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Codeine Withdrawal & Detox Guide

Medically Reviewed By: Benjamin Caleb Williams RN, BA, CEN

Written By: Phillippe Greenough

Article Updated: 09/24/2020

Number of References: 18 Sources

The symptoms of codeine withdrawal, while rarely dangerous, can be quite uncomfortable. These symptoms often include both psychological and physical issues that can be a big hurdle to recovery from codeine addiction. Here we will take a look at the exact causes of these symptoms, the specific symptoms themselves, the withdrawal timeline, contributing factors, and some effective treatments for reducing the discomfort and pain of codeine withdrawal symptoms.

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Codeine Pharmacology & Addiction

Codeine is a fairly weak opioid painkiller and cough suppressant that is derived from opium or morphine. It interacts with all 3 of the major opioid receptors, the μ (Mu), δ (Delta), and κ (Kappa), although its strongest effect by far is on the μ-opioid receptor. Codeine use results in a small portion of codeine metabolizing into morphine in the body, thereby increasing its analgesic (painkilling) effects. That being said, codeine is about 1/6th as potent as morphine per milligram, so it is certainly on the weaker side of common painkillers. It is also frequently used as a cough suppressant due to its potent antitussive effects.

The opioid system is responsible for a variety of functions including pain relief, mood, feelings of pleasure, and it has many downstream effects on other neurotransmitter systems including the serotonin, dopamine, and norepinephrine systems. Through chronic codeine use, these systems can undergo a process known as downregulation, which is the body’s attempt to maintain balance in the continued presence of codeine. This means that opioid receptors and some of the downstream neurotransmitter receptors will have their number and/or sensitivity reduced, thus taking more stimulation to produce an effect. This initially creates a tolerance to codeine, and further use results in physical dependence on the drug.

Once downregulation has occurred, someone will begin to feel physically ill when they do not use the drug. Continued codeine use will produce further neurological remodeling, where the brain undergoes structural changes to better operate in an opioid-downregulated environment. While downregulation is responsible for the immediate, physical symptoms of codeine withdrawal, remodeling is more responsible for the longer-lasting, psychological symptoms. These can last for weeks, months, or sometimes even years after someone stops using codeine. These changes are able to be reversed and healed, but this is a slow process that requires time and abstinence from codeine use.

Codeine Withdrawal Symptoms

The symptoms of codeine withdrawal can manifest both physically and mentally. Furthermore, codeine withdrawal can be divided into two distinct phases: acute and post-acute withdrawal. The acute phase is the first stage of withdrawal and can begin within hours of the last time someone used codeine. The acute symptoms are the most severe symptoms and are both physical and psychological in nature. The post-acute phase is by far the longest-lasting, but only exhibits psychological symptoms.

The acute symptoms of codeine withdrawal can begin shortly after the last codeine use. While not usually long-lasting, they can be quite uncomfortable. Even though codeine isn’t a particularly potent opiate, the physical symptoms can feel like a sudden and intense flu-like illness coupled with psychological stresses.

Some of the most common symptoms of codeine withdrawal include:

  • Diaphoresis (sweating)
  • Rhinorrhea (runny nose)
  • Stomach Cramps
  • Diarrhea
  • Loss of Appetite
  • Tremors and Shakes
  • Chills and Hot Flashes
  • Piloerection (goosebumps)
  • Aches in the Muscles, Joints, and Bones
  • Tachycardia (elevated heart rate)
  • Hypertension (increased blood pressure)
  • Anxiety
  • Depression
  • Irritability
  • Restlessness
  • Insomnia
  • Fatigue and Lethargy
  • Cravings for Codeine

These symptoms are not usually life-threatening, but they can lead to complications when combined with underlying health conditions. In particular, diarrhea and constant sweating can lead to dehydration and electrolyte imbalances. When this occurs in people who have diabetes or a heart condition, this may increase the chances of cardiovascular issues and complications such as diabetic ketoacidosis or hyperosmolar hyperglycemic nonketotic syndrome. While it may be recommended for anyone to enter a codeine detox center when expecting to undergo withdrawal, this is especially the case in diabetics or those with heart issues.

