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Synthetic cannabinoid receptor agonists (SCRA) are commonly encountered new psychoactive substances. Here we report the recent detection of ADB-BUTINACA in samples from patients attending United Kingdom emergency departments with toxicity after suspected drug misuse and describe the associated clinical features. Consenting adults (≥16 y) presenting to participating hospitals with toxicity after suspected drug misuse have been included in the Identification Of Novel psychoActive substances (IONA) study since March 2015. Demographic and clinical features are recorded and blood and/or urine samples analysed using high-resolution accurate mass liquid chromatography-mass spectrometry. By December 2021, analytical data were available for 1279 IONA participants and ADB-BUTINACA was detected in at least one sample from 10 (9 males, age range 16–51 median 45 years), all presenting since February 2021. Smoking 'spice' was reported by four patients, two had ingested edible "cannabis" gums and four reported heroin use (2 intravenous, 1 smoked, 1 route not known). Co-use of pregabalin (oral) and crack cocaine (smoked) were also reported. In 3 cases ADB-BUTINACA was the only substance detected, while in seven other substances of misuse were also detected including other SCRA, opioids, benzodiazepines cocaine and pregabalin. Clinical features reported in these 2 groups respectively included reduced level of consciousness (3/3, 6/7), agitation (0/3, 4/7), tachycardia (0/3, 3/7), seizures (1/3, 1/7), hallucinations (1/3, 1/7), hypotension (1/3, 1/7). Metabolic acidosis (1/3, 0/7) and respiratory acidosis (1/3, 0/7), All 10 patients recovered with supportive care, including intubation and ventilation for one case. The median length of hospital stay was 19 h (range 2.6–131 h). ADB-BUTINACA has recently emerged as a drug of misuse in England. Clinical features of toxicity are consistent with those of other SCRA and include reduced level of consciousness, respiratory and/or metabolic acidosis, seizures, confusion and hallucinations. [ABSTRACT FROM AUTHOR]

2,4-Dinitrophenol (DNP) is a highly toxic industrial chemical that is sometimes misused to reduce body fat. Toxicity following ingestion of DNP has recently become more common in the United Kingdom. This research was performed to document the frequency of DNP toxicity as reported to poisons centres in the United States (US) and United Kingdom (UK) and to identify the clinical features associated with fatality. Calls to UK and US poisons centres involving systemic exposure to DNP were extracted for the 12 calendar years 2007-2018. These were analysed using univariate and multivariate statistical techniques. There were 204 cases (n = 86, US; n = 118, UK) of systemic DNP exposure identified, of which 86% were under the age of 40 and 71% were males. Over the study period the incidence of reported DNP toxicity was higher in the United Kingdom than the United States (1.78 vs. 0.26 cases per million population) and annual case numbers have increased in both countries since 2011. Case fatality was high and did not differ significantly between countries (US 11.6%; 95% CI: 6.4–20.1%: UK 16.9%; 95% CI: 11.3–24.7%; X2(1) = 1.12, p = 0.29). Univariate analysis demonstrated significant associations between risk of death and the presence of hypoglycaemia (OR = 17.1, 95% CI 1.7–174.3), hypertonia (OR = 12.9, 95% CI 3.5–47.6), acidosis (OR = 12.5, 95% CI 4.8–32.9), raised lactate (OR = 8.3, 95% CI 2.4–28.4), hyperpyrexia (OR = 6.5, 95% CI 2.8–15.2), tachycardia (OR = 6.4, 95% CI 2.5–16.4), agitation or confusion (OR = 6.0, 95% CI 2.6–13.7), hypertension (OR = 5.6, 95% CI 1.9–16.4) and tachypnoea/dyspnoea (OR = 2.8, 95% CI 1.2–6.1). After backwards stepwise logistic regression, the following were retained as significant independent predictors of mortality: acidosis (OR = 5.4, 95% CI: 1.8 − 16.5), tachycardia (OR = 3.6, 95% CI: 1.2 − 11.0), agitation/confusion (OR = 3.4, 95% CI: 1.2 − 9.7) and hyperpyrexia (OR = 2.8, 95% CI: 1.0 − 7.4). DNP toxicity is uncommonly reported to poisons centres but has recently become more frequent in the United States and United Kingdom. Tachycardia, hyperpyrexia, acidosis, and agitation/confusion are independent risk factors for mortality and their presence should prompt rapid escalation to an intensive care environment for aggressive supportive treatment and monitoring. [ABSTRACT FROM AUTHOR]

