Accuracy of substance exposure history in patients attending emergency departments after substance misuse; a comparison with biological sample analysis.

CONTEXT: Acute toxicity caused by illicit substance use is a common reason for emergency department (ED) presentation. Knowledge of the substances involved is helpful for predicting and managing potential toxicity, but limited information is available about the accuracy of patient-reported substance exposure. This study assessed the accuracy of the history of exposure in those reporting use of a single substance by comparison with those identified by detailed toxicological analysis, focusing on synthetic cannabinoid receptor agonists (SCRA). METHODS: Adults (≥16 years) presenting between March 2015 and July 2021 to participating UK hospitals with toxicity after reporting use of a single illicit substance were included. Exposure details were documented from medical records and blood and/or urine samples analysed using high-resolution accurate mass liquid chromatography-mass spectrometry (HRAM LCMS). Sensitivity, specificity, and positive and negative predictive values of the exposure history were calculated by comparison with biological sample analysis ("gold standard"). RESULTS: Single substance exposure was reported for 474 (median age 33 years, IQR: 18 range 16-75, 80% males) patients. Analysis commonly identified multiple substances (Median 3, IQR 2-5). A history of exposure was documented for 121 of 151 patients where a SCRA or metabolite was detected on analysis (sensitivity 80.1%, 95% CI 72.9, 86.2%). Corresponding proportions were lower for 3,4-methylenedioxymethamphetamine (MDMA, 44/70, 62.9%., 95% CI 50.5%, 74.1%), heroin 41/108 (38.0% 95% CI 28.8-47.8%) and cocaine (22/56, 31.3%, 95% CI 20.9, 43.6%). CONCLUSIONS: Multiple undeclared substances were detected analytically in most patients reporting single substance use. Clinicians should be alert to the potential presence and toxicity of unreported substances when managing patients presenting after substance misuse.

Potential cyanide poisoning reported to the UK national poisons information service: 2008-2019.

INTRODUCTION: Cyanide is a prevalent, lethal chemical. Possible sources of exposure include products of combustion, plant material, industry, chemical warfare and terrorism. METHODS: Retrospective review of UK Poisons Information Database of telephone enquiries to the National Poisons Information Service between 1st January 2008 and 31st December 2019 where cyanide poisoning was considered a possibility. Data extracted included demographics, exposure source, clinical features, Poisoning Severity Score, lactate concentration and antidotes given. RESULTS: A total of 1,252 cases of suspected cyanide poisoning were identified, 239 (19%) involved children under 10 years. The commonest sources of exposure were ingestion of plant material (437 cases; 35%) and smoke inhalation (399; 32%). Smoke inhalation caused the majority of severe and fatal cases (139; 71%). Clinical features associated with fatal outcomes were cardiac arrest (OR 36.4; 95% CI 14.4-92.2), hypotension (15.8; 7.0-35.9), coma (10.8; 5.6-21.0) and lactic acidosis (7.8; 4.1-14.8). 110 patients (9%) were given an antidote and 40 patients (3%) died.Lactate concentrations correlate with Poisoning Severity Score category (r = 0.6, p < 0.0001). Serum lactate <2.0 mmol/L was associated with Poisoning Severity Score None or Minor (sensitivity 76%; specificity 86%) and >11.0 mmol/L was associated with fatal outcome (sensitivity 74%; specificity 80%). 61 cases (5%) had severe carboxyhaemoglobin toxicity (COHb >30%). This was associated with a fatal outcome (OR 7.0; 95% CI 1.5-33.7) and there was positive correlation between carboxyhaemoglobin and Poisoning Severity Score, r = 0.57, p < 0.0001. CONCLUSIONS: Most cases of ingestion of plant material involved children under five years and resulted in no or mild symptoms. In adults smoke inhalation was associated with the most severe poisoning. The lactate cut-off values associated with each severity score calculated in this study are lower than the values used by NPIS on TOXBASE. Analytical conformation of cyanide exposure was unavailable in the majority of case, limiting the strength of these conclusions.

Detection of flubromazolam in patients with suspected non-medical drug use attending emergency departments in the United Kingdom.

INTRODUCTION: Non-medical use of novel benzodiazepines has recently become common. Here, we describe the recent frequent detection of flubromazolam in patients attending United Kingdom emergency departments. METHODS: Adults presenting to participating hospitals with toxicity after suspected drug misuse were studied between March 2015 and January 2021. Clinical features were recorded using consistent methodology and biological samples analysed using liquid chromatography-tandem mass-spectrometry. RESULTS: Flubromazolam and/or its mono-hydroxylated metabolite were detected in samples from 14 of 957 patients, all presenting since July 2020. Reported clinical features included reduced level of consciousness (10), confusion/agitation (6) and acidosis (5) but multiple other substances were detected in all patients. All patients survived to discharge (length of hospital stay 3.0 to 213 h, median 24.1 h). There was no correlation between admission blood/serum flubromazolam concentrations (range 1.7-480.5 ng/ml, median 7.4 ng/ml) and Glasgow Coma Scale or length of hospital stay. In one patient who needed intubation and ventilation for five days, there was an exponential decline in flubromazolam concentrations with time (calculated half-life 39.8 h). Hydroxyl-flubromazolam was also identified at all time points. CONCLUSIONS: Flubromazolam has been detected frequently in drug users presenting to UK emergency departments since July 2020. Prolonged toxicity may occur as a result of the long half-life of flubromazolam and the production of metabolites likely to be active.

A public health based vision for the management and regulation of opioids.

