Author: Lisa Conatser, LPC

Opioids are a class of drugs that include some legally prescribed painkillers as well as illegal drugs, such as heroin and illicitly synthesized fentanyl. These drugs typically induce sedative effects, such as those associated with morphine.¹ All opiates are opioids, though fully and semi-synthetic opioids are not opiates, which is a term now associated with byproducts derived naturally from the opium poppy plant.² But how do opioids work? All opioids impact the brain similarly, and misuse of these substances can lead to dependence and addiction.

In this article:

• How Do Opioids Work in the Brain?
• Why Do People Misuse Opioids?
• Why Do Some People Like Opioid Effects and Others Do Not?
• How Opioid Use Can Progress to Dependence and Addiction
• What Are the Long-Term Effects of Opioid Use?

How Do Opioids Work in the Brain?

Your brain releases natural chemicals like endorphins that help relieve pain and stress in your body. These natural chemicals function similarly to how opioids work in the brain.

Molecules attached to cells in your brain and body, called opioid receptors, regulate your breathing and the feelings of pain and pleasure.³ When opioid drugs reach those receptors in your brain, they cause a release of a chemical called dopamine. Dopamine will give you feelings of euphoria, pleasure, and peacefulness, which is why doctors prescribe opioids as a pain reliever.

How Opioids Influence the Brain’s Reward Circuit

Such neurochemical activity happens in the limbic system of your brain, which controls feelings of pleasure that motivate behaviors. An overabundance and repetition of dopamine surges in the limbic system across the brain’s synapses, especially when associated with opioid misuse, can lead you to repeat harmful behaviors.³

This is all considered part of your brain’s so-called reward circuit because when you take an opioid, you are rewarded with good feelings and then want to repeat the same behaviors to receive the same reward. Your brain learns and adapts according to the activity of this reward circuit. So, when these euphoric feelings are caused by and associated with the repeated misuse of opioids, dependence and addiction can result due to your brain adapting along this new pathway.³

Why Do People Misuse Opioids?

Opioids can be safe and effective when you take them as prescribed by a doctor. Some of the circumstances in which doctors prescribe opioids are:

• To reduce pain after a surgery
• To relieve chronic pain from conditions like cancer
• To alleviate short-term pain from an injury

The feelings of euphoria associated with opioids often lead to misuse of the drug. Your brain’s reward circuit can lead you to long for those good feelings, causing involuntary and unintended cravings for the drug. If you use opioids in the long term, even when legally prescribed, you raise your risk of tolerance to the drug, eventually leading to dependence and addiction, or even fatal overdosing.⁴

What Does Misuse Look Like?

Misusing opioids can happen in various ways:³

• Taking your prescribed opioid in any other way than instructed by your doctor (taking higher doses, using it more often, snorting it rather than swallowing a pill, etc.)
• Taking an opioid medication that is not prescribed to you (even if you are taking it to relieve pain)
• Using an opioid drug to feel the euphoria or the “high”
• Mixing your opioid medication with another drug that is cautioned against by doctors (like alcohol)

Misuse happens with both legal prescriptions—especially when you do not follow the use instructions by medical professionals—and illegal substances. How opioids work in the brain is similar in both legally administered versions of the drug and illegal opioids. Some of the legally prescribed opioids are:⁵

• Hydrocodone
• Oxycodone
• Fentanyl
• Buprenorphine
• Methadone
• Oxymorphone
• Codeine
• Morphine
• Hydromorphone
• Meperidine
• Tramadol

Some illegal opioids are:

• Heroin
• Synthetic fentanyl

Why Do Some People Like Opioid Effects and Others Do Not?

While there are pleasurable effects of opioid drugs, there can also be negative side effects that could make you dislike the drug. These may include:

• Dry mouth
• Gastrointestinal issues, including constipation or nausea
• Anxiety or feeling jittery
• Impaired concentration

Drug-liking behavior is dependent on a few factors, both biological and environmental. The more intensely you experience the pleasurable feelings related to opioid use, the more you will like the drug and want to use it again. What makes the feelings more intense could be impacted by several things:⁶

• Genetic variations in your brain and how your pleasure center operates
• Using opioids when you are not experiencing severe pain
• Taking a higher dosage than is prescribed
• Using opioids over a long period

When you do like the effects of opioids, your brain stores memories of what it felt like when you used the drug and other environmental factors associated with that experience. These memories are called conditioned associations.⁶ This is why certain people, places, or things can trigger a craving and increase your desire for opioids.

