Codeine Addiction: Definition, Symptoms, Causes, Health Effects, and Treatment

Codeine addiction is a complex medical condition that occurs due to both physical and psychological dependence on opioid medication. Codeine is a weak narcotic pain reliever and cough suppressant that is similar to morphine and hydrocodone. Codeine leads individuals to take high doses to achieve pain-relieving effects repeatedly.

The symptoms of codeine addiction are a blue tinge to lips and fingernails, muscle twitches or spasms, dizziness, dry mouth, increased tolerance, withdrawal symptoms, secrecy, and social isolation.

The main causes of codeine addiction are genetic factors such as CYP2D6, OPRM1, ABCB1, family history, mental health disorders like GAD, SAD, PTSD, and SUD, environmental influences such as peer influence, stressful life events, availability and chronic pain conditions like migraine, irritable bowel syndrome, and arthritis.

The health effects of codeine addiction are nausea and vomiting, constipation, itching and rashes, difficulty urinating seizures, and stomach pain.

The treatment options for codeine addiction are medical detoxification, cognitive behavioral therapy (CBT), motivational interviewing, medications, and support groups.

What is Codeine?

Codeine is an opioid that works on opioid receptors and the nervous system. Codeine is distinct from benzodiazepine but it shares some similar effects with it. Codeine is effective in treating mild to moderate pain and is often recommended for alleviating persistent cough. The drug is usually prescribed for irritable bowel syndrome and diarrhea.

What are the different forms of codeine?

Codeine occurs in four different types including tablets, cough syrup, general liquids, and injections.

The different forms of codeine are listed below:

• Tablets: Codeine tablets are solid form or oral doses used for relieving pain and cough. Codeine is sometimes taken with analgesic medication for increasing effect.

• Cough Syrups: Cough syrups are the liquid form of codeine prescribed to help reduce persistent cough.

• General Liquids: General liquids are another oral form of delivering codeine. General liquids are used for treating pain, cough, allergy, or cold symptoms and are often prescribed to patients who have difficulty swallowing tablets.

• Injections: Injections are injectable forms of codeine that deliver codeine directly into the bloodstream and provide immediate pain relief.

What is Codeine Addiction?

Codeine addiction is a condition of physiological and psychological dependence on codeine. It is characterized by withdrawal symptoms upon discontinuation, according to the article titled "Codeine Addiction” published in the Canadian Medical Association Journal. The article highlights that codeine addiction is rare in the present but will become common in the future.

Codeine addiction is a chronic condition that leads to significant dysfunction, according to the study titled “DSM-5 Opioid Use Disorder Criteria”. Individuals who consume higher opioid doses or use it for longer periods often experience tolerance and withdrawal symptoms, leading to failure to fulfill responsibilities and impairment in occupational, social, and personal functioning.

Why is Codeine Addictive?

Codeine is addictive due to its effect on the body and brain. Codeine connects with opioid receptors in the brain and induces feelings of pain relief, relaxation, and euphoria. Individuals repeatedly use codeine for its pleasurable effects, leading to physical and psychological dependence. This dependence encourages individuals to take higher than prescribed doses or take it for extended periods, which in turn increases their addiction.

How Common is Codeine Addiction?

Codeine addiction is less common than stronger opioids such as fentanyl, oxycodone, hydrocodone, or heroin. People in the UK consumed 26.4% codeine, Iran accounts for 15.8%, and the United States used 7.6%, according to the study titled “Codeine Addiction Worldwide” in 2022.

About 33 million people consume codeine annually. Nearly 500,000 Americans fatally overdosed on opioid overdoses, including codeine, from 1999 to 2019, as per the data published by the Addiction Center on Aug 14, 2024.

The pediatric use of codeine in the US from 1996 to 2013 showed relative stability, with about 1.08 million in 1996 and 1.03 million in 2013, according to the article published by NIH. The study shows that children aged between 12-17 are more likely to use codeine as compared to younger children. The data shows a significant decline in the use of codeine, but over 1 million children still use it in 2013.

What are the Signs and Symptoms of Codeine Addiction?

The common signs and symptoms of codeine addiction are a blue tinge to lips and fingernails, muscle twitches or spasms, dizziness, dry mouth, increased tolerance, withdrawal symptoms, secrecy, and social isolation.

