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Fentanyl Withdrawal & Detox

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

Written By: Phillippe Greenough

Article Updated: 11/20/2020

Number of References: 12 Sources

Fentanyl has grown wildly in popular awareness recently as being a major contributor towards deaths due to the opioid crisis in America. Typically added to other drugs to boost potency, it is possible to become addicted to fentanyl and subsequently undergo fentanyl withdrawal. Here we will examine the particulars of fentanyl withdrawal including the symptoms and the timeline involved as well as the specific effects produced, both physical and psychological.

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What is Fentanyl Withdrawal?

Fentanyl withdrawal is similar to that of other opioid withdrawal syndromes, however, they do differ in terms of the time of onset as well as severity. Due to the intermediate half-life of fentanyl (between 3.5-12 hours), symptoms will emerge within hours of the last time someone used the drug. This differs depending on the exact analog of fentanyl someone was to use. There is a variety of fentanyl analogs that have increased potency, although as potency increases the half-life typically shortens. For the purposes of this article, however, we will stick to plain old fentanyl.

To understand fentanyl withdrawal a little better, it will be useful to know exactly how this drug works. Fentanyl is an opioid painkiller medication which is very similar to heroin and morphine, although it is much more potent than either. Its main mechanism of action is produced through very strong binding at the μ (Mu) opioid receptor as well as weaker binding at the κ (Kappa) and δ (Delta) opioid receptors. These receptors are part of the endogenous opioid system and are normally activated by endogenous opioid peptides. Endogenous just means that they are made inside the body. Fentanyl is an “exogenous” opioid, which means it came from outside the body. These opioid receptors are responsible for the perception of pain, aiding digestion, and maintaining reliable heart function among a wide range of other functions. Through the strong binding at these opioid receptors, large amounts of dopamine are released in the limbic system, also known as the “reward center” of the brain.

Through chronic use of fentanyl, these opioid receptors as well as parts of the limbic system undergo changes to balance out the constant, strong stimulation. This process is known as downregulation and is the brain’s attempt to protect nerve cells from neurotoxic overstimulation. If nerve cells get stimulated too strongly for too often they will suffer cell damage or even death, so this is the brain’s way of protecting itself. In effect, the brain will lower the number of opioid receptors and/or turn down the sensitivity of these receptors. This results in more fentanyl being required to produce the same effect.

This process of downregulation is responsible for tolerance to fentanyl and if use continues, physical dependence will be the end result. This occurs when downregulation has occurred (due to chronic fentanyl use) to the point where the brain and body will be unable to function properly unless someone continues to use fentanyl. The normal opioid peptides which are present in the brain will be unable to activate the opioid receptors since downregulation has lowered receptor numbers and raised their stimulation threshold above their ability to activate. This is where fentanyl withdrawal symptoms will begin to appear.

The Importance Of Detox

The symptoms of fentanyl withdrawal are extremely unpleasant and can even be dangerous in certain circumstances. Because of this, it is highly recommended for someone who is expecting to undergo fentanyl withdrawal to enter a fentanyl detox center. These centers have trained medical professionals, medications, and therapies to help minimize the discomfort and risks of fentanyl withdrawal, and to help someone establish a firm footing in recovery. Obtaining professional detox care can improve someone’s chances of long-term recovery, thereby reducing the risks of overdose and death that are commonly associated with fentanyl.

Finding a Fentanyl Detox

Fentanyl Withdrawal Symptoms

Acute withdrawal from fentanyl is by far the most uncomfortable phase and begins within hours of the last time someone used the drug. This phase is characterized by intense physical symptoms which can last around a week in addition to emerging and worsening psychological symptoms.

Some of the most frequently reported symptoms of fentanyl withdrawal include:

  • Intense Anxiety
  • Worsening Depression
  • Diaphoresis (extreme sweating) and Rhinorrhea (very runny nose)
  • Shaking and Tremor
  • Hot Flashes and Chills (commonly described as someone feeling hot inside, and cold outside)
  • Diarrhea and Nausea
  • Muscle, Joint, and Bone Pain
  • Insomnia
  • Extreme Restlessness and Irritability
  • Allodynia (perception of pain from normally non-painful stimulus)
  • Fatigue and Lethargy
  • Tachycardia and Hypertension (increased heart rate and blood pressure)
  • Lack of Appetite
  • Constant Yawning

The acute phase is very intense and symptoms may begin about 12 hours after the last time someone used fentanyl. The physical symptoms may begin mild, but will rapidly escalate over the next few days, usually reaching their peak around three or four days after they began. The psychological symptoms will typically begin slow, escalate quickly, and then plateau for several days or weeks during both acute and post-acute withdrawal.

