How Do Opioids Affect The Brain

Opioids are among the most common addictions in the US, right after alcohol and nicotine. According to the Substance Abuse and Mental Health Administration, 1.1 percent of Americans aged 12 and above have an opioid use disorder. That’s close to 2.7 million people. It’s a dangerous class of drug that can have lasting effects on the brain and lead to a chronic substance use disorder. In this article, let’s take an in-depth look at opioids and their effect on the brain, how withdrawal symptoms occur, and what treatment options are available.

Opioids and the Brain: The Basics

When you hear the word opioids, the first thing that comes to mind is probably morphine, fentanyl, or other prescription painkillers. However, these are synthetic opioids, and they get their name from the body’s natural pain-relieving system. Let’s have a look at the endogenous opioid system and its receptors.

The Endogenous Opioid System

This is among the most widely researched pain-relieving systems. It comprises neurons scattered around the nervous system that produce dynorphins, met- and leu-enkephalins, and beta-endorphins. These are opioids that work as neurotransmitters at three main types of opioid receptors, mu, delta, and kappa, to create an analgesic effect. Just like the endogenous system, opioid drugs stimulate these receptors to form analgesia and unpleasant side effects.

Opioid Receptors (mu, delta, and kappa)

Endogenous opioids induce an analgesic effect by binding to opioid receptors, which exist in the central and peripheral nervous systems. Generally, these three receptors, mu, delta, and kappa, differ in terms of cellular distribution, the opioid ligands they bind to, and the specific effects they produce.

Each receptor type is activated by a different agonist. For instance, mu receptors bind to ligands such as beta-endorphin. Most available opioid analgesics activate the mu receptors, so they reproduce the effects of endogenous opioid peptides.

This is because activating the mu receptors is critical for dependence. The difference is that endogenous opioids can only reach a specific level of potency, while synthetic opioids are refined to have a much stronger effect.

How Synthetic Opioids Work in the Brain

Earlier, it says that synthetic opioids copy their endogenous counterparts, but how? Here’s how they work in the brain.

Mimicking Endogenous Opioids

The body’s natural pain management mechanism, the endogenous opioid system, comprises opioid peptides and receptors. Synthetic opioids have the same appearance as endogenous peptides, so the receptors can’t tell the difference.

Binding to Opioid Receptors

Because of their similarity to opioid peptides, opioids bind to the receptors, which are G proteins on nerve cells in different parts of the body. This process blocks pain impulses traveling through the spinal cord and towards the brain. Although they’re similar in the way that they relieve pain, they can lead to side effects and are very addictive.

The Effects of Opioids on the Brain

The effects of Opioids on the brain are almost instant, as it offers a euphoric feeling by flooding your brain with dopamine. Since your brain can grow dependent on this abundance of dopamine, it can fuel your addiction.

Pain Relief and Euphoria

Opioids can bind to the part of the brain called the reward circuit, which produces an emotional high and a feeling of euphoria. The feeling is induced by flooding the brain with dopamine, which is a hormone that produces pleasure when it interacts with the brain.

Inhibition of Pain Signals

These drugs can even attach to the opioid receptors in different nerve cells, which inhibits the brain’s ability to process pain. So without these pain messages reaching the brain, the perception of pain significantly reduces. Its ability to restrict these pain messages is the reason why it is used in many painkillers.

Release of Dopamine and the Reward System

Potent opioids can trigger a release of dopamine in the brain, which is that gives people the feeling of an emotional high. The increase in dopamine means that dependence on the drug can significantly increase, as trying to quit can even lead to withdrawal symptoms.

Sedation and Respiratory Depression

Finally, opioids affect the part of the brain that controls breathing, suppressing them and slowing down your breathing as a result. Because of slower breathing, less oxygen will make its way to the brain, which can possibly lead to a possible coma or permanent changes in the brain.

Dangers of Opioid Overdose

Overdosing on opioids can lead to feelings of lethargy and reduced consciousness. More severely, it causes respiratory depression, which can lead to complications and is often fatal. It’s when the lungs don’t exchange oxygen and carbon dioxide effectively.

When carbon dioxide levels in the blood increase, it leads to respiratory acidosis, characterized by increased pH levels in the blood. A notable identifier of respiratory depression is slow and ineffective breathing, and it’s the main cause of death in the event of an overdose.

Opioid overdose can also lead to depression of the central nervous system, commonly referred to as CNS. It includes symptoms like lethargy, confusion, and slowed heart rate.

Effects of Opioids on the Body

Opioids affect a lot more than just the mind, as various bodily functions can be hindered. Along with developing a possible dependence on these drugs, it can also induce serious constipation.


OIC, or Opioid-Induced Constipation, is one of the most common side effects of taking Opioids. It can paralyze the muscles in the gastrointestinal tract while squeezing out moisture from stool, making it hard. This constipation can be deeply uncomfortable, especially when it manifests in the form of abdominal pain.

Impact on the Nervous System

Relying heavily on opioids can do serious damage to the nervous system, as the abundance of dopamine continues to increase tolerance and dependence. As a result, withdrawal symptoms become severe, and people can usually suffer from depression and anxiety.

Tolerance and Dependence

The body can develop a tolerance to opioid levels so that it can optimally function. However, this increased tolerance also means that smaller doses of opioids will no longer offer the same pain relief.

