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Morphine Withdrawal Timeline

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

Written By: Phillippe Greenough

Article Updated: 01/24/2021

Number of References: 22 Sources

The symptoms of morphine withdrawal are very uncomfortable and sometimes even painful. Morphine withdrawal can last around a week and symptoms include diarrhea, anxiety, deep aching, depression, and insomnia. In this article we will take a look at the mechanisms of morphine addiction, the effects and symptoms of morphine withdrawal, the timeline involved, and some effective treatments.

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Symptoms of Morphine Withdrawal

There can be a great deal of variation in the morphine withdrawal timeline between different people. This mostly has to do with post-acute symptoms, but even the acute and physical symptoms can differ; mostly due to someone’s morphine use habits. Morphine has a fairly short half-life of between 1.5 to 4 hours, although extended-release formulations can have half-lives of up to 13 hours. On average, withdrawal symptoms may begin about 6 to 8 hours after the last time someone used the drug. The acute symptoms of morphine withdrawal usually last a week or less and are followed by post-acute symptoms. The first week of withdrawal is fairly standard, usually only varying in the intensity of symptoms. The prolonged symptoms are where some substantial differences emerge between people and there may be many factors that influence them.

Morphine withdrawal can be divided into 2 distinct phases: acute and post-acute. The acute phase begins in the hours and days immediately after someone stops using morphine. This is the most physically uncomfortable phase of withdrawal. While rarely dangerous on their own, these symptoms may lead to dangerous complications if someone were to have a pre-existing health condition such as heart problems or diabetes. While the acute phase is by far the most uncomfortable phase of morphine withdrawal, it luckily does not last too long; usually about a week. These symptoms can be minimized and managed through medications and medical supervision.

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

Week 1

The first symptoms of morphine withdrawal are usually increased anxiety, sweating, and stomach discomfort. These usually start off quite mild and escalate over the next few hours and days. Chills and hot flashes may begin alongside insomnia and severe restlessness during the first night after symptoms began. Appetite often reduces or disappears and diarrhea is very common and usually occurs frequently alongside vomiting. Typically during the second day, someone will begin experiencing tremors and pain in their bones, joints, and muscles and may even have allodynia; sensations of pain from a normally non-painful stimulus. Cardiovascular effects are common and can include increased heart rate and elevated blood pressure. These symptoms will often escalate over the first two or three days, reach their maximum, and then slowly resolve over the next three days or so.

Some of the symptoms commonly experienced during the first week of morphine withdrawal can include:

  • Diaphoresis (constant sweating)
  • Rhinorrhea (runny nose)
  • Diarrhea and Stomach Cramps
  • Shakes and Tremors
  • Severe Insomnia
  • Increased Anxiety
  • Deep Depression
  • Intense Cravings for Morphine
  • Pain in the Muscles, Joints, and Bones
  • Severe Restlessness
  • Loss of Appetite
  • Nausea
  • Piloerection (goosebumps)
  • Hot Flashes and Chills
  • Tachycardia (rapid heart rate)
  • Hypertension (elevated blood pressure)
  • Allodynia (inability to experience pleasure)
  • Fatigue and Lethargy
  • Frequent Yawning

Week 2

The beginning of the second week usually shows some improvement, albeit minor. While most of the physical symptoms are often greatly improved, insomnia, sweating, and stomach issues usually last through a good portion of the second week. In addition, these symptoms may be joined by depression and cravings for morphine if they hadn’t already. Fatigue and lethargy are usually still common during this time, and appetite may be decreased, although it is usually better than the last week. Decreased appetite may be due more to psychological factors at this point, rather than physical symptoms. While diarrhea may have ceased by now, bowel movements are frequently very loose and uncomfortable. By the end of the second week, the physical symptoms are usually fully resolved.

Some symptoms that can be expected during the second week of morphine withdrawal may include:

  • Diaphoresis (constant sweating)
  • Rhinorrhea (runny nose)
  • Diarrhea
  • Minor Tremors
  • Moderate Insomnia
  • Anxiety
  • Moderate Depression
  • Strong Cravings for Morphine
  • Aches in the Muscles, Joints, and Bones
  • Restlessness
  • Reduced Appetite
  • Minor Nausea
  • Piloerection (goosebumps)
  • Hot Flashes and Chills
  • Allodynia (reduced ability to experience pleasure)
  • Fatigue and Lethargy
  • Frequent Yawning

Weeks 3 & 4

The third week often exhibits substantial improvement, as the physical and mental stresses of the most intense symptoms fade. Insomnia and bowel movements are usually well on their way to normal, and constant sweating has usually reduced greatly if not ceased. Energy levels may remain low and depression, anxiety, and cravings for morphine are often still present. After four weeks, someone will frequently be in a much better state, both physically and mentally. While psychological symptoms are usually still present, therapy and medications can reduce these while the brain repairs the damage done through prolonged morphine use. Anxiety, depression, and cravings may persist for several more weeks or months, and energy levels will take some time to return to normal.

