generation run 2026-04-24
66 min completedmodel pipeline-v5plan not recordedrun/43e7fbf3…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- low_confidence_taper
- case_report_generalizability
Reproduce
- inputs
- 39 source keys (listed under Sources)
- plan
- not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
- model
- pipeline-v5
- streams
- none — agent transcripts are persisted from 2026-09 onward
22 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | codeine related deaths forensic CYP2D6 genotype morphine | 6 | 2 | Forensic toxicology data, lethal concentration thresholds |
| 2 | PubMed | codeine abuse purple drank lean recreational use | 2 | 2 | Cultural context, street use, and epidemiology of recreational codeine |
| 3 | PubChem | codeine | 1 | 1 | Primary chemical identity verification |
| 4 | PubMed | codeine pharmacology opioid receptor binding affinity Ki | 4 | 3 | Primary receptor binding affinity data for codeine |
| 5 | PubMed | codeine CYP2D6 ultrarapid metabolizer toxicity death | 1 | 1 | Safety-critical CYP2D6 ultrarapid metabolizer case |
| 6 | WebSearch | codeine legal status scheduling DEA Schedule III UK Canada Australia 2026 | 10 | 2 | Legal scheduling status across major jurisdictions |
| 7 | PubMed | codeine antitussive cough suppression mechanism | 8 | 3 | Antitussive mechanism data |
| 8 | WebSearch | codeine discovery history Pierre-Jean Robiquet 1832 opium alkaloid isolation | 10 | 2 | Historical discovery narrative not available in PubMed |
| 9 | PubMed | codeine pharmacokinetics bioavailability metabolism CYP2D6 | 10 | 2 | Key PK and bioavailability data |
| 10 | PubMed | codeine half-life plasma protein binding pharmacokinetics human oral | 3 | 1 | Key PK parameters: Tmax, half-life, protein binding |
| 11 | OpenAlex | codeine Australia rescheduling over-the-counter 2018 pharmacist | 8 | 3 | Australia rescheduling evidence; promethazine+codeine interaction in purple drank |
| 12 | PubMed | PMID 32200566 | 1 | 1 | Confirms Australia 2018 rescheduling date and impact |
| 13 | PubMed | codeine clinical pharmacology analgesic antitussive mechanism | 5 | 2 | Comprehensive pharmacological review data; historical WHO documentation |
| 14 | WebSearch | codeine equianalgesic morphine 10:1 ratio bioavailability oral | 10 | 2 | Equianalgesic conversion data needed for pharmacology section |
| 15 | WebSearch | codeine Canada CDSA controlled drug schedule | 10 | 1 | Canada scheduling confirmed |
| 16 | PubMed | PMID 22492761 | 1 | 1 | Landmark pediatric safety paper driving FDA black box warning for codeine in children |
| 17 | WebSearch | codeine melting point solubility water physical properties CAS 76-57-3 | 10 | 2 | Physical property data not available from PubMed API |
| 18 | WebSearch | codeine UK Misuse of Drugs Act Schedule 5 Class B legal status prescription | 10 | 2 | UK scheduling confirmed |
| 19 | PubMed | PMID 4972938 codeine WHO review | 1 | 1 | Foundational historical WHO pharmacological review of codeine |
| 20 | PubChem REST API | CID 5284371 properties JSON | 1 | 1 | Chemical identity verification for brief data gaps (SMILES, InChIKey, CID) |
| 21 | Multiple | Codeine interaction ratings: tramadol lethal, ketamine lethal - verify | 4 | 2 | Safety-critical interaction rating verification |
| 22 | Multiple | Codeine pharmacological class verification - kappa vs mu receptor agonist | 3 | 3 | Flagging database error in pharmacological classification |
96 claims by section — every cited sentence, checked against its source
safety30 · 20 ok
Claim in safety — inconclusiveinconclusiveworking →
Morphine-to-codeine ratios were highly variable even when CYP2D6 genotype was known, indicating that genotype alone cannot reliably predict morphine levels in overdose.supported
High variability in morphine:codeine ratios even with CYP2D6 genotyping. j.forsciint.2012.01.019
Codeine produces less respiratory depression than morphine at clinically equivalent analgesic doses in humans, though it is paradoxically more toxic in some animal models due to convulsant properties.supported
Codeine more toxic to animals (convulsant) but less toxic to man than morphine (less respiratory depression). pmid:4972938
Three fatal or life-threatening cases in children post-adenotonsillectomy were linked to CYP2D6 gene duplications (ultrarapid metabolizer status).supported