With the minimal threshold for pain relief rising, an inability to get enough opioids to reach that threshold can lead to a person suffering from withdrawals.

Opioid Use Disorder and the Brain

It’s understood that opioids can affect the brain’s functions by inducing pleasurable feelings, but they can also lead to long-term effects. People with opioid use disorder show major changes in the brain and its processes.

Defining Opioid Use Disorder

Opioid use disorder is one type of substance use disorder. It’s characterized by a problematic pattern of misusing opioids, which results in impairment or distress. It’s a chronic disease with high rates of morbidity and mortality. That means it can result in the development of other disorders, such as mood disorders or alcohol use disorders, and even death. Due to the severity of withdrawal symptoms, the risk of relapse is high as well.

Changes in Brain Structure and Function

Based on research by the National Institute on Drug Abuse, prolonged use of opioids leads to changes in the brain’s medial temporal lobe and prefrontal cortex. One study that compared the brain matter volumes of people with and without opioid use disorder showed that the condition led to a volumetric loss in the amygdala.

The amygdala is located in the medial temporal lobe and is responsible for how we experience emotions. By changing the structure of these regions, opioids affect the brain’s reward, motivation, and self-control functions.

Altered Reward System

Opioids activate different brain circuits, one of which is the mesolimbic (midbrain) reward system. It works by generating signals in the ventral tegmental area, which cause the release of dopamine in the nucleus accumbens.

This release of dopamine leads to feelings of pleasure, and other parts of the brain form a memory that associates pleasurable feelings with the environment in which they occurred, i.e., in certain places or with specific people. This is a conditional association that leads to a craving for addictive substances whenever you come across that environment again.

Impaired Decision-Making and Self-Control

Research reviews show that the endogenous opioid system modulates major aspects of decision-making and cognitive control. The use of opioids can lead to reward-based decision-making because of a change in your valuation process. Therefore, you start to determine the worth of all actions based on whether they will lead to a reward and make a decision accordingly.

Opioid Withdrawal Symptoms

Long-term exposure to opioids can lead to physical dependence. It’s when the body finds it difficult to function without opioids, so when you stop taking the substance, you experience withdrawal symptoms. Opioid withdrawal syndrome can be life-threatening, and symptoms include dilated pupils, nausea, sleep disturbances, and autonomic hyperactivity.

Physical and Psychological Effects

When the opioid dosage is reduced, it can lead to withdrawal symptoms such as vomiting, irritability, restlessness, sleep disturbances, and diarrhea. Meanwhile, psychological symptoms can include the inability to experience pleasure, reduced motivation, depressed mood, and heightened feelings of anxiety.

The Role of the Brain in Withdrawal

When you first take an addictive substance, the pleasurable effects reinforce you to take it again. This can lead to tolerance, causing you to take the substance in greater doses as a way to achieve the initial ‘high.’

However, the absence of the substance can lead to negative emotions like depressed mood and anxious feelings. These stem from the extended amygdala, which is responsible for feelings of irritability, unease, and anxiety that come with substance withdrawal.

Once opioid use becomes an ingrained behavior, the main driver behind substance use is no longer positive reinforcement (achieving pleasurable feelings) but negative reinforcement (seeking relief from negative feelings).

Treating Opioid Use Disorder: The Role of Medication-Assisted Treatment

Although opioid use disorder is a chronic condition, treatment is possible as a way to manage symptoms and eliminate drug-seeking behavior. A crucial aspect of rehabilitative treatment is medication-assisted therapy. Because uncomfortable withdrawal symptoms increase the risk of relapse, medical professionals prescribe medication to alleviate symptoms. The luxury addiction treatment center can provide this therapy.

Methadone, Buprenorphine, and Naltrexone

Methadone, buprenorphine, and naltrexone are the three main medications that doctors prescribe during medication-assisted treatment. Methadone is a full-opioid agonist used for pain management and treating opioid use disorder. It reduces opioid cravings and withdrawal symptoms by blocking the effects of opioids.

Naltrexone works in a similar way and also blocks the effects of opioids. Meanwhile, buprenorphine is a partial agonist, so it binds to opioid receptors but doesn’t activate them as strongly as full agonists.

How Medications Can Help Restore Brain Function

The brain has an incredible ability to repair and heal itself. It does so by building new neural pathways as a way to adapt, a process called neural plasticity. While the brain can modify and reorganize itself after addiction, it will take time.

Factors like the period of substance abuse can affect how long the brain will take to heal. Regardless, the body must stop taking the addictive substance for the brain to start healing. That’s where medication-assisted treatment comes in.

By providing relief from uncomfortable withdrawal symptoms, medication can allow you to engage in activities that support neural plasticity.

Combining Medication with Counseling and Behavioral Therapy

Of course, there’s much more to the treatment process than just taking medication. The goal is to eliminate the urge to take opioids. For this, addiction specialists must address the psychological aspect of addiction.

Counseling is used in conjunction with medication to help you develop skills and self-confidence that help with recovery. Meanwhile, behavioral therapy is effective for developing new coping strategies when faced with situations that trigger urges.


Opioids are a class of substances that mimic the effect of opioid peptides in the body to produce pleasurable effects. As highly addictive substances, they can have long-lasting effects on the brain and bodily functions. Despite having a high potential for addiction and risk of relapse, treatment for opioid use disorder is still possible. With the right professional support and treatment plan, you can start your journey toward recovery.