Q&A: New wave of overdose epidemic features fentanyl combined with heroin, stimulants

Key takeaways:

• An analysis of fentanyl-positive drug tests indicated a rise in heroin and stimulant use alongside fentanyl.
• An expert broke down the latest trends and what physicians should know.

An analysis of recent drug use in the United States revealed unexpected trends in substances being used in tandem with fentanyl, according to an expert.

On Feb. 25, the CDC released its newest batch of provisional overdose data, announcing that, for the 12-month period ending in September 2024, overdose deaths in the U.S. dropped by 24%, compared with the previous year. From October 2023 to September 2024, 87,000 drug overdose deaths occurred, down from the previous year’s 114,000. This is an unprecedented decrease, according to the CDC. In fact, this is the smallest number of overdose deaths in any yearlong period since June 2020.

In a report from Millenium Health evaluating drug use through 2024, researchers examined the results of more than 1.4 million fentanyl-positive urine drug tests from U.S. patients who were diagnosed with a substance use disorder.

Healio spoke with Eric Dawson, PharmD, vice president of clinical affairs at Millennium Health, about the report’s key findings, surprising inverse trends and what primary care providers need to know.

Healio: Will you discuss the importance of this report and, more broadly, researching trends in the overdose crisis?

Dawson: Everybody has to appreciate that drug use in our nation is ever changing, and it seems to be changing more rapidly recently. Although fentanyl remains at the center of the crisis, there are other [drugs] that deserve our attention. Our Signals reports highlight very timely topics related to the overdose crisis and provide up-to-date information on key trends as we see them.

We do all of this because we believe it can help in several ways. At the individual practitioner level, the help there is that they know what drugs are prevalent in their local communities. For local advocacy and public health groups, they can better educate and prepare their communities on what's there and what may be coming. And then at a national level — regulators, policymakers, others — they gain insight into what impact their current efforts are having on the crisis and what resources they may need moving forward to respond more effectively.

Healio: What are the most important findings in this report?

Dawson: Fentanyl-associated polysubstance use continues to evolve at a rapid pace as this fourth wave [of the overdose epidemic] — as it's typically described — rolls on.

Secondly, as it relates to this fourth wave, this rise in stimulants is noted. In this report, codetection of methamphetamine or cocaine grew in every region of the country. Clearly, this fourth wave is still hot, and stimulants themselves are associated with significant clinical challenges. If that's not concerning enough, late in the year, we saw a rising tide of heroin co-use.

The stimulant piece — it's really hard to overstate the significance of this. It's not just that stimulants are dominating in every region of the country; it literally goes to the state level. We found methamphetamine or cocaine — with fentanyl — most commonly in every state with the exception of three: New Jersey, Illinois and Louisiana. We found heroin, interestingly enough, most commonly [in those states], but in the other 47 states, we found one of the stimulants. So, this fourth wave, again, is still gaining steam.

The last point, which I think is the most important, is polysubstance use remains the rule, not the exception. When you look within the population using fentanyl, we note in the report that over 93% of those urine specimens that were positive for fentanyl were also positive for other drugs. And it was certainly not limited to methamphetamine, cocaine and heroin; almost a third were positive for four or more drugs.

And it's not just the number of drugs, it's what these drugs are. Several of them have effects that are similar to fentanyl, so that obviously adds to the risk for that user, and a number of them are also now just part of the fentanyl mix. When we talk about fentanyl medicinally, we're talking about a single compound fentanyl. When we talk about illicitly manufactured fentanyl in the illicit fentanyl supply, it's really fentanyl plus any number of other things. Fentanyl, analog heroin, now more commonly xylazine and the list goes on and on. That obviously changes a user’s risk and makes it very challenging for treatment providers and first responders to do their work because they don't really know exactly what they're dealing with many times.

Healio: Why has there been a downturn in fentanyl use and a rise in heroin?

