Search Results (37)

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

Whilst “nootropics” are meant to treat a range of medical disorder-related cognitive impairments, the typically healthy “smart drugs” user ingests a range of drugs/molecules to achieve improved mental performance. Given the increasing levels of related concerns, this study aimed to provide an overview of the clinical pharmacological issues relating to both the most popular nootropics and the vast range of drugs that are being used as putative cognitive enhancers/smart drugs. In terms of the cognitive decline associated with neurological degenerative disorders, a significant variation in research methodology was observed. Therefore, the overall usefulness of these pharmaceuticals in various central nervous system disorders as supplements/adjuvant therapy needs to be better established before their widespread use can be recommended. The most popular smart drugs, self-administered to cope with high-perceived stress and academic/work-related pressure, were methylphenidate, modafinil, amphetamine-based compounds, and psychedelics. At present, however, there are relevant levels of uncertainty in terms of smart drugs’ effectiveness in improving executive functions. Addressing the health harms associated with cognitive enhancers’ intake remains challenging due to the lack of updated and contextualized epidemiological data. In particular, there appears to be a range of clinical concerns relating to the non-prescribed intake of stimulant smart drugs by otherwise healthy individuals. Enhanced training for prescribers, pharmacists, and healthcare professionals can strengthen monitoring and early intervention efforts. Full article

The illicit production and distribution of amphetamines present significant challenges to public health and law enforcement, particularly in Europe, where these substances dominate the stimulant market. This study aimed to profile amphetamines consumed within a Polish community by employing gas chromatography–mass spectrometry (GC-MS) and chemometric techniques to analyze their chemical composition and associated impurities. The optimized GC-MS methodology facilitated the identification of synthesis markers, precursor origins, and distribution patterns. Impurity profiling provided critical insights into regional production trends, including the use of specific precursors and adulterants. Chemometric analysis further enabled the classification of samples into distinct groups, shedding light on their origins and distribution chains. These findings underscore the potential of extending amphetamine profiling to include distribution-related compounds, offering a powerful tool for tracking production trends and enhancing forensic investigations in the fight against drug trafficking. Full article

The present study examined three hallucinogenic amphetamine derivatives, namely, 2,5-dimethoxy-4-iodoamphetamine (DOI) as well as 2,5-dimethoxy-4-methylamphetamine (DOM) and 4-methylmethcathinone (mephedrone). The objective of this study was to test the hypothesis that DOI, DOM, and mephedrone would increase the contractile force in isolated human atrial preparations in a manner similar to amphetamine. To this end, we measured contractile force under isometric conditions in electrically stimulated (1 Hz) human atrial preparations obtained during open surgery. DOI and DOM alone or in the presence of isoprenaline reduced the contractile force concentration-dependently in human atrial preparations. These negative inotropic effects of DOM and DOI were not attenuated by 10 µM atropine. However, mephedrone increased the contractile force in human atrial preparations in a concentration- and time-dependent manner. Furthermore, these effects were attenuated by the subsequent addition of 10 µM propranolol or pretreatment with 10 µM cocaine in the organ bath. Therefore, it can be concluded that amphetamine derivatives may exert opposing effects on cardiac contractile force. The precise mechanism by which DOI and DOM exert their negative inotropic effects remains unknown at present. The cardiac effects of mephedrone are probably due to the release of cardiac noradrenaline. Full article

The United Nations World Drug Report published in 2022 alarmed that the global market of illicit drugs is steadily expanding in space and scale. Substances of abuse are usually perceived in the light of threats to human health and public security, while the environmental aspects of their use and subsequent emissions usually remain less explored. However, as with other human activities, drug production, trade, and consumption of drugs may leave their environmental mark. Therefore, this paper aims to review the occurrence of illicit drugs in surface waters and their bioaccumulation and toxicity in fish. Illicit drugs of different groups, i.e., psychostimulants (methamphetamines/amphetamines, cocaine, and its metabolite benzoylecgonine) and depressants (opioids: morphine, heroin, methadone, fentanyl), can reach the aquatic environment through wastewater discharge as they are often not entirely removed during wastewater treatment processes, resulting in their subsequent circulation in nanomolar concentrations, potentially affecting aquatic biota, including fish. Exposure to such xenobiotics can induce oxidative stress and dysfunction to mitochondrial and lysosomal function, distort locomotion activity by regulating the dopaminergic and glutamatergic systems, increase the predation risk, instigate neurological disorders, disbalance neurotransmission, and produce histopathological alterations in the brain and liver tissues, similar to those described in mammals. Hence, this drugs-related multidimensional harm to fish should be thoroughly investigated in line with environmental protection policies before it is too late. At the same time, selected fish species (e.g., Danio rerio, zebrafish) can be employed as models to study toxic and binge-like effects of psychoactive, illicit compounds. Full article

