The answer depends on how you measure “abuse.” By sheer number of users, marijuana is the most widely used illicit drug in the United States, with 61.8 million people reporting use in 2023. But if you measure by harm, opioids are responsible for roughly 80,000 overdose deaths per year, accounting for 76% of all drug fatalities. Both substances sit at the center of the country’s drug landscape, though for very different reasons.
Marijuana: Most Widely Used by Far
Among people aged 12 and older, 61.8 million used marijuana in 2023, according to the national survey on drug use conducted by SAMHSA. That’s nearly seven times more than the next most commonly used illicit substance (hallucinogens, at 8.8 million). No other drug comes close in terms of raw user numbers.
What’s changed in recent years is not just how many people use cannabis but how often. Among adults 19 to 30, about 10% reported using marijuana on 20 or more days per month in 2023. For comparison, only 4% of that same age group reported drinking alcohol daily. Among adults 35 to 50, daily cannabis use (8%) matched or exceeded daily drinking for the first time. Cannabis use among adults has reached historic highs across every frequency measure, even as legalization has shifted public perception of the drug.
Opioids: The Deadliest Drug Crisis
Approximately 105,000 people died from drug overdoses in 2023. Nearly 80,000 of those deaths involved opioids. That makes opioids the single largest driver of drug-related death in the country, and it’s not particularly close.
The opioid crisis has evolved through distinct phases. It began with prescription painkillers in the late 1990s, shifted toward heroin in the 2010s, and is now dominated by illicitly manufactured fentanyl. Fentanyl is a synthetic opioid roughly 50 times more potent than heroin, and it has become the backbone of the illicit opioid supply. Mexican drug trafficking organizations produce the bulk of it using precursor chemicals sourced primarily from China.
The DEA found that in 2024, the average counterfeit pill contained about 1.94 milligrams of fentanyl, and roughly half of all seized pills contained 2 milligrams or more, a dose that can be lethal for someone without opioid tolerance. Fentanyl is also increasingly mixed into other drugs like cocaine and heroin, meaning people sometimes consume it without knowing.
New Adulterants Making Overdoses Harder to Reverse
The fentanyl supply is becoming more dangerous because of what’s being added to it. Xylazine, a veterinary sedative sometimes called “tranq,” has been showing up in fentanyl powder at steadily rising rates since 2020. Xylazine causes deep sedation and severe skin wounds at injection sites, and it doesn’t respond to naloxone (the standard overdose reversal drug).
An even newer concern is medetomidine, nicknamed “rhino tranq,” another veterinary anesthetic that is 200 to 300 times more potent than xylazine. When mixed with fentanyl, it makes overdoses significantly harder to reverse. Law enforcement has also identified a class of synthetic opioids called nitazenes, which can match or exceed fentanyl’s potency. At least 17 different nitazene compounds have been detected in drug samples across the country, with two new variants appearing for the first time in 2024.
Stimulants and Polydrug Use
Nearly half of all drug overdose deaths in 2023 involved both opioids and stimulants together. This reflects a growing pattern of polydrug use where methamphetamine or cocaine is combined with fentanyl, sometimes intentionally and sometimes because the supply is contaminated. Cocaine was used by 5 million people in 2023, making it the fourth most commonly used illicit substance after marijuana, hallucinogens, and misused prescription painkillers.
Prescription Drug Misuse
About 14.3 million people misused at least one prescription medication in a recent survey year. Prescription pain relievers remain the most commonly misused category, with roughly 8.7 million people taking them outside of how they were prescribed. Tranquilizers and sedatives account for about 4.9 million users, benzodiazepines about 3.9 million, and prescription stimulants about 3.7 million.
Prescription misuse has declined from its peak in the early 2010s as prescribing practices have tightened, but it remains a significant gateway into opioid use disorder. Many people who develop dependence on illicit fentanyl initially started with prescription painkillers.
What Teens Are Using
Among high school students, alcohol remains the most commonly used substance: 41% of 12th graders reported drinking in the past year in 2025. Cannabis ranked second at 26% of 12th graders, followed by nicotine vaping at 20%. All three substances have trended downward since the pandemic with no sign of rebounding, and cannabis use among 10th and 12th graders is at its lowest point in three decades.
The Economic Toll
The opioid crisis alone cost the U.S. an estimated $1.02 trillion in 2017, the most recent year with comprehensive cost data. That figure includes $471 billion tied to people living with opioid use disorder (healthcare, lost productivity, criminal justice involvement, and reduced quality of life) and $550 billion in costs associated with fatal overdoses. Each overdose death carries an estimated economic cost of more than $10 million when accounting for lost years of life. These numbers predate the fentanyl surge that accelerated after 2019, meaning the current cost is almost certainly higher.