Introduction: The emergence of novel psychoactive substances has changed the epidemiology of drugs used recreationally throughout Europe and have posed significant challenges for clinicians, researchers and regulators. Synthetic cannabinoid receptor agonists have made up a large proportion of these novel psychoactive substances. Developed for legitimate scientific research, synthetic cannabinoid receptor agonists are potent agonists at CB1 and CB2 receptors and there have been many case reports of severe or fatal toxicity following their recreational use. At least 180 analytically confirmed compounds belonging to this group of drugs have been reported in Europe as of January 2019. Synthetic cannabinoid receptor agonists have a complex molecular structure, consisting of four pharmacophore components termed the 'core', 'tail', 'linker' and 'linked' groups. This structural complexity offers multiple opportunities for chemical modification to evade drug control legislation based on chemical structure, and this explains the large numbers of individual products that have been detected. Objectives: To discuss the chemical structure of synthetic cannabinoid receptor agonists and to describe the different nomenclature used to identify individual compounds thereby increasing understanding of their chemical heterogenicity and the potential relevance of their molecular structure to the risk of toxicity. Methods: The European Database on New Drugs (EDND) and EMCDDA-Europol annual implementation reports (2010–2017) was searched for compounds with known agonist activity at CB1 and/or CB2 receptors. Information on the different names and chemical structures of each compound was extracted and analysed for patterns. PUBMED, Google Scholar and MEDLINE databases were searched, in addition to non-peer reviewed sources, for data on structure, structure-activity relationships and nomenclatures for each compound. Nomenclature of synthetic cannabinoid receptor agonists: The structural complexity of synthetic cannabinoid receptor agonists presents challenges for nomenclature. There are several nomenclature systems in use. Colloquial and clandestine names: Non-scientific names (e.g. AKB-48, 2NEI, XLR-11) have been used to refer to specific compounds and most have probably been invented by vendors, presumably for the purpose of successful marketing of recreational products, however such names do not convey useful information about structure. Systematic chemical names: Each compound has a systematic chemical name that describes its exact structure; however, it is complex, unwieldy, inaccessible to non-chemists and not suitable for routine communication or clinical use. Serial names: Represent iterative designations assigned to compounds produced as a series in a laboratory (e.g. 'WIN-', 'HU-', 'CP-', 'JWH-' and 'AM-'). This nomenclature does not provide structural information or reflect structural similarities between compounds. Systematic abbreviated names: Succinctly describe each compound utilising structural pharmacophores. The chemical motif in each pharmacophore group is assigned a unique code-letter and assembled into a name with the format of 'Linked Group – TailCoreLinker'. Frequently encountered groups include indole and indazole cores, amino-acid-like like groups, most notably methyl-3,3-dimethylbutanoate (MDMB), methanone linker groups and pentyl, 5-fluoropentyl and 4-fluorobenzyl tails. There has been inconsistent usage of this nomenclature, likely due to a lack of consensus and identification of code-letters for several chemical motifs. Emerging compounds and practices: Tricyclic carbazole and γ-carbolinone core analogues have been identified and may represent the next significant structural analogues to emerge onto the recreational market. There is a need to establish basic pharmacological and toxicological data for these analogues. Conclusions: There is a need for international consensus on the nomenclature used to name synthetic cannabinoid receptor agonists to ensure precise and effective communication between professional groups in the clinic and for the purposes of research and regulation, especially with the emergence of analogues of existing compounds and novel structural motifs. A well-defined nomenclature system also supports quick and accurate communication of the structure-activity of these compounds, potentially highlighting compounds that carry a significant risk of toxicity. [ABSTRACT FROM AUTHOR]

Dear Editor, There have recently been increasing episodes of severe toxicity involving synthetic opioids, especially in North America. While fentanyl and its analogues are commonly involved, there are increasing reports of toxicity from non-fentanyl opioids, including 2-benzylbenzimidazole ("nitazene") compounds, which are structurally unrelated to morphine or fentanyl (Figure 1) [[1]]. Synthesis, chemical characterization, and -opioid receptor activity assessment of the emerging group of "nitazene" 2-benzylbenzimidazole synthetic opioids. [Extracted from the article]

Background. On 3 September 2012, the licensed indication for acetylcysteine was changed in the United Kingdom (UK) so that all patients with a plasma paracetamol concentration above a '100 mg/L' (4 h post ingestion) nomogram treatment line after an acute paracetamol (acetaminophen) overdose should be treated. This is a lower threshold than that used in the United States, Canada, Australia, and New Zealand. Here we report the impact of this change in the UK on the management of patients with acute overdose in different paracetamol concentration ranges. Methods. This is a cohort study, consisting of a retrospective analysis conducted on prospectively collected audit data in three UK hospitals. Following appropriate ethical and data protection authority approval, data for patients presenting within 24 h of an acute timed single paracetamol overdose were extracted. Numbers of admissions and use of antidote in relation to different paracetamol concentration bands (< 100 mg/L; 100-149 mg/L; 150-199 mg/L; and ≥ 200 mg/L at 4 h) were analyzed for one-year periods before and after the change. Results. Comparing the year before with the year after the change, there was no change in the numbers of patients presenting to hospital within 24 h of acute timed paracetamol overdose (1246 before and 1251 after), but more patients were admitted (759 before and 849 after) and treated with acetylcysteine (389 before and 539 after). Of the 150 additional patients treated with acetylcysteine in the year following the change, 114 (76%, 95% CI: 68.4-82.6) were in the 100-149 group and 9 (6.0%, 95% CI: 2.8-11.1) in the 150-199 group. Conclusions. Changes to national guidelines for managing paracetamol poisoning in the UK have increased the numbers of patients with acute overdose treated with acetylcysteine, with most additional treatments occurring in patients in the 100-149 mg/L dose range, a group at low risk of hepatotoxicity and higher risk of adverse reactions. [ABSTRACT FROM AUTHOR]

