Medically Reviewed By: Benjamin Caleb Williams RN, BA, CEN
Written By: Phillippe Greenough
Article Updated: 01/24/2021
Number of References: 13 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. Fentanyl withdrawal may last around a week and some of the symptoms can include tremors, insomnia, deep depression, and intense anxiety just to name a few. 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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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.
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.
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.
A generalized overview of the fentanyl withdrawal timeline may go something like this:
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 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 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 first week, usually reaching their peak at around the fifth day since withdrawal symptoms began.
Some of the symptoms that could be expected during the first week of fentanyl withdrawal may include:
The acute phase is very intense and symptoms may begin about 12 hours after the last time someone used fentanyl. The psychological symptoms will typically begin slow, escalate quickly, and then plateau for several days or weeks during both acute and post-acute withdrawal.
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 worsening depression and strong cravings may also be expected. By the end of the second week, appetite should return to normal, and this will help stabilize any lingering stomach issues which are still present.
Some symptoms of fentanyl withdrawal which may be expected during the second week could include:
These symptoms should improve as the second week progresses, although they may still be present at a fairly high level overall.
By the third week, 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. 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.
Some symptoms that can persist throughout the third and fourth week may include:
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.
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:
These symptoms may often persist for many months to some degree, although they will reduce in intensity over time. This can be a psychologically 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 exercise, medications, and clinical therapy that can help ease the mental burden significantly.
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 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.
To understand fentanyl withdrawal a little better, it will be useful to know exactly how this drug works. Fentanyl is an opioid painkiller medication that 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 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.
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