Codeine

Our goal isn't to discourage appropriate opioid use—especially when prescribed by your GP or specialist—but to highlight important safety considerations, particularly around side effects, long-term use, and pain management.

What Makes Codeine Different

• Codeine is a prodrug, meaning it only becomes effective after being converted into another substance—in this case, morphine—within the body. Morphine is responsible for both the pain relief and the addictive potential of codeine (1).

• All opioids, including codeine, can cause opioid use disorder (OUD) with long-term use. OUD is more than just addiction—it involves changes to the brain and immune system that can make it harder to manage pain over time (2, 3, 4, 5, 8).

• Early-life stress, psychological trauma, and brain injuries are all known to increase the risk of opioid misuse and addiction. These experiences “prime” the immune system and make it more sensitive to opioids' harmful effects (6, 7).

• Codeine is often combined with paracetamol or ibuprofen in over-the-counter medications. While convenient, this can lead to serious side effects like kidney damage or gastrointestinal bleeding—especially at high or prolonged doses (1).
  
  

Advice for Managing Pain

If you’re taking codeine, especially with a history of trauma or brain injury, consider the following precautions:

• Communicate openly with your GP or specialist about your pain, mood, and treatment goals.

• Stick to the prescribed dose. Don’t increase or extend treatment without medical advice.

• Keep treatment short-term where possible—codeine is most effective in the early stages of use.

• Report any changes in mood (e.g. low mood, irritability, anxiety), physical symptoms (e.g. nausea, diarrhoea, sweating), or cravings—especially if these occur after missing a dose.

• If pain remains uncontrolled, ask your GP for a review rather than self-adjusting the dose.

Codeine Side Effects

Even though codeine is classified as a weak opioid, it's important not to underestimate its potential risks. Once inside the body, codeine is converted into morphine—an active compound responsible for pain relief, but also for side effects and addictive potential.

Respiratory Depression

Like all opioids, codeine can cause respiratory depression, particularly if taken in high doses or combined with alcohol or sedatives (e.g., benzodiazepines or sleeping tablets).
Opioids affect the brain in two ways:

1. Sedation – reducing alertness, much like sleeping tablets.

2. Suppression of the breathing centre – located in the brainstem, this effect can dangerously reduce the body’s ability to regulate breathing.

Warning signs include:

• Unusual drowsiness or confusion

• Slow, shallow breathing
  If you or someone you’re caring for shows these signs—especially after increasing a dose or combining medicines—seek immediate medical attention.

Important: Codeine passes into breast milk. Infants are extremely sensitive to its effects, especially if the mother is a fast metaboliser. Cases of serious harm and infant death have been reported (9,10,17).

These effects aren’t confined to cases of misuse. Serious side effects and drug interactions are a recognised healthcare concern—even with properly prescribed opioids. The British National Formulary (BNF) and other professional guidance highlight these risks.

Opioid Withdrawal Symptoms

Regular use of codeine—even at therapeutic doses—can lead to dependence and withdrawal symptoms when the medication is reduced or stopped.
This is known as opioid use disorder (OUD) and may develop even under medical supervision.

Common risk factors for OUD include:

• Psychological stress or trauma

• Traumatic brain injury

• Prolonged opioid use (more than 3 months)

• Lack of ongoing support or follow-up from a GP or specialist

• Multi-drug pain regimens

• Use of long-acting or patch-based opioid formulations

Withdrawal symptoms may include:

• Muscle pain or cramps

• Nausea, vomiting, or diarrhoea

• Restlessness or anxiety

• Irritability, low mood, or emotional numbness

• Insomnia

• Sweating, yawning, chills, or goosebumps

• Pupil dilation, teary eyes, or runny nose

• Lack of motivation or energy

Behavioural signs of developing dependence:

• Increasing the dose without medical advice

• Losing interest in hobbies or social life

• Declining performance at work or in relationships

• Needing codeine to feel “normal”

Other Side Effects

Most people experience at least one side effect while taking opioids. Some resolve over time, but others—like constipation or itching—often persist.

Common side effects:

• Nausea and vomiting (usually early in treatment)

• Constipation (especially common with codeine; may require treatment)

• Dry mouth

• Drowsiness or sedation

• Itching (pruritus)

• Fatigue or sleep disturbances

In palliative care settings, the frequency of these side effects has been documented (17,19):

*Constipation is the most consistent side effect and requires active management to avoid serious complications like bowel obstruction.

Mental and Cognitive Impact

Opioids may impair thinking, memory, and emotional regulation—especially during the start of treatment or dose changes.
Opioid-induced delirium is particularly relevant in older adults and is thought to be linked to inflammation in the brain.

The most important genetic factor in how your body handles codeine is your CYP2D6 type.

• If you're a poor metaboliser, codeine is unlikely to work.

• If you're an ultra-rapid metaboliser, it may be dangerous.
  Pharmacogenetic (PGx) testing can help identify both cases—helping your doctor choose safer, more effective pain relief.

Related Medications:

Other opioids that may be affected by CYP2D6 or similar pathways include:

• Tramadol

• Hydrocodone

• Fentanyl

• Alfentanil

• Morphine

If you’ve had issues with any of these medications before, or if you're planning a long-term treatment plan, PGx testing could be a valuable tool in optimising your care.