3 additional fatal or life-threatening codeine cases in children post-adenotonsillectomy; CYP2D6 functional gene duplications caused excessive morphine production. peds.2011-2538
Claim in safety — inconclusiveinconclusiveworking →
CYP2D6 phenotype is independently associated with adverse opioid outcomes in clinical populations.supported
CYP2D6 phenotype affects opioid response in both poor and ultrarapid metabolizers. Clinical outcomes data in primary care population. pgpm.s136341
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Forensic case series document codeine in the context of designer benzodiazepines, other opioids, and alcoholsupported
Fatal polysubstance case with codeine 0.23 mg/L, morphine 0.13 mg/L, thebaine 0.81 mg/L, and designer benzodiazepines. bkac098
A validated LC-MS method enables simultaneous quantification of codeine, C6G, norcodeine, morphine, M3G, and M6G in postmortem tissues.supported
Validated forensic method for codeine and metabolite quantification in postmortem tissues. bku145
Claim in safety — inconclusiveinconclusiveworking →
OTC codeine misuse has been documented across multiple countries and frequently involves patients who initially used codeine for legitimate pain management before developing dose escalation and compulsive redosing patternssupported
Survey of customers purchasing OTC codeine in Ireland, South Africa, England. Explores misuse, knowledge gaps, and perception of risk. jpps30049
OTC codeine misuse has been documented across multiple countries and frequently involves patients who initially used codeine for legitimate pain management before developing dose escalation and compulsive redosing patternssupported
OTC codeine misuse and dependence in Croatia pharmacists. Misuse and dependence potential of low-dose codeine products raises public health concerns. s12888-025-06881-6
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Physical and psychological dependence are both moderate — significantly less intense than morphine dependencesupported
Tolerance and dependence less frequent than morphine; less intense abstinence syndrome. pmid:4972938
The OTC codeine dependence burden is nonetheless substantial: codeine is the most commonly misused OTC medicine globally.partially supported
OTC medicine misuse systematic review; codeine is among the most commonly misused OTC medicines globally. s40545-021-00350-7
Codeine withdrawal is generally milder and shorter than morphine withdrawal, consistent with codeine's lower potency.supported
Tolerance and dependence less frequent than morphine; less intense abstinence syndrome. pmid:4972938
A published case report describes successful buprenorphine induction 23.5 hours after the last codeine dose, with an 18-day gradual taper producing only mild withdrawal symptoms.supported
High-dose codeine dependence case; buprenorphine induction after 23.5 hours post-last dose; 18-day taper with mild withdrawal symptoms. bcr-2025-268674
This mechanism is documented in forensic fatality series involving opioids with alcohol, benzodiazepines, and other sedatives.supported
Concurrent use of CNS depressants (benzodiazepines, codeine, ethanol) critical risk factor in methadone-related fatalities. j.forsciint.2015.01.004
Polydrug use involving alcohol and opioids is among the most common patterns in opioid-related fatalities.supported
Concurrent use of CNS depressants (benzodiazepines, codeine, ethanol) critical risk factor in methadone-related fatalities. Drug-drug interactions more important than tolerance reduction. j.forsciint.2015.01.004
Promethazine abuse in this context is independently associated with drug-related fatalities.supported
EMA data on promethazine misuse; often co-abused with opioids (codeine) in 'purple drank' preparations. Associated with drug-related fatalities. 0269881120959615
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
MAOIs: Serotonin syndrome risk is documented for opioids with serotonergic properties combined with monoamine oxidase inhibitors.supported
Codeine is listed among morphine analogues with serotonergic effects. In combination with serotonergic drugs (MAOIs, antidepressants), may provoke serotonin syndrome. s00482-015-1512-0
Claim in safety — inconclusiveinconclusiveworking →
