INTRODUCTION:New psychoactive substances (NPS) present a unique challenge in clinical, public health and drug-policy contexts. Continued diversity, unknown potency and often unintentional exposure can limit the accuracy of self-reported data. This study examined the accuracy of patient-reported NPS and illicit drug exposure in Australian emergency departments (ED). METHODS:Patient-reported drug exposure, clinical and toxicology data were extracted from the Emerging Drugs Network of Australia Clinical Registry between 1 July 2021 and 30 June 2024 for patients presenting with severe and/or unusual illicit drug toxicity in the ED. Blood samples were analysed using mass spectrometry. Agreement between reported and confirmed exposure was assessed using Cohen's kappa, sensitivity, specificity and likelihood ratios. Logistic regression analysis identified factors associated with discrepancies between reported and confirmed exposures. RESULTS:There were 2044 presentations: 64.6% male, median age 33 years (Q1-Q3, 26-41). Complete agreement between patient-reported and confirmed drug exposures was 14.3% (n = 293). Agreement between reported and confirmed NPS exposure was poor (κ = 0.38). 1522 (74.5%) had more drugs detected than reported. Older age (OR 1.03 [CI 1.02, 1.04]) was associated with higher odds of discrepancy. Attendance from a licensed venue (OR 0.44 [CI 0.28, 0.70]) and Glasgow Coma Scale of 13-15 (OR 0.44 [CI 0.33, 0.57]) were associated with lower odds. DISCUSSION AND CONCLUSIONS:Poor agreement between patient-reported and analytically confirmed drug exposure highlights the need for continued partnerships between EDs, clinical toxicologists, and forensic laboratories to identify substances involved in acute intoxications and support public health and harm reduction responses.

INTRODUCTION:Quantification of risk of seizure from individual illicit substances has traditionally relied on self-reported exposure. This study determined risk of seizure using data from emergency department presentations with analytically confirmed illicit substance exposure. METHODS:Data were extracted from the Emerging Drugs Network of Australia and Emerging Drugs Network of Australia-Victoria illicit substance exposure registries 2020-2025. Cases with analytically confirmed illicit substance exposures were categorised according to reported seizure occurrence. Odds ratios for seizure were calculated for individual drugs using three groups: individual drug including all co-detected substances, individual drug following exclusion of benzodiazepines, anticonvulsants, gabapentinoids, and individual drug following exclusion of benzodiazepines, anticonvulsants, gabapentinoids and gamma-hydroxybutyrate. RESULTS:Seizure occurrence in all cases (n = 6318) was 6.7% (n = 425). Seizure rate increased to 7.1% (n = 196/2748) when patients co-exposed to an anticonvulsant were excluded, and to 8.1% (n = 143/1665) with additional exclusion of gamma-hydroxybutyrate. Significantly increased odds of seizure were found for cocaine (odds ratio 3.8, 95% CI 2.5-5.8, P <0.001), 3,4-methyledioxymetafetamine (odds ratio 2.5, 95% CI 1.5-3.8, P <0.001) and delta-9-tetrahydrocannibinol (odds ratio 2.0, 95% CI 1.3-3.2, P = 0.005). Gamma-hydroxybutyrate positive cases consistently had decreased odds of seizure (odds ratio 0.58, 95% CI 0.4-0.8, P = 0.001). Methamphetamine demonstrated a consistent inverse association for seizure across all analytical groups (odds ratio 0.6-0.7), possibly reflective of high background prevalence and residual low-level detections rather than true pharmacological effect. Although positive, odds ratios for seizure for antihistamine, selective serotonin reuptake inhibitor, and ketamine exposures did not reach significance. CONCLUSIONS:In this cohort of analytically confirmed illicit drug exposures, cocaine, 3,4 methylenedioxymethamphetamine and delta-9 tetrahydrocannabinol were strongly associated with increased odds of seizure. Gamma-hydroxybutyrate was associated with decreased seizure odds. These findings underscore the importance of analytical toxicology surveillance in defining outcomes including seizure risk and informing harm-reduction strategies.

