Search Results (16)

Acute intoxications related to recreational drug use represent an increasing challenge for emergency departments (EDs). Worldwide, more than 600,000 deaths are attributable each year to illicit drug consumption, and in Switzerland approximately 190 deaths related to recreational drug use were reported in 2023. Most patients present after the use of recreational drugs such as stimulants (cocaine and amphetamines), opioids, cannabis or hallucinogens, with stimulants representing the majority of acute presentations in European emergency departments. In recent years, a sharp progression of amphetamine-like substance consumption derived from khat has been observed. Clinical presentations range from agitation, psychosis, seizures, and hyperthermia to respiratory depression, multi-organ failure and cardiac arrest. Emergency physicians are frequently the first to provide care, yet management is often complicated by the coexistence of multiple substances, the emergence of new psychoactive compounds, and the limited availability of toxicological testing in the acute setting. This narrative review summarises the current evidence and recommendations relevant for clinical practice. It is based on a literature search conducted in PubMed, EMBASE, Cochrane Library, but also grey literature such as MonAM, Infodrog and Tox Info Suisse regarding the specific Swiss context. The review highlights the recognition of typical toxidromes: stimulants causing sympathomimetic effects; opioids with mainly respiratory depression; hallucinogens and dissociatives; also, this review presents common pitfalls with drugs commonly encountered. Management emphasises oxygen administration, benzodiazepine sedation for agitation, and specific interventions like naloxone for opioids. Given rising trends in cocaine and novel psychoactive substance use, enhanced understanding of pharmacological profiles and standardised emergency protocols are critical for improving patient outcomes. Although specific treatment may be lacking for most drugs, novel psychoactive drugs pose new challenges due to lack of robust data preventing us from presenting a typical clinical picture and providing standardised care. This synthesis aims to support emergency physicians in the structured and evidence-based management of acute recreational drug intoxications. Full article

In recent years, the issue of drivers under the influence of medications and psychoactive substances as a cause of road accidents has gained increasing importance. This study aimed to assess the prevalence and blood concentration ranges of alcohol and psychoactive substances among drivers in northeastern Poland between 2013 and 2024. To determine the prevalence of medications and psychoactive substances in drivers’ blood, data were collected from 266 blood samples obtained from drivers (251 men and 15 women). Among these, 79 drivers died immediately, 61 drivers survived the accident, and 126 drivers were stopped for roadside checks. The presence of the studied substances was confirmed using gas chromatography combined with mass spectrometry detection (GC-MS) and liquid chromatography combined with mass spectrometry detection (LC-MS). Blood alcohol content was measured using headspace gas chromatography with a flame ionisation detector (HS-GC-FID). Psychoactive substances were detected in 152 of the 266 samples. Drivers testing positive for medications and psychoactive substances were most frequently stopped during roadside controls—67.46%. Among the total positive cases, psychoactive substances used alone or in combination included THC—46.3% (range 0.2–20 ng/mL), alcohol—26.8% (range 0.1–4.1‰), amphetamines—20.7% (range 15–2997 ng/mL), opiates—4.3% (morphine 66.0 ng/mL; methadone 174.0 ng/mL; ranges: tramadol 15.0–600.0 ng/mL; fentanyl 45.0–100.0 ng/mL), benzodiazepines—9.8% (ranges: diazepam 55.0–480.0 ng/mL; midazolam 17.0–1200.0 ng/mL; clonazepam 21.0–36.0 ng/mL), stimulants—6.10% (ranges: amphetamine 15.0–2997.0 ng/mL; cocaine 4.0–30.0 ng/mL; benzoylecgonine 38.0–602.0 ng/mL; PMMA 45.0–360.0 ng/mL; MDMA 20.0–75.0 ng/mL; mephedrone 37.5 ng/mL; alfa-PVP 120 ng/mL), psychotropic drugs—3.1% (carbamazepine 8.0–2100.0 ng/mL; zolpidem 233.0 ng/mL; citalopram 320.0 ng/mL; opipramol 220 ng/mL). The most commonly used substance among car and motorcycle drivers was THC (37.7% of car drivers and 60% of motorcyclists). Among operators of other types of vehicles, alcohol was the most frequently detected substance, present in 35% of cases. The majority of drivers (81.1%) were under the influence of a single substance. Among the drivers, 7.3% consumed alcohol in combination with at least one other substance, and 11.6% used two or more substances excluding alcohol. Among the psychoactive substances most frequently used alone or in combination with others, THC was predominant. Roadside testing, based on effects similar to alcohol intoxication, was mainly conducted on male drivers. Full article

