Impact of intravenous naltrexone on intravenous morphine-induced high, drug liking, and euphoric effects in experienced, nondependent male opioid users

Lynn R. Webster, Franklin K. Johnson, Joseph Stauffer, Beatrice Setnik, Sabrina Ciric

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Background: Opioid analgesics can be abused by crushing followed by solubilization and intravenous injection to attain rapid absorption. Morphine sulfate and naltrexone hydrochloride extended release capsules (EMBEDA®, MS-sNT), indicated for management of chronic, moderate to severe pain, contain pellets of morphine sulfate with a sequestered naltrexone core. Should product tampering by crushing occur, the sequestered naltrexone is intended for release to reduce morphine-induced subjective effects. Objective: This study compared self-reports of high, euphoria, and drugliking effects of intravenous morphine alone versus intravenous morphine combined with naltrexone in a clinical simulation of intravenous abuse of crushed MS-sNT. Methods: This single-center, randomized, double-blind, crossover study characterized subjective effects of naltrexone administered intravenously at the same ratio to morphine present in MS-sNT. Subjects were male and had used prescription opioids five or more times within the previous 12 months to get 'high' but were not physically dependent on opioids. The primary outcome was the response to the Drug Effects Questionnaire (DEQ) question #5, "How high are you now?" (100mm Visual Analog Scale [VAS]). The secondary outcome was the response to a Cole/Addiction Research Center Inventory (ARCI) Stimulation-Euphoria modified scale. Additional outcomes included response to VAS drug liking, the remaining DEQ questions, and pupillometry. Results: Administration of intravenous naltrexone following intravenous morphine diminished mean high (29.8 vs 85.2 mm), Cole/ARCI Stimulation- Euphoria (13.7 vs 27.8 mm), and drug-liking (38.9 vs 81.4 mm) scores (all p < 0.0001) compared with intravenous morphine alone. No serious adverse events occurred as a result of the tested ratio of naltrexone to morphine. Conclusions: Results in this study population suggest that naltrexone added to morphine in the 4% ratio within MS-sNT mitigates the high, euphoria, and drug liking of morphine alone, potentially reducing the attractiveness for product tampering. Assessment of the true clinical significance of these findings will require further study.

Original languageEnglish (US)
Pages (from-to)259-275
Number of pages17
JournalDrugs in R and D
Issue number3
StatePublished - 2011
Externally publishedYes


  • Morphine
  • Naltrexone
  • Opioid-abuse

ASJC Scopus subject areas

  • Pharmacology


Dive into the research topics of 'Impact of intravenous naltrexone on intravenous morphine-induced high, drug liking, and euphoric effects in experienced, nondependent male opioid users'. Together they form a unique fingerprint.

Cite this