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Morphine Withdrawal & Detox

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 morphine withdrawal are very uncomfortable and sometimes even painful. The variety of body systems affected during withdrawal can lead to a very unpleasant experience, both physically and mentally. Here 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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Morphine Pharmacology & Addiction

Morphine is the oldest natural opiate drug that is still commonly used today, both illicitly and medically. It is the gold standard by which the potency of all other opiates and opioids are measured in a potency-to-morphine ratio. 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. 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 profound downregulation becomes. 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 necessary and normal degree. 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.

Symptoms of Morphine Withdrawal

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.

Some of the most common symptoms of morphine withdrawal include:

  • Diaphoresis (constant sweating)
  • Rhinorrhea (runny nose)
  • Diarrhea and Stomach Cramps
  • Shakes and Tremors
  • Insomnia
  • Increased Anxiety
  • Depression
  • Cravings for Morphine
  • Aches and Pains in the Muscles, Joints, and Bones
  • Severe Restlessness
  • Loss of Appetite
  • Nausea
  • Piloerection (goosebumps)
  • Hot Flashes and Chills
  • Increased Heart Rate
  • Elevated Blood Pressure
  • Allodynia (inability to experience pleasure)
  • Fatigue and Lethargy
  • Frequent Yawning

While this 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, services that are provided at morphine detox centers. These symptoms are not usually dangerous in otherwise healthy people, although the sometimes severe discomfort can be reduced through medical treatment. Again, if someone had underlying health conditions, then these symptoms may increase their risks of dangerous outcomes and medical care would be highly recommended.

Post-Acute Morphine 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 act as a barrier to successful and long term recovery.

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

  • Increased Anxiety (especially social anxiety)
  • Depression
  • Fatigue and Lethargy
  • Cravings for Morphine
  • Insomnia
  • Increased 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.

Morphine Withdrawal Timeline

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 ~3 hours, so 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 this, which we will explore in detail a little later.

First Week

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.

Second Week

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 week two. 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 resolved.

Third Week

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. 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.

Fourth Week and Onwards

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.

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 Center Guide

Physical Effects Of Morphine Withdrawal

While not usually life-threatening, the effects of morphine withdrawal can be very uncomfortable. The effects that chronic morphine use causes in the opioid system and downstream neurotransmitter systems can result in a variety of unpleasantness once someone stops using the drug. Since the opioid system is a major moderator of pain perception, dysregulation in this system can cause a wide range of very uncomfortable or even painful effects. This discomfort can be so profound as to be the main reason someone keeps using the drug. Someone may dread these withdrawal effects so much as to keep using morphine in a withdrawal-avoidance manner.

The two systems that are most heavily affected are the gastrointestinal tract and the autonomic nervous system. The digestive system is hardest hit out of these two, as morphine use can slow and depress digestive functions, resulting in gastrointestinal distress during withdrawal. Again, in a normal healthy person, the cardiovascular effects are mildly uncomfortable but combined with underlying health issues, this could cause real problems, sometimes even death although this is rare.

Gastrointestinal Effects

The effects of morphine withdrawal on the gastrointestinal system can be quite intense. Morphine is a strong agonist at μ-opioid receptors, and aside from the brain, these receptors are prevalent in the intestines. In the digestive tract, they act to slow and calm peristaltic intestinal contractions, mediate gastric emptying, and affect sphincter muscle tone. Through prolonged morphine use, these opioid receptors in the gut also undergo downregulation. Once someone begins morphine withdrawal, the natural opioid peptides in the body can’t stimulate these receptors strongly enough for them to calm gastrointestinal function to the proper degree. This results in general gastrointestinal hyperactivity and a great deal of stomach discomfort.

Probably the greatest and most common effect of morphine withdrawal on gastrointestinal function is the prevalence of diarrhea. The normal intestinal contractions that push feces through the intestines are accelerated during morphine withdrawal, as the downregulated μ-opioid receptors can’t slow them down. This results in food moving through the intestines more rapidly than normal, resulting in ineffective digestion and diarrhea. This can worsen other withdrawal symptoms as less nutrition is extracted from whatever food is eaten, potentially leading to malnourishment. Stomach cramps and nausea are also pervasive, although they usually pose slightly less discomfort than frequent diarrhea.

Cardiovascular Effects

Aside from pain management, the opioid system also affects heart function, both through receptors in the brain as well as opioid receptors in the heart muscles themselves. The exact relationship between heart-based opioid receptors and heart function is currently unclear, but it is known that one of the most obvious effects of morphine withdrawal is that heart rate and blood pressure often become elevated. This most likely has multiple causes and contributors, both psychological and physical.

