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Cannabis, cocaine, 3,4-methylenedioxymethamphetamine, and lysergic acid diethylamide are psychoactive substances with a significant increase in consumption during the 21st century due to their popularity in medicinal and recreational use. New psychoactive substances (NPSs) mimic established psychoactive substances. NPSs are known as being natural and safe to consumers; however, they are neither natural nor safe, causing severe adverse reactions, including seizures, nephrotoxicity, and sometimes death. Synthetic cannabinoids, synthetic cathinones, phenethylamines, and piperazines are all examples of NPSs. As of January 2020, nearly 1000 NPSs have become documented. Due to their low cost, ease of availability, and difficulty of detection, misuse of NPSs has become a familiar and growing problem, especially in adolescents and young adults in the past decade. The use of NPSs is associated with higher risks of unplanned sexual intercourse and pregnancy. As many as 4 in 100 women seeking treatment for substance abuse are pregnant or nursing. Animal studies and human clinical case reports have shown that exposure to certain NPSs during lactation periods has toxic effects on neonates, increasing various risks, including brain damage. Nevertheless, neonatal toxicity effects of NPSs are usually unrecognized and overlooked by healthcare professionals. In this review article, we introduce and discuss the potential neonatal toxicity of NPSs, emphasizing synthetic cannabinoids. Utilizing the established prediction models, we identify synthetic cannabinoids and their highly accumulative metabolites in breast milk., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Psychoactive substances are ubiquitous in the environment at low concentrations, and tobacco, cannabis, etc. are all widely-existing examples. Given their potent biological activity, psychoactive substances are suspected to be harmful to the environment, and reports of their ecological risks are gradually increasing. Since the 1990s, the investigations into psychoactive substances have made remarkable progress, yet some research fields still need to be modernised. For example, the unification of standardised analytical methods as well as the supplementation of occurrence literature. In addition, a relatively lagging risk evaluation system caused by a lack of toxicity data is particularly in need of improvement. The purpose of this article is to develop a review of current research on psychoactive substances, including analytical methods, distribution in environmental compartments, and ecological risk assessment, as well as to point out deficiencies and development prospects and to offer motivation for enhancing the research level in this field., (Copyright © 2021. Published by Elsevier Ltd.)

The use of new psychoactive substances (NPSs) as a substitute for illegal drugs is increasing rapidly and is a serious threat to public health. 25C-NBF is a newly synthesized phenethylamine-type NPS that acts as a 5-hydroxyindoleacetic acid (5-HT) receptor agonist, but little is known about its pharmacological effects. Considering that NPSs have caused unexpected harmful effects leading to emergency and even death, scientific confirmation of the potential adverse effects of 25C-NBF is essential. In the present study, we investigated whether 25C-NBF has addictive and neurotoxic potential and causes neurochemical changes. In addictive potential assessments, high conditioned place preference (CPP) scores and stable self-administration (SA) were observed in the 25C-NBF groups (CPP [3 mg kg -1 ]; SA [0.01, 0.03, 0.1 mg kg -1 ]), suggesting the addictive liability of 25C-NBF. In neurotoxic potential assessments, 25C-NBF treatment (single super-high dose [1 × 15, 30, 40 mg kg -1 ]; repeated high dose [4 × 8, 15, 30 mg kg -1 ]) resulted in reduced motor activity (open field test), abnormal motor coordination (rota-rod test) and impaired recognition memory (novel object recognition test), suggesting that 25C-NBF is neurotoxic leading to motor impairment and memory deficits. Subsequently, immunohistochemistry showed that 25C-NBF treatment decreased tyrosine hydroxylase (TH) expression and increased ionized calcium-binding adapter molecule 1 (Iba-1) expression in the striatum. Taken together, our results clearly demonstrate the dangers of recreational use of 25C-NBF, and we suggest that people stop using 25C-NBF and other NPSs whose pharmacological effects are not precisely known.

Novel psychoactive substances (NPS) are new drugs of abuse. Over the last 10 years 50-100 new NPS have been detected for the first time each year. This has led to numerous deaths and challenges to healthcare providers and law-makers worldwide. We review preclinical studies of NPS and discuss how these studies have influenced legislative decisions. We focus on the UK legal system but include experiences from Europe. We reviewed manuscripts from 2008-2019 and have summarised the in vitro and in vivo data on NPS, highlighting how these studies define pharmacological mechanisms and how they might predict harm in humans. We found that only a small percentage of NPS have been examined in preclinical studies. Most preclinical studies of NPS focus on basic pharmacological mechanisms (46% of studies reviewed) and/or addictive liability (32%) rather than toxicity and harm (24%). Very few preclinical studies into NPS include data from chronic dosing schedules (9%) or female rodents (4%). We conclude that preclinical studies can predict harm to humans, but most of the predictions are based on basic pharmacology rather than demonstrated toxicity. Some of these studies have been used to make changes to the law in the UK and Europe and perhaps, because of the paucity of toxicology data, most NPS have been placed in the highly dangerous schedule 1 or Class A category in the UK. We suggest that in silico studies and high throughput toxicology screens might be the most economical way forward to rapidly screen the health harms of NPS., (© 2020 The British Pharmacological Society.)

