Founder
Dr. Roland Segal is a leading psychiatrist with extensive experience and is the Managing Partner and MD Psychiatrist at Legacy Recovery Center. After earning his medical degree from the University of Arizona, College of Medicine, he completed general psychiatry training at Banner Good Samaritan Medical Center in Phoenix, Arizona, and advanced his expertise through a forensic psychiatry fellowship at USC’s Keck School of Medicine.
With over a decade of diverse experience in clinical, administrative, and forensic psychiatry, Dr. Segal is double board-certified in General and Forensic Psychiatry. His previous roles include Chief Medical Officer at Valley Hospital in Phoenix, Arizona, and president of the Arizona Psychiatric Society. He has also served as the legislative committee chair and contributed to numerous state and national boards, committees, and organizations. Additionally, Dr. Segal teaches as a clinical assistant professor of psychiatry at the University of Arizona, College of Medicine, mentoring medical students and residents.
Dr. Segal acts as an expert psychiatry consultant for multiple superior and regional courts, including those in Maricopa and Yuma counties, Salt River, as well as city governments like Phoenix, Lake Havasu, and Mesa. He also consults for prominent organizations such as the United States Postal Service, Social Security Administration, Immigration Health Services, and the U.S. Departments of Justice and Homeland Security.
Guided by principles of objectivity, ethics, mindfulness, and cultural awareness, Dr. Segal remains dedicated to providing compassionate, inclusive psychiatric care, impacting lives across Arizona and beyond.
When many of us think of an overdose, the image is of a drug user found nodding off after heroin, with slow, shallow breathing as the primary sign.
However, overdoses look and act differently now, mainly because the drug supply has changed from heroin and pills to powerful synthetic drugs (especially opioids like fentanyl and similar substances) and mixtures of different drugs that include sedatives, stimulants, and additives such as xylazine and designer benzodiazepines.
This shift, along with the rise of polysubstance use, alters the onset and clinical presentation, which can include confusing and often contradictory symptoms, the response to naloxone, and the types of complications and injuries observed in the field and in the emergency department.
In this article, I explore the shift from heroin to fentanyl, the rise of dangerous adulterants such as xylazine, the new phenomenon of polysubstance toxicity, and implications for harm reduction and bystanders.
The Fentanyl Factor: Amplified Speed and Potency
Since 2015 or 2016, the opioid street supply in the U.S. has shifted from primarily heroin and prescription opioids to illicitly manufactured fentanyl because it is easy to manufacture and ship [1].
Fentanyl, a synthetic opioid 50–100 times more potent than many prescription opioids, has saturated the illicit drug market, appearing on the street not only in heroin but also in many other drugs [2].
Fentanyl and analogues now account for the majority of opioid overdose deaths in North America and are frequently combined with methamphetamine, cocaine, benzodiazepines, nitazenes, counterfeit pills, and other new psychoactive substances (NPS).
Unlike the slower respiratory depression of heroin, fentanyl’s potency causes a rapid onset of effects. Users can lose consciousness and stop breathing within minutes, giving bystanders a much smaller window to intervene.
The inconsistent distribution of fentanyl in a batch of drugs means that a dose that was safe yesterday could be lethal today.
Some Optimism With Overdose Deaths
Nonetheless, recent data show a 25.0% decline in overdose deaths from the year ending in March 2025 (77,648 overdose deaths) versus the previous year (103,529). This is a dramatic shift from relentlessly rising overdose deaths for much of the past 25 years. Most overdose deaths involve opioids at 66.2% in the year ending in March 2025; 57.9% involve synthetic opioids, including fentanyl and fentanyl analogs [3] [4].
The Dangerous Evolution of Polysubstance Abuse
Urine drug testing data from Millenium Health, a leading drug testing lab, showed significant drops in fentanyl detection in 2023–2024, followed by a rapid rebound in late 2024 into early 2025—mirroring overdose death data. A spike in heroin and other opioid detections in mid-2024 suggests the occurrence of a potential fentanyl supply shock.