Children under 12 years (any indication) — FDA black box warning based on CYP2D6-related pediatric fatalitiessupported
3 additional fatal or life-threatening codeine cases in children post-adenotonsillectomy; CYP2D6 functional gene duplications caused excessive morphine production. Demonstrated CYP2D6-dependent danger in pediatric opioid analgesia. peds.2011-2538
Post-tonsillectomy/adenoidectomy (any age) — airway vulnerability combined with unpredictable CYP2D6 metabolism creates unacceptable risksupported
3 additional fatal or life-threatening codeine cases in children post-adenotonsillectomy; CYP2D6 functional gene duplications caused excessive morphine production. peds.2011-2538
Post-tonsillectomy/adenoidectomy (any age) — airway vulnerability combined with unpredictable CYP2D6 metabolism creates unacceptable risksupported
Kaiser Permanente restricted codeine for children <7 years old following respiratory failure and death cases. 0194599815627810
Breastfeeding: FDA advisory (disputed — Zipursky & Juurlink 2020 argue the risk is implausible)supported
Reexamines the 'Toronto case' of infant death linked to maternal codeine/CYP2D6 ultrarapid metabolizer status. Argues the causal link is implausible. cpt.1882
pharmacology13 · 10 ok
Its direct affinity for opioid receptors is weak (Ki >100 nM at human mu-opioid receptor; Ki ~0.3 µmol/L at guinea pig cortical MOR), approximately 100–250× lower than morphine (Ki ~1.2 nM)supported
Experiments to obtain Ki values for 19 approved opioid drugs using a single binding assay in a cell membrane preparation expressing recombinant human MOR. Codeine Ki > 100 nM. j.yrtph.2010.12.007
Its direct affinity for opioid receptors is weak (Ki >100 nM at human mu-opioid receptor; Ki ~0.3 µmol/L at guinea pig cortical MOR), approximately 100–250× lower than morphine (Ki ~1.2 nM)supported
Codeine Ki at mu receptor ~0.3 micromol/L; at delta receptor ~5.9 micromol/L; at kappa receptor ~14 micromol/L. pmid:12420793
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
The pharmacological activity of codeine is predominantly mediated through its active metabolite morphine, produced by hepatic CYP2D6-catalyzed O-demethylation of the 3-methoxy group.partially supported
Codeine activity is not only via morphine conversion but also by codeine itself and metabolites norcodeine and codeine-6-glucuronide. pmid:25720726
Claim in pharmacology — inconclusiveinconclusiveworking →
Codeine itself, norcodeine, and C6G may contribute modest opioid activity independent of morphine conversion, though this contribution is pharmacologically minor at therapeutic doses.supported
Codeine activity is not only via morphine conversion but also by codeine itself and metabolites norcodeine and codeine-6-glucuronide. pmid:25720726
Intra-arterial (brainstem) administration suppresses cough, while spinal intrathecal administration does not — localizing the antitussive site to brainstem mu-opioid receptorssupported
Antitussive effect of codeine is brainstem-restricted, not spinal. Intra-arterial codeine suppresses cough; intrathecal does not. fphys.2021.640682
Intra-arterial (brainstem) administration suppresses cough, while spinal intrathecal administration does not — localizing the antitussive site to brainstem mu-opioid receptorssupported
Naloxone pretreatment abolishes codeine's cough-suppressive effects, confirming mu-opioid mechanism in antitussive action. Brainstem-restricted effect. 978-94-007-4549-0_9
Naloxone pretreatment completely abolishes codeine's antitussive effect, confirming the mu-opioid mechanism.supported
Naloxone pretreatment abolishes codeine's cough-suppressive effects, confirming mu-opioid mechanism in antitussive action. 978-94-007-4549-0_9
Opioid receptor agonism in the enteric nervous system reduces gastrointestinal motility, causing constipation and slowed intestinal transit — a peripheral opioid effect that is clinically prominent even at therapeutic doses.supported
Effects: analgesia, euphoria, sedation, respiratory depression, constipation, decreased GI motility. j.sjpain.2016.02.003
Codeine is classified as BCS Class I (high solubility, high permeability), with >90% of an oral dose absorbed from the gastrointestinal tractsupported
Codeine fraction absorbed >90% orally. Meets 'highly soluble' criteria. Class 1 BCS drug. jps.23977
Hepatic extraction is high, with clearance approximating hepatic blood flowsupported
