How Do Opioids Affect the Brain and What Are They?

If you've ever broken a bone or undergone surgery, you might have received a type of medication known as an opioid. When used as directed, opioids are a safe and effective way to alleviate pain. But they can also be dangerous and even deadly.

Heroin, a notoriously addictive illicit opiate, is responsible for approximately 36 overdose-related deaths per day in the United States, per the Centers for Disease Control and Prevention (CDC). However, similar drugs, including those manufactured for legitimate medicinal use, also contribute to thousands of deaths annually.

Understanding what opioids are and how they work can help you make safe, informed choices regarding your health and that of your loved ones.

What are opioids?

"Opioids are an umbrella term that includes both illegal substances and manufactured prescription medications," said Christine DeFranco, D.O., an emergency medicine physician at Holy Name Medical Center in Teaneck, New Jersey.

The terms 'opiates' and 'opioids' are incorrectly used interchangeably. What's the difference between opioids and opiates? Technically, opiates are natural substances derived from the poppy plant, while opioids are synthetically manufactured, per the State of Oregon Alcohol and Drug Policy Commission.

In a medical setting, opioids are prescribed to alleviate moderate to severe pain, according to DeFranco. Doctors usually prescribe them to treat acute pain, or pain that has a known cause and lasts less than three months, per the CDC. Common examples include post-operative pain and pain associated with a severe injury, such as a fracture. Opioids are also frequently prescribed to relieve cancer pain.

In recent years it has become increasingly customary to prescribe opioids for chronic, non-cancer pain, including back and arthritis pain, according to the CDC. But this usage is controversial, according to Paulo Negro, Ph.D., M.D., a medical and addiction advisor at All Sober in Maryland. That's because little evidence suggests opioids are effective for long-term use and ample proof indicates there are long-term opioid use complications. They can be dangerous.

What are the various types of opioids?

Opiates and opioids are available in several forms and formulations. All work similarly, and most produce comparable effects, though their potency runs the gamut from mild to extreme.

Opium, a narcotic extracted from poppy seeds, has been used since about 3400 B.C.E. for medicinal and recreational purposes. It is still cultivated and used worldwide, but most pharmaceutical companies and illegal drug manufacturers produce variations of the drug. Morphine, codeine and heroin can all be made with poppy plant derivatives.

Opioids, which account for most prescription types, are made entirely in a lab. But some, such as hydrocodone (Vicodin), hydromorphone (Dilaudid) and oxycodone (Oxycontin and Percocet), may be partially made from natural materials, according to the state of Oregon.

There are more than 500 types of pharmaceutical opioid chemicals, according to the state of Oregon. Some medications that contain opioid molecules like dextromethorphan are available over the counter in the form of common cough suppressants. However, most are only available via prescription.

Well-known opioid medications include fentanyl, methadone, dextropropoxyphene, loperamide, oxymorphone and meperidine.

Per the CDC, more than 191 million opioid prescriptions were dispensed in the United States in 2017, with dramatic variations in prescription rates between states. For example, providers in Alabama, the state with the highest number of prescriptions, wrote 107.2 prescriptions per 100 people. By contrast, providers in Hawaii, the state with the least number of prescriptions, issued 37 prescriptions per 100 people. Research indicates that the underlying health status of state populations does not explain the variation, according to the CDC.

All types of prescription and nonprescription opioids can potentially be dangerous, but some are more commonly associated with addiction, substance use and overdose deaths than others. In 2018, two-thirds of opioid-related overdose deaths nationwide involved synthetic substances, according to the World Health Organization (WHO).

The prevalence of opioids and related overdose deaths rose dramatically again during the COVID-19 pandemic. In 2020, synthetic opioids accounted for more than 82 percent of opioid-involved deaths, according to the CDC.

Among opioids, fentanyl is one of the most ubiquitous and dangerous, according to Rand Corporation, a nonpartisan, nonprofit think tank. Although various formulations of the drug are on the WHO Model List of Essential Medicines, it is widely misused. It was developed in 1959 and introduced as an anesthetic and analgesic in the 1960s, but its prevalence has soared in recent years on the black market.

Fentanyl is similar to morphine but 50 to 100 times more potent, per the National Institute on Drug Abuse (NIDA). Some of its analogs—those are chemically similar drugs—are less powerful, but others are more. Carfentanil, the most potent fentanyl analog found in the U.S., is approximately 10,000 times stronger than morphine, according to NIDA.

Research indicates illicit drug manufacturers and dealers are adding fentanyl to products such as heroin, cocaine, methamphetamine and MDMA, to increase their potency for little cost. Some sell fentanyl and its analogs in the guise of other prescription opioids.

According to NIDA, consumers may not realize they are taking such a potent substance, making it easier to become addicted or unintentionally overdose.

What is the opioid mechanism of action?

The human body produces opioids—they are called endogenous opioids—and contains a vast network of opioid receptors. These receptors, located throughout the nervous system, help to mediate brain circuits associated with pain, stress, respiration, gastrointestinal transit, mood and reward, according to Negro, in addition to endocrinological and immunological functions.

Exogenous opioids, or those made outside the body, mimic their endogenous counterparts and interact with receptors similarly to produce similar effects.

"Opioids work in the brain by interacting with protein receptors," said Dung Trinh, M.D., the chief medical officer at Healthy Brain Clinic in Long Beach, California. "When they bind to these receptors, opioids block pain signals from traveling between the brain and body and release hormones such as dopamine that create a feeling of euphoria.

"This is why opioids can be so addictive. They create an intense feeling of pleasure, even with intermittent use."

Other side effects include drowsiness, confusion, nausea, flushing, itching, constipation, slow reflexes and mental fog. These drugs can also slow breathing and heart rate, which can be fatal, especially in high doses or in combination with other substances.

Anyone taking an opioid should avoid sedative medications or substances because sedatives increase the risk of opioid overdose, according to Negro.

"Because the use of high opioid doses may cause respiratory depression, they need to be used judiciously in clinical practice and carry an inherent risk of overdose if used outside the context of medical care," Negro said. "Some of these molecules are quite powerful, such as fentanyl, and can cause respiratory depression even in very low doses."