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

Pain Med. 2013 Aug;14(8):1173-86. doi: 10.1111/pme.12148. Epub 2013 Jun 7.


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.

Trial registration: NCT01380093.

Keywords: Abuse Potential; Controlled-Release; Morphine; Naltrexone; Opioid; Opioid Antagonist; Pharmacodynamic Effects.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / pharmacokinetics
  • Analgesics, Opioid / pharmacology*
  • Area Under Curve
  • Body Mass Index
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Discrimination, Psychological / drug effects
  • Double-Blind Method
  • Endpoint Determination
  • Ethnic Groups
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Morphine / adverse effects
  • Morphine / pharmacokinetics
  • Morphine / pharmacology*
  • Naltrexone / adverse effects
  • Naltrexone / analogs & derivatives
  • Naltrexone / blood
  • Naltrexone / pharmacokinetics
  • Naltrexone / pharmacology*
  • Narcotic Antagonists / adverse effects
  • Narcotic Antagonists / pharmacokinetics
  • Narcotic Antagonists / pharmacology*
  • Opioid-Related Disorders / metabolism*
  • Pupil / drug effects
  • Tablets
  • Young Adult


  • Analgesics, Opioid
  • Delayed-Action Preparations
  • Narcotic Antagonists
  • Tablets
  • 6 beta-hydroxynaltrexone
  • Naltrexone
  • Morphine

Associated data