Post-Acute Codeine Withdrawal

The post-acute symptoms of codeine withdrawal, while strictly psychological in nature, should not be underestimated. These symptoms can sometimes be intense and quite long-lasting, and the general negative affect that they often produce can act as a barrier towards long-term recovery. Codeine relapse is a very real challenge, especially in the weeks immediately after someone stops using, and these psychological symptoms can make a return to codeine use seem very appealing. It is highly recommended that if someone has not already sought help from a detox center, that they reach out for psychiatric and therapeutic care to treat these symptoms.

Some of the most common symptoms of post-acute codeine withdrawal include:

  • Depression
  • Anxiety (particularly social anxiety)
  • Fatigue and Lethargy
  • Cravings for Codeine
  • Insomnia
  • Mood Swings
  • Irritability

These symptoms are often most intense in the first few weeks after someone stops using codeine. While they can last for a long time, they will often dissipate over time and with continued abstinence from codeine or other opiates. The depression and isolation that commonly result from anxiety in general, and social anxiety in particular, can act to keep someone away from support, care, and those who could offer help. These symptoms may be minimized with medications and therapy, but some level of discomfort can be expected, especially in the first few weeks of codeine withdrawal.

Codeine Withdrawal Timeline

The timeline for codeine withdrawal is quite similar to many other common opiates, such as morphine. The acute symptoms of codeine withdrawal may last around a week, usually appearing, plateauing, and resolving over this timeline. The post-acute symptoms may persist for much longer and there is some substantial variability in the duration of post-acute symptoms between individuals.

Codeine has a half-life of ~3 hours which is a common duration for many older opiates. With a very similar half-life to morphine, but roughly 1/6th the strength, the symptoms of codeine withdrawal may be similar, although less intense, than those of morphine along with a very similar timeline. With such a short half-life, physical withdrawal symptoms will begin within 6-8 hours of the last time someone used the drug. While these symptoms may begin mildly, they often escalate quickly over the first 24 hours after the last codeine use.

First Week

Depending on someone’s codeine use habits, symptoms will begin to appear within eight hours of the last codeine use. The first symptoms to appear are usually anxiety, sweating, and chills. The first night may exhibit insomnia and restlessness along with stomach issues such as cramps, loss of appetite, nausea, and diarrhea. The next day may introduce aches in the muscles, joints, and bones along with tremors or shakes. Sweating, runny nose, and chills or hot flashes will usually escalate over the first three days and someone’s energy levels will remain very low. The lack of adequate food or sleep will usually contribute to the discomfort someone experiences during the first week. Usually around three or four days after these symptoms begin, they will have reached their peak intensity for a time, before beginning a slow resolution over the following few days.

Second Week

The start of the second week usually shows great improvement from the first, with most of the physical symptoms of codeine withdrawal resolving with the possible exceptions of insomnia, yawning, and stomach issues. That being said, the psychological symptoms may have increased somewhat since the first week. Depression, anxiety, fatigue, restlessness, and cravings for codeine may be higher during the second week as the physical symptoms are no longer distracting from the psychological distress. Insomnia and restlessness may improve somewhat during the week, but yawning and the rest of the psychological symptoms may persist throughout.

Third Week

By this time, the physical symptoms are often totally resolved, or very close to it. Once stomach issues have resolved and appetite has returned to normal, someone can frequently experience substantial relief as healthy eating habits return. Combined with adequate sleep, this can go a long way towards improving someone’s state of mind and outlook. Craving, depression, lethargy, and anxiety usually remain at fairly high levels, although they may see some improvement during this week.

Fourth Week and Onwards

The fourth week after the last codeine use often shows great improvement. With several days of a healthy appetite and good sleep behind them, someone is often in a much better position to move forward with their recovery. While improvement has been made, this is not the time for someone to let their guard down or their determination waver. With the fading of the physical symptoms, the idea of returning to codeine use can seem more and more appealing and continued care is highly recommended. The psychological symptoms may persist for further weeks, months, or even years and someone will need help to treat these symptoms and reduce the impact they may cause on their life and recovery. While the most physically difficult time is behind, there is still work to be done.

