Introduction: The use of novel designer drugs has increased worldwide over the 
years. Etizolam is a designer benzodiazepine (BZD) that has raised concern 
because of its growing non-medical use, liability to tolerance and dependence, 
and related harms. Studies exploring the abuse liability and cognitive effects 
of etizolam outside the therapeutic doses are lacking. Aims: To explore the 
abuse liability of etizolam and the characteristics of patients affected by 
etizolam high-dose dependence in a nationwide tertiary referral addiction unit. 
To document the cognitive changes to etizolam high-dose use. Design and Methods: 
Sociodemographic and clinical data on subjects with etizolam high-dose use were 
retrospectively collected from a database of 1,293 patients consecutively 
admitted to the Addiction Medicine Unit, Verona University Hospital, Italy for 
detoxification from high-dose BZDs or Z-drugs dependence. Thorough 
neuropsychological testing explored the cognitive side effects of high-dose 
etizolam use. Results: We found eleven etizolam high-dose users, of which eight 
used etizolam only, and three used etizolam with other BZDs/zolpidem. All the 
patients were prescribed etizolam for medical reasons, i.e., anxiety and/or 
insomnia. Neuropsychological evaluation showed deficits of working memory, 
visuospatial memory and executive function in a 27-year-old woman who used 
etizolam 15 mg daily. Discussion: Our findings suggest that abuse and dependence 
liability of etizolam should be considered a public health and social problem. 
They offer preliminary evidence on the cognitive side effects of etizolam 
high-dose use. Conclusions: This report offers new information on the potential 
harms of etizolam in patients who are prescribed this drug for medical reasons.