Background. Although there are extensive systems in place for pharmacovigilance, similar systems for detecting adverse health effects relating to pesticide exposure are rare. In 2004, the National Poisons Information Service (NPIS) pesticide surveillance study was implemented to identify cases requiring health care contact in the UK. This report describes the epidemiology of pesticide exposures reported to poison centres in the UK over a 9-year period. Methods. Data on exposures were gathered through monitoring access to the NPIS's online clinical toxicology database TOXBASE® and through monitoring calls to the four NPIS units (Edinburgh, Cardiff, Newcastle and Birmingham). Severity was judged by both caller and NPIS staff. Results. During the 9 years, 34,092 enquiries concerning pesticides were recorded; 7,804 cases of pesticide exposure were derived from these enquiries. Exposures were predominantly unintentional and acute (6,789; 87.0%); 217 (2.8%) and 755 (9.7%) were chronic unintentional and acute deliberate self-harm exposures, respectively. The majority of cases occurred in children, especially the 0-4 year age group The minimum incidence of pesticide exposure requiring health care contact was 2.0 cases/100,000 population per year. Reported numbers were 6- to 25-fold greater than those picked up through other UK pesticide toxicovigilance schemes. There were 81 cases of severe toxicity and 38 cases of fatal exposure. Deliberate self-harm accounted for 62.3% of severe cases and 79% of deaths. Aluminium phosphide, paraquat, diquat and glyphosate were responsible for most severe and fatal cases. Conclusions. The data gathered from this pesticide surveillance study indicate that poison centre resources can usefully monitor pesticide exposures resulting in health care contact in the UK. The NPIS may usefully be one component of the UK's response to European legislation requiring surveillance of complications resulting from pesticide use. [ABSTRACT FROM AUTHOR]

Objective. To characterise the patterns of presentation, clinical effects and possible harms of acute toxicity following recreational use of alpha methyltryptamine (AMT) in the United Kingdom, as reported by health professionals to the National Poisons Information Service (NPIS) and to compare clinical effects with those reported after mephedrone use. Methods. NPIS telephone enquiries and TOXBASE® user sessions, the NPIS online information database, related to AMT were reviewed from March 2009 to September 2013. Telephone enquiry data were compared with those for mephedrone, the recreational substance most frequently reported to the NPIS, collected over the same period. Results. There were 63 telephone enquiries regarding AMT during the period of study, with no telephone enquiries in 2009 or 2010, 19 in 2011, 35 in 2012 and 9 in 2013 (up to September). Most patients were male (68%) with a median age of 20 years. The route of exposure was ingestion in 55, insufflation in 4 and unknown in 4 cases. Excluding those reporting co-exposures, clinical effects recorded more frequently in AMT ( n = 55) compared with those of mephedrone ( n = 488) users including acute mental health disturbances (66% vs. 32%; Odds Ratio [OR], 4.00; 95% Confidence Intervals [CI], 2.22-7.19), stimulant effects (66% vs. 40%; OR, 2.82; 95% CI 1.57-5.06) and seizures (14% vs. 2%; OR, 9.35; 95% CI 3.26-24.18). Conclusions. Although still infrequent, toxicity following reported exposure to AMT has been encountered in the United Kingdom since January 2011. Stimulant features, acute mental health disturbances and seizures are more frequently reported than in those presenting following reported use of mephedrone. [ABSTRACT FROM AUTHOR]

Background. Attention-deficit/hyperactivity disorder (ADHD) is widespread, with a national (United States) prevalence of nearly 10%. The 2011 changes in the diagnostic criteria will likely further increase the prevalence of this disorder. Little is known about the incidence of toxicity from unintentional poisonings of ADHD medications. This study attempted to determine the incidence of these ingestions and the corresponding financial impact in the United States. Methods. Four geographically different centers were chosen. Subjects with unintentional poisonings due to ADHD medications were included if the admission dates were between 2000 and 2002 (cohort A) or between 2009 and 2010 (cohort B). Using data from the participating hospitals and the number of monitored beds in each corresponding county, data were extrapolated on a national (United States) level. Results. Sixty-three subjects were admitted at four hospitals (18, cohort A and 45, cohort B). The crude incidence rate ratio increased in the later time frame as compared to that in the earlier time frame (incidence rate ratio, 3.13; 95% CI, 1.80-5.68; p < 0.0001). The median (IQR) charges per patient, adjusted for inflation, were $4780 ($3,895-$8,287) and $5912 ($3,432-$9,433) for cohorts A and B, respectively ( p = 0.57). If the subjects in the participating counties were only admitted to the participating hospitals, the annual charges, extrapolated throughout the United States for the two periods, would be $2,419,016 and $8,129,538, respectively. If the subjects were evenly distributed across all pediatric monitored beds in a given county, the annual charges extrapolated throughout the United States for the two periods would be $5,694,232 and $24,126,640, respectively. Conclusion. The incidence of unintentional poisonings from ADHD drugs is increasing and is associated with a significant cost. [ABSTRACT FROM AUTHOR]