Morphine and codeine both come from the opium poppy and are built almost the same way, differing by one small chemical group. Codeine does most of its work only after the body turns it into morphine.1Clinical Pharmacology & Therapeutics. Clinical Pharmacogenetics Implementation Consortium Guidelines for Codeine Therapy in the Context of Cytochrome P450 2D6 (CYP2D6) Genotype That makes codeine the milder of the two, but how well it works depends heavily on each person’s body. That unpredictability, more than raw strength, is why many doctors now move straight to a small dose of morphine instead.2NHS. Drug Management of Pain – Core Knowledge
Where Morphine and Codeine Come From
Morphine was the first active ingredient isolated from opium, by a German pharmacist’s assistant named Friedrich Sertürner in the early 1800s.3Rev. Bras. Anestesiol.. Opium and opioids: a brief history It went on sale in Europe and North America around 1820 and quickly became a popular painkiller.4Rev. Bras. Anestesiol.. Opium and opioids: a brief history Codeine followed when it was isolated from opium in 1832.5Rev. Bras. Anestesiol.. Opium and opioids: a brief history
Chemically, codeine is morphine with a small chemical cap, a methyl group, added.6Rev. Bras. Anestesiol.. Opium and opioids: a brief history This cap blocks the spot that lets morphine grab pain receptors strongly, so the body has to remove the cap to unlock most of codeine’s effect.
Many other opioids, such as hydrocodone and oxycodone, are made by modifying this same morphine-codeine backbone.7PubMed. Transformations of codeine to important semisynthetic opiate derivatives by Pseudomonas putida m10 All belong to one family and carry similar risks of dependence.
Because both act on the same receptors, they cause the same familiar effects: drowsiness, constipation, nausea, and slowed breathing at high doses. Codeine being milder doesn’t make it free of these.
How Your Body Turns Codeine Into Morphine
In the liver, an enzyme called CYP2D6 converts codeine into morphine; this is the gene a genetic test for codeine checks.8PubMed Central. Opioid Drugs in Patients With Liver Disease: A Systematic Review On its own, codeine binds weakly to the body’s main opioid receptor, far less tightly than morphine does.9PubMed. Uniform assessment and ranking of opioid μ receptor binding constants for selected opioid drugs So the amount of morphine your liver makes largely decides how much codeine helps you. Only a fraction of a codeine dose becomes morphine, which is one reason the overall effect is modest.
Up to 10% of people are poor metabolizers, meaning their CYP2D6 barely works, and they get little or no pain relief from codeine.10NHS. Drug Management of Pain – Core Knowledge In people with very low enzyme activity, morphine often can’t even be detected in the blood after a codeine dose.11PubMed. Codeine and morphine in extensive and poor metabolizers of sparteine: pharmacokinetics, analgesic effect and side effects In those same people, codeine eased pain no better than a dummy pill, while morphine still worked.12PubMed. Codeine and morphine in extensive and poor metabolizers of sparteine: pharmacokinetics, analgesic effect and side effects
Telling a prescriber that codeine or similar drugs gave you no relief at a proper dose is useful information, because it may point to low conversion. Mentioning whether morphine, which needs no conversion, worked helps too, since that points to the conversion step rather than to your pain being unusual.
A genetic test can help show it. A cheek swab or blood test shows how you process codeine, and doctors who used test results to choose painkillers gave slow converters better pain relief.13PubMed Central. CYP2D6-guided opioid therapy improves pain control in CYP2D6 intermediate and poor metabolizers: a pragmatic clinical trial
How Much Stronger Morphine Is
Codeine is about one-tenth as potent as morphine.14NHS. Drug Management of Pain – Core Knowledge So 240 mg of codeine a day, a common maximum, roughly equals 24 mg of morphine a day.15NHS. Drug Management of Pain – Core Knowledge The real effect varies widely between people because of the conversion step. Codeine tablets are typically dosed in tens of milligrams, while morphine for pain is often started at a few milligrams.
Doctors use the ratio as a rough guide when switching someone from one drug to the other. It isn’t a promise that a given dose will feel equivalent, so a switch is usually done cautiously, with the new dose started low and checked after a short time.
The World Health Organization’s pain ladder placed codeine at step 2 for moderate pain and morphine at step 3 for severe pain.16Archives of Disease in Childhood. Is it farewell to codeine? Codeine is often sold combined with paracetamol at step 2.17NHS. Drug Management of Pain – Core Knowledge Products such as co-codamol list the codeine and paracetamol amounts separately, and the paracetamol limit can cap how much you can take. Never stack two combination products.
Some doctors skip codeine and give a low dose of morphine when simple painkillers fail, because morphine works more predictably.18NHS. Drug Management of Pain – Core Knowledge Morphine needs no conversion, so the dose you take is the dose you get, and doctors can start low and adjust.
