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Designer Benzodiazepines
Published in Ornella Corazza, Andres Roman-Urrestarazu, Handbook of Novel Psychoactive Substances, 2018
Peter D. Maskell, Nathan E. Wilson
The demographics of NPS users around the world from surveys suggests that they are generally male (60–80%) with a median age of around 25 years old (Winstock et al., 2017; Soussan & Kjellgren, 2016); females tend to be slightly older (mean ~30 years) than males (mean ~27 years) (Soussan & Kjellgren, 2016). However, the mode for both genders was 18 (Soussan & Kjellgren, 2016; Soussan, Andersson, & Kjellgren, 2018). The high median age is probably due to the wide age range of people taking NPS (18–75 years). Over the past five years, ~30% had used nine or more NPS (Soussan & Kjellgren, 2016). In a study from 2016, etizolam was in the top five most frequently used NPS substances with 76% of users planning on using etizolam again (Soussan & Kjellgren, 2016). Users were also at that time using flubromazepam and diazepam. The users’ main reason for abusing benzodiazepines was ‘coping with life challenges’ and also as a social facilitator (Soussan & Kjellgren, 2016). The true picture of NPS benzodiazepine use and abuse around the world is hard to determine, but it is certainly growing.
Prevalence of Stimulant, Hallucinogen, and Dissociative Substances Detected in Biological Samples of NPS-Intoxicated Patients in Italy
Published in Journal of Psychoactive Drugs, 2021
Pietro Papa, Antonella Valli, Marcello Di Tuccio, Eleonora Buscaglia, Elena Brambilla, Giulia Scaravaggi, Mariapina Gallo, Carlo Alessandro Locatelli
Eleven different dissociative substances (Table 4) were identified in 115 patients (7.9% of total cases, 46.7% of positives). The 73% of users were male and the age of the patients ranged from 14 to 62 years (mean = 24.6). Intoxication by the illegal use of ketamine was diagnosed in 105 patients throughout the considered period. Forty-one times ketamine was the only detected NPS, while in 7 cases methoxetamine, an analogue of ketamine, was present. During the period 2012–2014 methoxetamine was identified in 13 other cases. Methoxyphencyclidine (MeO-PCP) and ethylketamine, analogues of ketamine, were detected in 2 cases, one positive for both substances, the other for MeO-PCP and methoxetamine. From 2013, diphenidine (2 cases) and methoxyphenidine (2 cases) appeared in our casuistry. Indeed, data literature (Wallach et al. 2016) report the presence of these substances as chemical research has been available on the internet since 2013 as a legal replacement for the ketamine analogues banned in some European countries. In 2019, 2 cases of phencyclidine and fluoroketamine, respectively, were observed. With regard to the association with different NPS, ketamine was associate with cathinones, atropine, PMMA, and DOC. The designer benzodiazepine flubromazepam was identified in an intoxication involving methoxphenidine (Valli et al. 2017). GHB was involved in an intoxication case with ketamine. Conventional drugs of abuse were detected in 53 of the ketamine-positive cases (50.1%), distributed as follow: 25.5% phytocannabinoids, 17.3% cocaine, 11.2% amphetamines, and 18.4% ecstasy.
Occurrence and time course of NPS benzodiazepines in Sweden – results from intoxication cases in the STRIDA project
Published in Clinical Toxicology, 2019
Matilda Bäckberg, Madeleine Pettersson Bergstrand, Olof Beck, Anders Helander
Consequently, cases that were only positive for 3-hydroxyphenazepam were considered as 3-hydroxyphenazepam exposure, whereas if phenazepam was also found, a phenazepam exposure was considered, although a co-exposure of both parent compound and metabolite may have been a fully possible scenario. However, the time when the first patients tested positive to 3-hydroxyphenazepam, in the absence of phenazepam, coincided with marketing of 3-hydroxyphenazepam by online suppliers and the first police seizure, where 3-hydroxyphenazepam was the only psychoactive substance identified [6]. Since 3-hydroxyflubromazepam has apparently only been detected as a metabolite of flubromazepam [15] and not sold separately as NPS, cases testing positive only for 3-hydroxyflubromazepam were considered as exposure of flubromazepam. For ketazolam, which was largely fragmented to diazepam in the LC–HRMS method (as also noted before [16]), a sample was only interpreted as ketazolam positive if both ketazolam and diazepam were detected in full scan analysis and the sample was confirmed to contain diazepam by PRM analysis.
Detection of flubromazolam in patients with suspected non-medical drug use attending emergency departments in the United Kingdom
Published in Clinical Toxicology, 2022
Mark Haden, Josephine Cashman, Andrew Ketchin, Rebecca Macfarlane, Shabana Issa, Michael Eddleston, Selina Hines, Simon Hudson, Simon L. Hill, Simon H. L. Thomas
Flubromazolam (8-bromo-6-(2-fluorophenyl)-1-methyl-4H-[1, 2, 4]triazolo-[4,3a] [1, 4]benzodiazepine) is a triazole analogue of flubromazepam structurally related to midazolam and alprazolam (Figure 1). It was patented in 1978 [1], but is not licensed as a medicine anywhere in the world. Non-medical use was first reported in Europe (Sweden) in 2014 and flubromazolam is now a controlled drug in many European countries including the UK [6]. The main feature of flubromazolam toxicity is sedation, which occurs at oral doses less than 0.5 mg and may be protracted [6–8] as a result of prolonged elimination and/or the presence of active metabolites. Hypotonia, amnesia, disorientation, miosis, mydriasis, tachycardia, and bradycardia have also been reported [7,9–12].