Post-Acute Withdrawal Symptoms

The post-acute withdrawal phase is significantly less intense but much longer lived, typically lasting for many weeks, months, or even years in some cases. This phase is characterized by strictly psychological symptoms which include very strong and persistent cravings for the drug. It is highly recommended to seek psychiatric support during post-acute withdrawal from fentanyl, as the psychological issues, if left untreated, greatly increase the risk of relapse.

Some of the most commonly experienced symptoms of post-acute withdrawal from fentanyl include:

  • Deep Depression
  • Strong Cravings for Fentanyl
  • Intense Anxiety (social anxieties in particular)
  • Insomnia (commonly manifests as difficulty falling asleep)
  • Fatigue and Lethargy
  • Constant Yawning

These symptoms may often persist for many months to some degree, although they will reduce in intensity over time. This can be an extremely uncomfortable and difficult time, as the subjective experience can make it seem like life without fentanyl is just not worth living. This attitude will improve with continued abstinence and therapies, medications, and support services that can help ease the mental burden significantly.

Fentanyl Withdrawal Timeline

The fentanyl withdrawal timeline is quite similar to many other opioids. It is always the most intense early on and will reduce substantially after the first week. The dramatic neurotransmitter disruptions produced through chronic fentanyl use will take time to heal and resolve, and discomfort should be expected while this happens. While the experience may vary somewhat between people, there is a fairly common symptom set and timeline. For most people, the experience will be a protracted ordeal, and medical help is highly recommended, especially in the first few weeks.

First Week

Due to the half-life of fentanyl being under 12 hours, someone can expect withdrawal symptoms to begin between 12 and 24 hours depending on their use habits. The first symptoms to appear are commonly growing anxiety, sweating, extremely runny nose, and mild tremor. An increasing restlessness and irritability will then emerge, with heart rate and blood pressure beginning to rise. Next, aches in the muscles, joints, and bones may begin accompanied by stomach cramps and frequent diarrhea. The first night will exhibit minor insomnia combined with profound fatigue and lethargy which will steadily worsen. These physical symptoms will intensify over the majority of the first week, usually reaching their peak at around the fifth day since withdrawal symptoms began.

Second Week

The second week may begin to exhibit some relief from the physical symptoms. By the beginning of the second week, there should be a significant reduction in the physical symptoms with the exception of sweating, yawning, and restlessness. Insomnia should still be present, although it may begin to improve towards the end of week two. Anxiety will still be very much present and is usually joined by depression and strong cravings. By the end of the second week, appetite should return to normal as well, and this will help stabilize any lingering stomach issues which are still present.

Third Week

By this time, there is commonly a significant improvement in someone’s symptoms and state of mind. While depression, anxiety, and cravings are still present, the worst of the physical symptoms will mostly be resolved. Insomnia may linger to some degree and energy and motivation levels will still be low most likely, but this may be the first time someone sees light at the end of the tunnel of fentanyl withdrawal.

Fourth Week and Onwards

The fourth week will be slightly better than the third week, with the physical symptoms being fully resolved by now. While insomnia may not be a serious issue, it may still be somewhat difficult to fall asleep. Cravings and depression should still be present, but anxiety may lighten by this point. Energy levels may be closer to normal by this time, but still a little low. It may take several more months for the rest of the symptoms to fully resolve, and treatment may be able to reduce the discomfort and speed this process along.

What Happens to Your Body During Fentanyl Withdrawal?

The physical effects of fentanyl withdrawal are not directly life-threatening but they are extremely uncomfortable and oftentimes painful. The severity of the neurotransmitter disruptions produced through fentanyl will result in the brain and body being thrown into chaotic disarray during withdrawal. The opioid system has effects on many other body systems, and this will be illustrated in visceral detail throughout the withdrawal experience. This will produce a variety of effects on multiple physical systems which includes:

Cardiovascular Effects

Due to the regulatory role that the opioid system indirectly plays in the cardiovascular system, disruptions in heart function are common symptoms of fentanyl withdrawal. Additionally, the withdrawal-induced increases in the neurotransmitter norepinephrine, an adrenaline regulator, will lead to increased blood pressure and heart contractility.

The calming effect that the opioid system normally has on heart rate will be absent during withdrawal and combined with the other symptoms of fentanyl withdrawal, someone’s heart rate will be elevated. The increased presence of adrenaline will amplify this effect as well. Adrenaline is a major contributor to the fight-or-flight response, so increased levels act to keep the body pumped up and hypervigilant. These two effects will combine to increase the discomfort of fentanyl withdrawal, and may increase health risks to those who have pre-existing heart conditions.

