Abstract
It is estimated that nearly a third of people who abuse drugs started with prescription opioid medicines. Approximately, 11.5 million Americans used prescription drugs recreationally in 2016, and in 2018, 46,802 Americans died as the result of an opioid overdose, including prescription opioids, heroin, and illicitly manufactured fentanyl (National Institutes on Drug Abuse (2020) Opioid Overdose Crisis. https://www.drugabuse.gov/drugs-abuse/opioids/opioid-overdose-crisis. Accessed 06 June 2020). Yet physicians will continue to prescribe oral opioids for moderate-to-severe pain in the absence of alternative therapeutics, underscoring the importance in understanding how drug choice can influence detrimental outcomes. One of the opioid prescription medications that led to this crisis is oxycodone, where misuse of this drug has been rampant. Being one of the most highly prescribed opioid medications for treating moderate-to-severe pain as reflected in the skyrocketed increase in retail sales of 866% between 1997 and 2007, oxycodone was initially suggested to be less addictive than morphine. The false-claimed non-addictive formulation of oxycodone, OxyContin, further contributed to the opioid crisis. Abuse was often carried out by crushing the pills for immediate burst release, typically by nasal insufflation, or by liquefying the pills for intravenous injection. Here, we review oxycodone pharmacology and abuse liability as well as present the hypothesis that oxycodone may exhibit a unique pharmacology that contributes to its high likability and abuse susceptibility. We will discuss various mechanisms that likely contribute to the high abuse rate of oxycodone including clinical drug likability, pharmacokinetics, pharmacodynamics, differences in its actions within mesolimbic reward circuity compared to other opioids, and the possibility of differential molecular and cellular receptor interactions that contribute to its selective effects. We will also discuss marketing strategies and drug difference that likely contributes to the oxycodone opioid use disorders and addiction.
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Acknowledgements
Tribute to Dr. Gavril Pasternak: Our manuscript is submitted as a part of the Special Issue to honor Dr. Pasternak. In memory of Gavril (Gav) Pasternak who pushed the boundaries of opioid pharmacology and through his research career revealed new insights into the complexity of drug interactions with opioid receptors. It is well acknowledged in clinical practice that there is a lack of complete cross-tolerance between opioid analgesic drugs. While there are likely various explanations for this phenomenon, Gav contributed to the understanding of how different opioid analgesics have unique pharmacological profiles and exhibit synergistic interactions between opioids or when combined with other non-opioid analgesic drugs.
Funding
Financial support is gratefully provided by the Shirley Hatos Neuroscience Research Foundation (CJE, CK, and CMC), National Institutes of Health (NIH) R01DA041781 (CMC), NIH 1UG3TR003148-01 (CMC), NIH 2P50 DA005010 (CMC, CJE, CK), and the Department of Defense W81XWH-15-1-0435 (CMC).
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Kibaly, C., Alderete, J.A., Liu, S.H. et al. Oxycodone in the Opioid Epidemic: High ‘Liking’, ‘Wanting’, and Abuse Liability. Cell Mol Neurobiol 41, 899–926 (2021). https://doi.org/10.1007/s10571-020-01013-y
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DOI: https://doi.org/10.1007/s10571-020-01013-y