These symptoms are listed below:

• Blue Tinge to Lips and Fingernails: Blue tinge to lips and fingernails known as cyanosis, happens when there's not enough oxygen in your blood, or you have poor blood circulation. Codeine increases the level of methemoglobin in the blood, reduces the blood flow, and causes bluish discoloration. The overdose of codeine increases serious symptoms, including slow and shallow breathing, muscle spasms, itchy skin, bluish tint to nails, lips, and skin, weak pulse, low blood pressure, and cyanosis, according to the article “Who is pushing patients to death by improper use of codeine? Time now to reorient physicians or ban the use of codeine” by Singhal, Garg, and Rahman in 2020.

• Muscle Twitches or Spasms: A muscle twitch or muscle spasm is both involuntary contractions of a muscle. Initially, it relieves pain, but persistent use leads to physical effects, including muscle twitches or spasms and cramps. Codeine interacts with the nervous system, which leads to muscle tightness as the body adjusts to the presence and absence of the drug.

• Dizziness:  Dizziness creates the false sense that you or your surroundings are spinning or moving. Regular use or taking it in excessive doses for a long time makes an individual's body adapt to its chemical balance. Reduction in codeine intake causes withdrawal symptoms, including dizziness and nausea. Codeine provides a ceiling effect for pain relief, but its higher doses lead to adverse effects, according to the article in the “Textbook of Orthopaedics, Trauma and Rheumatology.” It mainly causes constipation, nausea, and even drowsiness.

• Dry Mouth: A dry mouth is a condition when the salivary glands in the mouth don't make enough saliva to keep the mouth wet. Codeine binds to opioid receptors and reduces saliva production. The slow down of saliva causes a dry or cottony feeling in the mouth, difficulty swallowing, and increased thirst. Appetite and thirst, when used to treat cancer pain, assessed the impact of opioid treatment on patients in trials involving codeine, morphine, oxycodone, or morphine for treating cancer pain, according to the study titled “Impact of morphine, fentanyl, oxycodone or codeine on patient consciousness.” The result showed adverse symptoms associated with opioid medication, including constipation, somnolence, nausea, dry mouth, vomiting, anorexia, and dizziness.

• Increased Tolerance: Increased tolerance is having a greater acceptance or understanding of something or someone. Increased tolerance occurs when an individual's body becomes addicted to the drug and needs high doses for the same effects. As tolerance builds, individuals manage their pain or cravings with more than prescribed doses.

• Withdrawal symptoms:  Withdrawal symptoms occur upon the abrupt discontinuation or decrease in the intake of drugs such as codeine. The individual's body adapts to the codeine, and when they stop or reduce dosage, they experience withdrawal symptoms. Common withdrawal symptoms include muscle pain, insomnia, sweating, agitation, rapid heart rate, cravings for the drug, nausea, and vomiting.

• Secrecy: Secrecy is when the individual keeps secrets or maintains privacy. Individuals taking codeine often avoid discussions about drug use with their family and friends. They make excuses or lie about their activities and isolate themselves to hide their habits. This often arises from feelings of guilt, shame, and fear of judgment, which contributes to the addiction. An examination of two different perspectives on OTC codeine dependence was conducted in the research. In the second group, participants use codeine secretly and deliberately hide their use from others, according to the study titled “For Pain, No Shame’ and ‘My Secret Solace’: Accounts of over-the-counter codeine dependence using Q methodology.”

• Social Isolation: Social isolation is the complete lack of contact between an individual and society. People withdraw from social relationships for several reasons, including shame and guilt and prioritizing drug consumption rather than engaging with family and friends. This addiction changes an individual's behavior, and they become easily irritable, which pushes them to isolate themselves.

What are the causes of Codeine Addiction?

The causes of codeine addiction include genetic factors, mental health disorders, environmental influences, and chronic pain conditions.

The above causes are defined below:

• Genetic Factors: Genetic factors help to identify the inheritance of traits discretely. Variation in the opioid receptor system, e.g. OPRM1, increases medication sensitivity, leading some individuals to experience codeine cravings.  Genes, e.g. CYP2D6, mostly expressed in the liver and central nervous system, raise the dependence risk by making codeine faster. This quick metabolism results in higher morphine levels in the system and increases addiction. The ABCD1 gene impacts brain response to opioid and drug transport. If genetic variation decreases its efficiency, the drug does not absorb correctly, and this leads to high amounts of doses. The family history of codeine addiction makes certain people genetically vulnerable to addiction. Human molecular genetics reveals that the gene OPRM1 118A influences how μ-opioid reception works in the brain, as per the research on Genetic–epigenetic interaction modulates µ-opioid receptor regulation, by Oertel et al. in 2012. This variant reduces the receptor expression in individuals who use opioids. As a result, people with this variant require high doses, leading to increased misuse and addiction.