This review delves into the therapeutic applications of amphetamine-type stimulants such as lisdexamphetamine dimesylate, mixed amphetamine salts, 3,4-methylenedioxymethamphetamine (MDMA), dextroamphetamine, and phentermine. These compounds have been investigated for their potential in treating a range of psychiatric disorders, including attention deficit hyperactivity disorder (ADHD), drug dependence, post-traumatic stress disorder (PTSD), and obesity. Lisdexamphetamine dimesylate has shown promise in effectively treating ADHD symptoms in both children and adults. Additionally, it has been explored as a potential treatment for drug dependency and withdrawal, demonstrating encouraging results. Mixed amphetamine salts have also exhibited efficacy in reducing ADHD symptoms in adults. Future research should explore their potential use in treating bipolar disorder and cocaine dependence, considering the associated risks and benefits. MDMA-assisted psychotherapy has emerged as an innovative approach to treating PTSD, leading to sustained reductions in symptoms and even promoting post-traumatic growth. Furthermore, it has shown promise in managing anxiety related to life-threatening illnesses. Dextroamphetamine and phentermine have demonstrated efficacy in treating cocaine and opioid dependence, ADHD, and obesity. However, careful consideration and monitoring by medical professionals are essential due to the potential risks and benefits associated with them. In conclusion, amphetamine-type stimulants present a promising avenue for therapeutic interventions in various psychiatric conditions. Nevertheless, further research is necessary to comprehensively understand their mechanisms of action, dosage requirements, and long-term effects in different patient populations. Full article

Current research indicates that altered dopamine (DA) transmission in the striatum contributes to impulsivity and novelty-seeking, and it may mediate a link concerning a higher susceptibility to drug abuse. Whether increased susceptibility to drug abuse results from a hyperdopaminergic or hypodopaminergic state is still debated. Here, we simultaneously tracked changes in DA D_2/3 receptor (D_2/3R) availability and amphetamine-(AMPH)-induced DA release in relation to impulsivity and novelty-seeking prior to, and following, cocaine self-administration (SA) in Roman high- (RHA) and low- (RLA) avoidance rats. We found that high-impulsive/high novelty-seeking RHA rats exhibited lower D_2/3R availabilities and higher AMPH-induced DA release in the striatum that predicted higher levels of cocaine intake compared with RLAs. Cocaine SA did not alter striatal D_2/3R availability or impulsivity in RHA or RLA rats. Critically, cocaine exposure led to a baseline-dependent blunting of stimulated DA release in high-impulsive/high novelty-seeking RHA rats only, and to a baseline-dependent increase in novelty-seeking in low-impulsive/low novelty-seeking RLA rats only. Altogether, we propose that susceptibility to drug abuse results from an innate hyper-responsive DA system, promoting impulsive action and novelty-seeking, and producing stronger initial drug-reinforcing effects that contribute to the initiation and perpetuation of drug use. However, with repeated cocaine use, a tolerance to drug-induced striatal DA elevations develops, leading to a compensatory increase in drug consumption to overcome the reduced reward effects. Full article

Amphetamine is a psychostimulant drug with a high risk of toxicity and death when misused. Abuse of amphetamines is associated with an altered organic profile, which includes omega fatty acids. Low omega fatty acid levels are linked to mental disorders. Using the Comparative Toxicogenomic Database (CTD), we investigated the chemical profile of the brain in amphetamine-related fatalities and the possibility of neurotoxicity. We classified amphetamine cases as low (0–0.5 g/mL), medium (>0.5 to 1.5 g/mL), and high (>1.5 g/mL), based on amphetamine levels in brain samples. All three groups shared 1-octadecene, 1-tridecene, 2,4-di-tert-butylphenol, arachidonic acid (AA), docosahexaenoic acid (DHA), eicosane, and oleylamide. We identified chemical–disease associations using the CTD tools and predicted an association between DHA, AA and curated conditions like autistic disorder, disorders related to cocaine, Alzheimer’s disease, and cognitive dysfunction. An amphetamine challenge may cause neurotoxicity in the human brain due to a decrease in omega-3 fatty acids and an increase in oxidative products. Therefore, in cases of amphetamine toxicity, a supplement therapy may be needed to prevent omega-3 fatty acid deficiency. 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

