Opioids are a broad class of drugs that relieve pain by binding to specific receptors in the brain and spinal cord. The list is longer than most people expect: it includes familiar prescription painkillers like oxycodone and hydrocodone, surgical-strength drugs like fentanyl, old standbys like morphine and codeine, medications used to treat addiction, cough suppressants, and illegal substances like heroin. They fall into three categories based on how they’re made: natural, semi-synthetic, and fully synthetic.
Natural Opiates From the Poppy Plant
The opium poppy produces a milky sap containing more than 80 different alkaloids. The ones that matter most for medicine and misuse are morphine and codeine. Morphine remains the benchmark against which all other opioids are measured for strength. Codeine is weaker and is often combined with acetaminophen for mild to moderate pain. A third natural compound, thebaine, isn’t used directly as a painkiller but serves as the chemical starting point for manufacturing several semi-synthetic opioids.
Semi-Synthetic Opioids
Semi-synthetic opioids start with a natural compound from the poppy and are then chemically modified in a lab. This category includes some of the most commonly prescribed painkillers in the United States:
- Hydrocodone (brand name Vicodin): one of the most widely prescribed opioids, typically combined with acetaminophen for moderate pain.
- Oxycodone (OxyContin, Percocet): available in both immediate-release and extended-release forms, used for moderate to severe pain.
- Hydromorphone (Dilaudid): significantly stronger than morphine, often used in hospital settings.
- Oxymorphone (Opana): another high-potency option for severe pain.
- Heroin: derived from morphine, with no accepted medical use in the United States. It is classified as a Schedule I controlled substance.
Fully Synthetic Opioids
These are designed and manufactured entirely in a laboratory with no plant-derived starting material. They act on the same brain receptors as natural opiates but can differ enormously in potency and duration.
Fentanyl is the most well-known synthetic opioid. It is roughly 100 times more potent than morphine, meaning a dose measured in millionths of a gram can equal what would take several milligrams of morphine. Medical-grade fentanyl is used for surgical pain and in patches for chronic pain, but illicitly manufactured fentanyl has become the leading driver of overdose deaths in the U.S.
Other synthetic opioids include methadone, which acts more slowly and stays in the body longer than most opioids, and tramadol, a lower-potency option sometimes prescribed for moderate pain. Meperidine (Demerol) is an older synthetic opioid that has largely fallen out of favor due to side effects but is still occasionally used in hospitals.
Opioids Used to Treat Addiction
Two opioids are primarily used not for pain but to help people stop using other opioids. Methadone activates the same brain receptors as heroin or fentanyl but does so more slowly, which reduces cravings and withdrawal symptoms without producing a strong high. It has been used for this purpose for more than 50 years.
Buprenorphine (found in the brand-name combination product Suboxone) works differently. It activates opioid receptors to a lesser degree than methadone and can actually block other opioids from attaching to those receptors. This dual action helps reduce cravings while making it harder to get high from other opioids at the same time. When taken as prescribed, both medications are far less likely to produce the intense euphoria associated with misuse.
Opioids in Cough and Cold Medicines
Not all opioids are prescribed for pain. Codeine and hydrocodone are also found in prescription cough suppressants, often combined with antihistamines or decongestants. The FDA has restricted these products to adults 18 and older because the risks outweigh the benefits in children. Loperamide, the active ingredient in over-the-counter anti-diarrheal products, is technically an opioid as well, though it primarily acts on the gut rather than the brain when taken at normal doses.
How Opioids Are Scheduled
The DEA classifies most prescription opioids as Schedule II controlled substances, meaning they have legitimate medical uses but carry a high potential for misuse and dependence. This group includes morphine, oxycodone, hydrocodone, fentanyl, methadone, hydromorphone, oxymorphone, and meperidine. Products containing lower amounts of codeine (such as Tylenol with Codeine) and buprenorphine (Suboxone) are classified as Schedule III, reflecting a somewhat lower risk profile. Heroin sits in Schedule I, reserved for substances with no accepted medical use and a high potential for misuse.
Illicit and Emerging Synthetic Opioids
Beyond heroin and illegally manufactured fentanyl, newer synthetic opioids are appearing in the street drug supply. Carfentanil, a fentanyl analog originally developed for tranquilizing large animals, is thousands of times more potent than morphine and has been linked to clusters of overdose deaths. Other lab-created compounds like U-47700 and AH-7921 have surfaced in toxicology reports over the past decade.
The latest class raising concern is the nitazenes. Originally synthesized in the 1950s, these compounds began reappearing in the illicit supply around 2019. As of January 2024, forensic labs had identified at least 20 unique nitazene variants, including isotonitazene, metonitazene, and etonitazene. Some have been found pressed into counterfeit oxycodone tablets, making them especially dangerous for people who believe they’re taking a standard prescription pill. Nitazenes can be significantly more potent than fentanyl, and their rapid spread across North America and Europe has become a growing public health concern.
Common Side Effects Across All Opioids
Regardless of whether an opioid is natural, semi-synthetic, or fully synthetic, the drugs share a core set of side effects because they all act on the same receptors. Drowsiness, dizziness, nausea, vomiting, and constipation are the most common. Slowed breathing is the most dangerous, and it is the mechanism behind fatal overdoses. The risk of slowed breathing increases sharply when opioids are combined with alcohol, sedatives, or other drugs that depress the central nervous system.
Tolerance develops with regular use, meaning higher doses become necessary to achieve the same effect. Physical dependence can follow, producing withdrawal symptoms like muscle aches, insomnia, and intense cravings when the drug is reduced or stopped. These properties are shared across the entire class, from codeine at the milder end to fentanyl and nitazenes at the extreme.