High hepatic extraction drug. pmid:8227477
summary12 · 7 ok
Oral duration is 3–6 hours, with an elimination half-life of approximately 2.8 hours.supported
After 60mg oral codeine: Tmax 1.4h (healthy), Cmax 225 ng/mL, t1/2 2.8h, plasma protein binding ~30%. High hepatic extraction drug. pmid:8227477
Fatal pediatric cases in CYP2D6 ultrarapid metabolizers prompted an FDA black box warning in 2013, and Australia rescheduled codeine to prescription-only in 2018partially supported
3 additional fatal or life-threatening codeine cases in children post-adenotonsillectomy; CYP2D6 functional gene duplications caused excessive morphine production. peds.2011-2538
Fatal pediatric cases in CYP2D6 ultrarapid metabolizers prompted an FDA black box warning in 2013, and Australia rescheduled codeine to prescription-only in 2018partially supported
Australia rescheduled codeine to prescription-only in February 2018. Followed by increased sales of paracetamol, ibuprofen, and combination products. mja2.50552
The largest prospective trial examining CYP2D6 genotype and codeine analgesia (987 adults) was published in 2025.supported
987-patient prospective trial of paracetamol-codeine after day surgery; investigates CYP2D6 genotype effect on analgesic efficacy and adverse effects. aas.14549
Codeine binds weakly to mu-opioid receptors (Ki >100 nM at human MOR, approximately 100–250× lower affinity than morphine at Ki ~1.2 nM)supported
Experiments to obtain Ki values for 19 approved opioid drugs using a single binding assay in a cell membrane preparation expressing recombinant human MOR. Codeine Ki > 100 nM. j.yrtph.2010.12.007
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Acute overdose risk is moderate: forensic toxicology thresholds place toxicity at blood concentrations of 0.3 mg/L and potentially lethal concentrations at 1.6 mg/Lsupported
TIAFT toxicity threshold 0.3 mg/L; lethal threshold 1.6 mg/L. j.forsciint.2012.01.019
Claim in summary — inconclusiveinconclusiveworking →
Physical and psychological dependence are moderate, developing through mu-opioid receptor downregulation with repeated use; withdrawal is milder and shorter than morphine withdrawalsupported
Tolerance and dependence less frequent than morphine; less intense abstinence syndrome. pmid:4972938
pharmacokinetic-detail11 · 10 ok
CYP2D6 phenotype is associated with adverse opioid outcomes in clinical populationssupported
CYP2D6 phenotype affects opioid response in both poor and ultrarapid metabolizers. Clinical outcomes data in primary care population. pgpm.s136341
Peak plasma concentration (Cmax) following a 60 mg oral dose ranges from 172–225 ng/mL, achieved at a Tmax of 1.0–1.4 hourssupported
After 60mg oral codeine: Tmax 1.4h (healthy), Cmax 225 ng/mL, t1/2 2.8h, plasma protein binding ~30%. pmid:8227477
Oral codeine absorption exceeds 90%, consistent with its BCS Class I designation (high solubility, high permeability)supported
Codeine fraction absorbed >90% orally. Meets 'highly soluble' criteria. Class 1 BCS drug. jps.23977
Plasma protein binding is low (~30%), and hepatic extraction is high, with total clearance approximating hepatic blood flowsupported
After 60mg oral codeine: Tmax 1.4h (healthy), Cmax 225 ng/mL, t1/2 2.8h, plasma protein binding ~30%. High hepatic extraction drug. pmid:8227477
Codeine undergoes extensive hepatic metabolism via three principal pathways:supported
Codeine metabolism quantified across CYP2D6 phenotypes. CYP2D6 genotype strongly determines morphine production via O-demethylation. s40262-024-01433-9
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
An LC-MS method capable of simultaneously quantifying codeine, C6G, norcodeine, morphine, M3G, and M6G in postmortem tissues has been validated.supported
Validated forensic method for codeine and metabolite quantification in postmortem tissues. Validated range 1.5-300 ng/mL. bku145
CYP2D6 is one of the most polymorphic human cytochrome P450 enzymes, with clinically meaningful interindividual and interethnic variability:supported
CYP2D6 is highly polymorphic with interindividual and interethnic variation. Metabolizes ~20% of prescribed drugs. 14622416.2025.2565993
CYP2D6 is one of the most polymorphic human cytochrome P450 enzymes, with clinically meaningful interindividual and interethnic variability:supported