Gastrointestinal Effects

One of the ways that fentanyl prices its effects is through stimulation of μ opioid receptors. These exist in large numbers in the brain as well as the digestive tract. While they serve on function in the brain, their role in the gut is entirely different. In the GI tract, they act to control the stomach and intestinal muscles and aid digestion. Through chronic fentanyl use and subsequent downregulation, once fentanyl is removed this regulatory control is reduced, resulting in accelerated gut motility.

The most apparent effect of fentanyl withdrawal in the digestive tract is diarrhea. This is due to the intestinal muscles behaving in a hyperactive manner since they do not have the calming effect of μ opioids to slow and moderate them. This acts to push food through the intestines much more quickly than normal and prevents effective digestion. During fentanyl withdrawal, not only is someone not getting adequate nutrients from their food but they are also unnecessarily purging fluids which will result in dehydration. These gastrointestinal effects can worsen the other symptoms and make the subjective experience much more unpleasant.

Peripheral Effects

The peripheral effects of fentanyl withdrawal are quite variegated and do not necessarily fit into one body system. The wide range of physical processes that the opioid system effects are impressive and many of the symptoms of fentanyl withdrawal would seem totally unrelated to the pain relief this drug was originally intended for.

Some effects which result from increased norepinephrine or adrenaline include:

  • Dilated Pupils
  • Restlessness and Irritability
  • Insomnia
  • Shaking and Tremors

Some of the effects which result from endocrine or exocrine system disruptions include:

  • Blood Sugar Fluctuations
  • Diaphoresis and Rhinorrhea
  • Hot Flashes and Chills

Psychological Effects of Detoxing

The psychological effects of fentanyl withdrawal, while less obvious, can be more difficult to overcome than the physical symptoms. The very fact that they cannot be seen from the outside and their long duration can lead to someone suffering in silence unless they have the appropriate treatment and care. This experience can be very demoralizing and may seem hopeless at times. Time will heal these issues, but treatment can help while this healing occurs.

Cravings For Fentanyl

Cravings for fentanyl are by far the most commonly reported symptom during post-acute withdrawal. These cravings are due not only to the depressed mental states associated with fentanyl withdrawal but also to changes in the limbic system produced through fentanyl addiction. The limbic system is a major player in motivation and desire for satisfaction, and the strong connections that are made between pleasure and fentanyl use will greatly influence someone’s behavior and thoughts.

The dopamine disruptions which occur in parts of the limbic system will forge very strong unconscious relationships between any feeling of reward and pleasure to memories of fentanyl use. The strength with which fentanyl stimulates both the opioid and limbic systems will result in someone losing the ability to feel pleasure from normal activities and behaviors. The end result is that someone will unconsciously associate “feeling good” with using fentanyl. Due to the extremely negative experience of fentanyl withdrawal and the desire for relief, it is only natural for someone to crave and maybe obsess about using more fentanyl. These cravings will fade with time, but they can be extremely intense early on in fentanyl withdrawal.


Depression is an extremely common symptom of fentanyl withdrawal. While closely related to and heavily influenced by cravings, these are two distinct effects. The depression is a deep and overwhelming sensation of loneliness, hopelessness, and futility. The sense that all of the good times are behind someone will make life seem very bleak and pointless. In addition, the anxiety that frequently accompanies fentanyl withdrawal will work to encourage isolation and keep someone disconnected, further creating a sense of loneliness.

In addition to the neurological causes, the sudden loss of such a powerful, although unhealthy, coping mechanism can contribute to anxiety as well. The profound changes to dopamine, serotonin, norepinephrine, and opioid neurotransmitters will cause the brain to be very volatile during fentanyl withdrawal. This commonly manifests as depression, but may also cause wild mood swings. While antidepressants may help reduce the symptoms, psychological therapies have proven extremely effective at reducing depression related to fentanyl withdrawal as well. These psychological symptoms will all compound and amplify each other, so it is crucial that someone reaches out for help.

Increased Anxiety

Symptoms of anxiety are another extremely common psychological effect of fentanyl withdrawal. The exact causes are unclear, but it certainly involves abnormal levels of the neurotransmitter norepinephrine, and subsequently adrenaline. The opioid system, and in particular the κ opioid receptor, is known to influence levels of norepinephrine in the brain and blood. Disruptions in this system can lead to heightened awareness, anxiety, and vigilance.

These anxious symptoms can amplify the severity of cravings, and the isolationist tendencies encouraged by anxiety may worsen depression. These effects, while caused by fentanyl withdrawal, can feed off of each other and synergize to keep someone unwell and in pain. Seeking treatment for these psychological symptoms is highly recommended.

