Mother's little helper turned a foe: Alprazolam use, misuse, and abuse

Benzodiazepines are effective in managing anxiety and related disorders when used properly (short-term). Their inappropriate use, however, carries significant risks, involving amnesia, rebound insomnia, rebound anxiety, depression, dependence, abuse, addiction, and an intense and exceedingly prolonged withdrawal, among other complications. Benzodiazepines also amplify the effects of opioids and, consequently, have been implicated in approximately 30 % of opioid overdose deaths. Despite their unfavorable profile, sharp increases in medical and non-medical use of benzodiazepines have been steadily reported worldwide. Alprazolam (Xanax®), a potent, short-acting benzodiazepine, is among the most prescribed and abused anxiolytics in the United States. This medication is commonly co-abused with opioids, increasing the likelihood for oversedation, overdose, and death. Notwithstanding these risks, it is surprising that research investigating how benzodiazepines, such as alprazolam, interact with opioids is severely lacking in clinical and preclinical settings. This review therefore aims to present our current knowledge of benzodiazepine use and misuse, with an emphasis on alprazolam when data is available, and particularly in populations at higher risk for developing substance use disorders. Additionally, the potential mechanism(s) surrounding tolerance, dependence and abuse liability are discussed. Despite their popularity, our understanding of how benzodiazepines and opioids interact is less than adequate. Therefore, it is now more important than ever to understand the short- and long-term consequences of benzodiazepine/alprazolam use.