Drug and alcohol dependence
February 1, 2015
Laura Hondebrink, Johanna J Nugteren-Van Lonkhuyzen, Daan van der Gouwe et al.
119 citations
The number of new psychoactive substances (NPS) submitted for analysis in the Netherlands rose from 22 samples in 2007 to 431 in 2013. The most common NPS in 2013 were 2C-B, 4-FA, methoxetamine, and 6-APB. After 2012, more NPS were bought as the drug of choice rather than as adulterants. The Dutch Poisons Information Centre recorded 35 NPS exposures in 2013, most often involving 4-FA, mephedrone, MXE, 2C-B, and 6-APB. Neurological and psychological symptoms such as agitation and hallucinations, along with cardiovascular effects like hypertension and tachycardia, were frequently reported. The authors conclude that NPS availability and use are increasing and can cause pronounced clinical effects, recommending continued monitoring combined with clinical and analytical data.
Pharmacology & therapeutics
February 1, 2018
Laura Hondebrink, Anne Zwartsen, Remco H S Westerink
78 citations
More than 600 new psychoactive substances (NPS) have been reported, yet information on their neuropharmacological and toxicological effects remains limited, hampering risk assessment. A review of in vitro neuronal modes of action created effect fingerprints for frequently reported NPS classes: cathinones, cannabinoids, hallucinogenic phenethylamines, arylcyclohexylamines, and piperazine derivatives. The fingerprints highlight main modes of action—such as inhibition or reversal of monoamine reuptake transporters for cathinones and activation of 5-HT2 receptors for hallucinogenic phenethylamines—and identify additional targets, including dopamine, adrenergic, GABAA, and acetylcholine receptors, by relating effect concentrations to estimated...
Toxicology in vitro : an international journal published in association with BIBRA
December 1, 2017
Anne Zwartsen, Anouk H A Verboven, Regina G D M Van Kleef et al.
59 citations
A new high-throughput fluorescent assay can detect how illicit drugs and new psychoactive substances (NPS) inhibit monoamine reuptake transporters (DAT, NET, SERT). The assay uses a fluorescent monoamine-mimicking substrate in human embryonic kidney cells expressing these transporters. It successfully discriminated between common drugs (cocaine, amphetamine, MDMA), several NPS (e.g., α-PVP, 2C-B, 25B-NBOMe), and the antidepressant fluoxetine. Most IC50 values matched those from traditional radiometric assays and estimated human brain concentrations, though phenethylamines showed higher IC50 values on SERT, possibly due to experimental differences. The fluorescent assay is simpler, works under physiological conditions, requires no special facilities, and allows kinetic measurements, making it a good alternative to radiometric methods.
Critical Reviews in Toxicology
October 3, 2012
Saskia J. Rietjens, Laura Hondebrink, Remco H.s. Westerink et al.
51 citations
The clinical outcome after MDMA intake ranges from mild entactogenic effects to life-threatening intoxication, and the most relevant mechanisms causing acute adverse effects remain unclear. Genetic factors, such as polymorphisms in CYP2D6 causing poor metabolism, and interactions from polydrug use, like co-exposure with selective serotonin reuptake inhibitors (SSRIs), modulate MDMA pharmacokinetics and dynamics. While SSRIs can increase MDMA plasma levels, they can reduce clinical effects like blood pressure and body temperature, possibly via pharmacodynamic interaction at the serotonin reuptake transporter. Pretreatment with inhibitors of dopamine or norepinephrine transporters, or antagonists like carvedilol, ketanserin, and haloperidol, can reduce multiple MDMA-induced effects. Investigating these drugs for treating MDMA intoxication is worthwhile.
Drug and alcohol dependence
December 1, 2015
Johanna J Nugteren-Van Lonkhuyzen, Antoinette J H P van Riel, Tibor M Brunt et al.
48 citations
The number of new psychoactive substances (NPS) on the illicit drug market has increased markedly. Users often perceive their risk as medium or low, but these substances can pose serious health risks and have been linked to drug-related deaths. In Europe, frequently detected NPS include 2C-B, 4-fluoroamphetamine (4-FA), and benzofurans (5-APB/6-APB). A review of existing literature found that the clinical effects of these NPS are comparable to common illicit drugs like amphetamine and MDMA, suggesting that NPS toxicity can be managed using existing treatment guidelines based on clinical effects rather than the specific drug. However, information on health risks is limited to case reports complicated by confounders.
