Human abuse liability assessment of oxycodone combined with ultra-low-dose naltrexone
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Prescription opioid abuse has risen dramatically in the United States as clinicians have increased opioid prescribing for alleviation of both acute and chronic pain. Opioid analgesics with decreased risk for abuse are needed.
Preclinical and clinical studies have shown that opioids combined with ultra-low-dose naltrexone (NTX) may have increased analgesic potency and have suggested reduced abuse or dependence liability. This study addressed whether addition of ultra-low-dose naltrexone might decrease the abuse liability of oxycodone (OXY) in humans.
Materials and methods
This double-blind, placebo-controlled study systematically examined the subjective and physiological effects of combining oral OXY and ultra-low NTX doses in 14 experienced opioid abusers. Seven acute drug conditions given at least 5 days apart were compared in a within-subject crossover design: placebo, OXY 20 mg, OXY 40 mg, plus each of the active OXY doses combined with 0.0001 and 0.001 mg NTX.
The methods were sensitive to detecting opioid effects on abuse liability indices, with significant differences between all OXY conditions and placebo as well as between 20 and 40 mg OXY doses on positive subjective ratings (e.g., “I feel a good drug effect” or “I like the drug”), on observer- and participant-rated opioid agonist effects, and on a drug-versus-money value rating. There were no significant differences or evident trends associated with the addition of either NTX dose on any abuse liability indices.
The addition of ultra-low-dose NTX to OXY did not decrease abuse liability of acutely administered OXY in experienced opioid abusers.
KeywordsAbuse liability Ultra-low-dose naltrexone Oxytrex OPIOID PTI-801
Pain Therapeutics, Inc. provided medications and funding for this study. Company representatives also reviewed the manuscript prior to submission. The authors have no conflicts of interest relevant to this article. Dr. Lanier is an employee of Rock Creek Pharmaceuticals, Inc. and previously worked at Javelin Pharmaceuticals, Inc. In the past 3 years Dr. Bigelow has received consulting payments from Abbott Laboratories, Takeda Pharmaceuticals, Teva Pharmaceuticals, and Acura Pharmaceuticals, and through his university, has received research support from Titan Pharmaceuticals and Pain Therapeutics (for the present study). In the past 3 years, Dr. Strain has received professional services payments from Abbott Laboratories, Center for Substance Abuse Treatment, Friends Research Institute, Grunenthal USA, Progenics Pharmaceuticals, Reckitt Benckiser Pharmaceuticals, Schering Plough, Shire Pharmaceuticals, The Oak Group, and Titan Pharmaceuticals. The experiments conducted here complied with the laws of the United States. The authors have full control of the primary data and agree to allow the journal to review data if requested. We thank Paul Nuzzo for his invaluable help with statistical analysis. As well, we are indebted to and thank the many research assistants and nursing staff who helped conduct the study, manage the data, and prepare manuscript figures, especially Lilian Salinas.
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