Overdose deaths are falling, but America's illicit drug supply is re-engineering itself into lethal cocktails: fentanyl plus stimulants, sedatives, and novel synthetics that hide in party powders and pressed pills.
Why it matters: Those polydrug blends — nicknamed "pink cocaine," "rhino tranq," "benzo-dope" and others — are harder to detect, harder to reverse, harder to message against and can even result in the loss of limbs.
- That makes recent overdose declines fragile and public-health victories reversible if policy, testing and treatment don't catch up.
- "When we crack down on one drug, the market innovates," Sheila Vakharia, managing director of the Department of Research and Academic Engagement at the Drug Policy Alliance, tells Axios.
Catch up quick: The Trump administration has highlighted record fentanyl seizures at the southern border and credited tougher enforcement with helping drive overdose deaths down.
- The most recent provisional estimate projects 72,108 drug deaths for the 12 months ending September 2025 — a 19% decline year over year, per the CDC.
Yes, but: Experts say the domestic drug market is adapting in real time.
- Targeting fentanyl has incentivized illegal drug suppliers to experiment with other compounds that bypass detection, creating what Vakharia describes as a "whack-a-mole" cycle.
Zoom in: The spread of polydrugs can be mixtures of tranquilizers commonly used on animals, to psychostimulants that can keep one up for hours. Creaters often add pink or purple dye to make them more appealing and can mix drugs in kitchens.
- Fentanyl + stimulants pills: Anchorage, Alaska Police Chief Sean Case tells Axios that officers increasingly see pills that look pharmaceutical but contain fentanyl mixed with meth or other stimulants. Such drugs are spreading in Alaska Native communities.
- Veterinary sedatives xylazine and medetomidine are being mixed into fentanyl in multiple regions and are called tranq and rhino tranq. The drugs mimic heroin experiences but with a stronger, lasting high.
- Pink cocaine, or tusi, is a dangerous cocktail of drugs, commonly ketamine and ecstasy, sometimes mixed with methamphetamine or fentanyl. It's appearing in club scenes in U.S. cities.
- Benzo-dope, often fentanyl mixed with benzodiazepines or benzodiazepine-like sedatives, can produce sedation, hypnosis and relieve anxiety as users seek an intense opioid high.
Zoom out: The polydrugs are driving up crime in Alaska and putting pressure on emergency facilities, Case tells Axios.
- Police in small cities like Española, N.M., are reporting polydrug users sometimes walking around like zombies, while authorities in Los Angeles say the drugs are spreading in homeless camps.
Threat level: Naloxone, typically the first line of defense when someone is unresponsive from an opioid overdose, at times doesn't work alone on the overdoses from the new polydrugs, experts tell Axios.
- When someone is unresponsive, emergency workers may also have to treat cardiac arrest or something more severe, but they may not know whether tranquilizers or stimulants are driving symptoms.
- EMTs also may not know how potent novel synthetics may be.
- Forensic labs and coroners often lack resources to rapidly detect emerging compounds, meaning markets can shift months before data catches up.
Kaitlyn Brown, clinical managing director for America's Poison Centers, tells Axios clinicians often treat patients based on symptoms because toxicology results aren't immediately available.
- "There's no antidote for pink cocaine. We support breathing, heart rate and blood pressure while the drugs clear."
Between the lines: The crisis is getting quieter. Poly-drug use increasingly happens in private homes, clubs and small gatherings, not just visible street scenes. That reduces warning signs.
- And while overdose deaths are declining, experts warn that infectious diseases, severe wounds linked to xylazine, and stimulant-related cardiac crises remain serious risks.
- Vakharia said the abuse of tranq is also resulting in severe scars and emergency amputation of arms or legs.
The bottom line: As long as demand exists, suppliers will adapt. Enforcement may shrink one drug's footprint, but the chemistry shifts.
- The next phase of the crisis will depend on whether the country can keep pace with a drug market that is increasingly synthetic, decentralized, and designed to stay one step ahead.