Codeine metabolism quantified across CYP2D6 phenotypes. CYP2D6 genotype strongly determines morphine production via O-demethylation. s40262-024-01433-9
Population pharmacokinetic modeling quantifying CYP2D6 activity across phenotype groups in surgical patients has been conducted to support model-informed precision dosing.supported
Codeine metabolism quantified across CYP2D6 phenotypes. CYP2D6 genotype strongly determines morphine production via O-demethylation. s40262-024-01433-9
The terminal elimination half-life of codeine is approximately 2.8 hours in healthy adultssupported
After 60mg oral codeine: Tmax 1.4h (healthy), Cmax 225 ng/mL, t1/2 2.8h. pmid:8227477
history8 · 8 ok
2012: Kelly et al. reported three fatal or life-threatening cases in North American children following adenotonsillectomy, linked to CYP2D6 ultrarapid metabolizer status with gene duplications.supported
3 additional fatal or life-threatening codeine cases in children post-adenotonsillectomy; CYP2D6 functional gene duplications caused excessive morphine production. peds.2011-2538
2018 (February 1): Australia rescheduled codeine from over-the-counter (Schedule 3, pharmacist-only) to prescription-only, citing dependence and misuse concerns. The rescheduling was followed by measurable shifts in analgesic sales patterns.supported
Australia rescheduled codeine to prescription-only in February 2018. Followed by increased sales of paracetamol, ibuprofen, and combination products. mja2.50552
2018 (February 1): Australia rescheduled codeine from over-the-counter (Schedule 3, pharmacist-only) to prescription-only, citing dependence and misuse concerns. The rescheduling was followed by measurable shifts in analgesic sales patterns.supported
Australia codeine rescheduled to prescription-only February 1, 2018. Opioid prescribing in dentistry increased significantly post-rescheduling. s41598-020-65390-6
Promethazine abuse in this context is independently associated with drug-related fatalities.supported
EMA data on promethazine misuse; often co-abused with opioids (codeine) in 'purple drank' preparations. Associated with drug-related fatalities. 0269881120959615
Codeine constitutes approximately 2% of opium by weight and is biosynthesized in the poppy plant via the benzylisoquinoline alkaloid pathway from tyrosine precursorspartially supported
Codeine, morphine, and noscapine are pharmaceutical BIAs from Papaver somniferum. TyrAT is an enzyme in the biosynthetic pathway for these alkaloids. pp.111.185512
2009: The first reported neonatal death attributed to maternal codeine use during breastfeeding — the "Toronto case" — drew international attention. Subsequent critical reanalysis by Zipursky and Juurlink argued the causal link is implausible, citing the small quantities of opioids transferred through breast milk regardless of CYP2D6 genotype and the absence of other confirmed neonatal deaths despite widespread codeine use among breastfeeding mothers.supported
Reexamines the 'Toronto case' of infant death linked to maternal codeine/CYP2D6 ultrarapid metabolizer status. Argues the causal link is implausible. cpt.1882
2016: Kaiser Permanente implemented an electronic health record protocol restricting codeine prescribing for children under 7 years.supported
Kaiser Permanente restricted codeine for children <7 years old following respiratory failure and death cases. EHR-based protocol compliance study. 0194599815627810
The recreational preparation known as "purple drank" (also "lean" or "sizzurp") — codeine-promethazine cough syrup mixed with soft drinks and sometimes candy — originated in the Houston, Texas music scene in the 1960s and gained widespread popularity through hip-hop culture in the 1990s and 2000ssupported
Purple drank (codeine + promethazine + soda/alcohol). Used in Texas 1960s; widespread in 1990s. pmid:40982825
clinical-evidence7 · 7 ok
A randomized, placebo-controlled, double-blind, single-dose trial compared paracetamol 1000 mg + codeine 60 mg against ibuprofen (400, 600, 800 mg) and paracetamol (500, 1000 mg) in acute postoperative painsupported
Paracetamol 1000mg/codeine 60mg vs ibuprofen 400/600/800mg and paracetamol alone in post-surgical pain. s00228-021-03231-9
The number needed to treat (NNT) for at least 50% pain relief with paracetamol 1000 mg + codeine 60 mg is 2.3–3.1, indicating clinically meaningful analgesic benefit from the combinationsupported