BACKGROUND AND AIM:There is growing evidence of counterfeit benzodiazepine products containing other substances, including non-regulated benzodiazepine-type new psychoactive substances (NPSs). This study sought to compare detections of seized suspect counterfeit alprazolam products with clinical cases that reported use of an alprazolam-containing product to better characterise community use. DESIGN AND SETTING:Observational study set in Victoria, Australia, using data from the Victoria Police Drug Sciences Group (which compiles information about seized drugs submitted for evidential analysis and intelligence purposes) and the Emerging Drugs Network of Australia - Victoria (EDNAV) project (a prospective, observational study collecting clinical and analytical data for illicit drug-related presentations across a network of hospitals in Victoria, Australia). CASES:Police seizures expected to contain alprazolam (March 2020 and August 2022) and EDNAV cases with a reported exposure to an alprazolam-containing product (September 2020 and August 2022). MEASUREMENTS:Descriptive study outlining drug detections in seized tablets and blood samples from EDNAV cases, comparing patterns of detection and changes over time. FINDINGS:A total of 623 police seizures were analysed, most commonly products labelled as 'Xanax®' (n = 266), 'Kalma®' (n = 196) or 'Mylan®' (n = 124). Thirty percent of seizures contained alprazolam only. A benzodiazepine-type NPS was detected in 375 seizures (60.2%). Exposure to non-prescribed alprazolam was reported in 11.2% (n = 125/1112) of EDNAV cases, with 68.8% identifying as male and a median age of 26 years (range 16-68 years). Eighty-seven cases reported the use of 'Xanax®'. Alprazolam was detected in 19 EDNAV cases. A benzodiazepine-type NPS was detected in 78.4% of EDNAV cases. Both datasets saw a shift in detections from etizolam (2020) to clonazolam (2021) and then clobromazolam (2022). CONCLUSIONS:Suspect counterfeit alprazolam products seized by police in Victoria, Australia, in 2020 and 2022 commonly contained other drugs and/or new psychoactive substances, with an apparent limited consumer awareness of the tablet composition.

OBJECTIVES:To describe the frequency, severity, management and complications of guanfacine exposures in paediatric and adolescent patients referred to a state Poisons Information Centre or presenting to two EDs. METHODS:A multicentre, retrospective review of guanfacine exposures from July 2017 to October 2023 in patients aged ≤19 years that were discussed with the Victorian Poisons Information Centre or presented to the Royal Children's Hospital or Austin Health EDs, Melbourne. Demographic, clinical, management and outcome data were examined. RESULTS:There were 275 guanfacine exposures reported to the Poisons Information Centre, with a 16-fold increase in exposures over the study period. Of these, 173 (63%) were unintentional therapeutic errors, the majority (103) involving accidental double-dosing. Twenty-four cases presented to either of the study EDs and 38 cases from other hospitals were discussed with a clinical toxicologist. Of these 62 cases with a medical assessment, 32 reported lone guanfacine exposure. Hypotension, bradycardia and drowsiness were present in 9/32, 17/32 and 13/32 cases, respectively. Five (16%) patients received i.v. fluids. No patients required intubation, inotropic or vasopressor support. One patient who was co-exposed to marijuana required atropine. Prolonged orthostatic hypotension was observed in three of 32 cases, lasting a median of 36 h (range 24-42 h). CONCLUSIONS:Paediatric guanfacine exposures increased significantly over the study period. Isolated guanfacine ingestions were well tolerated, seldom requiring specific intervention. Clinicians need to be cognisant of the risk of prolonged orthostatic hypotension, and this must be excluded prior to discharge.

BACKGROUND:Comprehensive toxicology testing of emergency department (ED) presentations has become a prominent data source on novel psychoactive substances (NPS) in Australia. We describe the type and frequency of analytically confirmed NPS across five Australian states and 28 EDs between 2022 and 2023. METHODS:This is a prospective series of ED presentations with at least one confirmed NPS detection identified by the Emerging Drugs Network of Australia (EDNA) and Emerging Drugs Network of Australia Victoria (EDNAV). De-identified demographic and toxicology data were extracted for analysis. RESULTS:At least one NPS was detected in 646 ED presentations. Total detections was 1044 across 59 different compounds. The median age was 26 years (range 16-90 years) and 464 (71.8 %) were male. Benzodiazepine-type NPS comprised over three-quarters of all NPS positive cases (526, 81.4 %), bromazolam being most frequent (290, 44.9 % total cases). Twenty-four different novel stimulants were detected across 88 (13.6 %) presentations, N,N-dimethylpentylone (52, 8.0 % total cases) the most common. Novel opioids, dissociatives and synthetic cannabinoid receptor agonists made up a small proportion of total NPS positive cases. These findings directly informed nine public health harm reduction communications by multiple state government authorities warning of high-risk NPS detections. Traditional illicit drug co-detections were common (520, 80.5 %), in particular methylamphetamine (404, 62.5 %). CONCLUSION:Drug intelligence data generated in an acute harm setting such as the ED can provide early warning of drugs of concern circulating in the community, including NPS. This facilitates rapid community responses to reduce harm and inform subsequent public health responses.