The emergence of new psychoactive substances (NPS) in the global drug market since the 2000s has posed major challenges for regulators and law enforcement agencies. Among these, synthetic cathinones have gained prominence due to their stimulant effects on the central nervous system, leading to widespread recreational use. These compounds, often marketed as alternatives to illicit stimulants such as amphetamines and cocaine, have been linked to numerous cases of intoxication, addiction and death. The structural diversity and enantiomeric forms of synthetic cathinones further complicate their detection and regulation and pose challenges to forensic toxicology. In addition to their psychoactive and toxicological effects, new research suggests that cathinones may have antimicrobial properties. Compounds derived from Catha edulis (khat), including cathinone, have shown antimicrobial activity against multidrug-resistant bacteria such as Staphylococcus aureus and Escherichia coli, highlighting their potential role in the fight against antibiotic resistance. This article provides an overview of the chemistry, pharmacokinetics, pharmacodynamics, toxicological effects and potential antimicrobial applications of synthetic cathinones. The potential therapeutic use of cathinone-derived compounds to combat antimicrobial resistance represents an exciting new frontier in drug development, although further research is needed to balance these benefits with the psychoactive risks. Full article

Bile has emerged as an alternative matrix for toxicological investigation of drugs in suspected forensic cases of overdose in adults and intoxications in children. Toxicological investigation consists in screening and, subsequently, confirming the result with specific techniques, such as liquid chromatography with tandem mass spectrometry (LC-MS/MS). As there is no screening test on the market to test postmortem bile specimens, the novelty of this study was in investigating the applicability of a chemiluminescence immunoassay, designed for other matrices and available on the market, on bile and validate its use, testing the agreement with LC-MS/MS analysis. Bile specimens were obtained from 25 forensic cases of suspected death from overdose and intoxication. Sample preparation for bile screening consists simply in centrifugation and dilution. Confirmation analysis allows simultaneous identification of 108 drugs and was validated on bile. Kappa analysis assessed a perfect agreement (0.81–1) between the assays for benzodiazepines, methadone, opiates, cocaine, oxycodone, cannabinoids, buprenorphine and pregabalin; a substantial agreement (0.41–0.6) was reported for barbiturates. No agreement was assessed for amphetamines, due to an abundance of putrefactive amines in postmortem specimens. In conclusion, this fast and easy immunoassay could be used for initial screening of bile specimens, identifying presence of drugs, except amphetamines, with reliability. Full article

Abusing controlled substances, including cannabis and various drugs, can result in severe intoxication and even death. Therefore, a comprehensive postmortem analysis is crucial for understanding the underlying causes of such fatalities. This narrative review discusses the characteristics of commonly abused controlled substances, the methodologies employed in postmortem analysis, lethal dosage levels, mechanisms of toxicity, side effects, and existing regulations. The focus centers on seven prevalent groups of controlled substances, namely cannabis, opioids, amphetamine-type stimulants, cocaine, new psychoactive substances, and hallucinogens. These groups have been linked to an increased risk of fatal overdose. Most substances in these groups exert neurotoxic effects by targeting the central nervous system (CNS). Consequently, strict regulation is essential to mitigate the potential harm posed by these substances. To combat abuse, prescribers must adhere to guidelines to ensure their prescribed medications comply with the outlined regulations. Through an enhanced understanding of controlled substance abuse and its consequences, more effective strategies can be developed to reduce its prevalence and associated mortality. Full article