A direct physical cause seems to be the elevated levels of the neurotransmitter norepinephrine during morphine withdrawal. This neurotransmitter is a precursor and mediator of epinephrine (aka adrenaline) levels in the brain and blood. Epinephrine is both a hormone and a neurotransmitter, depending on where it is found in the body. Acting as a hormone in the blood, it is a major facilitator of the fight-or-flight response; a survival mechanism that can boost physical and cognitive performance for brief periods. The consistently elevated levels of norepinephrine during morphine withdrawal can cause increased heart rate, elevated blood pressure, and increases in blood sugar levels.

Secondary Effects

Aside from these major systems that suffer major effects of morphine withdrawal, there are a variety of other processes that are affected as well. These mostly fall under the umbrella of the autonomic nervous system, but these are all very common symptoms of morphine withdrawal and are caused either directly or indirectly from opioid system disruption.

Other effects of morphine withdrawal on the autonomic nervous system include:

  • Shaking or Tremors
  • Insomnia
  • Dilated Pupils
  • Diaphoresis (constant sweating)
  • Rhinorrhea (very runny nose)
  • Body Temperature Instabilities
  • Blood Sugar Increases

A common effect with no known cause is:

  • Frequent Yawning

Psychological Effects Of Morphine Withdrawal

The psychological effects of morphine withdrawal, while not as directly uncomfortable as the physical effects, can be very prolonged. These may sometimes persist for months or even years. The psychological effects are mostly depressive and dysphoric in nature but can also include hyperactive symptoms such as anxiety and strong cravings. Medications and therapy may be able to reduce or manage the symptoms, but it will take some time after ceasing morphine use for the brain to return to normal.

Depression

Morphine use, and subsequent opioid receptor downregulation, can affect a variety of other neurotransmitters downstream of the opioid system. This includes dopamine and serotonin systems, and these can heavily impact depression and overall mood. Dysphoria is a common symptom of morphine withdrawal, and this is a general malaise or feeling of unease. For moderate-to-heavy or long-term users, this can manifest as full-blown depression. The disruptions to dopamine and serotonin systems can result in an inability to feel good and a lack of enthusiasm or motivation to do things that used to make someone happy.

Aside from downregulation, the remodeling that can take place after prolonged downregulation can make these changes more concrete and long-lasting. The brain is often able to undo these changes, but this can be a very slow process. These depressive psychological effects can persist for as long as it takes to reverse this remodeling, although symptoms usually improve slowly as this is occurring. It’s not uncommon for this process to take months, and may even take years in some cases.

Anxiety

Another very common symptom of morphine withdrawal, anxiety may have causes both physiological and behavioral. The strong calming and general depressant effects of morphine may cause mental atrophy of someone’s ability to deal with the normal stresses of life. The opioid system and κ-opioid receptors, in particular, can affect mental states and mood, including depression and anxiety. Through disruptions produced by morphine addiction, a variety of anxiety symptoms can emerge as effects of morphine withdrawal. This can commonly manifest as generalized anxiety and also present as increased social anxiety.

Aside from the neurotransmitter imbalances and opioid system disruptions, anxiety can result from psychological issues as well. Using morphine as a coping mechanism can be a very powerful habit, albeit a very unhealthy one. The sudden loss of such a strong psychological tool can leave someone nervous, anxious, and in fear. This can synergize with any neurological imbalances to produce anxiety, sometimes profoundly so. These anxious symptoms will resolve with time, but this can be a slow process.

Cravings For Morphine

Similar to anxiety, cravings can have both behavioral and neurological contributors. Firstly, chronic morphine use can affect dopamine levels, particularly in the nucleus accumbens, a component of the limbic system. The limbic system is known as the “reward center” of the brain and is a complex made up of multiple components. Several components of the limbic system including the nucleus accumbens, hippocampus, and amygdala experience strong increases in dopamine during morphine use. Through prolonged use, dopamine receptors in these brain regions can undergo downregulation, and if use is continued they will undergo further structural changes known as remodeling as well.

These changes to parts of the limbic system will cause someone to lose the ability to experience pleasure or any strong positive feelings for that matter until the brain starts to regain pre-morphine levels of function. The desire to feel good coupled with the strong memories of the pleasure produced through morphine use will naturally cause someone to crave morphine and think about it often. In addition to these neurological causes, the use of morphine as a coping mechanism may also contribute to cravings, similarly to the way it contributes to anxiety. The loss of such a powerful coping mechanism can leave someone feeling helpless, and this could, in turn, lead to craving morphine as a means to feel better about their situation.