Drug addiction is a disease that is characterized by a compulsion, a desire to take different substances permanently or for a certain period of time. Numerous negative incidents, such as crimes, work accidents and traffic accidents, are related to using illegal substances. Therefore, urine drug cassette tests have become a screening tool. However, considering legal consequences of test result, the question arises of their performance and reliability. On this account, the main objective of this study was to evaluate the sensitivity and specificity of urine drug tests available on the commercial pharmaceutical market. Evaluated tests were immersed in synthetic urine diluent spiked with amphetamine at various concentrations also containing potentially interfering substances such as caffeine, paracetamol and acetylsalicylic acid, and after a certain period of time, it was observed whether the result was as expected. The reference method used in this study was high-performance liquid chromatography. The obtained results confirmed the declared cut-off as well as specificity of rapid diagnostic tests. Full article

According to the Center for Disease Control, there were more than 107,000 US drug overdose deaths in 2021, over 80,000 of which due to opioids. One of the more vulnerable populations is US military veterans. Nearly 250,000 military veterans suffer from substance-related disorders (SRD). For those seeking treatment, buprenorphine is prescribed to help treat opioid use disorder (OUD). Urinalysis is currently used to monitor buprenorphine adherence as well as to detect illicit drug use during treatment. Sometimes sample tampering occurs if patients seek to generate a false positive buprenorphine urine test or mask illicit drugs, both of which can compromise treatment. To address this problem, we have been developing a point-of-care (POC) analyzer that can rapidly measure both medications used for treatment and illicit drugs in patient saliva, ideally in the physi-cian’s office. The two-step analyzer employs (1) supported liquid extraction (SLE) to isolate the drugs from the saliva and (2) surface-enhanced Raman spectroscopy (SERS) to detect the drugs. A prototype SLE-SERS-POC analyzer was used to quantify buprenorphine at ng/mL concentrations and identify illicit drugs in less than 1 mL of saliva collected from 20 SRD veterans in less than 20 min. It correctly detected buprenorphine in 19 of 20 samples (18 true positives, 1 true negative and 1 false negative). It also identified 10 other drugs in patient samples: acetaminophen, amphetamine, cannabidiol, cocaethylene, codeine, ibuprofen, methamphetamine, methadone, nicotine, and norbuprenorphine. The prototype analyzer shows evidence of accuracy in measuring treatment medications and relapse to drug use. Further study and development of the system is warranted. Full article

EDM event attendees are a high-risk population for substance use and associated adverse effects. The aim of this study was to examine substance use at EDM events, focusing on associations between attendance motives and substance use. Sociodemographic characteristics, event specifics, past-year use, and attendance motives were assessed through an online survey. Participants were 1345 Belgian EDM event attendees (69.44% male, M_age = 22.63, SD_age = 4.03). Ecstasy/MDMA/Molly (52.28%), other synthetic hallucinogens (53.68%), ketamine (42.13%), amphetamines (40.45%), and alkyl nitrites (poppers) (32.76%) were most frequently used at festivals/outdoor parties/raves. In nightclubs, cocaine (32.29%) was shown to be prevalent as well, while other synthetic hallucinogens (15.79%) were less often consumed. At events with a more private character, cannabis (68.88%) and magic mushrooms (66.44%) were most frequently used. Aside from alcohol (47.76%), substance use in pubs/bars was negligible. Overall enjoyment was demonstrated to be the key attendance motive, which was succeeded by those relating to music and socialization. A wide range of motives proved to be more important to users (e.g., dance, exploration, escapism, excitement, alcohol, drugs) than non-users, while some were associated with the use of particular substances. The prevalence of substance use was shown to be dependent on the specifics of the setting. Moreover, the idea of a three-dimensional classification of the most principal motives for music event attendance was supported. Finally, correlations were estimated between attendance motives and substance use as well as specific substances. Results could enable more tailored approaches in prevention and harm reduction efforts as well as event management strategies. Full article

Over the last year, NPSs have been steadily on the rise in the illicit drug market. Among these, synthetic cathinones seem to become increasingly popular among young adults, mainly because of their ability to replicate the effects of traditional psychostimulant drugs, such as cocaine, MDMA and amphetamines. However, scarce data are available about the in vivo pharmaco-toxicology of these new substances. To this end, this study focused on evaluation of effects induced by repeated administration of mephtetramine (MTTA 0.1–30 mg/kg i.p.) in mice. This atypical cathinone highlighted a sensorial (inhibition of visual and acoustic reflexes) and transient physiological parameter (decrease in breath rate and temperature) change in mice. Regarding motor activity, both a dose-dependent increase (accelerod test) and biphasic effect (drag and mobility time test) have been shown. In addition, blood and urine samples have been analysed to enrich the experimental featuring of the present study with reference to evaluation of potential toxicity related to consumption of MTTA. The latter analysis has particularly revealed important changes in blood cells count and blood and urine physicochemical profile after repeated treatment with this atypical cathinone. Moreover, MTTA induced histological changes in heart, kidney and liver samples, emphasizing its potential toxicity. 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