTox 3.0, OCHEM, TEST, VEGA QSAR) was applied...
Archives of ToxicologyNovember 12, 2025Gilles Salles, Carolina Aparecida de Faria Almeida, Isabella de Carvalho Alves et al.
Ayahuasca is a psychoactive brew traditionally used in religious rituals by indigenous Amazonian populations and South American syncretic religions such as Santo Daime and União do Vegetal. Its psychoactive effects are primarily due to N,N-dimethyltryptamine (DMT), while harmine (HRE), a β-carboline alkaloid, inhibits monoamine oxidase (MAO), enabling DMT's oral bioavailability. Recent studies...
Archives of ToxicologyApril 19, 2025António B Pimpão, Luísa Teixeira-Santos, Nuno R Coelho et al.
We were pioneers in describing aryl hydrocarbon receptor (AhR) activation by chronic intermittent hypoxia (CIH) in a rat pre-clinical model. This model mimics hypertension (HTN) secondary to obstructive sleep apnea, enabling longitudinal investigation of hypertension development. Concerns about the influence of barbiturates on AhR-regulated enzymes led us to opt for ketamine/medetomidine...
Archives of ToxicologyMarch 10, 2025Yiling Tang, Linhao Xu, Zhenshuo Guo et al.1 citation
New psychoactive substances (NPS) are substances that are not controlled by international drug control conventions but are abused and pose a threat to public health. Proscaline and methallylescaline are two phenylethylamines with psychoactive and stimulant effects and are also derivatives of the classic hallucinogen mescaline. However, limited toxicity information on proscaline and...
Archives of ToxicologyMarch 1, 2025Junqi Chen, Ziteng Wang, Ching Yee Yong et al.3 citations
Psilocin is a well-studied controlled substance with potential psychotherapeutic applications. However, research gaps remain regarding its metabolism. Our objective was to elucidate a comprehensive Phase I metabolic profile of psilocin to support its forensic management and clinical development. We utilized human enzymes from various sources to characterize the Phase I metabolism of psilocin...
The phenylethylamine, 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'), is the prototypical example of an entactogen. Its original placement in highly restrictive drug usage categories in the US and UK, led to an inevitable restriction on MDMA neuroscience research and treatment. The dominant pharmacological effects of MDMA are its properties of release and inhibition of reuptake of amine...
Archives of ToxicologyMay 1, 2023Marie H Deventer, Mattias Persson, Antonio Laus et al.7 citations
New psychoactive substances (NPS) are introduced on the illicit drug market at a rapid pace. Their molecular targets are often inadequately elucidated, which contributes to the delayed characterization of their pharmacological effects. Inspired by earlier findings, this study set out to investigate the µ opioid receptor (MOR) activation potential of a large set of psychedelics, substances which...
3,4-Methylenedioximethamphetamine (MDMA; "ecstasy") is a psychotropic drug with well-known neurotoxic effects mediated by hitherto not fully understood mechanisms. The Na+- and K+-activated adenosine 5'-triphosphatase (Na+/K+ ATPase), by maintaining the ion gradient across the cell membrane, regulates neuronal excitability. Thus, a perturbation of its function strongly impacts cell homeostasis,...
Synthetic cannabinoid receptor agonists (SCRAs) pose a danger to public health. This study focused on individuals experiencing recreational drug toxicity who had used 5F-MDMB-PICA.Patient records were evaluated regarding vital signs, Glasgow Coma Scale (GCS) and clinical features. Liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) confirmed and quantified the presence...
2C (2C-x) is the general name for the family of phenethylamines containing two methoxy groups at the 2 and 5 positions of the benzene ring. The abuse of 2C family drugs has grown rapidly, although the abuse potential and neurotoxic properties of 2C drugs have not yet been fully investigated. In this study, we investigated the abuse potential and neurotoxicity of...
It has been brought to the authors' attention that Fig. 1 of "In vitro structure-activity relationship determination of 30 psychedelic new psychoactive substances by means of β-arrestin 2 recruitment to the serotonin 2A receptor" contained a mistake in the structures for 2C-B-FLY and Bromo-DragonFLY. This has now been corrected. The authors apologize for any inconvenience caused.
Serotonergic psychedelics, substances exerting their effects primarily through the serotonin 2A receptor (5-HT2AR), continue to comprise a substantial portion of reported new psychoactive substances (NPS). The exact mechanisms of action of psychedelics still remain to be elucidated further, and certain pathways remain largely unexplored on a molecular level for this group of compounds. A...
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...
3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a well-known hepatotoxic drug. Although its toxicity has been thoroughly studied at high concentrations, there is still insufficient knowledge on possible alterations of cell function at subtoxic concentrations, which are in fact more representative concentrations of intoxication scenarios. In this study, a gas chromatography-mass...
3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") is a widespread drug of abuse with known neurotoxic properties. The present study aimed to evaluate the differential toxic effects of MDMA in adolescent and aged Wistar rats, using doses pharmacologically comparable to humans. Adolescent (post-natal day 40) (3 × 5 mg/kg, 2 h apart) and aged (mean 20 months old) (2 × 5 mg/kg, 2 h apart) rats...
In the area of psychotropic drugs, tryptamines are known to be a broad class of classical or serotonergic hallucinogens. These drugs are capable of producing profound changes in sensory perception, mood and thought in humans and act primarily as agonists of the 5-HT2A receptor. Well-known tryptamines such as psilocybin contained in Aztec sacred mushrooms and N,N-dimethyltryptamine (DMT),...
Identification of the mechanisms by which drugs of abuse cause neuronal dysfunction is essential for understanding the biological bases of their acute and long-lasting effects in the brain. Here, we performed real-time functional experiments of axonal transport of mitochondria to explore the role of in situ mitochondrial dysfunction in 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy")-related...
3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is a recreational hallucinogenic drug of abuse known to elicit neurotoxic properties. Hepatic formation of neurotoxic metabolites is thought to play a major role in MDMA-related neurotoxicity, though the mechanisms involved are still unclear. Here, we studied the neurotoxicity mechanisms and stability of MDMA and 6 of its major human...
Archives of ToxicologyJanuary 2009Yoshio Nakagawa, Toshinari Suzuki, Sumiko Tayama et al.
The amphetamine-derived designer drugs have been illegally used worldwide as recreational drugs, some of which are known to be hepatotoxic in humans. To compare their cytotoxic effects, 3,4-methylenedioxy-N-methamphetamine (MDMA) and its related analogues, N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB), 3,4-(methylenedioxyphenyl)-2-butanamine (BDB) and...
The amphetamine designer drugs 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") and its N-demethylated analogue 3,4-methylenedioxyamphetamine (MDA or "love") have been extensively used as recreational drugs of abuse. MDA itself is a main MDMA metabolite. MDMA abuse in humans has been associated with numerous reports of hepatocellular damage. Although MDMA undergoes extensive hepatic...
The metabolism of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has recently been implicated in the mechanisms underlying ecstasy-induced neurotoxicity and hepatotoxicity. However, its potential role in ecstasy-induced kidney toxicity has yet to be investigated. Thus, primary cultures of rat and human renal proximal tubular cells (PTCs) were used to investigate the cytotoxicity induced by...