Benzofurans, also known by users as benzo fury or benzofury, are synthetic phenethylamines and constitute the third most prominent group of new psychoactive substances (NPS). As the use of these substances has been spread as an alternative to the classic illicit psychostimulants, such as amphetamines, their legal status was reviewed, resulting in an utter prohibition of these NPS in many countries worldwide. Herein, the prevalence of abuse, chemistry, biological effects, metabolism, and the potential harms and risky behaviors associated with the abuse of benzofurans are reviewed. The congeners of this group are mainly consumed recreationally at electronic dance music parties, in polydrug abuse settings. Benzofurans preferentially act by disturbing the functioning of serotonergic circuits, which induces their entactogenic and stimulant effects and is the reason behind the considerable number of recent benzo fury-related deaths. The slight interaction of these drugs with the dopaminergic system justifies the rewarding effects of these drugs. To date, published evidence on the mechanisms of toxicity of benzo fury is very limited but a body of research is now beginning to emerge revealing an alarming public health threat regarding the abuse of these NPS., (© 2019 John Wiley & Sons, Ltd.)

Aims: The use of new psychoactive substances (NPS) has become increasingly widespread over the last decade, in Japan and internationally. NPS are associated with a range of increasingly serious clinical, public, and social issues. Political measures to ameliorate the effects of NPS in Japan have focused on tightening regulation rather than establishing treatment methods. The current study sought to compare the neuropsychiatric symptoms of patients with NPS-related disorders across several years. We examined patients who attended specialized hospitals for treating addiction, to elucidate the impacts of legal measures to control NPS., Methods: Subjects (n = 864) were patients with NPS-related disorders who received medical treatment at eight specialized hospitals for treating addiction in Japan between April 2012 and March 2015. Clinical information was collected retrospectively from medical records., Results: Among psychiatric symptoms, the ratio of hallucinations/delusions decreased over time across 3 years of study (first year vs second year vs third year: 40.1% vs 30.9% vs 31.7%, P = 0.037). Among neurological symptoms, the ratio of coma/syncope increased over the 3-year period (7.8% vs 11.0% vs 17.0%, P = 0.002), as did the ratio of convulsions (2.8% vs 4.3% vs 9.7%, P = 0.001)., Conclusion: The symptoms associated with NPS were primarily psychiatric in the first year, while the prevalence of neurological symptoms increased each year. The risk of death and the severity of symptoms were greater in the third year compared with the first year, as regulation of NPS increased., (© 2019 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

An index of fatal toxicity for new psychoactive substances has been developed based solely on information provided on death certificates. An updated index of fatal toxicity (T f ), as first described in 2010, was calculated based on the ratio of deaths to prevalence and seizures for the original five substances (amphetamine, cannabis, cocaine/crack, heroin and 3,4-methylenedioxymethylamphetamine) * . These correlated well with the 2010 index. Deaths were then examined for cases both where the substance was and was not found in association with other substances. This ratio (sole to all mentions; S/A) was then calculated for deaths in the period 1993 to 2016. This new measure of fatal toxicity, expressed by S/A, was well-correlated with the index L n (T f ) of the original reference compounds. The calculation of S/A was then extended to a group of new psychoactive substances where insufficient prevalence or seizure data were available to directly determine a value of T f by interpolation of a graph of T f versus S/A. Benzodiazepine analogues had particularly low values of S/A and hence T f . By contrast, γ-hydroxybutyrate/γ-butyrolactone, α-methyltryptamine, synthetic cannabinoid receptor agonists and benzofurans had a higher fatal toxicity.

Long QT syndrome (LQTS), a congenital genetic disorder, can cause torsades de pointes (TdP), and lethal cardiac arrhythmia may result from ingestion of cardiotoxic drugs. Methamphetamine (MP) and new psychoactive substances (NPSs) can trigger TdP due to QT prolongation, leading to sudden death. We therefore analysed variations in the LQTS-associated genes KCNQ1 (LQT1) and KCNH2 (LQT2) using cardiac blood and myocardial tissue from subjects having died suddenly during MP or NPS use to investigate the relationship between congenital genetic abnormalities and sudden death during illegal drug use. We amplified and sequenced all exons of these genes using samples from 20 subjects, half of whom had died taking MP and half after using NPSs. G643S, a KCNQ1 missense polymorphism, was significantly more common among sudden deaths involving NPSs (6 subjects) than those involving MP (1 subject) and healthy Japanese subjects (P = 0.001). Notably, synthetic cathinones were detected in 2 of 3 cases involving G643S carriers. Previous functional analyses have indicated that the G643S polymorphism in the KCNQ1 potassium channel gene causes mild I Ks channel dysfunction. Our data suggest that use of NPSs, particularly synthetic cathinones, is associated with elevated risk of serious cardiac arrhythmia and sudden death for subjects carrying KCNQ1 G643S.

