Assessing the subjective and physiological effects of intranasally administered crushed extended-release morphine formulations with and without a sequestered naltrexone core in recreational opioid users

To evaluate the pharmacodynamic (PD) effects of morphine sulfate and naltrexone hydrochloride extended-release (MSN) capsules compared with controlled-release morphine sulfate (MS) and placebo when crushed and administered intranasally. The present study was a randomized, double-blinded, placebo-controlled, single-dose (30 mg), three-way crossover study in healthy, nondependent recreational opioid users. PD measures included assessment of subjective drug effects using visual analogue scales (VAS) ranging from 0 to 100 and assessments of pupil diameter. Blood samples were collected for pharmacokinetic analyses. Both MS and MSN showed significantly higher PD values compared with placebo. MSN showed significantly lower scores for drug liking and high VAS scores on both mean peak effect (Emax) (69.6 and 55.2, respectively) and in area under the effect curve over 2 h (86.3 and 66.7, respectively) following dosing compared with MS (Emax 87.6 and 86.6, respectively; area under the curve over 2 h 120.6 and 132.9, respectively; P