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Codeine: The Long-Term Effects


Codeine is a popular painkiller and cold medicine in the US used widely across the population. However, the drug can have major short and long-term side effects if used improperly. A person who has been using the drug continuously may suffer from codeine long-term effects like stomach pain and constipation. Heavy users may also experience seizures, vision problems, sexual dysfunction, depression, or other mental problems that make it hard to think clearly.

Other long-term effects of codeine include kidney and liver damage, memory problems, itching, irritation, hallucinations, fatigue, seizures, muscle spasms, heart problems, anxiety, and more.

Not everyone who takes codeine experiences long-term side effects, but it is very common for people who continuously used codeine for more than 3 days to experience tolerance to codeine. If they stop, they will suffer the side effects of physical dependence and withdrawal.

There is also a potential risk of addiction. Codeine addiction can negatively impact nearly every aspect of a person’s health as well as ruin relationships, finances, and employment. Furthermore, addiction to codeine can lead to a life-threatening overdose or death.

What Long-Term Effects Does Codeine Have on the Body?

Codeine is a depressant and an opioid narcotic painkiller that is also used for its anti-coughing (antitussive) and anti-diarrheal effects. The primary use of codeine is in cough syrups, which is why codeine is the most widely-used of all the opioids, but it is also prescribed in tablet painkillers. Codeine is considered a “prodrug,” meaning that once it is ingested, it must be broken down (metabolized) into another substance before it is absorbed. Codeine is broken down into morphine, the highly-addictive opioid that most people recognize as a powerful painkiller.

Codeine is metabolized by an enzyme in the liver called CYP2D6. You may be surprised to learn that not everyone is born with this enzyme or the ability to metabolize codeine into its active ingredient, morphine. For example, approximately 3-10% of people of Caucasian ancestry inherit two nonfunctional copies of the CYP2D6 gene. As a result, less codeine is broken down into morphine, and more slowly, so they feel less painkilling or euphoric effects from a normal dose. On the other hand, some people are “ultra-rapid metabolizers” of codeine. That means their body breaks down codeine into morphine much faster and more completely than “poor metabolizer” would.

The short-term and long-term effects of codeine depend on how the body metabolized codeine. People who take high doses of codeine continuously for more than a few days are likely to experience the symptoms of withdrawal if they suddenly quit, but the effects – and how long they last – depend on each person’s genetics, how much codeine they were taking, and how long they were taking it.

What are the Long-Term Effects of Codeine in the Brain?

Codeine works in the brain to stop pain and coughing, so the first place to look for long-term side effects and the symptoms of neurological dysfunction is in the central nervous system.

Once codeine is metabolized by the body and absorbed by the bloodstream, it passes through the blood-brain barrier and attaches itself to opioid receptors in the brain. These opioid receptors are normally used by endorphins and dopamine, which are the body’s natural “feel-good” chemicals that reward us for doing things that promote life, like eating and sex.

Codeine takes the place of endorphins and dopamine, producing a temporary feel-good rush that suppresses the urge to cough and makes a person care less about pain they are feeling. The brain immediately seeks to balance out this imbalance of chemicals by decreasing production of its own endorphins and dopamine.

What Happens When I use Codeine for a Long Time?

After a few days of continuously using codeine, the brain becomes physically dependent on codeine to function. Suddenly discontinuing codeine would produce symptoms of withdrawal which are a predictable group of symptoms resulting from an abrupt removal of a psychoactive drug. Some of the immediate effects of codeine withdrawal are irritability, jitteriness, increased pain sensitivity, depression, diarrhea, cramps, tremors or shaking, chills or sweating, watery eyes, runny nose, yawning, dilated pupils, goose-bumps, insomnia, and loss of appetite.

What is Withdrawal?

Withdrawal is a symptom of changes in the brain caused by codeine.  While the brain should begin to recover within about 2 weeks, there may also be long-lasting effects of codeine in the brain that cause symptoms for months or years after codeine is discontinued.

What is the Most Common Long-Term Withdrawal Symptom?

The most common long-term effect is a craving for codeine after the medication has been discontinued. These cravings are extremely challenging for people in pain. People who have been using codeine for a long time, especially people who became physically dependent after they were prescribed codeine for chronic pain, may develop a level of tolerance where the body can no longer naturally compensate for the absence of codeine – it does not make “natural painkillers.”

How Can You Mitigate Long-Term Effects?

It is possible to lessen the long-term effects of codeine by gradually tapering off the dosage. To achieve a comfortable transition off codeine after you have become physically dependent, it requires carefully balancing your brain’s ability to adapt to a gradual decrease in the daily dosage of codeine under the supervision of a doctor.

How Long Does It Take the Body to Recover from Codeine Abuse?

When quitting codeine, people who were formerly addicted to the drug often experience uncomfortable withdrawal symptoms like headaches, insomnia, muscle aches, fever, vomiting, sweating, stomach pains, diarrhea, depression, and powerful cravings for more codeine.

These symptoms may start within a few hours after the last dose of codeine was used by a person who has accustomed their body to a continuous dose. The symptoms can continue anywhere from 1 week to a few months. How long the effects of codeine withdrawal last depend on how much codeine the person was using when they quit taking it, and how dependent their brain had become on codeine.

