Why Are Opioids So Addictive?

Opioids bind to opioid receptors and trigger the release of dopamine, a neurotransmitter that is associated with reward and pleasure.[1] This creates a feeling of euphoria, which leads to an urge for more opioids. 

This cycle of drug use gains momentum over time. People who start with small doses, quickly find that a low dose no longer gives them the high they first experienced. To experience that effect again, they take a higher dose until that no longer works.[2] 

Over time, people take higher and higher doses. This ultimately builds up to a high-dose daily opioid addiction that can be almost impossible to break away from without medical intervention and treatment. 

What Makes Opioids So Addictive? 

For most people, it is possible to take a prescription opioid like OxyContin or codeine for a brief period without developing an addiction. For others, however, even short-term use can lead to a psychological dependence long before physical tolerance begins. 

Why do some people develop an addiction to opioids and others don’t? Several factors can contribute to the development of an addiction disorder, such as genetics, environment, and stress.[3] While not everyone will experience all these factors, most people who develop an opioid use disorder (OUD) will struggle with one or more.

These are some of the reasons that opioids are so addictive:

Opioid Receptors

Opioid receptors are part of the body’s natural ability to regulate pain, identify rewarding behaviors, and develop addictive behaviors. Opioid receptors are located within the nervous system, embedded in the outer part of nerve cells. When opioid molecules attach to these receptors, the chemical changes lead to feelings of pleasure and pain relief.[9]

The mesolimbic (or midbrain) reward system is activated by opioid drugs. Signals release dopamine in both the ventral tegmental area (VTA) and the nucleus accumbens (NAc), which causes feelings of pleasure. The brain takes a snapshot of this moment, associating the good feeling with the circumstances and environment in which the person takes drugs. These associations can make people crave drugs when they encounter similar circumstances.[6]

Effect on Dopamine

The brain’s reward system is designed to help us remember the people, places, and things that keep us alive. Dopamine signals make this possible. When we do something rewarding (like eat a nutritious meal), our brains release dopamine to encourage us to eat a similar food in the future.

Opioid drugs cause the brain to release an unusual amount of dopamine. Researchers at Yale Medicine say drugs can prompt the brain to release up to 10 times the amount of dopamine the brain might produce in response to a natural trigger.[10]

That dopamine release can harm brain cells, making them less responsive to the dopamine the body can produce naturally. People may keep using drugs to stave off depression caused by the damage.[10]

Dopamine can also tie simple triggers (like a person’s voice) to a profound craving for drugs that’s almost impossible to ignore.[10] These cravings can prompt people to take drugs even when they don’t want to do so.

Rising Opioid Tolerance

Opioid tolerance happens when the brain has been exposed to opioids and has changed as a result. People need to take bigger doses to achieve the effects that smaller doses once produced.

Researchers say tolerance develops because brain cells with opioid receptors become less responsive to the drugs. They point out that more opioids are needed to stimulate the VTA and the NAc. These key parts of the brain’s reward system won’t respond unless more drugs are available.[6]

The locus coeruleus in the brain also plays a role. Neurons in this part of the brain produce adrenaline to keep us awake, breathing, and alert. When people take drugs and they attach to the locus coeruleus, they feel sedated as a result. 

However, when people use opioids often, the locus coeruleus changes and produces jitters, anxiety, and muscle cramping when the drugs aren’t available. These changes can make people take drugs just to avoid feeling sick.[6]

Taking larger and larger opioid doses is dangerous. People who take too much may experience a life-threatening overdose.

Physical Dependence & Opioid Withdrawal

Physical dependence occurs when the body adjusts its function based on the presence of opioids in the system. Over time, chronic opioid use can change the brain, creating a need for opioids in order to achieve balance within the system.[6]

Because the body and brain perceives that opioids are necessary for basic functioning, if levels of opioids in the system drop, withdrawal symptoms appear quickly. They may include anxiety, restlessness, muscle aches, nausea, and intense cravings for the drug.[7] 

Because opioid withdrawal symptoms can last for weeks and be so intense, many people relapse when they try to stop using opioids. For this reason, it’s recommended to undergo opioid detox with the support and supervision of addiction treatment professionals. Relapse during a period of abstinence can be fatal. 

Psychological Dependence

Psychological dependence occurs when an emotional dependency on opioids develops, causing the person to feel compelled to use the drugs. This may develop before or after the physical dependence, but it is more common among those who are struggling with chronic pain or a mental health disorder like anxiety or depression that is soothed with the use of opioids. 

When this happens, the person may feel that they are unable to handle their mental health symptoms or their chronic pain without the use of opioids. As a result, they compulsively use opioids.

Availability

When opioids are readily accessible, people may try them, even if they never would have sought them out on their own. This can happen in a home where unused medications are stored in community medicine cabinets. For this reason, safe disposal of all excess opioid painkillers prescribed for the management of acute pain after an injury or surgery is recommended.[8] 

Potency

The potency of a given opioid can also increase the likelihood of addiction development. The stronger the drug is, the more intense the high experienced, and the more likely it is that someone will continue to seek out the drug.

What Does an Addiction Cycle Look Like?

In 2016, the U.S. Surgeon General published a report about substance use in America. Within that report, experts outlined an addiction cycle made up of three phases. Understanding what they are could be useful in understanding why opioids are addictive.

The addiction cycle involves the following three phases:[11]

• Intoxication: The person uses an intoxicating substance and experiences the pleasure and reward associated with them. The basal ganglia in the brain is deeply involved in this stage. The nucleus accumbens is involved in motivation and reward, and the dorsal striatum helps to form habits.
• Withdrawal: The drug begins to wear off, and the person experiences negative physical and emotional states. The extended amygdala is involved at this stage. This part of the brain is responsible for responses like “fight or flight” and stress.
• Anticipation: The person seeks out substances again. The prefrontal cortex in the brain, which helps to plan and prioritize, makes this step possible.

These steps repeat. Some people move through these stages several times in one day. With each repetition, the brain can develop a “changed set point,” at which dopamine levels are lowered and stress-related chemicals rise. Eventually, experts explain, the person will take more drugs to force the brain to release more dopamine, and when they don’t take drugs, they feel intense distress at the absence of the chemical.[6]