It’s widely known that substance misuse has increased dramatically over the last few years, with a higher incidence rate and overdose deaths at an all-time high. In 2020, nearly 1 in 4 people reported binge drinking and 37.3 million reported illegal drug use in a one-month span.
But hidden within that macro trend is a much more complex and deadly problem: polysubstance use (PSU)—the use of more than one substance, either on separate occasions or simultaneous/concurrently. The prevalence of PSU is startling: more than half of patients with substance use disorder (SUD) use more than one substance, and the number is much higher (nearly 70%) among opioid users. The average drug-dependent individual uses 3.5 substances, and 50% of all overdoses involved more than one substance—one reason for the three-fold higher mortality rate among those with PSU disorder compared to mono-substance use.
PSU disorder creates a number of major challenges for treatment providers, and its prevalence is forcing the treatment community to adapt standard protocols to account for this troublesome phenomenon.
Unique Dynamics & Risk Factors for PSU
It’s imperative that providers understand the dynamics of PSU and recognize that not all PSU is intentional. People mix substances for a variety of reasons: to manage cravings, avoid withdrawal symptoms (i.e., alcohol with benzodiazepine), enhance the effects of drugs, or to treat undesirable side effects. But for others, PSU could be unintentional: for example, an individual having 2-3 alcoholic drinks with their legally prescribed medications. These individuals often have no idea they may be creating a dangerous situation nor the compounding effects these drugs can have on one another.
Given PSU is such a common problem, providers should also learn the risks so they can be communicated with our patients and the larger community. We already know that multiple factors increase an individual’s risk of developing an SUD, but there are some substances that actually increase the risk of PSU. For example, the risk of heroin dependence is twice as high for someone who misuses alcohol, 3X higher for cannabis users, 15X greater for cocaine users, and 40X higher for prescription drug misusers. In fact, 30-80% of heroin users have reported also using cocaine, and deaths involving the use of cocaine and opioids have more than doubled. Of course, alcohol is one of the most commonly used drugs, so unsurprisingly, it is often mixed with others, intentionally or not.
Tips for Diagnosing & Treating PSU
One of the biggest challenges for providers is that identifying PSU isn’t always easy. The unfortunate reality is, many patients either don’t realize, or won’t admit to PSU, which makes providing safe, effect treatment difficult. In fact, not knowing patients’ full pharmacological history before beginning treatment can even put them at grave risk for severe detox reactions. PSU can also complicate medical detox and medication assisted treatment (MAT) because some substances can interact with medications used.
There’s no substitute for careful observation and frank communication with family and friends when it comes to gathering intake data about the patient. The need for thorough evaluation cannot be overstated. Providers should also support this investigation with toxicology screening as well and be sure to include fentanyl in the testing protocol. Because of the prevalence on the market of fentanyl mixed with opioids or cocaine, patients may not even realize they’re using—or addicted to—one of the most potent narcotics on the market.
Because PSU is associated with severe medical and psychiatric comorbidities, treatment must include psychosocial and pharmacotherapeutic elements. PSU patients are at a much higher risk of overall health issues like liver failure and heart attack, and the strong link between mental and behavioral health conditions, including suicidality, is well known. PSU can cause significant instability in depression, bipolar disorder and schizophrenia, creating the need for pharmacological treatment, which must be managed carefully in light of PSU.
Considering these complications, it’s no surprise that PSU treatment demands a much longer engagement. While most in the industry are lobbying for longer engagements for every patient, for PSU disorder, it’s essential. PSU is unfortunately associated with poor treatment outcomes. Substance use during recovery from PSU disorder is the norm rather than the exception, and relapses are common due to the higher impulsivity and reduced cognitive abilities that can result from long-term polysubstance use. This can lead to reduced ability to properly address maladaptive behavioral patterns, which can hinder recovery. As a result, those with PSU disorder may not only need continued and more acute support and monitoring during their recovery, but also easy access to readmission in the event they experience a relapse.
The Path Forward
There’s no doubt the prevalence of PSU creates exceptional challenges for providers. But we owe it to our patients to shift our approach to accommodate the growing need for this type of specialized treatment. Just like medical doctors treating any co-existing conditions—diabetics with wound-care needs, for example—we must broaden our expertise to address the whole person, take a long-term approach, and call-in specialty support when needed.

Dr. Lawrence Weinstein
Dr. Lawrence Weinstein is Chief Medical Officer of American Addiction Centers.