The Importance of Codeine Detox

Codeine withdrawal symptoms can be very uncomfortable, and this can sometimes be the main driver of someone’s continued codeine use. The fear and dread of withdrawal symptoms can be severe, and having help can not only reduce these symptoms but it may also help remove some of the apprehension and anxiety that often accompanies thoughts of withdrawal and detox. Getting help from a professional codeine detox center can provide medications, medical monitoring, and therapies to treat the symptoms and give someone the tools they need to build a firm foundation in recovery. This is often the first step toward long-term recovery and the importance and utility of entering a detox center cannot be overstated enough.

Codeine Detox Centers Guide

Physical Effects of Codeine Withdrawal

Even though the physical effects of codeine withdrawal are not usually life-threatening, they are often very uncomfortable. The downregulation that occurs to the opioid system and other, downstream neurotransmitter systems can produce a wide range of physical effects. These are most frequently centered on the gastrointestinal tract and cardiovascular system, although there are other secondary effects in other physical systems as well.

Gastrointestinal Effects

The effects of codeine withdrawal on gastrointestinal function can be some of the strongest effects of withdrawal. The opioid system has receptors all over the body and not just in the brain, with a large number of μ-opioid receptors in the gut. While these receptors perform one function in the brain, they fulfill a regulatory role in the digestive system by moderating and slowing certain functions. In the gut, μ-opioid receptors can slow intestinal muscle contractions (peristalsis), regulate the stomach passing its contents to the intestines, and also moderate sphincter muscle tone.

Once the opioid system has undergone downregulation and opioid drug use is ceased, these calming effects on digestion become disrupted, as the natural opioid peptides of the body have a reduced impact on opioid receptors, thus they cannot slow things as they normally would. The general effect of codeine withdrawal on digestion is a general acceleration and hyperactivity. The intestines are not slowed to the degree they normally would be, thus leading to stool moving quickly through them and resulting in diarrhea. This can also produce stomach cramps and pain.

Cardiovascular Effects

The opioid system also interacts with the cardiovascular system, both through downstream effects produced through opioid receptors in the brain and opioid receptors in the heart muscles themselves. The exact role that the opioid system plays in heart function is unclear at present, but it is known that cardiovascular issues, in particular hyperactive states, are common effects of codeine withdrawal. The most direct effect that codeine withdrawal can interact with heart function is probably through the levels and downregulation of the neurotransmitter norepinephrine.

Norepinephrine is both a neurotransmitter and a hormone depending on where it is found in the body. In the brain, it is related to attention, memory, and focus while acting as a hormone in the blood it can regulate levels of epinephrine (aka adrenaline), thereby increasing heart rate, blood pressure, and blood sugar levels. During codeine withdrawal, and opiate withdrawal in general, blood levels of norepinephrine are increased. This can result in a prolonged state of hypervigilance, increased heart rate, blood pressure, and increases in blood sugar levels. The psychological symptoms of codeine withdrawal may contribute to elevated heart rate and blood pressure as well by increasing tension and stress levels.

Secondary Effects

Aside from these two major systems, there are multiple secondary effects of codeine withdrawal as well. While these effects are mostly within the autonomic nervous system, they can manifest a variety of symptoms. These may manifest internally or externally and are all quite common effects of codeine withdrawal.

Some of the secondary effects from increased levels or sensitivity to norepinephrine include:

  • Tremors or Shaking
  • Insomnia
  • Dilated Pupils

Secondary effects due to endocrine or exocrine system disruption include:

  • Rhinorrhea (runny nose)
  • Diaphoresis (sweating)
  • Blood Sugar Instabilities
  • Hyper- or Hypothermia

A very common secondary effect with no known cause is:

  • Frequent Yawning

Psychological Effects of Codeine Withdrawal

While the physical effects of codeine withdrawal may be mostly resolved within a week or two, the psychological effects may persist for several weeks, months, or even a year or more. These effects may seem less severe than the physical symptoms, but they can act as a major hurdle towards continued recovery and sobriety. These effects may be simultaneously depressive and hyperactive, in the sense of depression coupled with cravings, anxiety, and irritability. The psychological effects also display great variability in both appearance and duration between individuals, with some people making a full recovery fairly soon, while others experience these symptoms for an extended time.