• Mental Health Disorders: Mental health disorders are characterized by a clinical disturbance in an individual's cognition, emotional regulation, or behavior. Individuals increase it to cope with emotional pain. Someone struggling with stress, anxiety, and depression self-medicated to reduce their symptoms through its use. Individuals with Trauma-related disorders like PTSD use codeine for temporary relief from anxiety and traumatic memories.  People with GAD and SAD often use it to overcome feelings of fear and social discomfort. Individuals with SUDs initially use this medication for managing the pain but quickly increase dependence due to its euphoric effects.

• Environmental Influences: Environmental influences impact the overall functioning of the body due to surroundings such as family dynamics, peer relationships, and community resources. Environmental factors increase the risk of codeine addiction. The individual uses codeine for relief from stressful life situations such as financial difficulties and family conflicts. Some experience peer influence to use codeine as a solution for emotional discomfort, increasing dependency. The ease of access to codeine in an individual's environment increases the likelihood of their use without a prescription. The misuse and dependence of codeine among medical and pharmacy students of Nigerian universities were found according to the study titled “Extent of misuse and dependence of codeine-containing products among medical and pharmacy students in a Nigerian University, published in BMC Public Health”. The results suggest the misuse is primarily driven by peer influence.

• Chronic Pain Conditions: Chronic pain is long-standing pain that continues beyond the usual recovery period. People with migraine and arthritis use it for managing persistent pain when other treatments are ineffective. People with irritable bowel syndrome use it to reduce abdominal pain and cramping. Initially, it provides relief, but its long-term use leads to its addiction.

What are the Health Effects of Codeine Addiction?

The health effects of codeine addiction are nausea and vomiting, constipation, itching and rashes, difficulty urinating, seizures, and stomach pain.

These health effects are described below:

• Nausea and Vomiting: Nausea and vomiting are both interlinked as nausea occurs prior to vomiting. Its frequent use or high doses disrupt the digestive system and induce feelings of queasiness. The medication shifts the brain's chemical balance and interferes with normal gut movements, leading to nausea and vomiting. The most common opioids, such as codeine, pholcodine, and dihydrocodeine, are used to treat coughs, according to the research titled “Cough: Causes, Mechanisms and Therapy" by Chung, Widdicombe & Boushey. In contrast, these medications have potential side effects on patients, such as drowsiness, constipation, and nausea.

• Constipation: Constipation is where hard feces are formed due to increased consumption of codeine. It affects the intestines and reduces muscle contractions, which help move waste through the system. The delays in bowel movements contribute to constipation.

• Itching and Rashes: Itching and rashes are areas of irritated or swollen skin. Codeine addiction often triggers itching and rashes. Codeine activates the mast and basophils, which release histamine into the body. Histamine causes various skin problems, including rashes and itching. The Bardet in 1874, analyzed the comparative effects of morphine, narceine, and codeine as per the study on “The skin eruptions of codeine. Journal of the American Medical Association” by Scheer & Keil. He found that the high codeine doses, from 0.2 to 0.4 grams, caused itching and generalized erythema in patients.

• Difficulty Urinating: Difficulty in urinating is the blockage that partially or fully prevents urine from leaving your bladder. The long-term use of codeine suppresses the parasympathetic nervous system, weakens bladder contraction, and makes it difficult to maintain urine flow. It impacts the brain's ability to signal bladder fullness, leading to a delay in urination. Prolonged consumption increases the risk of bladder damage and urinary tract infections (UTIs).

• Seizures: Seizures are sudden changes in behavior, movement, and consciousness due to abnormal electrical activity in the brain. Codeine addiction causes seizures, especially when people are taking high doses or with a history of epilepsy. The codeine disrupts the brain and leads to abnormal electrical activity, causing seizures. The risk increases when individuals combine medication with other substances.

• Stomach Pain: Codeine increases stomach pain by affecting the digestive system and bowel movements. It relaxes the digestive tract muscles, which results in cramping and bloating. Prolonged use increases the risk of intestine blockage, nausea, or severe constipation.

A clinical case of a male patient aged 24 who had attempted suicide. He ingested tablets containing caffeine, paracetamol, chlorpheniramine maleate, propyphenazone, and codeine, according to the study titled “A Different Cause of Mimicking Acute Abdominal Findings in the Emergency Department: Ingestion of Codeine and Caffeine Combinations” in 2012”. The patient experienced severe abdominal pain, which was due to both caffeine and codeine.

What are the symptoms of codeine withdrawal?

