What Happens During Opioid Withdrawal?


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When a person takes opioids for a prolonged period of time, they often develop a tolerance to the drug, meaning they need a larger dose to obtain the same effect. Over time, a person may become dependent on opioids, during which they begin to need them just to feel “normal,” otherwise they experience withdrawal symptoms.

Opioid withdrawal is a life-threatening condition that occurs when a person dependent on opioids stops or reduces their opioid intake. Withdrawal symptoms vary from person to person, but common symptoms include vomiting, digestive issues, and intense cravings for drugs. But what causes opioid withdrawal?

The Science of Opioid Withdrawal

The Locus Coeruleus

Many of the withdrawal symptoms associated with opioid use occur from changes in locus coeruleus, an area located at the base of the brain. Brain cells in the locus coeruleus are responsible for producing noradrenaline, which stimulates functions like wakefulness, breathing, blood pressure, and general alertness. Opioids suppress the production of noradrenaline, causing drowsiness, slowed breathing, and lowered blood pressure.

With chronic opioid use, the locus coeruleus increases the production of noradrenaline in an effort to normalize levels in the brain. Unfortunately, when a dependent person stops taking opioids to offset the increase in noradrenaline, they begin to feel anxious and jittery. They may also experience physical symptoms, like diarrhea and muscle cramps. These withdrawal symptoms are a key reason why many people struggle to stop using opioids.

Mesolimbic system

The mesolimbic system, also known as the reward pathway, is another area in the brain that may contribute to opioid withdrawal symptoms. The mesolimbic system is responsible for transporting dopamine from the ventral tegmental area (VTA) to the nucleus accumbens and the amygdala. The nucleus accumbens, specifically, is responsible for reward, desire, and the placebo effect.

When a person develops a tolerance to opioids, it may reduce the VTA’s release of dopamine into the nucleus accumbens. As a result, a person with opioid dependence may struggle to find pleasure in activities other than opioids.


Although uncommon, another consequence of opioid withdrawal is death. Death can occur as a result of two specific withdrawal symptoms: diarrhea and vomiting. If left untreated, persistent vomiting and diarrhea can lead to dehydration or elevated blood sodium levels, leading to heart failure.

It’s important to note that withdrawal-related deaths are preventable. Many documented cases of deaths resulting from opioid withdrawal occurred while individuals were neglected while incarcerated.

Assessing Opioid Withdrawal Symptoms

To assess withdrawal symptoms, clinicians use the Clinical Opioid Withdrawal Scale (COWS), an 11-point scale that measures the presence and severity of opioid withdrawal symptoms. The scale takes into consideration pulse rate, gastrointestinal symptoms (i.e., stomach cramps, nausea, loose stool, vomiting, or diarrhea), sweating, tremors, restlessness, yawning, pupil size, anxiety or irritability, bone or joint aches, gooseflesh skin, and a runny nose or tearing. The scale is designed to be used by clinicians in both inpatient and outpatient settings. Although many have argued the scale’s accuracy, it has been a helpful tool to those working with those experiencing opioid use disorder or addiction.

Reducing Opioid Withdrawal Symptoms

Opioid agonist therapy is highly effective in reducing withdrawal symptoms in those with an opioid use disorder. Opioid agonist therapy works by taking medications, such as methadone or buprenorphine, which activate the same receptors as the tolerated opioids, but slower or to a lesser extent. As a result, the person dependent on opioids does not experience a euphoric effect.

Instead, the medications allow the person to stop using opioids without the withdrawal symptoms and cravings that cause many people to relapse. The medicines used to treat opioid use disorder are also associated with remaining in recovery for longer and reducing the risk of overdose.

Opioid Use Disorder is Treatable

Opioid withdrawal symptoms are undesirable side effects of opioid dependence, and they are a key reason why people who use opioids continue to do so despite their adverse effects. By educating the public about opioid withdrawal and the treatment options available to help manage withdrawal symptoms, we can empower those with opioid dependence to seek treatment.

If you or someone you know is struggling with opioid addiction, effective help is available. Visit https://www.samhsa.gov/find-help/national-helpline for resources.

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