Key Takeaways:
- Fentanyl increasingly contains sedative adulterants like xylazine and medetomidine, plus stimulants, which is complicating standard opioid use disorder treatment protocols.
- Xylazine’s own withdrawal syndrome and its masking of opioid withdrawal signs are pushing providers toward microinduction and specialized medications like clonidine.
- Stimulants now co-occur with opioids in a large share of overdose deaths, yet no FDA-approved medication exists for stimulant use disorder.
- Test strips for xylazine and medetomidine remain unreliable, and federal funding for public distribution was recently barred, leaving providers to rely on clinical suspicion.
- With no medication available for stimulant use disorder, contingency management offers the most effective current path for treatment programs to fill that gap.
A patient stabilizes on buprenorphine, but the vital signs don’t add up. Blood pressure climbs, agitation sets in, and naloxone does nothing to change the picture. A decade ago, this presentation would have puzzled most addiction medicine providers. Today, it’s routine enough that clinicians in Philadelphia and Baltimore have learned to recognize it on sight, and the pattern is no longer confined to those East Coast markets. It’s showing up in Los Angeles, in Houston, and in a growing list of cities that had little to no exposure just a few years ago. The fentanyl supply no longer behaves like fentanyl alone.
Two shifts are doing most of the work, and clinical protocols haven’t caught up to either. Xylazine and other non-opioid sedatives are turning up in illicit fentanyl at rates that were unthinkable five years ago, and stimulants have become so entangled with the opioid supply that treating one without the other rarely works. Neither trend fits neatly into the frameworks most treatment programs built around opioid use disorder. Providers are now adjusting dosing, withdrawal management, and screening practices in real time, often without the benefit of standardized guidance.
How Fast the Supply Has Changed
A JAMA Network Open study of people who inject drugs across five major U.S. cities found fentanyl exposure nearly universal, but xylazine exposure varying sharply by geography, from near-total saturation in Philadelphia to lower but rising rates in cities like Los Angeles and Houston. Community drug-checking data from Los Angeles illustrates how quickly that can shift. Xylazine positivity among fentanyl-positive samples climbed from zero in early 2023 to roughly one in four to five samples by 2025, a statistically significant upward trend quarter over quarter.
Xylazine isn’t the only adulterant reshaping the supply. Medetomidine, a more potent alpha-2 agonist, has appeared alongside or in place of xylazine in several regions, and federal officials have flagged both substances as emerging threats alongside novel synthetic opioids. These adulterants create a consistent clinical challenge. They produce deep sedation and cardiovascular effects that naloxone cannot touch, because the mechanism of action has nothing to do with opioid receptors.
Stimulants Are No Longer a Side Issue
Sedative adulterants are only half of the equation. Stimulant-involved overdose deaths climbed for years even as the broader crisis evolved, and they’re only now beginning to ease, well after opioid deaths turned the corner. The CDC’s most recent provisional data, released in May 2026, shows overdose deaths involving cocaine and psychostimulants like methamphetamine finally declining alongside opioid deaths, but from a plateau that took years longer to form and hasn’t come down nearly as fast. The result is a stimulant burden that’s easing in absolute terms while staying just as embedded in the broader overdose picture.
That embeddedness is the real story. CDC surveillance data covering 2021 through mid-2024 found that stimulants were involved in 59% of overdose deaths, with 43% of all overdose deaths co-involving stimulants and opioids together. Nearly 70% of stimulant-involved deaths also involved illicitly manufactured fentanyl. The combination of fentanyl and stimulants has grown from a negligible share of overdose deaths in 2010 to roughly a third of them by 2021, according to research tracking what’s often called the fourth wave of the overdose crisis. Stimulants aren’t a separate problem running alongside the opioid crisis. For most patients, they’re part of the same presentation.
This matters clinically because stimulant use disorder has no FDA-approved medication. Programs built around medication for opioid use disorder can find themselves without an equivalent pharmacological tool for the stimulant side of a patient’s presentation, even when stimulant use is driving as much clinical risk as the opioid use.
Where Standard MAT Protocols Fall Short
The stimulant gap is a missing tool. The sedative adulterants create a different kind of problem by interfering with the tools providers already have. Buprenorphine and methadone dosing protocols were developed for a supply where opioids were the primary variable. Xylazine complicates that math in two ways. First, it produces its own withdrawal syndrome — marked by hypertension, agitation, and autonomic dysregulation — that can be mistaken for undertreated opioid withdrawal or for an unrelated medical emergency, particularly when a patient’s history of xylazine exposure isn’t known. Second, xylazine’s sedative effects can mask early signs of opioid withdrawal or overdose, complicating decisions about induction timing and dose titration.
