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There are concerns regarding the safety profile of this drug combination due to incidents of human misuse\/abuse. In this paper, we discuss the abuse liability of this drug combination based on currently available scientific evidence. We performed an in\u2010depth search of medical and scientific literature and found seven reported cases of human abuse of the TZ combination, two of which resulted in fatal outcomes. In most of these cases, drug administration was intentional indicating that the TZ combination was abused by humans. This finding is bolstered by the results of preclinical studies showing that the TZ combination produces rewarding effects in rats, although manifested only in pretreated subjects. Further studies revealed that the addictive effects of the TZ combination are influenced by pre\u2010exposure to other psychoactive drugs. Pre\u2010exposure to ketamine, diazepam, propofol, or ethanol facilitated the expression of the rewarding effects of the TZ combination. These findings support the hypothesis that the TZ combination was and can be used as a substitute or replacement drug. Altogether, the compiled evidence indicates that the TZ combination can potentially be abused by humans. Thus, careful use, dispensation, and monitoring of the TZ combination and associated substances are strongly advocated. Copyright \u00a9 2016 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/dta.1987","type":"journal-article","created":{"date-parts":[[2016,6,26]],"date-time":"2016-06-26T00:04:33Z","timestamp":1466899473000},"page":"760-767","source":"Crossref","is-referenced-by-count":13,"title":["The abuse liability of the NMDA receptor antagonist\u2010benzodiazepine (tiletamine\u2010zolazepam) combination: evidence from clinical case reports and preclinical studies"],"prefix":"10.1002","volume":"8","author":[{"given":"June Bryan","family":"de la Pe\u00f1a","sequence":"first","affiliation":[{"name":"Uimyung Research Institute for Neuroscience Sahmyook University  815 Hwarang\u2010ro Nowon\u2010gu Seoul 139\u2010742 Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Hoon","family":"Cheong","sequence":"additional","affiliation":[{"name":"Uimyung Research Institute for Neuroscience Sahmyook University  815 Hwarang\u2010ro Nowon\u2010gu Seoul 139\u2010742 Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,6,24]]},"reference":[{"key":"e_1_2_5_2_1","unstructured":"USFDA.Animal drugs at FDA. 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