And of great note, in 2025, 85% of people testing positive for fentanyl also tested positive for an illicit stimulant (primarily methamphetamine and cocaine)—the highest proportion ever recorded in the study’s datasets [5].
This and other data from the CDC show the complex and evolving nature of the illicit drug supply and the dangerous rise of polysubstance abuse [6].
The Rise of the “Tranq” Threat: Introducing Adulterants
A key element in the polysubstance shift in the illicit drug supply is the addition of non-opioid sedatives, most notably xylazine (known as “tranq”), an animal tranquilizer.
Xylazine, a veterinary sedative for large animals, is a non-opioid alpha-2 adrenergic agonist. It has quickly become a common additive in drugs; its involvement in overdose deaths jumped from less than 1% in 2015 to about 6–7% by 2020 in several US areas, which is a 20-fold increase.
Unlike a pure opioid overdose, xylazine causes profound sedation, muscle weakness, and slowed breathing that does not reverse with naloxone (Narcan). This means first responders may administer multiple doses of naloxone with little to no effect on the person’s level of consciousness, creating panic and uncertainty [7].
An overdose involving xylazine looks like a hybrid crisis. The person may be deeply sedated (like with an opioid) but also have extremely low blood pressure and a slow heart rate (unusual for a stimulant but common with this adulterant).
And research shows that fentanyl is nearly universally involved in xylazine-present overdose deaths [7].
How Overdoses Look Different Now
Fentanyl has a faster onset and more abrupt collapse than heroin. Its high potency and rapid central nervous system (CNS) penetration mean people may drop within seconds to minutes, often with minimal early-stage onset compared to slower-onset heroin overdoses clinicians saw a decade ago.
Classic opioid signs still occur (pinpoint pupils, respiratory depression, cyanosis, unresponsiveness) but are often more profound and sudden.
Xylazine and sedative adulterants add prolonged sedation, bradycardia (resting heart rate under 60 beats per minute), and hypotension that do not respond to naloxone. Patients may remain in a state of reduced consciousness, alertness, and mental clarity, between lethargy and stupor, even after adequate reversal of the opioid component.
Xylazine‐associated skin injuries, including necrotic ulcers (causing dying or dead tissue) at and away from injection sites, are now a characteristic feature in many regions and were rarely seen a decade ago at today’s scale.
Recurrent unconsciousness, falls, and hypoxic (deprivation of oxygen in tissues) episodes contribute to more traumatic injuries and pressure ulcers around overdose events than in earlier heroin‑dominant eras.
The Complexity of Polysubstance Use
Statistics show that polysubstance use is now the standard. As noted earlier and here again for emphasis, in 2025, a staggering 85% of people who tested positive for fentanyl also tested positive for a stimulant like methamphetamine or cocaine.
Polysubstance use makes it hard to see the effects of “pure opioids”: drugs like methamphetamine, cocaine, and synthetic stimulants can cause restlessness, a fast heart rate (over 100 beats per minute), and a high body temperature, either before or at the same time as breathing problems, leading to symptoms that can alternate between stimulant toxicity and deep sedation.
This combination creates a chaotic clinical picture. A person may have taken a stimulant that raises their heart rate and blood pressure and mixed that with a sedative that depresses their breathing.
The result is a “toxidrome” where symptoms mask each other. A patient might be unconscious but have a racing pulse, confusing bystanders who expect a quiet, slow-motion death.
Mixing stimulants and depressants puts extreme strain on the heart and cardiovascular system, increasing the risk of heart attack or stroke alongside respiratory failure.
Population Shifts with Fentanyl Use
Overdose deaths remain high but have recently plateaued or modestly declined in some US data, in part because fentanyl has saturated the opioid‑using population and fewer people are initiating high‑risk opioid use, while the use of medications for opioid use disorder (MOUD) has increased.
