Designer benzodiazepines: an update

ABSTRACT

Introduction

Designer benzodiazepines (DBs) are a subclass of novel psychoactive substances (NPS). DBs mimic the properties of approved and prescribed benzodiazepines.

Area covered

A systematic search of literature on DB classification, structure–activity relationships, pharmacologic properties, and adverse effects.

Expert opinion

The prevalence of DB use has increased substantially over the last decade. All DBs are full-agonist ligands at the gamma-aminobutyric acid type A-benzodiazepine (GABA_A-BZ) receptor system. This is not surprising, since DBs largely represent either minor structural modifications, or well-recognized active metabolites, of existing approved benzodiazepines. As such, the pharmacologic profile and associated risks and hazards of DBs are similar or identical to clinically approved and legitimately prescribed benzodiazepines, most of which have been in use for decades. Concurrent use of DBs along with other abusable or recreational drugs (alcohol, opioids, cocaine, stimulants, hallucinogens, other sedative-hypnotics) represents the principal public health risk. The increasing illicit availability and use of DBs is of concern and requires regulatory attention, but DBs do not rank highly among designer psychotropic agents in terms of health risk to humans.

KEYWORDS:

• Designer benzodiazepine (DBs)
• novel psychoactive substances (NPS)
• gamma-aminobutyric acid type A-benzodiazepine (GABA_A-BZ) agonist
• health risks

Article highlights

• Designer benzodiazepines (DBs), defined as benzodiazepine derivatives not approved for clinical use, have received increasing attention as illicit designer drugs having public health risks

• Essentially all DBs are either known endogenous metabolic products of approved and legitimately prescribed benzodiazepines, or minor molecular modifications of approved benzodiazepines

• All DBs are full-agonist ligands at the GABA-benzodiazepine receptor complex, and all have clinical anxiolytic, sedative, and hypnotic properties identical to existing approved benzodiazepines.

• Intrinsic clinical hazards of DBs are identical to those of approved benzodiazepines. The principal risks of DBs are associated with combined use together with more hazardous drug classes such as opioids, alcohol, antidepressants, barbiturates, or other CNS-active drugs.

• DBs rank low among illicit drug classes posing a public health hazard.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.