Even before behavioral disturbances, neuroleptics, amphetamine, and domperidone application rapidly emerged severe occlusion/occlusion-like syndrome, shared innate vascular and multiorgan failure in rats, comparable to occlusion/occlusion-like syndrome described with vessel(s) occlusion or similar noxious procedures application. As therapy, i.e., activation of the collateral pathways, “bypassing key” (activated azygos vein pathway, direct blood flow delivery), the stable gastric pentadecapeptide BPC 157 is a novel solution. Recently, BPC 157 therapy particularly counteracted neuroleptic- or L-NAME-induced catalepsy, lithium intoxication, and schizophrenia positive and negative symptoms (amphetamine/methamphetamine/apomorphine/ketamine). In rats with complete calvariectomy, medication (BPC 157 10 µg/kg, 10 ng/kg ip or ig) was given 5 min after distinctive dopamine agents (mg/kg ip) (haloperidol (5), fluphenazine (5), clozapine (10), risperidone (5), olanzapine (10), quetiapine (10), or aripiprazole (10), domperidone (25), amphetamine (10), and combined amphetamine and haloperidol) and assessed at 15 min thereafter. All neuroleptic-, domperidone-, and amphetamine-induced comparable vascular and multiorgan failure severe syndrome was alleviated with BPC 157 therapy as before major vessel(s) occlusion or other similar noxious procedures. Specifically, all severe lesions in the brain (i.e., immediate swelling, hemorrhage), heart (i.e., congestion, arrhythmias), and lung (i.e., congestion, hemorrhage), as well as congestion in the liver, kidney, and gastrointestinal (stomach) tract, were resolved. Intracranial (superior sagittal sinus), portal, and caval hypertension and aortal hypotension were attenuated or eliminated. BPC 157 therapy almost annihilated arterial and venous thrombosis, peripherally and centrally. Thus, rapidly acting Virchow triad circumstances that occur as dopamine central/peripheral antagonists and agonist essential class-points, fully reversed by BPC 157 therapy, might be overwhelming for both neuroleptics and amphetamine. Full article

According to the EU Early Warning System (EWS), synthetic cathinones (SCs) are the second largest new psychoactive substances (NPS) class, with 162 synthetic cathinones monitored by the EU EWS. They have a similar structure to cathinone, principally found in Catha Edulis; they have a phenethylamine related structure but also exhibit amphetamine-like stimulant effects. Illegal laboratories regularly develop new substances and place them on the market. For this reason, during the last decade this class of substances has presented a great challenge for public health and forensic toxicologists. Acting on different systems and with various mechanisms of action, the spectrum of side effects caused by the intake of these drugs of abuse is very broad. To date, most studies have focused on the substances’ cardiac effects, and very few on their associated neurotoxicity. Specifically, synthetic cathinones appear to be involved in different neurological events, including increased alertness, mild agitation, severe psychosis, hyperthermia and death. A systematic literature search in PubMed and Scopus databases according to PRISMA guidelines was performed. A total of 515 studies published from 2005 to 2022 (350 articles from PubMed and 165 from Scopus) were initially screened for eligibility. The papers excluded, according to the criteria described in the Method Section (n = 401) and after full text analyses (n = 82), were 483 in total. The remaining 76 were included in the present review, as they met fully the inclusion criteria. The present work provides a comprehensive review on neurotoxic mechanisms of synthetic cathinones highlighting intoxication cases and fatalities in humans, as well as the toxic effects on animals (in particular rats, mice and zebrafish larvae). The reviewed studies showed brain-related adverse effects, including encephalopathy, coma and convulsions, and sympathomimetic and hallucinogenic toxidromes, together with the risk of developing excited/agitated delirium syndrome and serotonin syndrome. Full article

MDMA (3,4-methylenedioxymethamphetamine; commonly referred to as “Molly” or “ecstasy”) is a synthetic compound, structurally and pharmacologically similar to both amphetamines and mescaline. MDMA differs somewhat from traditional amphetamines in that it is not structurally similar to serotonin. Cocaine is rare and cannabis is consumed less frequently than in Western Europe. Heroin is the drug of choice for the poor in Bucharest, Romania’s capital of two million people, and alcoholism is common in villages where more than a third of the population lives in poverty. By far, the most popular drugs are Legal Highs (Romanians call them “ethnobotanics”). All of these drugs have significant effects on cardiovascular function that contribute significantly to adverse events. Most adverse cardiac events occur in young adults and are potentially reversible. Poisoning among patients aged 17 years and over was commonly seen in the Emergency Departments of a large tertiary hospital in the city centre, accounting for 3.2% of all patients. In a third of the poisonings, more than one substance was used. Intoxication with ethnobotanicals was the most frequently observed, followed by use of drugs from the amphetamine group. The majority of patients presenting to the Emergency Department were male. Therefore, this study suggests further research on hazardous alcohol consumption and drug abuse. Full article

