Designer benzodiazepines’ pharmacological effects and potencies: How to find the information

Abstract

Background: Scientific data on the psychopharmacological effects of new psychoactive substances (NPSs) are scarce. Web fora contain a wealth of information posted by users as trip reports (TRs), but the reliability of the reports remains questionable because of the nature of the used molecule and the potential for dose inaccuracies. We focused on the TRs of designer benzodiazepine (DBZD) users since their psychopharmacological effects are similar to prescription benzodiazepines (BZDs). Moreover, the impact of functional groups on the BZD rings with regards to the potency has been fairly/quite studied, allowing structural analysis. Methods: DBZDs offering more than 15 TRs with at least two accounts on experienced effects were included. Data were analyzed with the empirical phenomenological psychological method. Reported effects were analyzed and the pharmacological potencies of DBZDs were compared by calculating a ‘potency score’. Results: In total, 197 TRs for clonazolam, deschloroetizolam, diclazepam, etizolam, flubromazepam, flubromazolam, meclonazepam, metizolam, nifoxipam and pyrazolam were analyzed. Effects similar to prescription BZDs were reported for all the selected DBZDs. Pyrazolam was reported to be the most anxiolytic DBZD, flubromazolam the most hypnotic, etizolam the most euphoric and flubromazolam and clonazolam as the most amnesic DBZDs. Diclazepam and pyrazolam were not reported to induce euphoria. Flubromazepam, flubromazolam, clonazolam and meclonazepam were the most potent and deschloroetizolam, nifoxipam, metizolam and pyrazolam the least potent. The chemical structure of the different DBZDs and the functional groups on the BZD rings confirmed this ranking, except for nifoxipam. Conclusions: When information on NPSs obtained from Internet fora are abundant, it could be considered as an appreciable data source.

Designer drugs: mechanism of action and adverse effects

“…5) have become available, some of which are precursors or metabolites of prescription benzodiazepines and are approved for medical use in other countries (Bäckberg et al 2019;Manchester et al 2018). Effects of designer benzodiazepines reported on internet forums resemble those of prescription benzodiazepines (El Balkhi et al 2020). Chronological overviews of the appearance of benzodiazepine designer drugs on the recreational drug market were recently published (Manchester et al 2018;Moosmann and Auwärter 2018).…”

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

“…Other substances reported more than once were cannabis (3), heroin (3), ketamine (3) and "spice" (3). Larger numbers of substances were identified analytically in samples from these participants including other benzodiazepines (12), opioids (10), cocaine (9), gabapentinoids (7), synthetic cannabinoid receptor agonists ("spice", 5) and ketamine (4, Table 1).…”

“…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][7][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][10][11][12].…”

New psychoactive substances: a review and updates

“…178 Reports on internet forums also suggest that users experience anticonvulsant, muscle relaxant and amnesic properties. 179 Chemical structure. The base structure is the fusion of a benzene ring and a diazepine ring, individual compounds varying widely according to additions to the base structure, for example, 2-keto compounds (diazepam), 3-hydroxy compounds (temazepam), 7-nitro compounds (clonazepam), Triazolo compounds (alprazolam) and Imidazo compounds (midazolam).…”

“…Data on the effects and harms of new synthetic benzodiazepines remains somewhat limited at this time, but early studies have shown anxiolytic, anticancer, anticonvulsant, antipsychotic, muscle relaxant, antituberculosis and antimicrobial actions. 179,185 Adverse effects include a sedative-hypnotic toxidrome and can include confusion, dizziness, drowsiness fatigue, as well as auditory and visual hallucinations, delirium, seizures, deep sleep and coma, 184 and atypical symptoms such as agitation, hyperthermia and tachycardia. 186 Abrupt cessation may lead to withdrawal symptoms, such as anxiety, panic attacks, restlessness, insomnia and convulsions.…”