Depression

One of the most common symptoms of codeine withdrawal, depression can sometimes last for a long time after someone ceases codeine use. This can have both neurological and behavioral causes, but both add up to the same effect; depression, sometimes severe, that can persist for a long time. From a neurological standpoint, disruptions to both dopamine and serotonin systems are likely to blame. Both of these neurotransmitters can affect mood with dopamine acting to produce positive feelings including pleasure and excitement, while serotonin acts as a mood elevator and stabilizer. Due to remodeling in both of these systems through downstream effects of chronic opioid system overstimulation, they may be unable to perform their functions properly until normal function returns. This can take a long time and has several contributing factors, which we will explore in-depth down below.

Depression may seem minor at first, but this can lead to suicidal ideation in severe cases, which is a very serious issue. Unfortunately, suicide is not unheard of during opioid withdrawal, and this risk needs to be taken very seriously. Medical monitoring and support are important, but psychological care and treatment are also recommended to help someone deal with symptoms of depression and try to cope with these symptoms in a helpful way. Connection with peers who have similarly gone through withdrawal and made it out the other side may be especially helpful. Knowing that life is possible after codeine and that others have made it through this difficult process can be encouraging and may help foster hope.

Another cause may be behavioral in nature in the form of the loss of such a powerful, although very unhealthy, coping mechanism as codeine use. Opioids, in general, can strongly dampen negative emotions while producing artificial positive feelings and it is common for someone to become reliant on them to deal with the normal stresses of life. Once this way to cope is suddenly removed, a sense of loss or hopelessness is a fairly common symptom. When combined with the neurological causes, this can create a depressive state, sometimes profoundly so, and can lead someone to feel that life without codeine is simply not worth living. This will resolve over time, and therapy, medications, and continued care can help to reduce the discomfort as well as shorten the time until someone experiences relief.

Cravings For Codeine

Cravings are another very common effect of codeine withdrawal, both acute and post-acute. These cravings also have causes both neurological and behavioral in the form of the loss of coping mechanisms, neurotransmitter imbalances, and neurological remodeling. The loss of codeine as a coping mechanism can contribute to cravings in a similar manner to the way it contributes to depression. Someone will want relief from the stresses of withdrawal, and later, life without codeine and will naturally crave the substance that brought them such great relief in the past.

From a neurological perspective, downregulation and subsequent remodeling may be the largest contributor to codeine cravings. Another downstream effect of opioid system overstimulation is on the neurotransmitter dopamine, particularly in areas of the limbic system. The limbic system is also known as a “reward center” of the brain and is responsible for feelings of pleasure, behavior-related reward, and plays a role in linking memories to emotions. Through dopamine downregulation in certain areas of the limbic system like the amygdala, hippocampus, and nucleus accumbens, the brain will undergo remodeling to better operate in this downregulated environment. During withdrawal, dopamine will be unable to stimulate these pleasure and reward areas to the normal degree, and the strong association between pleasure and the memory of using codeine will naturally cause someone to crave codeine use for a sense of relief, or just to feel good at all. This will resolve with time and continued abstinence from codeine use, and medications or therapies may be able to help in the meantime.

Anxiety

One more very common effect of codeine withdrawal is increased anxiety. This can appear as generalized anxiety but usually manifests more strongly as social anxiety. While it may seem minor, this can have a very detrimental effect on someone’s chances of recovery. Breaking free from codeine addiction is a difficult process, and almost always requires help from others. The fear of, or desire to avoid, others can work to keep someone unwell and prevent them from being fully engaged in their recovery. This also has both neurological and behavioral effects similar to cravings and depression.

The neurological causes of anxiety have to do with neurotransmitter disruptions in the serotonin and norepinephrine systems. Serotonin can have a relaxing effect, and due to downregulation and remodeling, it may not have the same impact it once had, leading to increased levels of baseline anxiety. Norepinephrine may be a greater contributor in the sense that levels of this neurotransmitter are often increased during codeine withdrawal. Being a large component of the “fight-or-flight” mechanism, increased levels can lead to a constant state of hypervigilance. This may increase baseline anxiety as well but may play a larger role in social anxiety. The state of hypervigilance can lead to greater stress when there are more people around, as the body being in fight-or-flight mode has more potential threats to surveil, thus leading to increased anxiety. This will also reduce with time, but this can be a slow process. Medications and therapies can provide some relief while the brain reverts to pre-codeine levels of function.