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What Factors Influence the Intensity of Withdrawal?

While fentanyl withdrawal is fairly standard, there is still quite a bit of symptom variability between individuals. There are several factors that can contribute to the intensity and the duration of fentanyl withdrawal. While some of these are choices someone makes, others are entirely beyond their control. Some people may make a complete recovery within weeks, while others may suffer intense symptoms for many months.

Some factors which can heavily influence both the intensity and duration of fentanyl withdrawal include:

  • The amounts of fentanyl someone used
  • The length of time that someone used fentanyl
  • A genetic predisposition for addiction
  • Co-occurring mental health issues

The factors which have the greatest impact on both the intensity and duration of fentanyl withdrawal are the amounts and length of fentanyl use. The amounts of fentanyl someone used will directly affect the degree of downregulation that the brain performs. The greater the degree of downregulation, the more intense the symptoms will be. Likewise, the longer someone uses fentanyl the more complete downregulation will become. This will subsequently take longer to reverse once fentanyl withdrawal has begun, resulting in a longer withdrawal period.

Genetics and pre-existing mental health issues both contribute to withdrawal, but in a more indirect manner. Addiction has some genetic component which makes people more or less susceptible to engage in addictive behaviors. This may also speed up the progression of their use leading to larger quantities used, and used with greater frequency. Mental health issues such as depression occur very frequently with addiction, and while the exact relationship is unclear they certainly affect each other. Someone with depression may be more likely to use fentanyl more frequently and accelerate their use more rapidly than someone who does not suffer from depression. While not necessarily a cause of fentanyl use, there is certainly a strong correlation.

Fentanyl Withdrawal Treatments

There are a variety of treatment options available for the professional care and treatment of fentanyl withdrawal. These treatment options will absolutely give someone a better chance of long-term recovery, as well as a less unpleasant experience while undergoing fentanyl withdrawal. The first step is finding a fentanyl detox center to help with the acute withdrawal phase. These centers are staffed by medical professionals and offer the most effective medications, therapies, and support services for the treatment of fentanyl withdrawal.

While withdrawal from fentanyl is not directly life-threatening on its own, it is extremely uncomfortable. The medications and medical monitoring provided by these fentanyl detox centers will be able to reduce the discomfort and the risks during this intense experience. Additionally, having supportive therapies will greatly reduce the risk of relapse, and help to give someone a solid foundation in recovery.


There is currently only 1 non-opioid medication that is FDA approved for the treatment of fentanyl withdrawal, but there is a wide range of other medications that can effectively treat individual symptoms as they arise. The goal of these medications is to minimize the discomfort and risks of withdrawal and help someone to make it through the experience as safely and comfortably as possible.

Some of the most commonly used classes of medication which are used in the treatment of fentanyl withdrawal include:

  • Other, Weaker Opioids
  • Antidepressants
  • Anti Anxiety Medications
  • Blood Pressure Medications (such as α agonists or β blockers)
  • Non-Narcotic Sleep Aids
  • Antidiarrheals
  • Antihistamines

This is just a broad and simple rundown of some of the most common medications, but there are certainly others. Some of these are strictly for treating the acute phase, while others are more applicable to the post-acute phase. Additionally, different people will find certain medications more or less effective, so seeking medical help to discover an individual’s preference is critical.


In addition to medications, there are multiple therapies that can help in the treatment of the psychological symptoms of fentanyl withdrawal. The intense cravings, depression, and anxiety may benefit from therapeutic and clinical treatment options and help prepare someone for life after fentanyl. As with the medications, some people will find certain therapies more effective than others, but there are some common and effective treatments that are frequently used.

Some of these treatments include:

  • Behavioral Therapy
  • Group and Individual Counseling
  • Nutrition Classes and Fitness Therapy
  • Addiction Education
  • Coping Skills Development
  • Aftercare Planning

These are just a few therapeutic techniques that have proven effective, but there are many others. Finding the most effective treatment is part of each individual’s journey, and entering a fentanyl withdrawal and detox treatment center will give someone the resources to discover which treatment options are right for them.

The first step in fentanyl addiction treatment is often to enter a fentanyl detox center. These facilities can help someone through the worst of the physical withdrawal symptoms and refer them to further treatment options with which to continue their recovery. Having as many tools as possible will be a huge benefit, and these centers will provide someone with a wealth of tools. Life after fentanyl addiction is possible, but it may not be easy. Someone will need as much help as they can get, and help is available so long as someone is able to speak up and ask for it.

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