Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (859 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: N-Methylmorphine; N Methylmorphine; Morphinan-6-ol, 7,8-didehydro-4,5-epoxy-3-methoxy-17-methyl-, (5alpha,6alpha)-; Isocodeine; Codeine Phosphate; Ardinex.
Where it fits in the MeSH classification
- Broader topics
- Morphine Derivatives
- Narrower topics
- Hydrocodone; Oxycodone
Related concepts
Research landscape
PubMed indexes 8,404 records tagged with the MeSH heading “Codeine” (counts retrieved 2026-10-31). 1,384 of them (16.5%) were published from 2020 onward, and the busiest period so far is through 1999 with 3,151 records.
Reviews account for 491 records (5.8%) and meta-analyses for 61. Randomized controlled trials number 1,259 (15.0%) as a share of all records on the topic. Randomized trials make up a comparatively large share of this literature, which means many treatment questions have been tested directly.
Show the data
| Period | Records |
|---|---|
| through 1999 | 3,151 |
| 2000-2009 | 1,349 |
| 2010-2019 | 2,520 |
| 2020 onward | 1,384 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 491 | 5.8% |
| Meta-analyses | 61 | 0.7% |
| Randomized controlled trials | 1,259 | 15.0% |
Method: PubMed query "Codeine"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
Safety and efficacy of an oxycodone vaccine: Addressing some of the unique considerations posed by opioid abuse [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Among vaccines aimed at treating substance use disorders, those targeting opioids present several unique medication development challenges.
- Closing excerpt
- These data support further study of OXY-dKLH as a potential treatment for oxycodone abuse and suggest that vaccination might also reduce the severity of oxycodone overdose.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (275 words)
Among vaccines aimed at treating substance use disorders, those targeting opioids present several unique medication development challenges. 1) Opioid overdose is a common complication of abuse, so it is desirable for an opioid vaccine to block the toxic as well as the addictive effects of opioids. 2) It is important that an opioid vaccine not interfere with the action of opioid antagonists used to reverse opioid overdose or treat addiction. 3) Some opioids are immunosuppressive and chronic ongoing opioid use could interfere with vaccine immunogenicity. 4) Although antibody-bound oxycodone is unable to enter the brain because of its size, it might still be able to activate peripheral opioid receptors. To assess vaccine impact on opioid toxicity, rats vaccinated with oxycodone conjugated to keyhole limpet hemocyanin subunit dimer (OXY-dKLH) adsorbed to alum or controls vaccinated with dKLH were compared with regard to oxycodone-induced hotplate analgesia and oxycodone-induced respiratory depression and bradycardia. Vaccination shifted the dose-response curves to the right, representing protection, for each of these endpoints. Naloxone was equally effective in both OXY-dKLH and control groups, providing complete and rapid reversal of respiratory depression. The administration of a long-acting naltrexone formulation during vaccination did not impair vaccine immunogenicity in mice. Similarly, serum anti-oxycodone antibody titers were not altered by continuous morphine infusion during vaccination compared to opioid-naïve controls. Competitive ELISA assay showed negligible or low affinity of immune antiserum for endogenous opioids or opioid antagonists. In vitro receptor binding assays showed that antibody-bound oxycodone does not activate mu opioid receptors. These data support further study of OXY-dKLH as a potential treatment for oxycodone abuse and suggest that vaccination might also reduce the severity of oxycodone overdose.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 29194445 · DOI · PMC5711015
Molecular Adaptations in the Rat Dorsal Striatum and Hippocampus Following Abstinence-Induced Incubation of Drug Seeking After Escalated Oxycodone Self-Administration [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Repeated exposure to the opioid agonist, oxycodone, can lead to addiction.
- Closing excerpt
- Decreases in striatal mu opioid receptor protein expression in the LgA rats may serve as substrates for relapse to drug seeking because these changes occur in rats that showed incubation of oxycodone seeking.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (237 words)
Repeated exposure to the opioid agonist, oxycodone, can lead to addiction. Here, we sought to identify potential neurobiological consequences of withdrawal from escalated and non-escalated oxycodone self-administration in rats. To reach these goals, we used short-access (ShA) (3 h) and long-access (LgA) (9 h) exposure to oxycodone self-administration followed by protracted forced abstinence. After 31 days of withdrawal, we quantified mRNA and protein levels of opioid receptors in the rat dorsal striatum and hippocampus. Rats in the LgA, but not the ShA, group exhibited escalation of oxycodone SA, with distinction of two behavioral phenotypes of relatively lower (LgA-L) and higher (LgA-H) oxycodone takers. Both LgA, but not ShA, phenotypes showed time-dependent increases in oxycodone seeking during the 31 days of forced abstinence. Rats from both LgA-L and LgA-H groups also exhibited decreased levels of striatal mu opioid receptor protein levels in comparison to saline and ShA rats. In contrast, mu opioid receptor mRNA expression was increased in the dorsal striatum of LgA-H rats. Moreover, hippocampal mu and kappa receptor protein levels were both increased in the LgA-H phenotype. Nevertheless, hippocampal mu receptor mRNA levels were decreased in the two LgA groups whereas kappa receptor mRNA expression was decreased in ShA and LgA oxycodone groups. Decreases in striatal mu opioid receptor protein expression in the LgA rats may serve as substrates for relapse to drug seeking because these changes occur in rats that showed incubation of oxycodone seeking.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 30155791 · DOI · PMC6477015
Brain-Derived Extracellular Vesicle microRNA Signatures Associated with In Utero and Postnatal Oxycodone Exposure [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Oxycodone (oxy) is a semi-synthetic opioid commonly used as a pain medication that is also a widely abused prescription drug.