The purpose of this investigation was to assess the prevalence and associated factors of four alcohol use indicators among male and female school adolescents in Bolivia. In total, 7931 participants (M = 15.5 years, SD = 1.6) responded to a questionnaire in a cross-sectional nationally representative school survey in Bolivia in 2018. The proportion of current alcohol use was 26.4%, heavy alcohol use 11.1%, ever having been drunk 24.1%, and trouble resulting from alcohol use 21.4%. Among boys, older age, current cannabis use, multiple sexual partners, being in a physical fight, school truancy, soft drink intake, injury and psychological distress increased the risk of current alcohol use and/or heavy drinking. Among girls, older age, multiple sexual partners, fast food intake, being in a physical fight, school truancy, sedentary behaviour and psychological distress increased the risk of current alcohol use and/or heavy drinking. Older age, multiple sexual partners, current cannabis use, low parental support and school truancy were associated with trouble from alcohol use and history of intoxication in both sexes. Among boys, ever having used amphetamines, fast food intake, injury, peer support, and being in a physical fight were associated with ever having been drunk; and among girls, sedentary behaviour and psychological distress increased the odds of ever having been drunk. The study found that more than one in ten adolescents engage in heavy alcohol use, and several sex specific factors are identified for four alcohol use indicators. Full article

Stimulants belonging to the amphetamine group nowadays pose an undeniable worldwide threat to the life and health of users. Intoxications of domestic animals also occur, which can either be accidental or related to intentional human action. This study presents the first ever reported case of a simultaneous amphetamine and methamphetamine intoxication of a cat, along with the results of toxicological studies. Blood, urine, vitreous humor and liver were collected during the cat’s autopsy and analyzed by UHPLC─QqQ─MS/MS. The sample preparation technique was based on one-step precipitation of proteins with cold acetonitrile. The determined amphetamine concentrations in the collected biological materials were 93.4 ng/mL in blood, 496.6 ng/mL in urine, 589.2 ng/mL in the vitreous humor and 291.2 ng/g in liver, respectively. Methamphetamine concentrations were 45.5 ng/mL in blood, 263.1 ng/mL in urine, 351.2 ng/mL in vitreous humor, and 97.7 ng/g in liver. Other substances were also found in the biological material, i.e., diazepam, oxazepam and nordiazepam. Cases of intentional or accidental poisoning of pets with psychoactive substances are a serious problem, carrying the risk to the health and life of the animal. Therefore, it is important to increase awareness of the high risk of poisoning of domestic animals, as well as to learn about the incompletely understood mechanisms of pharmacokinetics of various drugs in animals, including cats. Full article

Methamphetamine (MA) level in urine has been used for judgment in MA consumption. Metabolism and intoxication of MA are correlated with the activity of cytochrome P450 2D6 (CYP2D6). The activity score (AS) is a potential tool for predicting exposure and personalized dose of drugs metabolized by CYP2D6. Prediction of the CYP2D6 activity score might be described as MA intoxication. The objective of this study was to categorize the CYP2D6 activity score using the urinary amphetamine (AM)/MA ratio. Urine samples (n = 23,258) were collected. The levels of MA and AM were determined by a gas chromatography–nitrogen–phosphorus detector. The log AS was calculated by an AM/MA ratio and classified into four groups following the percentile position: lower than the 2.5th, the 2.5th–the 50th, the 50th–97.5th, and greater than the 97.5th percentile, respectively. The AS value for males presented was less than 0.024, 0.024–0.141, 0.141–0.836, and greater than 0.836. Meanwhile, the AS values were revealed to be lower than 0.023, 0.023–0.148, 0.148–0.850, and higher than 0.850 for females. The AS value of CYP2D6 can be applied to describe the toxicity of MA in forensic crime scenes and relapse behavior. Full article

