Clinical Update April 2026

Key Messages

• This groundbreaking study from the University of Bath and MANDRAKE provides the first global quantitative analysis of street bromazolam, a potent and unlicensed novel benzodiazepine;

·     Laboratory testing revealed high variability in dosing and frequent visual imitation of legitimate benzodiazepine pharmaceuticals;

·     The rapid surge in bromazolam-related deaths, often involving complex polysubstance use with pregabalin and cocaine, underscores a growing and unpredictable public health challenge;

·     The lack of pharmacological data combined with high volatility in individual dosing endangers vulnerable populations and complicates harm-reduction measures.

Article Summary

This study was conducted by a team from the University of Bath and MANDRAKE, the Manchester Drug Analysis and Knowledge Exchange at Manchester Metropolitan University. The authors conducted quantitative chemical analysis of 47 tablets from 20 batches of novel benzodiazepine bromazolam which had been submitted for testing by drug and alcohol services and UK police forces. After homogenisation, the authors undertook structural analysis with NMR spectroscopy prior to gas chromatography electron ion mass spectrometry, allowing for quantitative determination of the total dose of bromazolam available in each tested batch.

Visually, the appearance of the tablets frequently imitated commercial Xanax (alprazolam) or diazepam tablets, some containing brand information from international pharmaceutical companies. Analysis showed that the median dose of bromazolam per tablet was 0.50 mg, with a range of 0.09 mg to 5.4 mg. Most crucially, dosing differed significantly by batch and between tablets with identical appearances, while one batch was found to be adulterated with a minor quantity of cocaine.

Data were then compared with information on post-mortem records from the UK National Programme on Substance Use Mortality (NPSUM). Detections of bromazolam in post-mortem cases rose from 28 in 2021 to 160 in 2023, while bromazolam was implicated as a causative factor in 328 deaths between 2021 to 2024. Polysubstance use was universal in the sampled population with all deaths having at least one additional illicit or prescribed drug or medication present, and an average of seven per death (most commonly pregabalin, cocaine and diazepam). Use of at least one other benzodiazepine was detected in 64.4% of cases. Between 2021 to 2024 bromazolam rose from being implicated in 7.5% (28 out of 375) of novel benzodiazepine related deaths to being implicated in 73.5% (75 out of 102).

Commentary

Until recently, the illicit benzodiazepine market largely consisted of diverted prescription diazepam (Valium), alprazolam (Xanax) and temazepam (Restoril). The landscape has now changed, with the European Monitoring Centre for Drugs and Drug Addiction now monitoring 36 novel benzodiazepines. Among these, bromazolam is a potent novel benzodiazepine that has not been licensed for medical use in any territory. Owing to the lack of clinical testing, we currently have little information regarding safe dose, onset or duration of action, toxicity profile or the nature or likelihood of adverse effects. The unknown pharmacodynamic and kinetic profile suggests that bromazolam use presents considerably higher risk than illicit use of diverted medicines.

Preliminary dosage information presented on a popular harm-reduction website called “TripSit” indicates that 0.5 – 1 mg bromazolam should be considered light dosage, 1 – 2 mg medium and 2 – 4 mg strong dosage (2), however this has not been verified by clinical trials and there is no evidence basis other than self-reporting by users. A number of batches tested during the course of this study contained higher than the maximum TripSit “strong” dose, and we must conclude that it is significantly harder to minimise the risks to users when there is such clear variability of dosing during clandestine production. The great range seen even between tablets of identical appearance further highlights the dangers presented by novel benzodiazepine usage, as does the inclusion of trace elements of other illicit drugs within the sample.

Why Is This Important?

Gardner et al. present an invaluable contribution to our understanding of trends in novel benzodiazepine use and their study does much to shine light on this neglected area. This study represents the first quantitative analysis of “street” bromazolam globally and, as can be seen from the trend data from NPSUM, it could not come too soon. While bromazolam use remains a smaller portion of the overall market, the risks are concentrated among highly vulnerable polysubstance-using populations. The primary challenge is the drug’s unpredictable quality and as yet unknown safety profile. Gardner et al. have undoubtedly done much to elucidate this difficult and challenging topic, and they provide a necessary foundation for future clinical and policy responses.

References