Effects of concurrent intravenous morphine sulfate and naltrexone hydrochloride on end-tidal carbon dioxide

Single-center, placebo-controlled, double-blind crossover study. Non-dependent male opioid users were randomized to receive single IV doses of placebo, 30 mg morphine alone, and 30 mg morphine + 1.2 mg naltrexone. EtCO2 was measured by noninvasive capnography.Significant differences in EtCO2 least-squares means across all treatments for maximal effect (Emax) and area under the effect curve (AUE0-2, AUE0-8, AUE0-24) were detected (all p ≤ 0.0011). EtCO2 Emax values for morphine + naltrexone were significantly reduced vs morphine alone (42.9 mm Hg vs 47.1 mm Hg, p < 0.0001) and were not significantly different vs placebo (41.9 mm Hg). Median time to reach maximal effect (TEmax) was delayed for morphine + naltrexone vs morphine alone (5.0 h vs 1.0 h).Results provide preliminary evidence that the naltrexone:morphine ratio within MS-sNT is sufficient to significantly reduce EtCO2 when administered intravenously to non-dependent male recreational opioid-users. Further studies with multiple measures of respiratory-function are warranted to determine if risk of respiratory depression is also reduced by naltrexone in the tampered formulation.In the United States in 2007, more than one-third (36%) of all poisoning deaths involved opioid analgesics (drugs usually prescribed to relieve pain) [1]. Since 1999, poisoning deaths in the United States involving opioid analgesics have more than tripled [1,2]; deaths from opioid analgesics have surpassed those from heroin and cocaine [3,4].Although prescription opioids may be formulated for oral use, they are often taken intravenously or intranasally when abused [5,6]. As tolerance to opioid psychoactive effects increases with use over time, the user often progresses from the oral route to the intranasal or intravenous (IV) route to attain greater opioid effects and more rapid onset of action [5,7-10].Respiratory depression is the leading cause of death following opioid overdose [11]. Opioids interact with μ-opioid receptors, reducing