More codeine is not a safe way to get more relief: going past the daily maximum adds side effects and risk, while relief may not improve for someone who converts it poorly. If a labeled dose isn’t controlling your pain, ask the prescriber about a different drug rather than taking extra.
Why Codeine Can Be Dangerous for Some People
Some people are ultrarapid metabolizers, meaning they turn codeine into morphine unusually fast.19Clinical Pharmacology & Therapeutics. Clinical Pharmacogenetics Implementation Consortium Guidelines for Codeine Therapy in the Context of Cytochrome P450 2D6 (CYP2D6) Genotype In them, normal codeine doses have caused severe or life-threatening morphine poisoning.20Clinical Pharmacology & Therapeutics. Clinical Pharmacogenetics Implementation Consortium Guidelines for Codeine Therapy in the Context of Cytochrome P450 2D6 (CYP2D6) Genotype Unusual sleepiness or confusion after a normal first dose is a reason to stop and contact a clinician rather than push through.
Signs of too much morphine include unusual sleepiness or being hard to wake, slow or shallow breathing, confusion, and pinpoint pupils. Treat these as an emergency and call for help.
The same risk reaches breastfed babies. Fast-converting mothers can pass morphine to the baby in milk, so watch for poor feeding or limpness, and ask about alternatives before taking codeine while nursing.
In 2013 the US FDA said codeine must not be used for children under 18 after tonsil or adenoid surgery.21PubMed. Continued Prescribing of Periprocedural Codeine and Tramadol to Children after a Black Box Warning In 2017 it extended the warning to all children under 12 and to tramadol.22PubMed. Continued Prescribing of Periprocedural Codeine and Tramadol to Children after a Black Box Warning A child’s ability to convert codeine is hard to predict, and a child can’t easily describe early signs of an overdose. If a child is offered codeine or tramadol, ask whether a non-opioid option will do.
Medicines can swing the effect either way. Some antidepressants, including fluoxetine and paroxetine, block codeine’s conversion to morphine.23NHS. Drug Management of Pain – Core Knowledge People taking them may get little relief. Alcohol or sleeping tablets taken with codeine add to drowsiness and breathing risk, whatever your genes. Tell your prescriber every medicine you take before starting codeine.
What Each Drug Is Used For
Codeine also calms coughing by acting on opioid receptors in the brain.24PubMed Central. Central and peripheral mechanisms of narcotic antitussives: codeine-sensitive and -resistant coughs It reduces the urge to cough through the brain’s cough control centre rather than the airways themselves. It is generally used for dry, persistent coughs and doesn’t treat the infection or irritation behind them.
The same liver conversion happens whether codeine is taken for a cough or for pain, so a fast converter can still receive too much morphine. Codeine cough syrups are restricted or prescription-only in many countries, non-opioid cough remedies exist, and children should not be given codeine cough medicine.
Morphine has a different extra job. Low-dose morphine is used in end-of-life care to ease severe breathlessness.25PubMed. Experience of morphine therapy for refractory dyspnea as palliative care in advanced heart failure patients In people with advanced heart failure, starting doses around 5 mg a day eased breathlessness and slowed breathing within 24 hours.26PubMed. Experience of morphine therapy for refractory dyspnea as palliative care in advanced heart failure patients
Low-dose morphine reduces the brain’s sense of air hunger, so the person feels less distressed even if their lungs are unchanged. The doses are well below those used for pain.
How Long Codeine and Morphine Show Up on a Drug Test
On common urine screens using a 300 ng/mL cutoff, morphine was detectable for about 15 to 44 hours after a dose.27PubMed. Forensic drug testing for opiates. V. Urine testing for heroin, morphine, and codeine with commercial opiate immunoassays Codeine stayed detectable longer, about 33 to 54 hours.28PubMed. Forensic drug testing for opiates. V. Urine testing for heroin, morphine, and codeine with commercial opiate immunoassays The opiate screen reacts to both drugs, so it can’t tell which one you took.29PubMed. Forensic drug testing for opiates. V. Urine testing for heroin, morphine, and codeine with commercial opiate immunoassays
Those hours are measured ranges from a particular kind of test and cutoff, so your own result could fall outside them. Dose, how often you take the drug, and how your kidneys and liver work can all shift how long it shows up.
Screening results after codeine vary a lot, so labs confirm positives with a second, precise test.30PubMed. Forensic drug testing for opiates. V. Urine testing for heroin, morphine, and codeine with commercial opiate immunoassays Confirmation can show codeine alongside morphine, which is expected because your body makes morphine from codeine. Poppy seeds can also cause opiate positives.
If you have a valid prescription, a positive screen is expected and not a failure. When a workplace test is coming, tell the testing process about your prescription when asked, and keep the pharmacy label or a note with the drug, dose, and prescriber handy. Don’t stop or change a prescribed medicine on your own just to pass a test; discuss any concerns with the prescriber. A medical review officer contacts the person before reporting a positive and checks whether there is a valid explanation.