How Opioid Use Can Progress to Dependence and Addiction

Misusing opioids or using prescribed opioids for a long time can progress into a physical dependence on the drug. Your brain has a natural process of releasing a chemical called noradrenaline (NA) that manages your wakefulness, muscle tone, and respiratory functions. The progression of how opioid use begins to impact the release of NA in your brain is as follows:⁶

• Before opioid use, your brain produces natural chemicals that link to opioid receptors and activate enzymes that trigger the release of NA to maintain alertness, muscle tone, and respiration.
• When you use an opioid drug, it links to the opioid receptors, preventing those natural chemicals and enzymes from doing their job to release NA. This is what leads to the effects of feeling sedated and calm.
• Your brain will begin to compensate for this by increasing its supply of the enzymes needed to produce more NA even when the opioid drug is present. This means you will begin to experience less intense reactions to the opioid than when you first started using it and may increase your usage in an attempt to feel the same intensity.
• At this point, when you try to stop using opioid drugs, your brain is still producing an excessive amount of NA, but now without the inhibitory impact of the drug. This is what causes withdrawal symptoms.

As mentioned above, opioids also impact your brain’s reward system. Over time, your brain will come to rely on the opioid interaction to release dopamine, which means you may not feel pleasure from activities such as eating or exercise as you did before using opioids. This also leads to compulsive use and dependence on the drug.

What Are the Signs of Opioid Dependence and Addiction?

If you are concerned that you or someone you know may be misusing opioids, there are a few signs you can look for, including:

• The inability to stop using opioids, even when negative consequences occur
• Cravings for the drug
• Drowsiness
• Changes in sleep habits
• Weight loss
• Frequent flu-like symptoms
• Decreased libido
• Changes in exercise habits
• Isolation from family or friends

What Are the Long-Term Effects of Opioid Use?

Opioids not only have negative effects on your brain, but long-term use can also have an impact on other functions in your body. Long-term side effects of opioid use include:⁷

• Constipation
• Nausea, vomiting, and bloating
• Sleep-disordered breathing
• Respiratory depression
• Cardiovascular events
• Dizziness and sedation
• Increased risk of fractures
• Sexual dysfunction
• Infertility
• Compromised immune system

Many of the short-term and long-term effects of opioid misuse are reversible once you detox and stop using the drug.

Treatment does exist for opioid misuse and is very effective. Treatment often involves medically assisted detox and ongoing individual and group therapy to deal with underlying issues related to your drug use. If you or someone you know is misusing opioids, please call 800-934-1582(Who Answers?) to discuss treatment options.

Resources

1. Hemmings, H. C., Egan, T. D. (2013). Basic Pharmacology. In H. C. Hemmings & T. D. Egan (Eds.), Pharmacology and Physiology for Anesthesia: Foundations and Clinical Application (pp. 254-256). Elsevier/Saunders.
2. Offermanns, S., & Rosenthal, W. (2008). Opiates. In Encyclopedia of Molecular Pharmacology (2nd ed., p. 903). Springer.
3. National Institute on Drug Abuse. Prescription Pain Medications (Opioids). United States Department of Health and Human Services National Institutes of Health.
4. National Institute on Drug Abuse. Opioids. United States Department of Health and Human Services National Institutes of Health and Human Services.
5. National Library of Medicine. Pain medications – narcotics. United States Department of Health and Human Services National Institutes of Health.
6. Kosten, T. R., & George, T. P. (2002). The Neurobiology of Opioid Dependence: Implications for Treatment. Science & practice perspectives, 1(1), 13–20.
7. Baldini, A., Von Korff, M., & Lin, E. H. (2012). A Review of Potential Adverse Effects of Long-Term Opioid Therapy: A Practitioner’s Guide. The primary care companion for CNS disorders, 14(3).