The Current State of the Polydrug Use Epidemic

Many people assume when people have a substance use disorder (SUD), their issue is with one substance, such as alcohol or opioids. The reality is that most people with an SUD are polysubstance abusers.

Opioid Use Disorder (OUD) Deaths Are Really Polydrug Overdoses

Polydrug use is the new normal and a significant factor in opioid-related overdose deaths. Of course, fentanyl and other opioids can cause deaths by themselves. However, as more individuals take multiple drugs, the risks of death increase due to the lethality of drug interactions. Among opioid-related deaths, nearly two-thirds (63%) involve other substances, such as cocaine, methamphetamine, or benzodiazepines, according to the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition, the combination of benzodiazepines and opioids significantly increases respiratory depression risks, and nearly half of benzodiazepine overdose deaths include synthetic opioids like fentanyl. About 15% of opioid overdose deaths involve alcohol, a drug that further suppresses the central nervous system. Opioids are also implicated in over 50% of methamphetamine- and cocaine-related fatalities. Deaths involving both cocaine and opioids rose fivefold between 2010 and 2022, primarily due to fentanyl.

Nora Volkow, MD

Source: National Institute of Drug Abuse

A September 2024 Millennium Health study analyzed urine drug test (UDT) results from more than 4 million patients testing positive for fentanyl. The results: Nearly 93% of fentanyl-positive specimens in 2023 contained additional drugs. “And that is huge,” said Nora Volkow, MD, director of the National Institute on Drug Abuse (NIDA). Volkow and other addiction experts report that the dramatic increase in the meth and fentanyl combination use is of major concern. Methamphetamine, a highly addictive drug with serious cardiovascular and psychiatric risks, was identified in 60% of fentanyl-positive tests last year, an 875% increase since 2015. “I never, ever would have thought this,” Volkow said.

Speedballing—taking both a stimulant and a depressant drug—is becoming more typical; for example, both methamphetamine and cocaine were detected in fentanyl-positive specimens more frequently than was the combination of heroin and prescription opioids.

Dangerous combinations increase overdose vulnerability and may lessen responses to overdose reversal agents like Narcan, making treatment challenging; for example, there is no FDA-approved reversal medication for stimulant overdose.

Urine and blood testing determine the causes of drug deaths. However, they cannot reveal a users’ intent. This means that the data confirm polydrug use is the norm; however, it’s unclear if people intentionally combined drugs for an extra high or mistakenly believed they were using only one drug.

Drug Festivals and Events

Every year, tens of thousands of “Burners” travel to Nevada's Black Rock Desert for Burning Man. This festival is associated with polydrug use of cannabis, MDMA, LSD, and other hallucinogens like psilocybin. Some festivals like Shambhala and Lightning in a Bottle have implemented harm reduction strategies, including drug testing stations and educational materials.

A 2024 study revealed a bump in planned drug usage at music festivals. According to this year’s Drug Safety at Music Festival Study, 84% of 2024 festival attendees planned to use drugs on festival grounds, a 10% increase from last year. Cannabis was most common (65.3%), followed by cocaine (46.5%), psychedelics, MDMA, and ketamine. Polydrug use, including combining substances like cocaine and MDMA, was most common. The report revealed 3 out of 5 people planned to purchase drugs onsite at a festival.

The survey noted participants experienced health risks like dehydration, heatstroke, and “bad trips,” as well as risky behaviors like unprotected sex and reckless driving.

Polydrug Suicides

Sometimes, people purposely use dangerous combinations of drugs because they want to die. Among suicides caused by drugs, leading drug categories were antidepressants, prescription opioids, and benzodiazepines, although these deaths have decreased or leveled off in recent years.

Alcohol and Polydrug Use

Smokers drink, and drinkers smoke. This is what we used to teach medical students, and it’s still true today. For example, about 80% of people with alcohol use disorder (AUD) smoke cigarettes, compared to about 14% of the U.S. population. The co-use of alcohol and tobacco is particularly concerning because it increases the risk of cancer more than either drug alone. Most adults seeking treatment for alcohol misuse as their primary drug report using another drug in addition to alcohol. About a third of individuals with AUD use cannabis. In addition, about 25% also use stimulants like cocaine or methamphetamine. This co-use is more common among younger adults and may amplify the adverse effects of each substance, such as cognitive impairment and risky behaviors.

Around 10% of alcohol abusers abuse opioids, including prescription painkillers or heroin. Younger adults with AUD are more likely to use cannabis and stimulants, while older adults are more likely to combine alcohol with prescription drugs.

Co-use patterns, such as combining alcohol and tobacco or alcohol and cannabis, are associated with worse treatment outcomes and higher relapse rates. Treatment services should be designed accordingly to maximize the likelihood of treatment engagement and success.

Addiction Essential Reads

When Free Will Fails People With Opioid Use Disorders

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Cocaine

Polysubstance use is highly prevalent among individuals with cocaine use disorder (CUD)—most people with CUD (about 85%) smoke cigarettes. Nicotine and cocaine are frequently co-used due to their synergistic stimulant effects. Up to 40% of individuals with CUD use cannabis, often for its calming effects or as part of recreational patterns. Many people with CUD use methamphetamine or prescription stimulants, further complicating their health outcomes. Around 20% of individuals with CUD use opioids, including heroin or fentanyl, heightening risks of overdose.

The Tragic Polydrug Death of Liam Payne

One Direction star Liam Payne died unexpectedly at the age of 31 in 2024 after he fell off a balcony in Buenos Aires. Officials found traces of drugs, drug paraphernalia, and alcohol in his hotel room, and multiple drugs were found in Payne’s system: alcohol, cocaine, benzodiazepines, crack, and pink cocaine. Prosecutors claimed the singer was on a polydrug bender the night before and morning of his fatal fall.

Cocaethylene: A New Psychoactive Substance

Using cocaine with alcohol creates a third new drug: cocaethylene. Cocaethylene is more potent than cocaine or alcohol alone. It also remains much longer in the body than cocaine, and its toxic effects last longer. Cocaethylene is the only known instance of a new psychoactive substance being formed entirely within the body.

Alcohol raises blood levels of cocaine and cocaethylene. Alcohol itself can increase cravings for cocaine. Cocaine is highly reinforcing and addicting, but when taken with alcohol, it is even more pleasurable, reinforcing, and addictive. This makes it harder to stop using.

Summary

Most of our medication-assisted addiction treatments are one medicine for one SUD, and all of our addiction diagnoses are single-drug diagnoses, while drug-using behavior is predominantly polydrug. AA & NA are treatments that have worked for some members by being polydrug treatments. Drug users, in essence, have conducted a real-life study of maximizing brain reward, and it appears from their behavior that they prefer polydrug use, risks, and all.

Unintentional overdose deaths quadrupled from 2010-2022. Most were polydrug overdoses with alcohol, marijuana, opioids, benzodiazepines, methamphetamine, cocaine, or other drugs present at death. Surveys, in-person reporting, and research studies show that polydrug use is increasing, expected by attendees at clubs, but especially prevalent at electronic dance music events and festivals. The "Fourth Wave” of America’s opioid overdose epidemic is a polydrug use epidemic.