Benzodiazepines (BDZs) are gamma-amino-butyric acid type A (GABA-A) receptor positive allosteric modulators widely prescribed for anxiety, insomnia and other conditions (1).

The increasing use of novel designer BZD derivatives has been recently reported in countries, where these chemical compounds do not have marketing authorization as medicinal products (2).

Etizolam is a short-acting (half-life 5–7 h) thienodiazepine designer BZD with high affinity for the GABA-A receptor and anxiolytic and sedative properties (3).Buy  Etizolam is currently approved for therapeutic use and marketed in three countries, namely India, Italy and Japan, but available from the Internet for research purposes worldwide (4). The few available comparative studies reported that etizolam may induce less tolerance than lorazepam and may have lesser sedative effects than alprazolam and diazepam (4). The lower allosteric potency at the α1 subunit of the GABA-A receptor has been proposed as one reason for the reduced liability of etizolam to tolerance and dependence (5).

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). Some questions on etizolam side-effects profile are still unanswered. Evidence on etizolam safety is based on preclinical studies and case reports. Common adverse effects of etizolam include drowsiness, sedation and slurred speech, but this drug is considered generally well-tolerated in terms of cognitive side effects (4). The auditory P300 was found to be prolonged with etizolam, but this slowed brain response showed habituation, while attention and memory appeared to be unaffected by etizolam (8). Therapeutic etizolam doses (0.25–1 mg) had no effect on cognition in patients with anxiety (9) and on psychomotor performance and vigilance (10). Cognitive effects to higher doses of etizolam are still unexplored.Buy Etizolam.

High-dose dependence of BZDs or related Z-drugs (e.g., zolpidem, zopiclone, eszopiclone, zaleplon), i.e., daily intake ≥5 times the recommended maximum daily dosage (1) is an emerging substance use disorder estimated to affect 0.16% of the adult population in Switzerland (11), associated to poor quality of life (12), and cognitive dysfunction (13). Data on etizolam high-dose dependence are lacking.Buy Etizolam.