Assessment of pharmacodynamic effects following oral administration of crushed morphine sulfate and naltrexone hydrochloride extended-release capsules compared with crushed morphine sulfate controlled-release tablets and placebo in nondependent recreational opioid users.

OBJECTIVES

To compare the pharmacodynamic effects, including self-reports of "drug liking" and "high," of crushed morphine sulfate and naltrexone hydrochloride extended-release capsules (MSN), crushed morphine sulfate controlled-release (CR) tablets, and placebo in an abuse potential study.

DESIGN

Randomized, double-blind, placebo-controlled, three-way crossover study.

SETTING

Single-center.

SUBJECTS

Nondependent recreational opioid users.

INTERVENTIONS

Orally administered crushed MSN (120-mg morphine sulfate and 4.8-mg naltrexone hydrochloride), crushed 120-mg morphine sulfate CR, and placebo.

OUTCOME MEASURES

Subjective ratings (100-point visual analog scales) of positive drug effects (drug liking, high, good effects, take drug again, and overall drug liking), any effects, and negative effects (bad effects, feel sick, nausea, sleepy, and dizzy), along with pupillometry, pharmacokinetic (PK), and safety assessments.

RESULTS

Crushed morphine sulfate CR significantly increased ratings of all positive subjective measures relative to placebo (P < 0.0001). Crushed MSN significantly decreased all positive subjective ratings compared with morphine sulfate CR (P ≤ 0.005), but significantly increased ratings compared with placebo (P < 0.03). Peak pupil diameter was significantly larger for MSN than morphine sulfate (P < 0.0001). PK analysis of morphine plasma concentrations indicated that Cmax was significantly lower and tmax significantly longer for crushed MSN compared with crushed morphine sulfate CR. Plasma concentrations of naltrexone and 6-β-naltrexol were present following crushed MSN.

CONCLUSIONS

This study demonstrated that when crushed and administered orally to nondependent recreational opioid users, MSN was associated with significantly lower scores on all positive subjective measures including drug liking and high, and significantly less pupil constriction compared with crushed morphine sulfate CR.