Dawson: First, let's talk about just the downturn in fentanyl use. On the positive side, many tremendous efforts have been made to increase access to substance use disorder treatment. We're seeing that all over the country. There is an increase in prescribing medications for opioid use disorder. There's been significant effort to educate the public. There are fentanyl test strips that have been developed so if someone purchases some drug material, they can check to see if fentanyl is in it or not. All of those things — and I'm sure there are many others on the positive side — have reduced fentanyl use. On a more somber note, some are suggesting that the massive loss of life due to fentanyl use has simply made for a smaller pool of people who are available to use fentanyl. I guess that there's some truth to that.

From a supply standpoint, what we're seeing is not just a rise in heroin; it's really that heroin is being added to or there's an adulteration of the fentanyl supply. We believe it's happening early in the distribution chain before it comes into the country because of the incredible consistency we've seen in the extent and timing of the rise of heroin detection in the population using fentanyl, especially across much of the West. This rise in heroin in this population using fentanyl literally happened in a month. From August to early September, we went from finding very little heroin in that group to finding significant amounts, and it was consistent across most of the Western states. And it's just hard to believe that users of these drugs in these different states would all decide at the same time to now use more heroin. It clearly seems to be something that is a supply-side phenomenon.

Healio: How does this shift impact people, communities and the health care system?

Dawson: The rise in heroin has its positive aspects in that fentanyl is harder to get or it may be diluted, and that’s mostly a good thing given its potency. It's certainly a reason why there has been a reduction in fatal overdoses and fentanyl detection in human drug tests. But what can easily be forgotten about is that this disruption has happened in the face of continued demand for opioids. Given this demand, drug trafficking organizations are likely seeking alternatives to fentanyl, and they're seeking drugs that most likely will produce a similar effect: euphoria and sedation. Heroin, right now, seems to be the alternative of choice.

The good news is that as a dwindling or weakened fentanyl supply is bolstered by heroin — which is 50 times less potent — then we should see a continued reduction in fatal overdoses.

As [the available data] move into the last part of 2024 into early 2025, I think that's where it gets really interesting. We have to watch very closely because a continued disruption in illicit supply channels plus limited supplies of heroin means that drug trafficking organizations will seek other alternatives to fentanyl, including carfentanil, an extremely potent fentanyl analog, [or] xylazine, a nasty drug that causes a number of side effects. To the extent these trafficking organizations begin to use those drugs as alternatives to fentanyl, we could certainly see a turnaround in the reduction of fatal overdoses.

Healio: What do you expect the next wave to look like?

Dawson: It's easy to want to say that methamphetamine and cocaine use will continue to rise within the population using fentanyl because those trends are so consistent. Methamphetamine and cocaine have been rising now for a number of years. But the honest answer is, we don’t know. Illicit drug supplies can shift quickly and other factors, like changes in policy law enforcement efforts and so many other things, can influence these changes in the drug supply. In these matters, it's difficult to make projections.

Healio: What is the take-home message for PCPs here

Dawson: There are many PCPs who care for those with substance use disorder. Additionally, some PCPs manage long-term pain. There just doesn't seem to be enough pain management providers to handle that patient load, and so PCPs often find themselves playing that role. A number of medications that are used in pain management are directly involved in misuse, whether that be some of the prescribed opioids, or even noncontrolled substances like gabapentin. For a PCP that's managing long-term pain knowing what local substance use looks like will help them identify which meds they're prescribing that may need to be carefully monitored, depending on the patient's needs.

For drugs that are trending upward — like the stimulants and heroin currently — and in large supply in communities, they're likely going to be what patients with a substance use disorder, with pain, under the care of a PCP would be expected to obtain should they return to drug use. Physicians can use that knowledge to counsel patients. There's never been a more dangerous time to return to drug use.

References:

• CDC reports nearly 24% decline in U.S. drug overdose deaths. Available at: https://www.cdc.gov/media/releases/2025/2025-cdc-reports-decline-in-us-drug-overdose-deaths.html. Published Feb. 25, 2025. Accessed March 4, 2025.
• Provisional drug overdose death counts. Available at: https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm. Published Feb. 25, 2025. Accessed March 4, 2025.
• Signals report: The continued evolution of the ‘fourth wave’ of America’s overdose crisis. Available at: https://www.millenniumhealth.com/signalsreport/. Published February 2025. Accessed Feb. 27, 2025.