title: Impact of intravenous naltrexone on intravenous morphine-induced high, drug liking, and euphoric effects in experienced, nondependent male opioid users.
abstract: 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 drug-liking 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?" (100 mm 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.
authors: Lifetree Clinical Research, Salt Lake City, UT 84106, USA. LRWebsterMD@gmail.com
authors: Lynn R
authors: LR
authors: Webster
authors: Franklin K
authors: FK
authors: Johnson
authors: Joseph
authors: J
authors: Stauffer
authors: Beatrice
authors: B
authors: Setnik
authors: Sabrina
authors: S
authors: Ciric
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D004347:Drug Interactions; D005059:Euphoria / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D009271:Naltrexone / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D009293:Opioid-Related Disorders / Q000188:drug therapy* / Q000378:metabolism; D010146:Pain / Q000188:drug therapy; D010147:Pain Measurement / Q000187:drug effects; D019966:Substance-Related Disorders / Q000188:drug therapy / Q000378:metabolism; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D004338:Drug Combinations; D009292:Narcotic Antagonists; C550436:morphine, naltrexone combination; D009271:Naltrexone; D009020:Morphine