The number of new psychoactive substances (NPS) has increased significantly, especially within the last 5 years. The EMCDDA conducts risks assessments of such substances, especially in relation to serious adverse events. Examination of the individual health risks of a substance is a fundamental requirement of the process. Based on a number of considerations, the Toxicological Significance Score has been developed to support the risk assessment of NPS by allowing the role of a substance in deaths to be better assessed and classified., (Copyright © 2017 John Wiley & Sons, Ltd.)

Chiral discrimination has become one of the most important fields in analytical and medicinal chemistry, and forensic toxicology. The enantiomers may have different binding to proteins that may lead to many pharmacological and toxicological differences between them, including kinetic (at the absorption, distribution, metabolism and excretion level) or dynamic (level of potency and efficacy or even differences in mechanism of action) variations. Cathinone derivatives are chiral compounds, sold via the internet for recreational use, and little is known about their enantiomeric selectivity. Consequently, it is of crucial importance for the development of resolution methods to obtain pure enantiomers to study their biological effects. In the last few years, techniques for chiral drug analysis, as chromatography, have been developed and some works related to the analytical enantiomeric resolution of synthetic cathinones were described. However, information about synthetic cathinones in the literature is scarce specially concerning single enantiomers. In this mini-review, analytical chiral resolution and biological differences between enantiomers of cathinone derivatives will be addressed.

The purpose of this paper is to review the most common and quickest growing classes of novel, or new, psychoactive substances. Abuse of novel psychoactive substances continues to increase, resulting in subsequent increases in hospitalizations. Furthermore, the chemical structures are ever-changing and substances are increasing in potency. Reviewing the chemistry behind these agents will facilitate a better understanding of the toxicity associated with them and allow for successful identification of and management in the critical care unit. Being familiar with the most common psychoactive substances and trends of abuse, as well as the challenges health care providers face when managing intoxication, is essential to the overall understanding and care of these critically ill patients.

Objective: The objective of this study is to explore the users' perspectives regarding the effects and toxicity of cathinones., Methods: A systematic search of Internet discussion forums yielded 303 threads relevant to the research objectives. The threads were analysed by conventional content analysis where concepts were developed from codes and themes., Results: The study identified 3 main themes in relation to cathinone use, effects, and toxicity. The first theme considered the modalities of intake of cathinones in relation to the derivative taken (mainly mephedrone, 3-methylmethcathinone, and methylenedioxypyrovalerone), route of administration (eyeballing, insufflation, smoking, intravenous, oral, rectal, and sublingual), multidrug use, and purity of the cathinone derivative. The second theme characterised the main effects of cathinones, that is, increased energy, euphoria, and empathogenic. Toxic effects were reported regarding the nervous system (anxiety, hallucinations, nervousness, and paranoia), cardiovascular system (angina, myocardial infarction, and tachycardia), skin (discolouration, itching, and allergy), and renal system (difficulty in urination). Drug-drug interactions were also reported including multiple drug use between cathinones, stimulants, depressants, and hallucinogens., Conclusions: The Internet discussion forums provide useful sources of information regarding the effects and toxicity of cathinones, which can be taken into account when assessing the safety of drugs., (Copyright © 2017 John Wiley & Sons, Ltd.)

Objective: To investigate the profile, effects, and toxicity of novel psychoactive substances (NPS)., Methods: A systematic literature review was conducted between May 2015 and February 2016 and included 19 databases. Search terms included "novel psychoactive substance(s)," "effect(s)," and "toxicity" and their synonyms. Studies included were those from any country, in any language, and between January 2007 and April 2015. Studies published before 2007 and those regarding the synthesis of NPS were excluded. Data were extracted by evaluating the titles, abstract, and full text, respectively. Consequently, the extraction yielded 20 studies., Results: Forty-three NPS derivatives of 8 main pharmacological classes were identified. NPS were mostly used among young adults and adults within the age range of 16-64 years old. Cathinones and synthetic cannabinoids were the most prevalent among the aforementioned classes. The main desired effects of NPS use were empathy and increased ability to socialise. Reported toxicity associated with the use of NPS included cardiovascular, neurological, and psychoactive adverse reactions., Conclusions: Despite the unique subjective effects associated with the use of NPS, harmful effects could be severe and/or lethal. Therefore, there is a need to develop research in the area of NPS and promote awareness among healthcare professionals., (Copyright © 2017 John Wiley & Sons, Ltd.)