Prohibition of the possession of opioids for non-medical purposes and medical/pharmaceutical commercialization of opioids are important contributors to the current opioid overdose epidemic. A new model of regulation is urgently required. Within the context of a public health framework, we explore supply control, demand reduction, health promotion, and harm reduction and describe an alternative regulatory model that includes access for medical and non-medical purposes. Oversight of this proposed new system would include a control structure with an explicit public health mandate to minimize harms and maximize benefits of opioids. Medical access would be achieved through multi-disciplinary teams who would prescribe a range of opioids for 1) pain, 2) treatment for patients who develop opioid use disorder, and 3) other medical indications. Non-medical access could be achieved through models that would allow adults to purchase and use opioids for either supervised or take-home use. We describe three possible models to support jurisdiction specific discussions around the world. The first includes education and training that could result in certification with a basic or advanced license or a purchase authorization card. The second includes mandatory training that allows general access to opioids, but excludes people with problematic opioid use. The third model has optional training and excludes people with problematic opioid use. Allowing for inclusion of people dependent on the current illegal market during transition is highlighted. With any of these models, this approach, while attending to illegal market drivers, would result in a greatly reduced illegal opioid market and its attendant toxic products, reduced violence and corruption, and at the same time, provide a sharper focus for medical use with more appropriate prescribing and indications.

LSD Overdoses: Three Case Reports.

OBJECTIVE: In academic settings around the world, there is a resurgence of interest in using psychedelic substances for the treatment of addictions, posttraumatic stress disorder, depression, anxiety, and other diagnoses. This case series describes the medical consequences of accidental overdoses in three individuals. METHOD: Case series of information were gathered from interviews, health records, case notes, and collateral reports. RESULTS: The first case report documents significant improvements in mood symptoms, including reductions in mania with psychotic features, following an accidental lysergic acid diethylamide (LSD) overdose, changes that have been sustained for almost 20 years. The second case documents how an accidental overdose of LSD early in the first trimester of pregnancy did not negatively affect the course of the pregnancy or have any obvious teratogenic or other negative developmental effects on the child. The third report indicates that intranasal ingestion of 550 times the normal recreational dosage of LSD was not fatal and had positive effects on pain levels and subsequent morphine withdrawal. CONCLUSIONS: There appear to be unpredictable, positive sequelae that ranged from improvements in mental illness symptoms to reduction in physical pain and morphine withdrawal symptoms. Also, an LSD overdose while in early pregnancy did not appear to cause harm to the fetus.

MDMB-CHMICA: Availability, Patterns of Use, and Toxicity Associated With This Novel Psychoactive Substance.

BACKGROUND: MDMB-CHMICA (methyl 2-[[1-(cyclohexylmethyl)indole-3-carbonyl]amino]-3,3-dimethylbutanoate) is a synthetic cannabinoid receptor agonist that has been detected in several recreational drug products in Europe since August 2014. OBJECTIVES: This article aims to describe the prevalence of use, availability, and desired and adverse effects of MDMB-CHMICA. METHODS: Data were collated from published scientific literature, and systematic searches were conducted of publically available Internet sources (the "gray literature"), including websites offering to sell MDMB-CHMICA and Internet discussion forums featuring user reports. RESULTS: There are two case reports of fatalities in the published literature and one series of analytically confirmed cases of intoxication with MDMB-CHMICA. Seventy-eight websites offered to sell MDMB-CHMICA and a range of quantities were available with discounts for purchase of larger quantities (from 0.25 g at $27.95/g to 100 kg at $1.28/g). We identified 36 reports from MDMB-CHMICA users on Internet discussion forums dated October 2014 onwards. The most common positive effect reported by users was euphoria (11; 30.6%) and almost all reports (33; 91.7%) described one or more adverse effects, most commonly palpitations (11; 30.6%), vomiting (9; 25.0%), loss of consciousness (6; 16.7%), visual hallucinations (6; 16.7%), chest pain (5; 13.9%), and anxiety (5; 13.9%). CONCLUSIONS: This systematic review of qualitative and scientific data relating to MDMB-CHMICA shows that it is widely available from Internet-based suppliers. Users describe a spectrum of effects that are consistent with other synthetic cannabinoids, but there was a high prevalence of adverse effects, and both users and suppliers warn of its high potency.

A Public-Health-Based Vision for the Management and Regulation of Psychedelics.

The Health Officers Council of British Columbia has proposed post-prohibition regulatory models for currently illegal drugs based on public health principles, and this article continues this work by proposing a model for the regulation and management of psychedelics. This article outlines recent research on psychedelic substances and the key determinants of benefit and harm from their use. It then describes a public-health-based model for the regulation of psychedelics, which includes governance, supervision, set and setting controls, youth access, supply control, demand limitation, and evaluation.

Controlling illegal stimulants: a regulated market model.

Prohibition of illegal drugs is a failed social policy and new models of regulation of these substances are needed. This paper explores a proposal for a post-prohibition, public health based model for the regulation of the most problematic drugs, the smokable and injectable stimulants. The literature on stimulant maintenance is explored. Seven foundational principles are suggested that could support this regulatory model of drug control that would reduce both health and social problems related to illegal stimulants. Some details of this model are examined and the paper concludes that drug policies need to be subject to research and based on evidence.

Illicit i.v. drugs. A public health approach.

This article explores, from a public health perspective, the harm done by Canadian drug laws, to both individuals and society. It challenges the perceived dichotomy of legalization and criminalization of intravenous drugs. The article then expands the discussion by exploring eight legal options for illicit drugs and examines how these options interact with the marginalization of users, the illicit drug black market, and levels of drug consumption. While the main focus of this article is intravenous drugs, it draws some lessons from cannabis research.