INTRODUCTION:Nitazenes are a group of potent synthetic opioids that have had increasing prominence as novel psychoactive drugs in the last 5 years. We describe emergency department nitazene-related presentations. METHODS:This is a prospective series of patients with analytically confirmed nitazene presentations identified by the Emerging Drugs Network of Australia and Emerging Drugs Network of Australia Victoria. Both studies' databases were searched between July 2020 and February 2024 with clinical data and blood nitazene concentrations abstracted. RESULTS:There were 32 presentations, 23 (72%) males, with a median age of 31 years (range 18-63 years). Only five (16%) intentionally ingested a nitazene, with most (12, 38%) believing they had taken alternative opioids. Co-exposures occurred in 31 (97%), mostly metamfetamine. Naloxone was administered in 23 (72%) presentations, with a median total dose of intravenous naloxone within 1 h post hospital presentation of 400 μg (interquartile range [IQR] 160-450 μg). Four (13%) received a naloxone infusion. Thirteen (41%) were admitted to the intensive care unit. The median length of stay was 17 h (IQR 7-39 h). Protonitazene was the commonest nitazene detected in 23 (72%) presentations with a median concentration of 2.0 μg/L (range 0.7-15 μg/L). The lowest concentration of protonitazene in a patient that received naloxone was 0.7 μg/L. DISCUSSION AND CONCLUSIONS:Most patients were unaware they were using nitazenes. Given their potency, this has important implications for harm, particularly in those not intentionally using opioids. Nitazene exposure was mostly unintentional. Naloxone use was common and standard dosing regimens appeared effective in most cases.

Hexahydrocannabinol (HHC) is a semi-synthetic hydrogenated derivative of delta-9-tetrahydrocannabinol (THC). HHC emerged within global markets in 2021and has been detected within unregulated cannabis products. A 32-year-old male presented to hospital 1.5 h following ingestion of a single gummy, which had been sold as a THC product. Symptoms included nausea, vomiting, slurred speech, a subjective feeling of whole-body numbness, and an inability to move his head. Examination revealed an apparent dissociative state, sinus tachycardia (118 beats per minute), mydriasis, confusion, and tachypnoea (24 breaths per minute). There was no objective focal neurological deficit. Investigations including haematology and biochemistry were normal. Management was supportive and symptoms resolved within eight hours of ingestion. Serum analysis revealed the HHC isomers 9R-hexahydrocannabinol (9R-HHC) and 9 S-hexahydrocannabinol (9 S-HHC). No other pharmaceutical or psychoactive substance was detected. HHC can be manufactured using cannabidiol as a precursor and can be administered via inhalation, orally and sublingually. The 9R-HHC isomer is the primary psychoactive component. HHC is rapidly absorbed, crosses the blood-brain-barrier and is hepatically metabolised. User reports of HHC adverse effects include anxiety, nausea, and “paralysing effects”. Cases of HHC exposure reported in the literature describe palpitations, chest tightness, ‘respiratory pause’, seizures, dysarthria, dyskinesia, hallucinations, mydriasis, myalgias and acute psychosis. This case of analytically confirmed HHC exposure describes multi-system toxicity including gastrointestinal effects, and dissociative-like neurological effects, and serves as a reminder of the dangers of unregulated products sold within the illicit drug market.

The proliferation of novel psychoactive substances (NPSs) continues to challenge toxicology laboratories. In particular, the United Nations Office on Drugs and Crime considers designer benzodiazepines to be a current primary threat among all NPSs. Herein, we report detection of a new emerging designer benzodiazepine, clobromazolam, using high-resolution mass spectrometry and untargeted data acquisition in combination with a "suspect screening" method built from the crowd-sourced HighResNPS.com database. Our laboratory first detected clobromazolam in emergency department presenting intoxications included within the Emerging Drugs Network of Australia-Victoria project in the state of Victoria, Australia, from April 2022 to March 2023. Clobromazolam was the most frequent designer benzodiazepine detected in this cohort (100/993 cases, 10%). No patients reported intentional administration of clobromazolam, although over half reported exposure to alprazolam, which was detected in only 7% of cases. Polydrug use was prevalent (98%), with phenazepam (45%), methylamphetamine (71%) and other benzodiazepines (60%) most frequently co-detected. This is the first case series published in the literature concerning clobromazolam in clinical patients. The identification of clobromazolam in patients presenting to emergency departments in Victoria demonstrates how high-resolution mass spectrometry coupled with the HighResNPS.com database can be a valuable tool to assist toxicology laboratories in keeping abreast of emerging psychoactive drug use.