Intravenous use of a psychostimulant drug containing methcathinone (ephedrone) and manganese causes an irreversible extrapyramidal syndrome in drug abusers. We aimed to reproduce the syndrome in mice to evaluate dopaminergic damage. C57/B6 mice were intraperitoneally injected once a day with the study drug or saline for a period of 27 weeks. Motor activity was recorded in an automated motility-box. After 13 and 27 weeks of treatment, ex vivo digital autoradiography was performed using [ 11 C]dihydrotetrabenazine ([ 11 C]DTBZ). After 27 weeks of treatment [ 11 C]DTBZ autoradiography demonstrated a significant increase in the striatum-to-cerebellum binding ratio compared with saline treated controls. At the same time point, there was no evident change in motor activity. Increased [ 11 C]DTBZ binding may indicate vesicular monoamine transporter type 2 (VMAT2) function is altered. The lack of extrapyramidal symptoms in animals could be attributed to low dosing regimen or high metabolic rate., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Context: Recreational use of Synthetic Cannabinoid Receptors Agonists (SCRAs) has become increasingly common in many countries and may cause severe toxic effects., Objective: To describe the clinical features of toxicity in seven men after analytically confirmed exposure to MDMB-CHMICA, a recently described indole-based SCRA., Materials and Methods: Clinical information and biological samples (blood, urine) were collected from patients with severe toxicity after suspected use of novel psychoactive substances. Samples were analyzed by data-independent liquid chromatography-tandem mass spectrometry (LC-MS/MS)., Case Reports: All seven cases were men who presented to hospitals in England between July and October 2015; six reported smoking "legal high" products. In all cases, MDMB-CHMICA was identified in blood samples taken on admission to hospital. Other substances were identified in four cases (methadone 1, methiopropamine 1, other SCRAs 2). Clinical features in all seven cases and in the three exposed to MDMB-CHIMICA alone included acidosis (7/7 and 3/3) which was respiratory (3/7 and 3/3), metabolic (3/7 and 0/3) or mixed (1/7, 0/3), reduced level of consciousness (6/7 and 3/3), mydriasis (5/7 and 3/3), tachycardia (5/7 and 2/3), bradycardia (2/7 and 1/3), tonic-clonic convulsions (2/7 and 1/3) and agitation (3/7 and 1/3). Recovery occurred within 24 h in all cases except one male also exposed to methiopropamine., Conclusions: Analytically confirmed exposure to MDMB-CHMICA was associated with acidosis (often of respiratory origin), reduced level of consciousness, mydriasis, heart rate disturbances and convulsions.

Substances of abuse induce alteration in neurobehavioral symptoms, which can lead to simultaneous exacerbation of liver injury. The biochemical changes of liver are significantly observed in the abused group of people using illicit drugs or drugs that are abused. A huge amount of work has been carried out by scientists for validation experiments using animal models to assess hepatotoxicity in cases of drugs of abuse. The risk of hepatotoxicity from these psychostimulants has been determined by different research groups. Hepatotoxicity of these drugs has been recently highlighted and isolated case reports always have been documented in relation to misuse of the drugs. These drugs induce liver toxicity on acute or chronic dose dependent process, which ultimately lead to liver damage, acute fatty infiltration, cholestatic jaundice, liver granulomas, hepatitis, liver cirrhosis etc. Considering the importance of drug-induced hepatotoxicity as a major cause of liver damage, this review emphasizes on various drugs of abuse and addiction which induce hepatotoxicity along with their mechanism of liver damage in clinical aspect as well as in vitro and in vivo approach. However, the mechanisms of drug-induced hepatotoxicity is dependent on reactive metabolite formation via metabolism, modification of covalent bonding between cellular components with drug and its metabolites, reactive oxygen species generation inside and outside of hepatocytes, activation of signal transduction pathways that alter cell death or survival mechanism, and cellular mitochondrial damage, which leads to alteration in ATP generation have been notified here. Moreover, how the cytokines are modulated by these drugs has been mentioned here., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

In recent years, the spread of new psychoactive substances has dramatically increased in term of availability of both number of compounds and chemical families. In November 2012, 4,4'-Dimethylaminorex (4,4'-DMAR), a novel synthetic stimulant, was first detected in the Netherlands. Between June 2013 and June 2014, thirty-one deaths associated with the consumption of this new drug have been registered across Europe. In this MiniReview, we have summarized the chemical, pharmacological and toxicological information about this new legal high., (© 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Health care providers are seeing an increased number of patients under the influence of several new psychoactive drug classes. Synthetic cannabinoids, cathinones, and piperazines are sought by users for their psychoactive effects, perceived safety profile, minimal legal regulations, and lack of detection on routine urine drug screening. However, these drugs are beginning to be recognized by the medical community for their toxic effects. The neuropsychiatric and cardiovascular toxicities are among the most common reasons for emergency medical treatment, which in some cases, can be severe and even life-threatening. Management strategies are often limited to supportive and symptomatic care due to the limited published data on alternative treatment approaches. The purpose of this article is to offer health care providers, emergency medical personnel in particular, an awareness and understanding of the dangers related to some of the new psychoactive drugs of abuse. The background, pharmacology, toxicity, management, detection, and legal status of each class will be discussed., (© The Author(s) 2014.)