What Increases the Risk of Long-Term Effects?

Other risk factors can also increase the likelihood of long-term effects and the duration of withdrawal. For example, people who also used alcohol in excessive amounts while abusing codeine are more likely to experience side effects. Mental illnesses like depression or anxiety may also be exacerbated by a person self-medicating with codeine.

Liver Damage

Liver damage is a serious long-term effect of codeine. It is especially common in people who abuse codeine in cough syrup or cold-and-flu medications that also contain Tylenol (acetaminophen). There is a narrow difference between a “safe” dose and a toxic overdose of acetaminophen – and the consequence of overdose is liver failure. Furthermore, codeine itself is processed by the liver into morphine, and a person who is overloading their liver with both codeine and acetaminophen can easily suffer from hepatitis, liver failure, or death.

Stomach Problems

Codeine medications for migraines and pain sometimes also contain ibuprofen, naproxen, or aspirin. These other ingredients are all painkillers called Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). They are safe for short-term use at appropriate dosages, but long-term use of codeine plus NSAIDs can cause long-term effects on the stomach and digestive system. One of the most common problems is stomach ulcers which are painful sores that do not heal easily. NSAIDs increase the risk of stomach ulcers because they destroy the protective mucous lining in the stomach and upper intestines.


Like other opiates, codeine frequently causes constipation and painful abdominal cramps. These long-term effects of codeine occur because it activates the opioid receptor sites that are found on the smooth muscles of the intestines. Codeine slows down peristalsis (the worm-like movements which propel food and fecal matter through the gut). This has the effect of firmer stools being passed less frequently.


Codeine abuse can carry a risk of pancreatitis, which is caused by digestive juices backing up into the pancreas, causing inflammation. Codeine slows down the muscle contractions that normally regulate the flow of digestive juices between the pancreas and the intestines. Pancreatitis is more likely to affect people with long-term constipation from codeine.

Breathing Problems

One of the most serious codeine long-term side effects is respiratory depression, which means that a person’s breathing is abnormally slow. It is very dangerous. Breathing problems, or breathing that is unusually noisy, shallow, or difficult, can be signs of a codeine overdose.

Even if a person has not overdosed, long-term codeine use can cause sleep apnea, a disorder in which breathing stops temporarily while a person is asleep. Sleep apnea and respiratory depression can lead to extremely low oxygen levels in the bloodstream, coma, or death. A person who has trouble breathing after taking codeine should be taken to a hospital immediately.

Psychological Effects

Codeine abuse can worsen a wide range of psychological long-term effects, such as irritability, anxiety, mood swings or depression. These psychological side effects are often more intense for people who already had a mental illness before they started taking codeine. Codeine has a numbing effect that can temporarily relieve anxiety and other symptoms of mental illness, which is why some people use codeine to self-medicate.

However, unless the underlying illness is diagnosed and treated appropriately, codeine can actually exacerbate the problem by damaging the brain’s ability to cope with emotions. As the brain reduces its production of endorphins and dopamine, the underlying problem becomes more severe, and the brain becomes reliant on codeine to function normally.

Codeine causes a major change in brain chemistry that can make it almost impossible to quit, especially for a person who is relying on it to control a mental illness like depression. Underlying illnesses may also increase the risk that a codeine abuser will develop other long-term problems, like a painkiller addiction, in which they lose the ability to stop themselves from using codeine.


It’s important to remember that addiction is not the same thing as dependence. Physical dependence is a normal long-term effect of codeine in which the body develops a tolerance to codeine and craves more of it to function normally and avoid withdrawal. Addiction is different. It is characterized by psychological changes in the brain after continuous codeine abuse.

A person who is addicted to codeine is unable to stop using it. They seek out codeine, despite consequences on their life, work, finances, school, family, and relationships. Many people abusing codeine do not even get high – they simply need the drug to function and feel “normal” every day. If a codeine user can’t stop using the medication when it is ruining their life, he or she will need specialized drug treatment to have the hope of a full recovery from their addiction.

Involuntary Movements

Codeine floods the brain with the neurotransmitter dopamine. This creates a feeling of happiness and well-being. In high doses, it is dopamine that produces the euphoric “buzz” or “high” of opiates. When dopamine is produced excessively, it can cause the body to make involuntary movements or tics. This is why long-term codeine abusers may experience tremors, twitches, trembling, or shaking hands.


In some cases, seizures are also associated with heavy long-term use of codeine. Seizures occur when the electrical activity in the brain is abnormally increased. There is a potential risk of brain damage or death for seizures lasting more than 30 minutes. People with kidney problems (renal dysfunction) are more likely to suffer seizures from codeine because their kidneys do not remove it very well from the blood.

Cardiovascular System Effects

Codeine can have dangerous long-term effects on the heart. Studies show that using codeine for more than 6 months increases the risk of having a heart attack by 62% compared to hydrocodone. Furthermore, studies of patients with arthritis found that when opiate painkillers like codeine were compared to NSAID painkillers like ibuprofen, opiates were associated with a 77% increased risk of cardiovascular events. Codeine is known to cause low blood pressure (hypotension), slowed heart-rate, palpitations or irregular heartbeat, and even cardiac arrest.


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