Impact of intravenous naltrexone on intravenous morphine-induced high, drug
liking, and euphoric effects in experienced, nondependent male opioid users.
Author(s): Webster LR, Johnson FK, Stauffer J, Setnik B, Ciric S.
Affiliation(s): Lifetree Clinical Research, Salt Lake City, UT 84106, USA. LRWebsterMD@gmail.com
Publication date & source: 2011, Drugs R D. , 11(3):259-75
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.