Unlabelled: The definition New psychoactive substances (NPS) refers to emerging drugs whose chemical structures are similar to other psychoactive compounds but not identical, representing a "legal" alternative to internationally controlled drugs. There are many categories of NPS, such as synthetic cannabinoids, synthetic cathinones, phenylethylamines, piperazines, ketamine derivatives and tryptamines. Tryptamines are naturally occurring compounds, which can derive from the amino acid tryptophan by several biosynthetic pathways: their structure is a combination of a benzene ring and a pyrrole ring, with the addition of a 2-carbon side chain. Tryptamines include serotonin and melatonin as well as other compounds known for their hallucinogenic properties, such as psilocybin in 'Magic mushrooms' and dimethyltryptamine (DMT) in Ayahuasca brews., Aim: To review the scientific literature regarding tryptamines and their derivatives, providing a summary of all the available information about the structure of these compounds, their effects in relationship with the routes of administration, their pharmacology and toxicity, including articles reporting cases of death related to intake of these substances., Methods: A comprehensive review of the published scientific literature was performed, using also non peer-reviewed information sources, such as books, government publications and drug user web fora., Conclusions: Information from Internet and from published scientific literature, organized in the way we proposed in this review, provides an effective tool for specialists facing the emerging NPS threat to public health and public security, including the personnel working in Emergency Department.

Objectives: The study regards n. 267 drug related deaths submitted to toxicological analyses for forensic purpose, since 2008 to 2012, at the Laboratory of Forensic Toxicology of the Second University of Napoli (SUN), Italy. Among the cases studied (94% males and 6% females) the 13.1% regards foreign citizens., Methods: For each case autopsy findings and all drugs detected were recorded. In addition other epidemiological data such as age, race, gender, place and circumstance of death were also supplied. A systematic toxicological analysis (STA) for illicit drug, other pharmaceuticals, new psychotropic substances and ethanol has been applied on the specimens collected at autopsy and all positive results were confirmed by a quantitative analysis (GC/MS or LC-MS/MS)., Results: Toxicological results shows that simultaneous use of multiple illicit drugs was responsible of the largest mortality rate (57.7%), in both males and females. In the polydrug use the cocaine was the most detected substance. The association of heroin/cocaine was identified in the 22.5% of deaths. The finding of only one drug was correlated with an opiate drug for the 14.2% and with cocaine for the 4.5% of cases. The distribution by age and gender demonstrates an increase in deaths among males aged over 30 years and among women older than 35 years. The territorial distribution of the deaths in the different surrounding areas and in the residential quarters of the Naples city demonstrates that the 76% of deaths occurred in a place different from the usual residence., Conclusion: Results obtained demonstrate that prevails, at present, the need to specifically explore the changing patterns of polydrug use among addicts, because studying the prevalence of mortality subsequent to the consumption of a single illicit drug may be insufficient to guide preventive policies in public health.

Recreational use of the cathinone derivative 3,4-methylenedioxypyrovalerone (MDPV; "bath salts") has increased worldwide in past years, accompanied by accounts of health and legal problems in the popular media and efforts to criminalize possession in numerous jurisdictions. Minimal information exists on the effects of MDPV in laboratory models. This study determined the effects of MDPV, alongside those of the better studied stimulant d-methamphetamine (METH), using rodent models of intravenous self-administration (IVSA), thermoregulation and locomotor activity. Male Wistar rats were trained to self-administer MDPV or METH (0.05 mg/kg/infusion, i.v.) or were prepared with radiotelemetry implants for the assessment of body temperature and activity responses to MDPV or METH (0-5.6 mg/kg s.c.). METH and MDPV were consistently self-administered within 10 training sessions (mg/kg/h; METH Mean = 0.4 and Max = 1.15; MDPV Mean = 0.9 and Max = 5.8). Dose-substitution studies demonstrated that behavior was sensitive to dose for both drugs, but MDPV (0.01-0.50 mg/kg/inf) showed greater potency and efficacy than METH (0.1-0.25 mg/kg/inf). In addition, both MDPV and METH increased locomotor activity at lower doses (0.5-1.0 mg/kg, s.c.) and transiently decreased activity at the highest dose (5.6 mg/kg, s.c.). Body temperature increased monotonically with increasing doses of METH but MDPV had a negligible effect on temperature. Stereotypy was associated with relatively high self-administered cumulative doses of MDPV (∼1.5 mg/kg/h) as well as with non-contingent MDPV administration wherein the intensity and duration of stereotypy increased as MDPV dose increased. Thus, MDPV poses a substantial threat for compulsive use that is potentially greater than that for METH., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Introduction: In recent years, cases of severe adverse effects from recreational use of synthetic cannabinoids (SC) have established that these agents represent a novel toxicologic hazard., Case Report: A 21-year-old male presenting as a vehicular trauma victim was noted with diffuse pulmonary infiltrates related to chronic inhalation of multiple synthetic cannabinoid-containing products. Chest imaging revealed bilateral, subacute lung infiltrates; histopathological analysis of bronchial and alveolar tissues revealed an inflammatory process. An extensive workup failed to identify infectious, malignant, autoimmune, or hematologic causes of the syndrome, and toxicological analysis of the blood and body fluids confirmed the presence of multiple synthetic cannabinoids and metabolites. The patient recovered after an 8-day ICU course, wherein he received antibiotics, steroids, and mechanical ventilation., Discussion: This case contributes to the currently evolving knowledge about SC agents, adding a rarely described pulmonary complication to the growing list of adverse effects associated with these products.

