Codeine’s most common side effects are constipation, drowsiness, and nausea. As an opioid, it also carries risks of slowed breathing, physical dependence, and dangerous interactions with other substances. The severity of these effects varies significantly from person to person, partly because of genetic differences in how your body processes the drug.
How Codeine Works in Your Body
Codeine is a prodrug, meaning it doesn’t do much on its own. Your liver converts it into morphine, and that morphine is what actually relieves pain and suppresses cough. Only about 5 to 10 percent of a codeine dose gets converted to morphine. Roughly 80 percent is broken down into inactive compounds and eliminated. This relatively small conversion rate is why codeine is considered a milder opioid, but it’s also why genetic differences matter so much. Some people convert far more codeine into morphine than others, dramatically changing the risk profile.
Common Side Effects
Most people who take codeine at standard doses experience at least one of these effects:
- Constipation: The most persistent side effect. Opioids slow the muscles in your digestive tract, and this doesn’t improve much with continued use the way other side effects do.
- Drowsiness and sedation: Codeine depresses central nervous system activity, which commonly causes sleepiness, reduced alertness, and slower reaction times.
- Nausea and vomiting: Especially common when you first start taking it or when doses increase.
- Dizziness and lightheadedness: Particularly when standing up quickly.
- Itching: Opioids trigger histamine release, which can cause mild to moderate skin itching even without an allergic reaction.
These effects tend to be dose-dependent. Once you go above 60 mg per dose, side effects increase without much additional pain relief.
Effects on Thinking and Mood
Codeine can produce mild euphoria, which is part of what makes it habit-forming. But it can also cause the opposite: a flat or low mood, mental fog, and difficulty concentrating. In older adults, opioid use is associated with measurable declines in processing speed and executive function, the kind of thinking involved in planning, problem-solving, and switching between tasks. People with higher cumulative opioid exposure show more pronounced cognitive slowing over time.
In older adults specifically, opioids are also linked to delirium and, in some cases, hallucinations. These effects are more likely at higher doses or when codeine is combined with other sedating medications.
Respiratory Depression
The most dangerous acute side effect of any opioid is respiratory depression: your breathing slows down, becomes shallow, or stops entirely. With codeine at normal doses in a typical adult, this risk is low. It rises sharply in three situations: taking too much, combining it with other depressants, or having a genetic profile that causes your body to convert far more codeine to morphine than expected.
Early warning signs include unusual sleepiness, confusion, very slow or irregular breathing, and bluish discoloration of the lips or fingertips. Respiratory depression can progress to coma and death if untreated.
Why Genetics Change the Risk
Your liver uses a specific enzyme called CYP2D6 to convert codeine into morphine. The gene that controls this enzyme varies widely across the population. Most people are “normal” metabolizers, but a meaningful percentage fall at the extremes.
Ultra-rapid metabolizers produce far more morphine from the same codeine dose. In one published case from the New England Journal of Medicine, a patient given small doses of codeine for a cough developed a coma and respiratory failure. His blood morphine level was 20 to 80 times higher than expected. The concentration of morphine-related compounds can be up to 45 times higher in ultra-rapid metabolizers compared to people at the other end of the spectrum. There is no reliable way to know your metabolizer status without genetic testing, and most people taking codeine have never been tested.
On the other end, poor metabolizers get almost no pain relief from codeine because they convert very little of it to morphine. They still experience many of the side effects from codeine itself and its inactive metabolites.
Risks for Children
Children are especially vulnerable to codeine’s risks. The FDA has placed its strongest warning against using codeine for pain control after tonsil or adenoid removal surgery. This contraindication applies to all children undergoing these procedures because there’s no practical way to identify which children are ultra-rapid metabolizers beforehand. Several deaths in children have been linked to standard codeine doses in this setting, all involving ultra-rapid metabolism that produced 5 to 30 times more morphine than normal.
For other types of pain in children, the FDA advises that codeine should only be used when the expected benefits clearly outweigh the risks. Many pediatric guidelines now recommend avoiding codeine in children under 12 entirely.
Dangerous Combinations
Mixing codeine with other substances that slow your central nervous system multiplies the risk of sedation, respiratory failure, and death. The most dangerous combinations involve benzodiazepines (commonly prescribed for anxiety and insomnia) and alcohol.
The numbers are striking. A North Carolina study found that overdose death rates among patients taking both opioids and benzodiazepines were 10 times higher than among those taking opioids alone. Having a current benzodiazepine prescription nearly quadrupled the risk of fatal opioid overdose. In a separate analysis, alcohol was involved in about 1 in 5 opioid-related emergency department visits and a similar proportion of opioid-related deaths.
These risks apply to codeine-containing cough medicines just as they do to stronger opioid painkillers. The FDA considers the pharmacology similar enough that all the same warnings apply.
Dependence and Withdrawal
Physical dependence can develop with regular codeine use, even at prescribed doses. Your body adjusts to the presence of the drug, and stopping abruptly produces withdrawal symptoms. These typically begin within 12 to 24 hours after the last dose and can include muscle aches, restlessness, anxiety, sweating, runny nose, teary eyes, yawning, insomnia, nausea, vomiting, diarrhea, and goosebumps. Pupil dilation and visible goosebumps are two of the most reliable physical indicators of opioid withdrawal.
Codeine withdrawal is generally less severe than withdrawal from stronger opioids like morphine or heroin, but the symptoms follow the same pattern. For most people, the worst physical symptoms resolve within a week, though sleep disruption and low mood can linger longer. Psychological cravings may persist well beyond the physical withdrawal period, which is why dependence on even a “mild” opioid like codeine can be difficult to break without support.