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What Everyone Needs to Know About Polysubstance Use

People are now overdosing on multiple drugs at once. Here’s what to know.

Key points

  • Sometimes, people are addicted to multiple drugs they are using.
  • Polysubstance use is not new. It was fairly common back in the '80s and even before.
  • Drug makers and dealers want to get their customers hooked and come back for more.

A massive survey recently released by a national drug-testing company strongly suggests we are well into the “fourth wave” of the opioid crisis.

The three previous waves were driven by 1) prescription opioids; 2) heroin; then 3) fentanyl. The fourth and current wave involves using opioids such as fentanyl combined with other lethal substances, including methamphetamines, cocaine, and xylazine (“tranq” or “tranq dope”).

These tragic findings don’t surprise me. I’m the chief medical officer of a large addiction treatment center based in Jacksonville, Florida, and we’ve seen polysubstance use—that’s two or more drugs used at the same time or close in time—with our patients for a few years now.

Polysubstance Use Seems to Be Skyrocketing

The Millenium Health report is based on 4.1 million urine samples collected from people receiving drug addiction care between 2013 and 2023.

A key finding: Of the fentanyl-positive urine samples collected, 93 percent contained other illicit substances as well. More alarming still is that in the last year covered by the survey (2023), 60 percent of fentanyl-positive samples contained methamphetamine.

A potent, highly addictive stimulant that is fully capable of causing a lethal overdose all by itself, meth becomes even more dangerous and unpredictable when mixed with depressants like fentanyl and heroin.

Let's Dispense With the “Balancing Each Other Out” Myth

At our treatment center, people who come to us addicted to meth and heroin, for example, sometimes admit they were using the stimulant and depressant together as a way to balance out the two drugs in hopes of getting that just-right high. This is extremely faulty thinking and practice.

Why? Because combining them can mask the effect of one or both drugs, which may trick people into thinking the drugs aren’t doing anything. That sometimes makes them take more, which increases the risk of an overdose.

Mixing alcohol (a depressant) with other drugs is also common, and people do it with the same idea of “balancing out” the two substances. People combine cocaine or meth with alcohol as well.

Bottom line: Mixing alcohol in all those ways increases the risk of an overdose and can irreparably damage the brain, heart, and other organs.

Hidden Dangers of Unintentional Polysubstance Use

We drug screen all our patients when they’re admitted. Sometimes, we find drugs in their system they didn’t know they were taking.

That’s an example of people engaging in unintentional polysubstance use. Fentanyl is often the culprit in these cases, just as it is with intentional polysubstance use.

Either way, fentanyl can kill. For years, illicit manufacturers and dealers have added fentanyl to other illegally manufactured drugs, often in pill form. People think they’re taking a standard prescription pill with no idea it may contain a lethal dose of fentanyl.

Final point on fentanyl: This easily concealed drug gets added to meth, to counterfeit pills intended to look like prescriptions, and to weed and other drugs. In all those instances, the user may not know there’s fentanyl included and may have zero tolerance for it. That’s when overdose risk goes way up.

Polysubstance Use Treatment Can Be Complicated

When people enter addiction treatment with a recent history of polysubstance use, they are sometimes addicted to both of the drugs (it’s usually two) they’ve been using. In those cases, the detoxes can actually conflict with each other, which makes treatment tricky and dangerous.

More commonly, however, the withdrawals are more extreme simply because of the potency of the drugs.

That leads to another key point: Polysubstance use is not new. It was fairly common back in the '80s and even before.

What is new and deadly, and a key part of the so-called fourth wave of the opioid epidemic, is the higher toxicity of these drugs. That’s what is killing so many people.

What to Do If You Witness an Overdose

Because so many polysubstance use overdoses involve fentanyl, an opioid, it’s important to know that Narcan (naloxone) nasal spray is now available over the counter. This increasingly common product can quickly reverse an opioid overdose. While Narcan doesn’t work on non-opioid drugs like methamphetamine or cocaine, if it’s an opioid overdose, Narcan can save lives.

Here's the Centers for Disease Control and Prevention (CDC) simple five-step procedure if you suspect a person is overdosing:

  1. Call 911 immediately.
  2. Administer Narcan if available.
  3. Try to keep the person awake and breathing.
  4. Lay the person on their side to prevent choking.
  5. Stay with them until emergency workers arrive.

Final Thoughts on Surging Polysubstance Use

In so many instances, when two or more drugs appear in one pill or product, there’s a simple reason for that combination: to make it more addictive. Illicit drug manufacturers and dealers do this to get their customers hooked so they come back for more. For them, it’s a sales tactic.

We see the fallout from that every day in the patients who come to our treatment center—and in those people who never make it to us.

Facebook/LinkedIn image: Prostock-studio/Shutterstock


(2024). The "Fourth Wave": The Rise of Stimulants and the Evolution of Polysubstance Use in America’s Fentanyl Crisis. Millenium Health.…

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