A new illegal psychotropic substance appeared in Hungary during the first months of 2011. Acutely hospitalized patients with psychosis disclosed using a new type of designer drug, previously unknown to clinicians. As the new drug became better known, the cases with acute intoxication were often also transported to toxicology departments. In this study we summarize 5 short case studies that demonstrate the heterogeneous symptoms associated with MDPV abuse, and draw attention to the frequently occurring delusions, and the extended risk of intravenous substance use. Present case studies include patients with and without psychiatric history, regular and occasional users, intravenous and other routes of administration. In the short run antipsychotic therapy reduced the symptoms in all cases, but there is no clear therapeutic guideline for the treatment of patients having psychiatric problems associated with these drugs at the present time. The laboratory examination is unresolved as well. Mephedrone, MDPV and recent drugs have drawn attention to the problem of designer drugs again. This article examines the interaction of drug consumption trends and changes in law, apropos of the presented cases. This information can be helpful for the future treatment of MDPV or other designer drug users. Possible research and therapeutic implications are also discussed.

Little is known about 3,4-methylene-dioxy-pyrovalerone (MDPV), a new designer drug that has become popular in Hungary in the last couple of months. At the same time, its consumption, as a consequence of its low street-price, rises so fast that the event can be considered an epidemic. This paper reviews the chemistry, biochemistry and metabolism of MDPV. Then, on the basis of a few international reports and the author's own clinical observations, it discusses MDPV intoxication and withdrawal. In the metabolism of MDPV, the most important catalyst is the CYP2C19 isoenzyme, but the CYP1A2 and the CYP2D6 isoenzymes also play a crucial role. The formed catechols are conjugated with either glucuronic acid or sulfate. It is important to note that MDPV is consumed either together or in a sequence with other illicit drugs of abuse. As far as it can be established, MDPV use increases the activity and vigilance, decreases appetite and claim to sleep, but it can also provoke cardiac sensations and disturbance of perception. In the course of coming down, withdrawal after MDPV use, bone and muscle pain, hypersomnia, disturbance of vision are experienced, but panic attack may also occur. The appearance of new designer drugs on the market draws attention to a need of paradigm changing in spiritual field. Unless it happens these negative trends likely will speed up.

Background: There has been an increase in the popularity of designer drugs known as "Bath Salts" in the United States. These products commonly contain mephedrone, mephylone, methylenedioxypyrovalerone (MDPV), or other cathinone derivatives with psychoactive properties similar to amphetamine and cocaine. Although recently outlawed, abuse of these products continues to occur in Mississippi., Methods: We report a 19-year-old male who presented with paranoia and auditory as well as visual hallucinations. Auditory effects included voices that prompted him to kill people. The patient displayed anxiety, paranoia, and exhibited repeated bouts of inappropriate laughter. Urine toxicology analysis via GC/ MS detected MDPV, a compound structurally similar to methylenedioxymethamphetamine (MDMA)., Conclusions: Clinicians should be aware that these designer drugs are not detected with common immunoassay drug screens. Symptoms most commonly associated with these substances include tachycardia, delusions, hallucinations, and paranoia. Psychosis, self harm, and death have been associated with some cases.

The numerous premature deaths, medical complications and socio-economic repercussions of drug and alcohol addiction suggest that improvements in treatment strategies for addictive disorders are warranted. The use of pharmacogenetics to predict response to medication, side effects and appropriate dosages is relatively new in the field of drug addiction. However, increasing our understanding of the genetic factors influencing these processes may improve the treatment of addiction in the future. We examined the available scientific literature on pharmacogenetic advancements in the field of drug addiction with a focus on alcohol and tobacco to provide a summary of genes implicated in the effectiveness of pharmacotherapy for addiction. In addition, we reviewed pharmacogenetic research on cocaine and heroin dependence. Thus far, the most promising results were obtained for polymorphisms in the OPRM1 and CYP2A6 genes, which have been effective in predicting clinical response to naltrexone in alcoholism and nicotine replacement therapy in smoking, respectively. Opinions differ as to whether pharmacogenetic testing should be implemented in the clinic at this time because clinical utility and cost-effectiveness require further investigation. However, the data summarized in this review demonstrate that pharmacogenetic factors play a role in response to addiction pharmacotherapy and have the potential to aid in the personalization of addiction treatments. Such data may lead to improved cessation rates by allowing physicians to select medications for individuals based, at least in part, on genetic factors that predispose to treatment success or failure rather than on a trial and error basis., (© 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.)

Based on a 3-year sample of expert opinions concerning the question of complete intoxication (n = 90), methodology and results are presented. Since more than half of the offenders (n = 53) claim amnesia regarding the circumstances of the offence, this subjective amnesia is considered methodologically. If the file contains observations on the offender's behaviour, it is generally possible to assess if the offender was still able to self-reflect and act in a purposeful way. If so, complete intoxication must be negated independent of the objective degree of alcohol or drug intoxication, and the subjective amnesia claimed by the offender is implausible. In the assessment procedure of complete intoxication a decision tree is used. 37/90 offenders showed no significant memory impairment as well as no psychiatric diagnosis, thus excluding both criminal irresponsibility and complete intoxication. The assessment of subjective amnesia and total intoxication was based on the following information from the decision tree: in 51 (47 males, 4 females) of the 53 offenders claiming subjective amnesia the file contained behavioural observations at the time of the offence. Only in two cases, a considerable lack of information prevented a clear decision regarding the question of complete intoxication. Despite the fact that only in about 50% of the offenders claiming subjective amnesia evidence of alcohol or drug influence was demonstrated according to the files, the question of complete intoxication could be successfully evaluated in all but two cases according to the decision tree.

