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Codeine Withdrawal Timeline

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

Written By: Phillippe Greenough

Article Updated: 11/22/2021

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.

In This Article:

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. 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.

A general overview of the codeine withdrawal timeline may look something like this:

Week 1

Depending on someone’s codeine use habits and specific genetics, symptoms will begin to appear within eight hours of the last codeine use. 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.

Symptoms that are commonly experienced during the first week of codeine withdrawal can 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)
  • Intense Anxiety
  • Depression
  • Irritability
  • Restlessness
  • Insomnia
  • Fatigue and Lethargy
  • Strong 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.

Week 2

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.

Some common symptoms that are experienced during the second week of codeine withdrawal can include:

  • Anxiety
  • Depression
  • Irritability
  • Restlessness
  • Insomnia
  • Fatigue
  • Cravings for Codeine
  • Minor Aches in the Muscles, Joints, and Bones
  • Diarrhea
  • Loss of Appetite

These are usually still very noticeable but have often improved significantly compared to the first week.

Weeks 3 & 4

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. The fourth week after the last codeine use usually shows a complete recovery from physical symptoms and only minor lingering psychological symptoms.

  • Anxiety
  • Depression
  • Irritability
  • Restlessness
  • Insomnia
  • Fatigue
  • Cravings for Codeine

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, recurrent cravings can make the idea of returning to codeine use 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.

Post-Acute Withdrawal

Post-acute codeine withdrawal is a minor, but long-lived form of the psychological symptoms of withdrawal. They can often persist for weeks, months, or sometimes even years in rare cases.

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

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

The post-acute symptoms of codeine withdrawal, while strictly psychological in nature, should not be underestimated. These symptoms can be disruptive and sometimes quite long-lasting and can act as a barrier to long-term recovery. Codeine relapse is a very real threat, 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.

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.

More About Codeine 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.

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.

Article References (In Addition to 5 in-article references)

  1. 1 Pharmaceutical Methods: Recent Updates on Codeine
  2. 2 Clinical Chemistry: Plasma and Oral Fluid Pharmacokinetics and Pharmacodynamics after Oral Codeine Administration
  3. 3 British Journal of Anaesthesia: Codeine Phosphate in Paediatric Medicine
  4. 4 World Health Organization: Codeine and its Alternates for Pain and Cough Relief
  5. 5 The Pharmacogenomics Journal: Pharmacokinetics of Codeine and its Metabolite Morphine in Ultra-Rapid Metabolizers due to CYP2D6 Duplication
  6. 6 The New England Journal of Medicine: Codeine Intoxication Associated with Ultrarapid CYP2D6 Metabolism
  7. 7 The Journal of Clinical Investigation: Studies of the Mechanism of the Antidiarrheal Effect of Codeine
  8. 8 Handbook of Experimental Pharmacology: Insights into the Role of Opioid Receptors in the GI Tract - Experimental Evidence and Therapeutic Relevance
  9. 9 Journal of Gastroenterology: Physiology, Signaling, and Pharmacology of Opioid Receptors and Their Ligands in the Gastrointestinal Tract - Current Concepts and Future Perspectives
  10. 10 European Heart Journal Acute Cardiovascular Care: Heart Failure due to Stress Cardiomyopathy - A Severe Manifestation of the Opioid Withdrawal Syndrome
  11. 11 University of Pittsburgh Medical Center: Stress-Induced Cardiomyopathy Resulting from Abstinent Opioid Withdrawal
  12. 12 Anesthesiology: Sympathetic Neural Activation Evoked by μ-Receptor Blockade in Patients Addicted to Opioids Is Abolished by Intravenous Clonidine
  13. 13 Cerebral Cortex: Prefrontal Cortical Norepinephrine Release Is Critical for Morphine-induced Reward, Reinstatement and Dopamine Release in the Nucleus Accumbens

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