What Factors Influence The Intensity of Codeine Withdrawal?

There can be a wide range of variation in both the intensity and duration of codeine withdrawal between individuals. This has a variety of contributing factors, some of which are well understood, while the exact role of others is still somewhat mysterious. Some of these factors are based on choices someone makes, such as their codeine use habits, but others are completely out of their control, such as genetics.

Some factors that can influence the intensity and the duration of codeine withdrawal symptoms include:

  • The amount of codeine someone used
  • The length of time someone used codeine
  • Co-occurring mental health issues
  • A genetic predisposition toward addiction

Certainly, the greatest contributing factors out of these are directly related to someone’s codeine use habits. The amounts of codeine someone used can most heavily affect the intensity of codeine withdrawal symptoms. The more someone uses the drug, the more downregulation occurs in the opioid system, thus the more imbalance their brain is during the acute phase of withdrawal. This may also affect the duration of withdrawal but in a more indirect way. The length of time someone used codeine has the strongest effect on the duration of post-acute codeine withdrawal symptoms. The longer someone used codeine, and subsequently kept their opioid system downregulated, the more extensive the neurological remodeling becomes. The more remodeling occurs, the longer it takes to reverse, thus the longer the post-acute codeine withdrawal symptoms will usually last.

Co-occurring mental health issues can contribute to the intensity of codeine withdrawal, but in a more indirect way than someone’s codeine use habits. Due to the fact that psychological symptoms like depression and anxiety are such common effects of codeine withdrawal, if someone has a pre-existing mental health issue they may experience worse psychological symptoms during withdrawal; both acute and post-acute. Additionally, it may take someone longer to recover from these psychological symptoms if they have a co-occurring mental health issue, especially a depressive or anxiety disorder.

Genetics definitely plays a role in addiction, although the exact extent of this role is currently unclear. It is known that addiction tends to run in families, indicating a genetic component that influences someone’s propensity for addictive behaviors. As far as this relates to withdrawal intensity or duration, it would be a tangential relationship at best. If someone has an increased likelihood of substance abuse, then they may, for example, begin using codeine in larger amounts earlier than someone with no such genetic predisposition. They may also use it much more regularly, thus leading to greater downregulation, remodeling, and subsequent withdrawal symptoms whenever they do quit using the drug.

Codeine Withdrawal Treatments

The challenges of overcoming codeine addiction can be great, and they often require help for someone to stand a realistic chance of successful long-term recovery. There are many treatments currently available for codeine addiction treatment, and more are being developed right now. The opioid crisis in America has prompted research into new and more effective treatments to help people heal from this sometimes devastating illness.

There are medications available to help treat the physical symptoms of codeine withdrawal, as well as some of the psychological symptoms, and therapies to help treat the psychological symptoms in both the short and long-term. Both of these treatment modalities can help someone to successfully complete withdrawal in a somewhat comfortable way, and help them develop new skills to build a new life in recovery.

Medications

A fairly recent medication, lofexidine (Lucemyra), was approved in 2018 by the FDA for the treatment of opioid withdrawal syndrome. This is the first non-opioid medication that is approved to treat opioid addiction, however, there are many other medications that have proven useful in this application. These may be used to treat individual symptoms as they arise, whereas lofexidine can treat many symptoms of codeine withdrawal, all at once.

Some of the medications most commonly used to treat codeine withdrawal include:

  • Antidiarrheals
  • Certain Blood Pressure Medications (usually for anxiety)
  • Sleep Aids
  • Antidepressants
  • Anti-Anxiety Medications
  • Antihistamines
  • Opioid Antagonists (for post-acute symptoms)

These are just some broad classifications of the medications used, and there are multiple choices per class. Some of these may be best used short-term, while others can safely be used for extended periods to treat some of the longer-lasting codeine withdrawal symptoms. Also, everyone is going to respond a little differently to certain medications, so thankfully, there are many options to choose from. Having the guidance and support of a professional codeine detox center can help someone find the most effective medication for them.

