Prescription ·Strong evidence ·Reviewed May 2026
A potent semi-synthetic opioid analgesic used for the management of moderate to severe pain when non-opioid alternatives are inadequate. Available as immediate-release (often combined with acetaminophen as Percocet) and extended-release (OxyContin) formulations. Due to its high abuse potential, oxycodone is a Schedule II controlled substance.
The bottom line
Evidence rating strong. Most-documented uses: effective relief of moderate to severe pain, available in immediate- and extended-release formulations, multiple combination products available. 10 sources indexed (2006–2022), with 4 interaction records on file.
Core mechanism
Acts as a full agonist at mu-opioid receptors in the central nervous system, with some activity at kappa and delta opioid receptors. Binding to mu receptors in the brain and spinal cord inhibits ascending pain signal transmission, alters pain perception, and produces analgesia. Also activates the descending inhibitory pain pathway and produces euphoria, contributing to abuse potential.8,9
Can be taken with or without food; high-fat meals may increase absorption of extended-release formulation; swallow ER tablets whole
FDA Black Box Warning: Concurrent use of opioids and benzodiazepines can result in profound sedation, respiratory depression, coma, and death. This is one of the most dangerous drug-drug interactions in clinical practice.
Recommendation: Avoid concurrent prescribing whenever possible. If combined, use the lowest doses for the shortest duration. Inform patients about the risk of respiratory depression. Ensure naloxone is available.
Controlled human studies show that THC-dominant cannabis can interact meaningfully with oxycodone. One respiratory study found oxycodone reduced ventilatory response and inhaled THC did not further worsen ventilation in healthy volunteers, but THC slightly increased sedation. Another study found smoked cannabis enhanced analgesia from low-dose oxycodone and increased some oxycodone abuse-liability ratings, which can make extra dosing and impairment more likely.
Recommendation: Avoid combining THC-dominant cannabis with oxycodone unless the prescriber managing your opioid therapy knows. Do not drive, use alcohol, or add other sedatives after using both. Seek emergency help for slow breathing, inability to stay awake, repeated vomiting, confusion, or blue lips.
Alcohol substantially increases the respiratory depression caused by oxycodone. In a controlled human study, oxycodone reduced ventilation and alcohol caused a further drop, with more apneic events. Older adults and people with lung disease or sleep apnea are especially vulnerable.
Recommendation: Do not drink alcohol while taking oxycodone. Avoid driving, sleeping alone after accidental co-use, or taking any extra sedatives. Call emergency services if breathing becomes slow, shallow, noisy, or difficult to wake from.
St. John's Wort can induce CYP3A activity, and oxycodone exposure is clinically sensitive to CYP3A induction and inhibition. Using them together may reduce oxycodone levels and analgesia; stopping St. John's Wort can then raise oxycodone exposure again. This can cause unstable pain control, withdrawal symptoms, or unexpected sedation if oxycodone is adjusted during the interaction.
Recommendation: Avoid starting or stopping St. John's Wort while taking oxycodone unless your prescriber is managing the change. Do not increase oxycodone on your own if pain worsens after adding St. John's Wort. Watch for withdrawal or loss of pain control when starting it, and for sedation or slow breathing after stopping it.
Numbered references. Citations throughout the page link here.
Hou XB, Chen DD, Cheng TF et al.. Meta-analysis of efficacy and safety of sustained release oxycodone hydrochloride rectal administration for moderate to severe pain. PloS one. 2022
Teoh L, McCullough M, Taing MW. Efficacy of oxycodone for postoperative dental pain: A systematic review and meta-analysis. Journal of dentistry. 2022
Lozano-López MT, Gamonal-Limcaoco S, Casado-Espada N et al.. Psychosis after buprenorphine, heroin, methadone, morphine, oxycodone, and tramadol withdrawal: a systematic review. European review for medical and pharmacological sciences. 2021
Zhou J, Wang Y, Jiang G. Oxycodone versus morphine for cancer pain titration: A systematic review and pharmacoeconomic evaluation. PloS one. 2020
Tan HP, Conroy T. The Effectiveness of Intravenous Oxycodone in the Treatment of Acute Postoperative Pain: A Systematic Review. Journal of perianesthesia nursing : official journal of the American Society of PeriAnesthesia Nurses. 2018
King SJ, Reid C, Forbes K et al.. A systematic review of oxycodone in the management of cancer pain. Palliative medicine. 2011
Reid CM, Martin RM, Sterne JA et al.. Oxycodone for cancer-related pain: meta-analysis of randomized controlled trials. Archives of internal medicine. 2006
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