By Kevin Shanks, D-ABFT-FT
What are Designer Benzodiazepines?
Designer benzodiazepines are substances synthesized to mimic the effects of traditional benzodiazepines, which are commonly prescribed for anxiety, insomnia, and other conditions. Unlike their pharmaceutical counterparts, designer benzodiazepines are often created in clandestine laboratories with the intention of circumventing the controlled substances act and other legal restrictions. These benzodiazepine compounds have similar sedative and anxiolytic effects but may also come with unpredictable purity, potency, and adverse effects mainly due to their unregulated production. Their emergence and proliferation on the illicit market present significant challenges for public health officials, coroners and medical examiners, and law enforcement, as they can lead to substance abuse, pose serious health risks to users, and potentially cause death in overdose.
Benzodiazepines work by affecting the central nervous system, primarily through action via gamma-aminobutyric acid (GABA). GABA is an inhibitory neurotransmitter that helps reduce excitability of neurons and essentially calms the brain’s activity. When the substance binds to the GABA receptor, chloride channels in the receptor open – this allows chloride ions to enter the nerve cell. This influx of chloride ions makes the neuron more negatively charged, which makes it less likely to relay a signal and slows down brain activity, which results in sedative, muscle relaxant, and anxiety reducing effects. While effective for their intended pharmaceutical uses as medications, benzodiazepines can also lead to tolerance, dependence, and withdrawal symptoms if used for prolonged periods or at high doses. Common adverse effects of the use of these compounds include drowsiness, tiredness, sedation, loss of motor coordination, slurred speech, amnesia, and respiratory depression.
Some examples of designer benzodiazepines are:
- Bromazolam – Bromazolam is a drug that has a history in pharmaceutical drug development as it was first synthesized in the 1970s as XLI-268, but it was never approved for medicinal use. The first emergence of bromazolam on the illicit drug market in the United States was in 2019, but it did not become prevalent until more recently. The substance is the brominated analog of alprazolam, meaning it has a bromine atom in the place of the typical chlorine atom. It is not currently considered a controlled substance by the United States Federal government.
- Clonazolam – Clonazolam is a drug that was first reported in 1971 in scientific research, but it did not become a pharmaceutical medication. Reports include strong sedative effects. It has recently been sold online as a novel psychoactive substance and in 2023, it was made a Schedule I controlled substance in the United States by the Federal government.
- Etizolam – Etizolam is a substance that was first patented in 1972, but is currently used as a pharmaceutical medication for the treatment of anxiety and insomnia in Italy and India. It is not authorized for use as a medicine in the United States and was first detected in the States in 2015-2016. It became a Schedule I controlled substance at the Federal level in 2023.
- Flubromazepam – Flubromazepam is a drug that also has a history in pharmaceutical drug development. It was first synthesized in 1960, but it did not receive any further study as a medicine. It appeared on the illicit drug market in 2012, but didn’t gain any traction for several years. Flubromazepam is a fluorinated analog of phenazepam, a benzodiazepine used as a medicine in Russia, meaning it has a fluorine atom in the place of the typical chlorine atom. It is not currently considered a controlled substance by the United States Federal government.
- Gidazepam (Desalkylgidazepam) – Gidazepam is a benzodiazepine used in Russia as a pharmaceutical medication for anxiety and certain cardiovascular disorders such as cardiac arrhythmias. Gidazepam acts as a prodrug and is rapidly metabolized to an active metabolite, desalkylgidazepam, which has a very long half-life (87 hours). Gidazepam is not currently considered a controlled substance by the United States Federal government.
Chemical Structure of the Designer Benzodiazepine Bromazolam Drawn by Kevin G. Shanks (2024)
The most recent data from the Drug Enforcement Administration’s (DEA) National Forensic Laboratory Information System in 2022 showed that the designer benzodiazepines clonazolam (5th), bromazolam (6th), etizolam (8th), flualprazolam (10th), and flubromazepam (14th) were now in the top 15 reported tranquilizers and depressants in the United States. Each of these compounds have been previously implicated in human intoxication cases involving driving motor vehicles as well as being involved in or associated with toxicity leading to fatality.
Because of these trends, Axis recently introduced an all-encompassing Designer Benzodiazepines panel of testing. This panel scope includes adinazolam, bromazolam, clonazolam and metabolite 8-aminoclonazolam, etizolam, flualprazolam, flubromazepam, flubromazolam, gidazepam (as desalkylgidazepam). This streamlined panel allows for easier potential identification of designer benzodiazepines in your medical-legal investigation.
As always, if you have questions about these substances and how they may apply to your toxicology casework or investigation, please reach out to our forensic toxicology experts by email ([email protected]) or phone (317-759-4869, Option 3).