Some symptoms of morphine withdrawal that may persist throughout the third and fourth week may include:

  • Anxiety
  • Depression
  • Cravings for Morphine
  • Mild Restlessness
  • Allodynia (reduced ability to experience pleasure)
  • Fatigue
  • Insomnia
  • Irritability
  • Frequent Yawning

This time can be crucial in someone’s recovery, as they begin to feel better it is not uncommon for someone to think they can safely use morphine again around this time. Continuing care and treatment are extremely important, even after the physical symptoms have resolved.

Post-Acute Withdrawal

The post-acute withdrawal symptoms will persist for longer than the physical symptoms, although their duration can vary greatly between individuals. These are strictly psychological symptoms, but they can nevertheless pose a grave threat to someone’s continued sobriety and recovery. Most commonly manifest as depressive or anxious symptoms, these may encourage someone to isolate and can act as a barrier to successful and long term recovery.

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

  • Anxiety (especially social anxiety)
  • Depression
  • Low Energy Levels
  • Cravings for Morphine
  • Minor Insomnia
  • Irritability

Post-acute symptoms may begin during the first phase of withdrawal alongside the physical symptoms, but they will persist far longer than the physical symptoms. That being said, the intensity usually reduces a good deal after the first few weeks or so and continues to do so the longer someone stays away from morphine use. Both medications and therapy can be quite effective at reducing these symptoms and providing healthy coping mechanisms for someone to deal with them in constructive ways.

What Factors Influence The Intensity Of Morphine Withdrawal?

Morphine withdrawal is a very unpleasant experience, to be sure, but the degree of unpleasantness can vary between people. Some factors that contribute to this variation are behavioral, while others are physiological in nature and thus beyond someone’s control. These factors can influence the duration as well as the intensity of morphine withdrawal symptoms.

Some factors that may affect the symptoms of morphine withdrawal include:

  • The duration of morphine use
  • The amounts of morphine someone used
  • Co-occurring mental health issues
  • A genetic predisposition towards addiction

The largest contributors to morphine withdrawal are certainly the duration of drug use as well as the amounts of morphine used. The duration of use most directly affects the duration of the post-acute, or psychological, symptoms of morphine withdrawal. The longer morphine is used, the more structural changes the brain undergoes in the form of remodeling. This is a slow process that takes time to perform, and thus takes time to undo after morphine use ceases. The amounts of morphine used can directly contribute to the intensity of physical and psychological symptoms, both short term and long term. The more morphine someone uses, the more downregulation occurs and thus the more intense the physical symptoms are once withdrawal begins. Likewise, the more downregulation occurs, the more remodeling can occur, thus the longer it takes to undo which results in more protracted psychological symptoms.

Co-occurring mental health issues may contribute to the psychological symptoms of morphine withdrawal, although this is in an indirect manner. Since depression and anxiety are very common effects of morphine withdrawal, if someone had either of these symptoms as a result of a pre-existing mental health issue they may experience more intense symptoms during withdrawal. Additionally, the risks may be increased regarding their chances of long term recovery, as relapse is a real threat, and the more severe the psychological symptoms during withdrawal, the higher the chance of relapse.

Genetics certainly influences someone’s chances of exhibiting addictive behavior, although the amount of influence, and the exact manner of influence, is currently unclear. It is possible that neuroplasticity is a factor, as this is the brain’s ability to adapt and change to circumstances, such as undergoing downregulation and remodeling. It may be that a higher degree of neuroadaptive potential can cause someone to become addicted to a drug more quickly than someone without such potential, as the brain can adapt to it quicker, thus producing withdrawal symptoms sooner.