Neurotoxicology
May 1, 2018
Anne Zwartsen, Laura Hondebrink, Remco Hs Westerink
42 citations
All eight new psychoactive substances (PMMA, α-PVP, methylone, MDPV, 2C-B, 25B-NBOMe, BZP, TFMPP) and two classic illicit drugs (cocaine, methamphetamine) rapidly and concentration-dependently decreased the weighted mean firing rate and weighted mean burst rate of rat primary cortical cultures grown on multi-well microelectrode arrays during a 30-minute acute exposure. Cocaine most potently inhibited firing (IC50 9.8 μM), while methamphetamine and PMMA were much less potent (IC50 100 μM and 112 μM). Among cathinones, MDPV and α-PVP had comparable IC50 values (29 μM and 21 μM), but methylone was 10-fold less potent (IC50 235 μM).
Neurotoxicology
September 1, 2019
Anne Zwartsen, Laura Hondebrink, Remco Hs Westerink
22 citations
The effects of several new psychoactive substances (NPS) and illicit drugs on neuronal activity were tested in rat brain cells grown on microelectrode arrays. After 30 minutes of exposure, all compounds reduced neuronal activity in a dose-dependent manner. Extending exposure to 5 hours did not cause further decreases. After a 19-hour washout period, activity fully recovered only for methamphetamine, cocaine, and benzylpiperazine; partially recovered for MDMA, PMMA, and α-PVP; and did not recover at the highest concentrations of MDPV, 2C-B, 25B-NBOMe, and TFMPP. Low concentrations of methylone and 2C-B actually increased activity after washout. The ability of neural networks to regain activity after drug exposure appears unrelated to drug class or potency. Complete recovery was rare, which is concerning.
Annals of emergency medicine
September 1, 2020
Johanna J Nugteren-Van Lonkhuyzen, Dylan W de Lange, Antoinette J H P van Riel et al.
12 citations
Most poisonings from the psychedelic drug 2C-B result in moderate toxicity, even at high doses up to 192 mg. Among 59 patients for whom a poison center was consulted, 32 were followed up; 53% reported high doses (over 20 mg). Moderate poisoning occurred in the majority of both low-to-moderate and high-dose groups. Common symptoms included dilated pupils, agitation or aggression, hallucinations, confusion, anxiety, high blood pressure, and rapid heart rate. No severe cases were observed. The clinical course was usually short-lived (up to 24 hours) and typically involved hallucinations along with mild physical effects.
Therapeutic drug monitoring
April 1, 2020
Funda Inan, Tibor M Brunt, Ramon R Contrucci et al.
9 citations
The novel phenethylamines 4-fluoroamphetamine (4-FA) and 2,5-dimethoxy-4-bromophenethylamine (2C-B) are among the ten most used new psychoactive substances among high-risk users, and their use is also common in people with depression, ADHD, and those engaging in risky sexual behavior. A systematic review of literature on interactions between these phenethylamines and antidepressants, ADHD medications, and antiretrovirals found very limited pharmacokinetic data; only one case report suggested a possible interaction between 4-FA and ADHD medication. Pharmacodynamic profiles indicate potential interactions between both 4-FA and 2C-B with antidepressants and ADHD medications, primarily involving monoamine oxidases for both substances, with monoamine transporters more specific to 4-FA.
Addiction (Abingdon, England)
July 7, 2026
Johanna J Nugteren-Van Lonkhuyzen, Irma S Van den Hengel-Koot, Claudine C Hunault et al.
Between 2012 and 2025, the annual rate of poisonings from new psychoactive substances (NPS) reported to the Dutch Poisons Information Center rose by 19% per year, with the number of poisonings increasing from 32 to 829. Among 19,316 total recreational drug poisonings, 4,289 involved NPS. Cathinones, phenethylamines, and benzodiazepines accounted for 83% of NPS poisonings, though the dominant category shifted over time: benzodiazepines in 2012 and 2024, phenethylamines from 2013 to 2018, and cathinones from 2019 to 2023 and 2025. The most frequently reported NPS were 3-MMC, bromazolam, 4-FA, 2C-B, and mephedrone. Poisonings with other NPS categories were rare, and none involved aminoindanes or piperazines.