Excessive consumption of highly processed foods, such as chips, crisps, biscuits and coffee, exposes the human to different doses of acrylamide. This chemical compound has a multidirectional, adverse effect on human and animal health, including the central and peripheral nervous systems. In this study, we examined the effect of different doses of acrylamide on the enteric nervous system (ENS) of the porcine jejunum. Namely, we took into account the quantitative changes of neurons located in the jejunum wall expressing substance P (SP), galanin (GAL), a neuronal form of nitric oxide synthase (nNOS), the vesicular acetylcholine transporter (VAChT) and cocaine- and amphetamine-regulated transcript (CART). The obtained results indicate that acrylamide causes a statistically significant increase in the number of neurons immunoreactive to SP, GAL, VAChT and CART in all types of examined enteric plexuses and a significant drop in the population of nNOS-positive enteric neurons. Changes were significantly greater in the case of a high dose of acrylamide intoxication. Our results indicate that acrylamide is not indifferent to ENS neurons. A 28-day intoxication with this substance caused marked changes in the chemical coding of ENS neurons in the porcine jejunum. Full article

In forensic toxicology, amphetamine intoxications represent one of the most common case groups and present difficult questions for toxicologists. Estimating the time of consumption and the current influence of the stimulant is particularly difficult when only total amphetamine concentrations are considered. Stereoselective analysis and the consideration of metabolites can provide valuable information to facilitate interpretation. An enantioselective liquid chromatography−tandem mass spectrometry (LC-MS/MS) method for detection of amphetamine, norephedrine and 4-hydroxyamphetamine was developed. Validation showed satisfactory selectivity, sensitivity, linearity (0.5–250 ng/mL), precision and accuracy for all enantiomers. The method was applied to a collective of 425 forensic serum samples and 30 serum samples from psychiatric inpatients stating their last time of amphetamine consumption. Norephedrine and 4-hydroxyamphetamine were detected more frequently at higher amphetamine concentrations and at lower amphetamine (R)/(S) concentration ratios, possibly indicating recent consumption. Mean (R)/(S) ratio of amphetamine was 1.14, whereas higher ratios (mean 1.36) were found for amphetamine concentrations below 100 ng/mL. The (R)/(S) ratios of psychiatric inpatients significantly correlated with the reported time intervals to last consumption. The use of amphetamine (R)/(S) ratios and the simultaneous detection of metabolites are promising factors that can facilitate estimation of consumption time and current impairment. Full article

Sex and gender deeply affect the subjective effects and pharmaco-toxicological responses to drugs. Men are more likely than women to use almost all types of illicit drugs and to present to emergency departments for serious or fatal intoxications. However, women are just as likely as men to develop substance use disorders, and may be more susceptible to craving and relapse. Clinical and preclinical studies have shown important differences between males and females after administration of “classic” drugs of abuse (e.g., Δ9-tetrahydrocannabinol (THC), morphine, cocaine). This scenario has become enormously complicated in the last decade with the overbearing appearance of the new psychoactive substances (NPS) that have emerged as alternatives to regulated drugs. To date, more than 900 NPS have been identified, and can be catalogued in different pharmacological categories including synthetic cannabinoids, synthetic stimulants (cathinones and amphetamine-like), hallucinogenic phenethylamines, synthetic opioids (fentanyls and non-fentanyls), new benzodiazepines and dissociative anesthetics (i.e., methoxetamine and phencyclidine-derivatives). This work collects the little knowledge reached so far on the effects of NPS in male and female animal and human subjects, highlighting how much sex and gender differences in the effects of NPS has yet to be studied and understood. Full article

In recent years, a significant increase in the consumption of products containing large amounts of acrylamide (e.g., chips, fries, coffee), especially among young people has been noted. The present study was created to establish the impact of acrylamide supplementation, in tolerable daily intake (TDI) dose and a dose ten times higher than TDI, on the population of galanin-like immunoreactive (GAL-LI) stomach neurons in pigs. Additionally, in the present study, the possible functional co-operation of GAL with other neuroactive substances and their role in acrylamide intoxication was investigated. Using double-labelling immunohistochemistry, alterations in the expression of GAL were examined in the porcine stomach enteric neurons after low and high doses of acrylamide supplementation. Generally, upregulation in GAL-LI immunoreactivity in both myenteric and submucous plexuses was noted in all stomach fragments studied. Additionally, the proportion of GAL-expressing cell bodies simultaneously immunoreactive to vasoactive intestinal peptide (VIP), neuronal nitric oxide synthase (nNOS) and cocaine- and amphetamine- regulated transcript peptide (CART) also increased. The results suggest neurotrophic or/and neuroprotective properties of GAL and possible co-operation of GAL with VIP, nNOS, CART in the recovery processes in the stomach enteric nervous system (ENS) neurons following acrylamide intoxication. Full article