More About Morphine Addiction

To get a better idea of the profound discomfort that morphine withdrawal produces, it may be helpful to understand how morphine works. Morphine is a pure opiate that is an opioid receptor agonist, or activator. It creates strong stimulation at all 3 major opioid receptors; the μ (Mu), δ (Delta), and κ (Kappa) receptors, although its strongest interaction is with the μ-opioid receptor. This strong interaction with the opioid system of the brain and body can produce various downstream effects in many other systems, including dopamine, serotonin, and norepinephrine neurotransmitter systems. Some of the direct effects of strong opioid receptor stimulation are the feeling of a strong euphoria, pain relief, relaxation, and drowsiness.

Once someone has been using morphine regularly for some time, the brain and body will begin to adapt. The general depressant effects of the drug will be reduced as the body makes changes to better operate in the continued presence of morphine. The brain and body undergo a process known as downregulation once they have been exposed to morphine, and the longer it is used the more downregulation occurs. This process is the desensitization of the opioid receptors that morphine activates, resulting in someone needing more of the drug to produce the same effects. This initially builds tolerance, and if done for longer periods, can lead to physiological dependence. Once someone develops dependence, continued use of morphine can lead to further, structural changes in the brain through a process called remodeling. This is a slow process that takes time to occur, and likewise, takes time to reverse once morphine use stops.

Once a physical dependence on the drug has developed, someone will become mentally and physically unwell if they go a while without using the drug. The opioid system becomes “downregulated” to such a degree that the natural opioid peptides made by the body cannot activate the opioid receptors to the degree necessary for healthy function. This produces withdrawal symptoms when someone suddenly stops using the drug, and these can become very uncomfortable. Additionally, the psychological symptoms of morphine withdrawal arise from these same problems and can last for extended periods, sometimes months or even years.

The Importance Of Morphine Detox

Morphine withdrawal symptoms, while not normally dangerous, are extremely unpleasant. Even if someone is not in life-threatening danger, it is still recommended to seek medical help. Aside from making the experience less unpleasant, entering a morphine detox center can improve someone’s chances of successful long term recovery. Not only do these centers act as a medical care facility, but they can also make referrals for further treatment and continuing care after detox has been completed. Entering one of these programs can provide a wealth of resources and give someone the support they need to successfully change their life.

Morphine Detox Centers

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

  1. 1 Merck Manuals Professional: Opioid Toxicity and Withdrawal
  2. 2 British Journal of Pain: Basic Opioid Pharmacology - An Update
  3. 3 Iranian Journal of Medical Sciences: Attenuation of Morphine Withdrawal Syndrome by Various Dosages of Curcumin in Comparison with Clonidine in Mouse - Possible Mechanism
  4. 4 Journal of Pediatric Neurosciences: Effect of Nimodipine on Morphine-related Withdrawal Syndrome in Rat Model - An Observational Study
  5. 5 Acta Pharmacologica Sinica: Clonidine Attenuates Morphine Withdrawal and Subsequent Drug Sensitization in Rhesus Monkeys
  6. 6 Journal of the American Pharmacists Association: Lofexidine Versus Clonidine for Mitigation of Opioid Withdrawal Symptoms - A Systematic Review
  7. 7 Journal of Clinical Pharmacy and Therapeutics: Opioid Withdrawal Symptoms, A Consequence of Chronic Opioid Use and Opioid Use Disorder - Current Understanding and Approaches to Management
  8. 8 American Society of Addiction Medicine: National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use
  9. 9 Government of South Australia: Opioid Withdrawal Management
  10. 10 Biological Psychiatry: Neurobiology of Opioid Addiction - Opponent Process, Hyperkatifeia, and Negative Reinforcement
  11. 11 Pain Medicine: Opioids, Pain, the Brain, and Hyperkatifeia - A Framework for the Rational Use of Opioids for Pain
  12. 12 Journal of Pain and Symptoms Management: Pharmacokinetic–Pharmacodynamic Modeling of Opioids
  13. 13 Anesthesiology: Pharmacokinetic-Pharmacodynamic Modeling of Morphine-6-glucuronide-induced Analgesia in Healthy Volunteers - Absence of Sex Differences
  14. 14 Frontiers in Psychiatry: The Kappa Opioid Receptor - From Addiction to Depression, and Back
  15. 15 Depression and Anxiety: Kappa-Opioid Antagonists for Psychiatric Disorders -From Bench to Clinical Trials
  16. 16 Acta Pharmacologica Sinica: The Role of the Dynorphin/κ-Opioid Receptor System in Anxiety
  17. 17 Indian Journal of Psychiatry: The Limbic System

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