@article{ref1,
title="Human abuse potential of an abuse-deterrent (AD), extended-release (ER) morphine product candidate (morphine-ader injection-molded tablets) versus extended-release morphine administered orally in nondependent recreational opioid users",
journal="Pain medicine",
year="2016",
author="Smith, Michael D. and Webster, Lynn R. and Lawler, John and Lindhardt, Karsten and Dayno, Jeffrey M.",
volume="",
number="",
pages="pnw174-pnw174",
abstract="OBJECTIVE. To compare the relative human abuse potential of intact and manipulated morphine abuse-deterrent, extended-release injection-molded tablets (morphine-ADER-IMT) with that of marketed morphine sulfate ER tablets  Methods. This randomized, double-blind, triple-dummy, active- and placebo-controlled, 4-way crossover, single-center study included adult volunteers who were experienced, nondependent, recreational opioid users. Participants were randomized 1:1:1:1 to placebo, morphine-ADER-IMT (60 mg, intact), morphine-ADER-IMT (60 mg, manipulated), and morphine ER (60 mg, manipulated) and received 1 dose of each oral agent in crossover fashion, separated by ≥5 days. Pharmacodynamic and pharmacokinetic endpoints were assessed, including the primary endpoint of peak effect of Drug Liking (E max ) via Drug Liking Visual Analog Scale (VAS) score and the secondary endpoints of time to E max (TE max ) and mean abuse quotient (AQ; a pharmacokinetic parameter associated with drug liking).   Results. Thirty-eight participants completed the study. Median Drug Liking VAS E max was significantly lower after treatment with manipulated morphine-ADER-IMT (67) compared with manipulated morphine ER (74; P  =   0.007). TE max was significantly shorter after treatment with manipulated morphine ER compared with intact ( P  <   0.0001) or manipulated ( P  =   0.004) morphine-ADER-IMT. Mean AQ was lower after treatment with intact (5.7) or manipulated (16.4) morphine-ADER-IMT compared with manipulated morphine ER (45.9).   Conclusions. Manipulated morphine-ADER-IMT demonstrated significantly lower Drug Liking E max compared with manipulated morphine ER when administered orally. Morphine-ADER-IMT would be an important new AD, ER morphine product with lower potential for unintentional misuse by chewing or intentional manipulation for oral abuse than currently available non-AD morphine ER products.<p /> <p>Language: en</p>",
language="en",
issn="1526-2375",
doi="10.1093/pm/pnw174",
url="http://dx.doi.org/10.1093/pm/pnw174"
}