Nutt and colleagues' 'rational' scale to assess the harms of commonly used drugs was based on ratings by a panel of experts. This survey aimed to assess drug users' views of the harms of drugs using the same scale. As users' drug choices are not solely based on harms, we additionally assessed perceived benefits. The survey was hosted at http://www.nationaldrugsurvey.org. UK residents reported their experience of 20 commonly used substances; those with direct experience of a substance rated its physical, dependence-related and social harms as well as benefits. A total of 1501 users completed the survey. There was no correlation between the classification of the 20 drugs under the Misuse of Drugs Act and ranking of harms by users. Despite being unclassified substances, alcohol, solvents and tobacco were rated within the top ten most harmful drugs. There was a remarkably high correlation (r = 0.896) overall between rankings by users' and by experts. Ecstasy, cannabis and LSD were ranked highest by users on both acute and chronic benefits. These findings imply that users are relatively well informed about the harms associated with the drugs they use. They also suggest that the current UK legal classification system is not acting to inform users of the harms of psychoactive substances.

This paper reviews the current use agents influencing the central nervous system. Among them are new synthetic psychoactive drugs, "legal highs" (herbal and synthetic), anabolic steroids, untypical adulterants to classic drugs of abuse, unusual mixtures, dietary supplements, energising drinks and substances similarly acting to alcohol. All these agents were characterized regarding to their acting on human organism, impairing on driving ability and legal regulations that means the Drug Addiction Counteraction Act of 29 July, 2005, the Road Traffic Act of 20 June, 1997 and the Ministry of Health Decree concerning the list of substances acting similarly to alcohol, and the conditions and the methods for carrying out examinations for the presence of these substances in the human body of 11 June 2003. The variety of abused, used and misused agents leads to the application of very sensitive analytical methods of their detection (screening), identification (confirmation) and quantification. Attention has been drawn to some specific difficulties caused currently by the identification of active components of "legal highs" in biological fluids, which influences the diagnosis of poisoning by these substances. The inconsistence of legal regulations allowing for arbitrary interpretation of the results of toxicological analyses concerning even forensic purposes has been critically discussed. It has been proposed that the manner of legal controlling of new psychoactive agents should be changed.

Legal highs offered by online shops and smart shops are blends of natural substances and synthetic additives which have an actual or perceived psychoactive effect which stimulates central nervous system, are supposed to improve mood and alter the perception of reality. Advertisements of these substances tempt potential buyers with a promise of a legal narcotic high, because these substances are not included on the lists of controlled substances. Easy access and the sense of safety make these products the reason of acute toxicity. This article presents the symptomatology of acute legal high toxicity based on the symptoms observed in patients hospitalized at the Department of Toxicology and Internal Diseases in Poznań. Most of the symptoms concerned the central nervous system (mental confusion, hallucinations, agitation, anxiety, phobias, logorrhea, weakness, dizziness and somnolence) and the circulatory system (hypertension, tachycardia, chest pain) and dilated pupils. This article also points out to diagnostic difficulties in cases of acute legal highs toxicity. In none of the cases described was it possible to prove the toxicity by the positive results of toxicological tests, because the methods used in regular clinical practice to test the presence of psychoactive substances do not detect legal highs.

Psychoactive drug use by pregnant women has the potential to effect fetal development; the effects are often thought to be drug-specific and gestational age dependent. This article describes the effects of three drugs with similar molecular targets that involve monoaminergic transmitter systems: cocaine, methamphetamine, and selective serotonin re-uptake inhibitors (SSRIs) used to treat maternal depression during pregnancy. We propose a possible common epigenetic mechanism for their potential effects on the developing child. We suggest that exposure to these substances acts as a stressor that affects fetal programming, disrupts fetal placental monoamine transporter expression and alters neuroendocrine and neurotransmitter system development. We also discuss neurobehavioral techniques that may be useful in the early detection of the effects of in utero drug exposure.

This review summarizes the major metabolic pathways of the drugs of abuse, tetrahydrocannabinol, cocaine, heroin, morphine, and codeine, in humans including the involvement of isoenzymes. This knowledge may be important for predicting their possible interactions with other xenobiotics, understanding pharmaco-/toxicokinetic and pharmacogenetic variations, toxicological risk assessment, developing suitable toxicological analysis procedures, and finally for understanding certain pitfalls in drug testing. The detection times of these drugs and/or their metabolites in biological samples are summarized and the implications of the presented data on the possible interactions of drugs of abuse with other xenobiotics, ie, inhibition or induction of individual polymorphic and nonpolymorphic isoenzymes, discussed.