Addition of codeine to paracetamol reduces NNT from 5 to 2.3-3.1. pmid:25720726
Kelly et al. (2012) documented three fatal or life-threatening cases post-adenotonsillectomy in children with CYP2D6 gene duplications.supported
3 additional fatal or life-threatening codeine cases in children post-adenotonsillectomy; CYP2D6 functional gene duplications caused excessive morphine production. peds.2011-2538
The largest prospective trial to date enrolled 987 adults receiving paracetamol-codeine after ambulatory surgery to investigate the effect of CYP2D6 genotype on analgesic efficacy and adverse effectssupported
987-patient prospective trial of paracetamol-codeine after day surgery; investigates CYP2D6 genotype effect on analgesic efficacy and adverse effects. aas.14549
The most recent meta-analytic systematic review evaluated the analgesic efficacy and adverse effects of paracetamol-codeine combination specifically in third molar surgerysupported
Systematic review and meta-analysis of paracetamol + codeine for postoperative pain after third molar surgery. s2724-6329.25.05216-7
Luk et al. (2016) reported Kaiser Permanente's institutional protocol restricting codeine in children under 7 years in response to FDA safety communications.supported
Kaiser Permanente restricted codeine for children <7 years old following respiratory failure and death cases. EHR-based protocol compliance study. 0194599815627810
The Zipursky and Juurlink (2020) critical reanalysis of the landmark breastfeeding case challenged the causal attribution on pharmacological grounds.supported
Reexamines the 'Toronto case' of infant death linked to maternal codeine/CYP2D6 ultrarapid metabolizer status. Argues the causal link is implausible. cpt.1882
neuroscience5 · 3 ok
Codeine's antitussive action is localized to brainstem cough centers, as demonstrated by the selective efficacy of intra-arterial (but not intrathecal) codeine administration and abolition of antitussive effect by naloxone.supported
Antitussive effect of codeine is brainstem-restricted, not spinal. Intra-arterial codeine suppresses cough; intrathecal does not. fphys.2021.640682
Codeine's antitussive action is localized to brainstem cough centers, as demonstrated by the selective efficacy of intra-arterial (but not intrathecal) codeine administration and abolition of antitussive effect by naloxone.supported
Naloxone pretreatment abolishes codeine's cough-suppressive effects, confirming mu-opioid mechanism in antitussive action. Brainstem-restricted effect. 978-94-007-4549-0_9
Codeine's antitussive action is localized to brainstem cough centers, as demonstrated by the selective efficacy of intra-arterial (but not intrathecal) codeine administration and abolition of antitussive effect by naloxone.supported
Naloxone pretreatment abolishes codeine's cough-suppressive effects, confirming mu-opioid mechanism in antitussive action. Brainstem-restricted effect. 978-94-007-4549-0_9
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
receptor-pharmacology4 · 1 ok
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Classification as a "kappa-opioid receptor agonist" is unsupported by published binding data — codeine has the lowest affinity for kappa receptors (Ki ~14 µmol/L) of the three opioid receptor subtypes tested.supported
Codeine Ki at mu receptor ~0.3 micromol/L; at delta receptor ~5.9 micromol/L; at kappa receptor ~14 micromol/L. pmid:12420793
comparative-pharmacology3 · 2 ok
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Codeine produces less respiratory depression than morphine at clinically equivalent analgesic doses, though it is paradoxically more toxic in some animal models due to convulsant properties.supported
Codeine more toxic to animals (convulsant) but less toxic to man than morphine (less respiratory depression). pmid:4972938
A Prescrire International review emphasized that "weak" opioids including codeine are "no less risky than morphine" when CYP2D6 variability is accounted for, challenging the traditional potency-based risk hierarchy.supported
No evidence weak opioids carry lower addiction risk than low-dose morphine. pmid:27042732
chemistry2 · 0 ok
legal-status1 · 0 ok
Claim in legal-status — inconclusiveinconclusiveworking →