- Closing excerpt
- In summary, our studies identified for the first time, key BDE miRNA signatures in IUO- and PNO-exposed offspring, which could impact their brain development as well as synaptic function.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (199 words)
Oxycodone (oxy) is a semi-synthetic opioid commonly used as a pain medication that is also a widely abused prescription drug. While very limited studies have examined the effect of in utero oxy (IUO) exposure on neurodevelopment, a significant gap in knowledge is the effect of IUO compared with postnatal oxy (PNO) exposure on synaptogenesis-a key process in the formation of synapses during brain development-in the exposed offspring. One relatively unexplored form of cell-cell communication associated with brain development in response to IUO and PNO exposure are extracellular vesicles (EVs). EVs are membrane-bound vesicles that serve as carriers of cargo, such as microRNAs (miRNAs). Using RNA-Seq analysis, we identified distinct brain-derived extracellular vesicle (BDEs) miRNA signatures associated with IUO and PNO exposure, including their gene targets, regulating key functional pathways associated with brain development to be more impacted in the IUO offspring. Further treatment of primary 14-day in vitro (DIV) neurons with IUO BDEs caused a significant reduction in spine density compared to treatment with BDEs from PNO and saline groups. In summary, our studies identified for the first time, key BDE miRNA signatures in IUO- and PNO-exposed offspring, which could impact their brain development as well as synaptic function.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 31861723 · DOI · PMC7016745
Protective Role of Oxycodone in Myocardial Oxidative Stress and Mitochondrial Dysfunction Induced by Ischemia-Reperfusion [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Ischemia-reperfusion (I/R) injury is a significant clinical problem impacting the heart and other organs, such as the kidneys and liver.
- Closing excerpt
- These findings suggest that oxycodone exerts significant protective effects against I/R injury by activating the AMPK pathway, offering new potential therapeutic targets for myocardial protection.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (148 words)
Ischemia-reperfusion (I/R) injury is a significant clinical problem impacting the heart and other organs, such as the kidneys and liver. This study explores the protective effects of oxycodone on myocardial I/R injury and its underlying mechanisms. Using a myocardial I/R model in Sprague-Dawley (SD) rats and an oxygen-glucose deprivation/reoxygenation (OGD/R) model in H9c2 cells, we administered oxycodone and inhibited AMP-activated protein kinase (AMPK) with Compound C (C.C). Our results showed that oxycodone significantly reduced lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) production while stabilizing mitochondrial membrane potential (MMP). Western blot and RT-qPCR analyzes confirmed that oxycodone enhances AMPK phosphorylation and upregulates the expression of Silent Information Regulator 1 (SIRT1) and Peroxisome Proliferator-Activated Receptor γ Coactivator 1α (PGC-1α), thereby protecting myocardial cells. These findings suggest that oxycodone exerts significant protective effects against I/R injury by activating the AMPK pathway, offering new potential therapeutic targets for myocardial protection.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 39865943 · DOI · PMC11837462
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update [5]
- Research article Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype [6]
- Research article Pharmacogenetics and human molecular genetics of opiate and cocaine addictions and their treatments [7]
- Research article Oxycodone [8]
- Research article Respiratory depression and brain hypoxia induced by opioid drugs: Morphine, oxycodone, heroin, and fentanyl [9]
- Research article Single-patient data meta-analysis of 3453 postoperative patients: oral tramadol versus placebo, codeine and combination analgesics [10]
References
- Raleigh MD, Peterson SJ, Laudenbach M, Baruffaldi F, Carroll FI, Comer SD, et al.. Safety and efficacy of an oxycodone vaccine: Addressing some of the unique considerations posed by opioid abuse. . 2017. PMID 29194445 · DOI · PMC5711015
- Blackwood CA, Hoerle R, Leary M, Schroeder J, Job MO, McCoy MT, et al.. Molecular Adaptations in the Rat Dorsal Striatum and Hippocampus Following Abstinence-Induced Incubation of Drug Seeking After Escalated Oxycodone Self-Administration. . 2019. PMID 30155791 · DOI · PMC6477015
- Shahjin F, Guda RS, Schaal VL, Odegaard K, Clark A, Gowen A, et al.. Brain-Derived Extracellular Vesicle microRNA Signatures Associated with In Utero and Postnatal Oxycodone Exposure. . 2019. PMID 31861723 · DOI · PMC7016745
- Jiang Y, He H, Jia X. Protective Role of Oxycodone in Myocardial Oxidative Stress and Mitochondrial Dysfunction Induced by Ischemia-Reperfusion. . 2025. PMID 39865943 · DOI · PMC11837462
- Crews KR, Gaedigk A, Dunnenberger HM, Leeder JS, Klein TE, Caudle KE, et al.. Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin Pharmacol Ther. 2014. PMID 24458010 · DOI · PMC3975212
- Crews KR, Gaedigk A, Dunnenberger HM, Klein TE, Shen DD, Callaghan JT, et al.. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype. Clin Pharmacol Ther. 2012. PMID 22205192 · DOI · PMC3289963
- Kreek MJ, Bart G, Lilly C, LaForge KS, Nielsen DA. Pharmacogenetics and human molecular genetics of opiate and cocaine addictions and their treatments. Pharmacol Rev. 2005. PMID 15734726 · DOI
- Kalso E. Oxycodone. J Pain Symptom Manage. 2005. PMID 15907646 · DOI
- Kiyatkin EA. Respiratory depression and brain hypoxia induced by opioid drugs: Morphine, oxycodone, heroin, and fentanyl. Neuropharmacology. 2019. PMID 30735692 · DOI · PMC6500744
- Moore AR, McQuay JH. Single-patient data meta-analysis of 3453 postoperative patients: oral tramadol versus placebo, codeine and combination analgesics. Pain. 1997. PMID 9085303 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.