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.

Morphine Withdrawal Treatments

Breaking free from morphine addiction is no easy feat, and more often than not it requires help. Thankfully, there are many options for treatment including medications, therapies, and specialized detox programs. Due to the high numbers of Americans needing opioid detox due to the opioid crisis, there has been a recent surge in research and development for opioid addiction treatments.

Morphine withdrawal, while rarely fatal, can be a very uncomfortable experience. Medications can reduce the uncomfortable physical symptoms, as well as some of the psychological ones, while therapies and counseling can give someone support and an emotional outlet during this often difficult time. In addition, entering a professional detox center can give someone referrals to further addiction care once detox has been completed.

Medications

Lofexidine was recently approved by the FDA to be used in the treatment of opioid withdrawal. Other than this medication, there are many effective options with a long track record that have proven effective at treating individual symptoms as needed. Some of these medications classes are used specifically during the initial phase of withdrawal, while others are strictly for the post-acute symptoms. There are also those that may be used throughout the entire morphine withdrawal syndrome.

Some medications commonly used to treat morphine withdrawal symptoms include:

  • Sleep Aids
  • Antidiarrheals
  • Anti-Anxiety Medications
  • Antidepressants
  • Opioid Antagonists (for post-acute symptoms)
  • Antihistamines
  • Certain Blood Pressure Medications (specifically β-blockers or α-agonists)

These are just the broad categories of medications used, and there are multiple medications available from each class. Some of the stronger examples of these classes may be used only for the physical effects of morphine withdrawal while some of the subtler medications can be used safely for long periods, such as antidepressants and blood pressure medications (for their anti-anxiety properties). Everyone has their own unique responses to medications, so it may take a few tries to find the most effective ones. This is where close medical supervision and support can really be critical.

Therapies

Aside from medications, therapies can be quite effective at reducing psychological morphine withdrawal symptoms. The therapeutic approach does not usually provide relief as immediately as medications, but they are nonetheless effective and helpful. Therapy can be especially helpful to those suffering from co-occurring mental health issues and/or those who suffered trauma either before or during their morphine use.

Some therapies that have proven effective for treating morphine withdrawal include:

  • Group Therapy
  • Individual Counseling
  • Behavioral Therapies
  • Coping Skills Development
  • Mindfulness & Meditation Practices
  • Aftercare Planning

Therapy can be an extremely useful tool towards building a stable foundation in recovery. Similar to medications, everyone will respond to certain therapies differently, so it may take some exploration to find the right one. This can depend on someone’s unique experiences or needs, as certain therapies are better for certain types of healing. Having trained psychiatric and clinical therapy professionals to guide, support, and advise someone through the experience of morphine withdrawal and detox can be invaluable and potentially life-changing.

Even though morphine withdrawal is rarely fatal, entering a morphine detox center is highly recommended. These centers have trained medical professionals on staff to help reduce the physical symptoms and mental health experts who can offer therapies and support for the uncomfortable psychological symptoms. Aside from making the ordeal less uncomfortable, having this kind of structure, support, and resources can increase someone’s chances of long term recovery. Life after morphine addiction is possible, but it often requires help. Luckily, help is available; all that’s required is the courage to reach out and ask for it.

References For This Article

  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 Addiction: Yes, People Can Die From Opiate Withdrawal
  8. 8 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
  9. 9 American Society of Addiction Medicine: National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use
  10. 10 Government of South Australia: Opioid Withdrawal Management
  11. 11 Biological Psychiatry: Neurobiology of Opioid Addiction - Opponent Process, Hyperkatifeia, and Negative Reinforcement
  12. 12 Pain Medicine: Opioids, Pain, the Brain, and Hyperkatifeia - A Framework for the Rational Use of Opioids for Pain
  13. 13 Journal of Pain and Symptoms Management: Pharmacokinetic–Pharmacodynamic Modeling of Opioids
  14. 14 Anesthesiology: Pharmacokinetic-Pharmacodynamic Modeling of Morphine-6-glucuronide-induced Analgesia in Healthy Volunteers - Absence of Sex Differences
  15. 15 Frontiers in Psychiatry: The Kappa Opioid Receptor - From Addiction to Depression, and Back
  16. 16 Depression and Anxiety: Kappa-Opioid Antagonists for Psychiatric Disorders -From Bench to Clinical Trials
  17. 17 Acta Pharmacologica Sinica: The Role of the Dynorphin/κ-Opioid Receptor System in Anxiety
  18. 18 Indian Journal of Psychiatry: The Limbic System

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