Therapies

Aside from medications, there is a variety of therapeutic techniques that have been found effective in treating codeine addiction. While these may not provide the immediate benefits that some medications can, they are nonetheless helpful and can make a decisive difference in the chances of someone’s successful, and long-term, recovery. While it often takes commitment and adherence to therapy practices, the benefits can be extremely helpful in reducing the psychological stresses and discomfort of post-acute codeine withdrawal.

Some of the therapies most commonly used to treat codeine withdrawal symptoms include:

  • Behavioral Therapy
  • Individual Counseling
  • Group Therapy
  • Addiction Education
  • Coping Skills Development
  • Aftercare Planning

Just like with medications, everyone is going to respond a little differently to different therapies. It may take time to find which approach can most effectively provide relief from someone’s unique needs and challenges. Having clinical therapists available to use as a resource and guide can greatly reduce the time it takes to find the most effective therapies. While it takes time, continued willingness, honesty, and self-examination can provide some very real benefits in the long run.

Entering a codeine detox center can provide professional therapists, clinicians, doctors, nurses, and psychiatrists who will mobilize the arsenal of modern medicine towards helping someone recover from codeine addiction. It may not seem like it at times, but there is a life after codeine, and this life can be as bright and vivid as someone wants; all it takes is the courage to ask for help, and the willingness to receive that help. Recovery doesn’t have to wait, it can start right now.

References For This Article

  1. 1 FDA AccessData: Codeine Sulfate Tablet Label
  2. 2 Pharmaceutical Methods: Recent Updates on Codeine
  3. 3 Clinical Chemistry: Plasma and Oral Fluid Pharmacokinetics and Pharmacodynamics after Oral Codeine Administration
  4. 4 British Journal of Anaesthesia: Codeine Phosphate in Paediatric Medicine
  5. 5 Mayo Clinic Proceedings: Opioid Metabolism
  6. 6 British Journal of Anaesthesia: Pharmacogenetics of Codeine Metabolism in an Urban Population of Children and its Implications for Analgesic Reliability
  7. 7 World Health Organization: Codeine and its Alternates for Pain and Cough Relief
  8. 8 The Pharmacogenomics Journal: Pharmacokinetics of Codeine and its Metabolite Morphine in Ultra-Rapid Metabolizers due to CYP2D6 Duplication
  9. 9 The New England Journal of Medicine: Codeine Intoxication Associated with Ultrarapid CYP2D6 Metabolism
  10. 10 The Journal of Clinical Investigation: Studies of the Mechanism of the Antidiarrheal Effect of Codeine
  11. 11 Handbook of Experimental Pharmacology: Insights into the Role of Opioid Receptors in the GI Tract - Experimental Evidence and Therapeutic Relevance
  12. 12 Journal of Gastroenterology: Physiology, Signaling, and Pharmacology of Opioid Receptors and Their Ligands in the Gastrointestinal Tract - Current Concepts and Future Perspectives
  13. 13 Neuropsychopharmacology: Reciprocal Catecholamine Changes during Opiate Exposure and Withdrawal
  14. 14 European Heart Journal Acute Cardiovascular Care: Heart Failure due to Stress Cardiomyopathy - A Severe Manifestation of the Opioid Withdrawal Syndrome
  15. 15 University of Pittsburgh Medical Center: Stress-Induced Cardiomyopathy Resulting from Abstinent Opioid Withdrawal
  16. 16 Anesthesiology: Sympathetic Neural Activation Evoked by μ-Receptor Blockade in Patients Addicted to Opioids Is Abolished by Intravenous Clonidine
  17. 17 Cerebral Cortex: Prefrontal Cortical Norepinephrine Release Is Critical for Morphine-induced Reward, Reinstatement and Dopamine Release in the Nucleus Accumbens
  18. 18 Biological Psychiatry: Neurobiology of Opioid Addiction - Opponent Process, Hyperkatifeia, and Negative Reinforcement

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