Etizolam: A rapid review on pharmacology, non‐medical use and harms

Abstract

Issues. Etizolam is a thienodiazepine derivative, with high affinity for the benzodiazepine site of GABA A receptors. It is often referred to as a new (or novel) psychoactive substance, a 'designer' benzodiazepine or a 'street benzodiazepine'. Increasing reports of non-medical use, identification of etizolam as an ingredient in counterfeit medications and the common identification of etizolam in drug-related deaths, highlight the need for a greater understanding of etizolam. Approach. A rapid narrative review was conducted using PubMed and Google Scholar to synthesise what is known about etizolam to answer two research questions: (i) Does the pharmacological or toxicological profile of etizolam differ from other benzodiazepines?; and (ii) What is the nature and context of non-medical use and harms related to etizolam? Key Findings. Etizolam has a higher potency as an anxiolytic but lower lethality compared with diazepam. Few harms are documented with the therapeutic use of pharmaceutical products. Harms appear to be predominantly related to the use of etizolam in illicitly manufactured pills and occur almost exclusively in the context of mixed-drug toxicity. Conclusion. In therapeutic doses, there is little to suggest that etizolam is more harmful than other benzodiazepines. Most harms with etizolam appear to be related to the wide availability of illicitly manufactured pills, which are taken in unknown doses and combined with other substances. Current harm reduction advice, including avoiding combining opioids and benzodiazepines, remains relevant and increasingly important within an emerging culture of non-medical use. [Nielsen S, McAuley A. Etizolam: A rapid review on pharmacology, non-medical use and harms. Drug Alcohol Rev 2020;39: [330][331][332][333][334][335][336]

Deaths from novel psychoactive substances in England, Wales and Northern Ireland: Evaluating the impact of the UK psychoactive substances act 2016

“…Our analysis also indicates a resurgence in deaths with detections of the NPS benzodiazepines flualprazolam and etizolam. This complements research published by McNamara et al on the increased use of these benzodiazepines in vulnerable populations in Ireland (Mc Namara et al, 2019), a trend which has also emerged on a global scale (Nielsen and McAuley, 2020). The lower number of deaths involving other NPS anxiolytic/sedatives may -like the established stimulants -be a case of anxiolytic/ sedative NPS use being displaced by increasingly available MDA controlled benzodiazepines, such as alprazolam (Hockenhull et al, 2019) and indeed etizolam itself -the latter both prior to and after its control under the MDA in May 2017.…”

High-Dose Dependence and Cognitive Side Effects to Medical Prescription of Etizolam

“…These findings support the conclusion of the recent WHO-ECDD report that abuse/dependence liability of etizolam should be considered as a public health and social problem (4). They are also in keeping with individual users reports on forums like Bluelight.org (20) and Erowid.org (21) that describe tolerance, craving and withdrawal to etizolam (7).…”

“…A consistent increase in the non-medical use and the illicit drug market of etizolam has been reported since 2014, being this drug implicated in several deaths in Scotland, United Kingdom, and to a lesser extent in the United States and Sweden ( 4 , 6 ). A recent review concluded that few harms are documented with the therapeutic use of etizolam, being predominantly related to its non-medical use in illicitly manufactured pills and in the context of mixed-drug toxicity, in particular in combination with opioids ( 7 ). The World Health Organization Expert Committee on Drug Dependence (WHO-ECDD) considered etizolam abuse or dependence liability as an effectively public health and social problem ( 4 ).…”

Invited Commentary: Drug Checking for Novel Insights Into the Unregulated Drug Supply

“…The veterinary anesthetic xylazine is increasingly appearing in overdose fatalities ( 42 , 43 ) and may cause atypical ulcers beyond the injection site ( 44 , 45 ). Phenacetin, caffeine, etizolam, and synthetic cannabinoids are also increasingly used as adulterants ( 46 , 47 ). In North Carolina, we detected niacin (which can cause severe flushing) in heroin-fentanyl samples, revealing that there is much we do not yet understand.…”