Codeine Potency Compared to Morphine

Codeine is approximately 1/10th (0.1) to 1/6th (0.17) as potent as oral morphine, making it significantly weaker as an analgesic. 1

Established Potency Ratios

The relative effectiveness of codeine compared to oral morphine has been consistently documented across multiple cancer pain management guidelines:

Codeine requires 6-10 times the dose of morphine to achieve equivalent analgesia 1
The most commonly cited conversion factor is 0.17, meaning 100 mg of codeine equals approximately 17 mg of oral morphine 1
Some sources report an even lower potency ratio of 0.1-0.2, suggesting codeine may be as weak as 1/10th the strength of morphine 1

Codeine is a prodrug that requires conversion to morphine for analgesic effect, which creates significant variability in its effectiveness 1:

Codeine must be metabolized by the cytochrome P450 enzyme CYP2D6 to produce morphine, its active metabolite 1
CYP2D6 exhibits genetic polymorphism affecting 7-10% of the Caucasian population who are "poor metabolizers" 1, 2
Poor metabolizers experience reduced or no analgesic effects from standard codeine doses because they cannot convert it to morphine 1, 2
Conversely, "ultrarapid metabolizers" may experience overdose and respiratory depression from standard doses 3

Research demonstrates codeine's limited and inconsistent analgesic value:

Single-dose studies show codeine 60 mg is not consistently superior to placebo for postoperative pain 4
In head-to-head comparisons, morphine 10 mg provides more effective and longer-lasting analgesia than codeine 60 mg (putatively equianalgesic doses) 5
Codeine demonstrates a ceiling effect on analgesia that morphine does not exhibit 6
Pain intensity ratings decreased in a dose-related manner for morphine but not for codeine, suggesting limited dose-response relationship 6

Codeine carries similar risks to morphine without superior safety 3:

All dose-dependent adverse effects of morphine (respiratory depression, sedation, constipation, nausea) occur with codeine 3
No evidence exists that codeine has lower addiction risk than low-dose morphine at equivalent analgesic efficacy 3
Adverse events occur with equal frequency in both extensive and poor metabolizers, meaning patients who get no analgesia still experience side effects 2
Respiratory depression can occur in ultrarapid metabolizers after brief exposure to standard codeine doses 3

Modern pain management guidelines increasingly recommend against using codeine as a first-line opioid 1:

For moderate cancer pain, low-dose morphine has significantly higher response rates and earlier onset compared to codeine 1
Opioid-related adverse effects are comparable between low-dose morphine and codeine, but morphine provides more reliable analgesia 1
The unpredictable efficacy due to genetic variability makes codeine require at least as much vigilance as morphine despite its "weak opioid" classification 3

Do not assume codeine is safer than morphine - it has the same adverse effect profile without consistent efficacy 3
Do not use standard equianalgesic tables without considering genetic variability - 7-10% of patients will not respond 1, 2
Do not rely on codeine for acute severe pain - it has delayed and unpredictable onset compared to morphine 5, 6
Avoid codeine in patients with renal insufficiency - like morphine, its metabolites accumulate and cause neurotoxicity 1