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

Opioid use disorder (OUD) deaths are really mixed drug overdoses

Compound abuse is the new normal and a significant factor in opioid-related overdose deaths. Of course, fentanyl and other opioids can cause death by themselves. However, as more individuals take multiple drugs, the risk of death increases 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 Abuse of drugs and Mental Health Services Administration (SAMHSA). In addition, the combination of benzodiazepines and opioids significantly increases breathing Depression risks, and nearly half of benzodiazepine overdose deaths include synthetic opioids such as fentanyl. About 15% of opioid overdose deaths involve alcohol, a drug that further depresses the central the nervous system. Opioids are also implicated in over 50% of methamphetamine- and cocaine-related deaths. Deaths involving both cocaine and opioids increased fivefold between 2010 and 2022, mainly due to fentanyl.

Nora Volkow, MD

Source: National Institute of Drug Abuse

A September The 2024 Millennium Health study analyzed urine drug test (UDT) results from more than 4 million patients who tested positive for fentanyl. The results: Almost 93% of fentanyl-positive samples in 2023 contained additional drugs. “And that’s huge,” says Nora Volkow, MD, director of the National Institute on Drug Abuse (NIDA). Volkow and other addiction experts report that the dramatic increase in the combination use of meth and fentanyl is of great 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 would never, ever have believed this,” Volkow said.

Speedballing – take both stimulant and a depressant drug — becoming more typical; for example, both methamphetamine and cocaine were detected in fentanyl-positive samples more often than the combination of heroin and prescription opioids.

Dangerous combinations increase vulnerability to overdose and can reduce responses to overdose-reversing agents such as Narcan, making treatment challenging; for example, there is no FDA-approved reversal medicine for stimulant overdose.

Urine and blood tests determine the causes of drug deaths. However, they cannot reveal a user’s intent. This means that the data confirms that mixed abuse is the norm; however, it is unclear about humans intentionally combined drugs for an extra high or mistakenly thought 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 mixed abuse of cannabis, MDMA, LSD and other hallucinogens such as psilocybin. Some festivals like Shambhala and Lightning in a Bottle have been carried out damage reduction strategies, including drug testing stations and educational materials.

A 2024 study revealed a spike in planned drug use at music festivals. According to this year’s Study of drug safety at music festivals84% of 2024 festival attendees planned to use drugs on the festival grounds, up 10% from last year. Cannabis was most common (65.3%), followed by cocaine (46.5%), psychedelics, MDMA and ketamine. Mixed use, including combining substances such as cocaine and MDMA, was most common. The report revealed that 3 out of 5 people planned to buy drugs on site at a festival.

The survey noted that participants experienced health risks such as dehydration, heat stroke and “bad trips”, as well as risky behaviors such as unprotected six and careless driving.

Mixed drug suicide

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

Use of alcohol and mixed drugs

Smokers drink and drinkers smoke. This is what we used to teach medical students, and it is still true today. For example, about 80% of people with alcohol abuse (AUD) smoke cigarettes, compared to about 14% of the US population. The combined use of alcohol and tobacco is of particular concern because it increases the risk of cancer more than either drug alone. Most adults who seek treatment for alcohol abuse as a primary drug report using another drug in addition to alcohol. Approximately one-third of individuals with AUD use cannabis. In addition, about 25% also use stimulants such as cocaine or methamphetamine. This co-use is more common among younger adults and can amplify the negative effects of each substance, such as cognitive impairment and risk behaviors.

About 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.

Cocaine

Polysubstance use is highly prevalent among people with cocaine addiction (CUD) – most people with CUD (about 85%) smoke cigarettes. Nicotine and cocaine are often used together because of their synergistic stimulant effects. Up to 40% of individuals with CUD use cannabis, often for its sedative effects or as part of recreational patterns. Many people with CUD use methamphetamine or prescription stimulants, further complicating their health outcomes. About 20% of individuals with CUD use opioids, including heroin or fentanyl, which increases the risk of overdose.

Liam Payne’s tragic mixed drug death

One Direction star Liam Payne died unexpectedly at the age of 31 in 2024 after falling from a balcony in Buenos Aires. Officers found traces of drugs, drug paraphernalia and alcohol in his hotel room, and several drugs were found in Payne’s system: alcohol, cocaine, benzodiazepines, crack and pink cocaine. Prosecutors claimed the singer was on a mixed drug binge the night before and the morning after his fatal fall.

Cocaine: a new psychoactive substance

Using cocaine with alcohol creates a third new drug: cocaethylene. Cocaine is more potent than cocaine or alcohol alone. It also stays in the body much longer than cocaine, and its toxic effects last longer. The Cocaet is the only known example of one new psychoactive substance is formed entirely in the body.

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

Summary

Accidental overdose deaths quadrupled from 2010-2022. Most were mixed abuse overdoses with alcohol, marijuana, opioids, benzodiazepines, methamphetamine, cocaine, or other drugs present at death. Surveys, personal reporting and research studies show that mixed use is on the rise, which is expected of club attendees but is particularly common at electronic dance music events and festivals. The “fourth wave” of America’s opioid overdose epidemic is a mixed abuse epidemic.