Buprenorphine dosing has already been shifting for reasons that predate xylazine, and the adulterant compounds the problem. The traditional approach waits for moderate withdrawal before starting buprenorphine, which assumes a predictable opioid half-life that fentanyl and its analogs don’t offer. That unpredictability has pushed providers toward microinduction, or starting buprenorphine in small doses while a patient continues using their opioid of choice to avoid precipitated withdrawal. Xylazine adds a further wrinkle. By blunting the visible signs of withdrawal, it makes the traditional timing cue even less reliable, reinforcing the case for induction strategies that don’t depend on waiting for withdrawal to appear.
For the withdrawal syndrome itself, case reports and small systematic reviews are beginning to fill in what a modified approach looks like. Clonidine has emerged as the most consistently recommended first-line treatment for xylazine withdrawal, typically started around 0.1 mg every eight hours and titrated against blood pressure, with tizanidine, guanfacine, or lofexidine as alternatives when clonidine isn’t tolerated. Severe cases have required dexmedetomidine in monitored settings, along with adjunctive gabapentin, low-dose antipsychotics, or benzodiazepines to manage agitation. Several published protocols also recommend prioritizing opioid withdrawal management in xylazine toxicity cases, given how often xylazine misuse co-occurs with other opioids.
None of this is yet standardized into consensus guidelines the way opioid withdrawal management is. Providers are largely working from case series, regional health department bulletins, and emerging systematic reviews rather than an established protocol.
Screening Practices Haven’t Caught Up
Even an informal protocol only works if a provider knows to reach for it. Most standard toxicology panels, including many used in emergency departments and treatment intake, don’t test for xylazine or medetomidine by default. That gap means a substantial share of xylazine and medetomidine exposure is likely going undetected in patients presenting with opioid use disorder. One published case report noted that a hospital’s lack of routine xylazine toxicology screening left the care team relying on history-taking and clinical suspicion to identify a withdrawal syndrome that didn’t match typical opioid withdrawal.
Point-of-care xylazine test strips exist, but their real-world performance has been mixed. A Los Angeles-based drug-checking evaluation found the strips correctly identified only about half of confirmed xylazine-positive fentanyl samples. Specificity was stronger (around 89%), with lidocaine, a common cutting agent, responsible for most false positives. That access is also getting harder, not easier. SAMHSA reversed its earlier position in April 2026, barring grantees from using federal funds, including State Opioid Response and Tribal Opioid Response program dollars, to purchase fentanyl, xylazine, or medetomidine test strips for public distribution. Programs that relied on that funding are already losing it, which makes provider-level testing infrastructure, not just harm-reduction distribution, more important to maintain independently.
For treatment programs, the practical takeaway is that a negative standard opioid screen doesn’t rule out a sedative-involved presentation, and providers in any region should have a low threshold for xylazine-specific testing given how quickly the substance has spread west.
Adjusting for a Supply Without a Stimulant Medication
The sedative side of this problem is a detection gap. The stimulant side is still the missing tool from earlier: there’s no medication to reach for, and that absence has pushed contingency management into a more central role. The federal incentive cap that had long limited its use rose from $75 to $750 per patient per year in January 2025, a change that aligned policy with a body of research that had found the previous cap too low to produce meaningful behavior change. Contingency management has shown effectiveness not only for reducing stimulant use on its own, but for supporting treatment adherence among patients receiving medication for co-occurring opioid use disorder. That combination is increasingly the norm rather than the exception given how often stimulants and opioids now show up together in overdose data.
For programs without existing contingency management infrastructure, this represents a meaningful gap to close. Behavioral approaches like cognitive behavioral therapy and the Matrix Model remain useful complements, but the evidence base consistently points to contingency management as the most effective single intervention currently available for stimulant use disorder.
These adjustments build on medication for opioid use disorder as the foundation of care, adapting it for a supply and patient population that have become more complicated than the protocols were originally designed to handle. Providers who build that flexibility into screening and treatment now will be better positioned for whatever this supply does next.
Dr. Ryan Cole is a licensed clinical psychologist and the founder of Achieve Whole Recovery and Brain and Body Integration. He earned his doctorate in clinical psychology from The Chicago School of Professional Psychology in 2012 and launched Brain and Body Integration a year later. In 2017, he founded Achieve Whole Recovery to expand access to psychiatry, addiction medicine, and mental health and addiction counseling for individuals across Colorado. Dr. Cole has built both practices around a simple standard: Patients shouldn’t have to wait to get help. That principle drives Achieve Whole Recovery’s mission to deliver access and excellence in care, backed by same-day appointments and statewide telehealth.