The symptoms of codeine withdrawal are restlessness, muscle aches, sweating, insomnia, diarrhea, nausea, and intense cravings. Codeine withdrawal occurs when a person abruptly stops or significantly reduces the intake of codeine after prolonged use. This process involves a range of physical and psychological symptoms as the body reacts to the absence of the drug. Codeine withdrawal symptoms typically begin within 12-24 hours after the last dose, according to the study titled "Opioid Withdrawal Syndrome: Clinical Aspects and Treatment Strategies" by Dr. Robert P. Smith published in NIH.

The early stage of codeine withdrawal is marked by flu-like symptoms such as runny nose, yawning, and tearing eyes. It progresses to more severe symptoms like vomiting, rapid heart rate, and elevated blood pressure. This phase is generally intense and peaks within 48-72 hours, according to the study titled "Managing Opioid Withdrawal: Strategies and Treatments" by NIH. Psychological symptoms include anxiety, irritability, and mood swings, which persist for weeks. Cravings for codeine often remain strong, posing a risk for relapse. Medical supervision and supportive care during this phase to manage symptoms and reduce the risk of complications are very important, as per the research titled "Psychological Impacts of Opioid Withdrawal and Relapse Prevention".

How to Prevent Codeine Addiction?

To prevent codeine addiction, take proper medical guidance, follow recommended doses, and avoid prolonged use. Take codeine only as prescribed by a healthcare provider, following recommended doses, and avoiding extended use beyond the prescribed duration. Clear communication about risks and regular monitoring of the usage of codeine help reduce dependency, according to the study titled "Guidelines for Opioid Prescribing to Minimize Misuse and Dependence."

Avoiding triggers is essential for minimizing addiction risk. Patients should steer clear of environments or situations where codeine misuse occurs. Developing coping mechanisms, like exercise or counseling, is crucial for managing pain or stress without reliance on codeine. Behavioral therapies effectively build resilience against codeine cravings, as per the study titled "Behavioral Approaches to Opioid Misuse Prevention."

Maintaining recovery involves ongoing support and medical follow-up. Engaging in aftercare programs, attending support groups, and exploring non-opioid pain management options are vital. Strategies like Cognitive Behavioral Therapy (CBT) and medication-assisted treatments (MATs) are recommended for those with a history of addiction.

How Is Codeine Addiction Different From Other Drug Addictions? 

Codeine addiction is different from other drug addictions because it develops gradually due to its milder effects, whereas others like tramadol addiction occur faster because of its combined opioid and serotonin effects, which make it more intense. Cocaine addiction is driven by rapid and powerful euphoric highs, contrasting codeine’s slower onset and sedative nature. Morphine addiction is marked by a quicker and stronger physical dependence compared to codeine, which has a lower potency and slower withdrawal onset.

Are the withdrawal symptoms from codeine and tramadol similar? 

Yes, withdrawal symptoms from codeine and tramadol share similarities, but there are some differences due to their distinct mechanism of action and pharmacological properties. Both medications share common withdrawal symptoms, such as nausea, vomiting, fatigue, diarrhea, sweating, mood swings, irritability, chills, and anxiety, but tramadol addiction causes additional symptoms due to its serotonin-norepinephrine reuptake inhibitors (SNRIs) properties.

The SNRI effects lead to heightened anxiety, cognitive disturbance, seizures, hallucinations, disorientation, and tinnitus, which are more intense in tramadol than usually observed in codeine withdrawal.

Does codeine and cocaine use lead to the development of addiction?

Yes, both codeine and cocaine use lead to the development of addiction. Codeine is primarily used to relieve pain and suppress cough. It turns into morphine and interacts with opioid receptors in the brain, leading to pain reduction and euphoria. It increases addiction due to its pleasurable sensation. When people take higher doses or use them for extended periods they develop tolerance and physical dependence, resulting in addiction.

Whereas cocaine is a strong stimulant, which creates intense euphoria and pleasure. It suddenly increases dopamine and results in increased energy, alertness, and feeling of happiness. Its regular use alters the brain chemistry and function and results in tolerance. Individuals with time crave more cocaine to recreate the same euphoria, leading to cocaine addiction.

Is codeine less potent than morphine?

Yes, codeine is less potent than morphine due to its less pain-relieving ability. Codeine is used to alleviate mild to moderate pain and suppress cough. It requires conversion into Morphine, which provides an analgesic effect. Individuals need a high amount of doses to achieve pain relief.

On the other hand, Morphine is a powerful opioid medication used to treat severe pain. It is useful in cases like serious injuries and after surgery, but has a great risk for morphine addiction. It binds to opioid receptors in the brain and spinal cord and creates strong analgesic effects. It requires fewer doses, usually 10-20 mg, to relieve pain, compared to codeine, which requires around 100 mg to get a similar effect.