Benzodiazepines and benzodiazepine-like substances belong to the drugs prescribed and consumed most frequently. While acute toxicity is low in comparison to other hypnotics, physical and psychological dependence can develop during continuous ingestion of these drugs over months. Withdrawal symptoms can therefore develop, if the ingestion of these drugs is stopped abruptly. If a withdrawal of benzodiazepines is considered, this should be discussed in detail with the patient and be performed gradually over months. Faster withdrawals or withdrawal in polytoxicomanic patients should be performed in a specialized unit. After a successful withdrawal, patients should have psychological support in order to prevent relapses.

Administration of drugs of abuse to human volunteers is an important and valuable clinical research procedure. The College on Problems of Drug Dependence recognizes the value and importance of such research and affirms its position that, with proper care, such research can be conducted safely and ethically. This report describes some of the procedures commonly used in human research with drugs of abuse and addresses some of the issues to be considered by researchers and by review committees to insure that such research has an acceptable risk/benefit ratio.

The new cognition-enhancing agent nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide, DM-9384, CAS 77191-36-7) was assessed for dependence liability in rats using the DAF (drug admixed food) method and an intravenous self-administration system. In the physical dependence test, nefiracetam and codeine phosphate were administered to rats mixed with food for 43 days in a gradually increasing dosage schedule, followed by feeding a drug-free normal diet to detect signs of withdrawal. After the withdrawal, rats in the nefiracetam treated groups showed no withdrawal symptoms (e.g. body weight loss) and exhibited greater body weight gains than control. On the other hand, rats in the codeine phosphate treated group showed overt withdrawal symptoms (e. g. soft stool, diarrhea, vocalization) and a significant body weight loss, suggesting development of physical dependence on the drug. It was concluded that nefiracetam did not possess physical dependence liability in rats. In the reinforcement liability test, through an indwelling cannula implanted into the right jugular vein rats were allowed to self-administer nefiracetam, morphine hydrochloride or pentobarbital for 14 days. Saline was administered to negative control animals for the same period. The daily frequency of self-administration increased progressively with time in rats of the morphine hydrochloride and pentobarbital groups. In the nefiracetam groups, it remained comparable to or was even lower than that in the saline control group. When compared with the saline control, the group mean frequency of self-administration showed a tendency to be small for nefiracetam, whereas the morphine hydrochloride and pentobarbital showed greater frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal laboratory studies can provide useful information concerning the potential of drugs for abuse. Over the past 50 years, methods have been developed for use with animal subjects which allow the evaluation of pharmacological properties of drugs which are particularly relevant to their abuse. The methods for preclinical drug abuse liability testing are reviewed under six heading: (1) establishment of the degree of pharmacological equivalence to known drugs of abuse, (2) drug discrimination studies, (3) tests of tolerance and cross-tolerance, (4) tests of physical dependence capacity, (5) drug self-administration tests of reinforcing effects, and (6) evaluation of toxicity and performance impairment at self-administered doses. Preclinical studies can be helpful early in drug development to select lead compounds with low abuse potential for further study. In the case of new or already marketed medications, animal testing can often compliment and extend abuse liability evaluation in human subjects. The results of abuse potential evaluation studies can be useful in making decisions about the possible need for regulation under national and international drug laws, and thus play an important role in drug abuse prevention.

The substitution of either bromazepam, diazepam, methaqualone, mazindol, nortriptyline or bupropion for pentobarbital, in dependent rats, was assessed using a continuous drug infusion method. Male, Sprague-Dawley rats were made dependent on pentobarbital during 12 days of continuous, intraperitoneal, pentobarbital infusion. On Day 13, pentobarbital was replaced with either saline, vehicle, or one of the drugs of interest and rats were infused for 24 h. On Day 14, all rats were infused, for 24 h, with saline. Changes in both body weight and behavioral indices of withdrawal were assessed during Day 13 and 14. It was observed that bromazepam and methaqualone substituted for pentobarbital in a dose-dependent fashion. Diazepam also substituted in pentobarbital dependent rats but, inexplicably, the low dose of diazepam provided better substitution than did the higher dose. On the other hand, neither mazindol or nortriptyline substituted for pentobarbital and there was a tendency for exacerbation of the withdrawal signs. Finally, it was noted that the low dose of bupropion appeared to decrease the severity of the withdrawal symptoms. The data supports the view that the substitution of compounds for pentobarbital, in dependent rats, is limited to those compounds which, presumably, possess similar mechanisms of action in the CNS.

Abuse of medicines and alcohol pose particular problems with those carrying out professional work involving movement (drivers, crane operators etc.). Most accidents are caused by ethyl alcohol, however, other substances cannot be excluded, either. This paper has been aimed at the verification of the efficiency of thin-layer chromatography and tests applied in toxicological analyses of acute poisonings in the detection of lower concentrations of certain addictive medicines. The studies were carried out on biological material (urine) of subjects who had been given, for therapeutic purposes, increased doses of medicines. The group involved 156 patients from I Clinic of Psychiatry, Medical Academy of Lódź, and the Department of Disaccustoming and Psychiatry in Zgierz.