Forensic Science International
October 23, 2020
Anna Åstrand, Davide Guerrieri, Svante Vikingsson et al.
21 citations
Sixty new psychoactive substances (NPS) and their metabolites, including opioids, cannabinoids, and serotonergic hallucinogens, were screened for their ability to activate μ-opioid, CB1, 5-HT1A, and 5-HT2A receptors. Most substances activated their intended target receptor. Among μ-opioid agonists, 2-fluorofentanyl (EC50 = 1.0 nM), carfentanil (EC50 = 2.7 nM), and acrylfentanyl (EC50 = 2.8 nM) were the most potent, with a >1500-fold potency range across compounds. Furanylfentanyl, 4-methoxybutyrylfentanyl, and valerylfentanyl acted as partial agonists. On the 5-HT2A receptor, bromo-dragonfly was the most potent (EC50 = 0.05 nM, 400 times more potent than LSD), followed by NBOMe compounds (EC50 0.11–1.3 nM). Off-target μ-opioid activation occurred for piperazines, phenethylamines, and tryptamines. The synthetic cannabinoid metabolite 3-carboxy indole PB-22 activated 5-HT2A. Bromo-dragonfly activated all four receptors. These findings highlight complex, often overlapping targets among NPS.
Archives of toxicology
May 1, 2023
Marie H Deventer, Mattias Persson, Antonio Laus et al.
7 citations
Some psychedelic substances that carry the N-benzyl phenethylamine (NBOMe) structure can activate the µ opioid receptor (MOR), an off-target effect confirmed by two different assays. This activation was blocked by the opioid antagonist naloxone, indicating these NBOMes bind to the same opioid binding pocket as conventional opioids. Molecular docking showed plausible interactions of 25I-NBOMe with MOR similar to those of opioids. However, MOR activation occurred only at high concentrations, making relevant opioid toxicity in vivo unlikely at physiologically relevant levels. Small modifications to the NBOMe structure could yield more potent MOR agonists with dual MOR/5-HT2A activation potential.
Basic & clinical pharmacology & toxicology
February 1, 2025
Magnus A B Axelsson, Hanna Lövgren, Robert Kronstrand et al.
6 citations
New psychoactive substances (NPS) are a health hazard due to unpredictable toxicity and unknown prevalence. Analyzing 34,183 oral fluid samples from 9,468 psychiatric and addiction care patients in a Swedish region during 2019–2020, 58 different NPS were detected in 481 samples from 201 patients, totaling 618 findings. NPS use was more common in males and patients aged 25 or older. Ketamine use was associated with most NPS classes except cannabinoids; fentanyl, methadone, tapentadol, and clonazepam also correlated with multiple NPS classes. More traditional drugs of abuse correlated with sedative/hypnotic NPS, suggesting broader use. Mitragynine correlated negatively with other NPS but positively with opioid abstinence remedies buprenorphine, loperamide, and tapentadol, indicating its use for opioid withdrawal.
Archives of Toxicology
May 20, 2026
Caitlyn Norman, Dean Acreman, Meera Bissram et al.
Ethylbromazolam, a new designer benzodiazepine, has emerged in Canada, the UK, Australia, and Germany, with increasing detections since November 2024 and a concurrent decrease in bromazolam detections, likely due to bromazolam's international control on December 3, 2024. Other designer benzodiazepines like desalkylgidazepam and clobromazolam have also increased. In vitro patch clamp assays show ethylbromazolam has similar activity at the GABA-A receptor as bromazolam, with EC50 values of 10.1 nM and 15.2 nM respectively, indicating comparable pharmacological activity and potential harm. Ongoing market monitoring is recommended.
British Journal of Pharmacology
May 5, 2026
Giorgia Corli, Deborah Rudin, Dino Luethi et al.
Some new synthetic cannabinoid receptor agonists (SCRAs) also directly activate the serotonin 5-HT₂A receptor, which may contribute to unexpected psychiatric side effects. Many SCRAs with a valinamide or tert-leucinamide head moiety showed in vitro activity at the 5-HT₂A receptor at high concentrations. In mice, the compound AB-5′F-BUTINACA caused neurological changes, sensorimotor alteration, antinociception, hypothermia, reduced breath rate, and hypolocomotion. These effects were mediated by both CB₁ and 5-HT₂A receptors, as they were prevented by selective antagonists. The findings indicate potential risks of SCRA consumption that could exacerbate unexpected psychiatric conditions.
British journal of pharmacology
July 14, 2026
Darta Stalberga, Robert Kronstrand, Bianca Schranz et al.
Synthetic cathinones, a large class of new psychoactive substances, primarily inhibit dopamine, norepinephrine, and serotonin transporters, with high dopamine transporter selectivity linked to abuse potential. In vitro testing of 58 substances showed that N-pyrrolidine cathinones combined with methylenedioxy groups—MDPiHP, MDPEP, and MDPV—had the highest potency at the dopamine transporter. Other N-pyrrolidine cathinones, such as 3F-α-PHP, 3F-α-PiHP, and 4F-α-PiHP, showed the greatest dopamine transporter selectivity relative to the serotonin transporter. Chloromethcathinone and methylmethcathinone compounds, like 3-CMC, displayed an amphetamine-like profile with comparable potency at dopamine and norepinephrine transporters. Some cathinones at high concentrations and phenethylamines at micromolar concentrations also activated the 5-HT2A receptor, while 2C-like arylcyclohexylamines targeted the receptor without transporter inhibition. The majority of compounds, especially N-pyrrolidine cathinones, suggest high abuse potential based on their dopamine transporter selectivity.