At the same time, overdose deaths involving combinations of stimulants, opioids, xylazine, and counterfeit pills have increased, further diversifying presentations, which complicates treatment approaches and highlights the need for targeted interventions to address these emerging patterns.
Practical Implications for Recognition and Harm Reduction
Clinically, you still look for the core opioid triad—respiratory depression, pinpoint pupils, and unresponsiveness—but you now expect more mixed pictures, faster decompensation, and variable naloxone responsiveness.
Naloxone Response and Managing an Overdose
Because fentanyl is so potent and often present with other CNS depressants, responders may need higher or repeated naloxone dosing compared with what was often sufficient for heroin or oxycodone overdoses ten years ago.
Naloxone still reverses the opioid component, but it does not touch xylazine, benzodiazepines, or alcohol, so “partial” responses—improved respirations without full arousal—are more common [8].
The short duration of naloxone’s effects compared to the long-lasting synthetic opioids can cause patients to become sleepy again after they initially get better, meaning they need longer monitoring than was typical in earlier waves of the epidemic.
The Old Rules No Longer Apply
The old rules of “lay them on their side and give Narcan” are no longer sufficient. Bystanders must call 911 immediately and be prepared to administer rescue breathing, as naloxone may not fully revive the person.
Multiple Doses
Instructions now often emphasize that if one dose of naloxone doesn’t work, give a second, as the potency of fentanyl may require it [9] [10].
Visibility of Use
With the rise of stimulant co-use, overdoses are occurring more frequently among people who smoke or snort drugs, not just those who inject, expanding the demographic and settings where overdoses happen.
A Shift in Harm‑Reduction Priorities
In this new context, priorities for harm reduction have shifted:
- Widespread access to take-home naloxone
- Teaching that more than one dose might be necessary
- Focusing on rescue breathing and airway support
- Informing people that xylazine and other non-opioid sedatives in the drugs can lead to long-lasting unconsciousness and unusual injuries, even if naloxone is used
Compassionate Addiction Treatment in Arizona at Legacy Recovery Center
Legacy Recovery Center is a highly rated, premier addiction and mental health treatment center in Arizona. Legacy is owned and operated by two psychiatrists with over 40 years of combined experience, complemented by a robust therapeutic team.
Our multidisciplinary approach combines psychiatric evaluation, medication management when appropriate, evidence-based therapy, and trauma-informed care to support stabilization and long-term recovery. By treating complex psychiatric cases in a structured residential setting, the team helps clients move from crisis and instability toward clarity, safety, and long-term healing.
Sources
[1] MacMillan C. 2024. Why Is Fentanyl Driving Overdose Deaths? Yale Medicine.
[2] NIDA. 2025. Fentanyl.
[3] Dowell, D. et al. 2025. Why have overdose deaths decreased? Widespread fentanyl saturation and decreased drug use among key drivers. The Lancet Regional Health Americas. Volume 51, 2025. 101226,
[4] CDC. 2025. Understanding the Opioid Overdose Epidemic.
[5] Millenium Health. 2026. Fentanyl Overdose Deaths Plummet but Unchecked Illicit Stimulant Use Threatens to Reshape America’s Drug Use Epidemic. Signals Report Vol. 8.
[6] CDC Overdose Prevention. 2024. Polysubstance Overdose.
[7] Rimawi, M., and D. Hamlin. 2025. Xylazine: A Review of Intoxication, Overdose, and Withdrawal Symptoms. American Journal of Psychiatry Residents’ Journal. Volume 20, Number 3.
[8] Friedman, J., et al. (2022). Xylazine spreads across the US: A growing component of the increasingly synthetic and polysubstance overdose crisis. Drug and alcohol dependence, 233, 109380.
[9] UPMC. 2025. Fentanyl Overdose.
[10] OC Children’s Therapeutic Arts Center. nd. Recognizing and Responding to Opioid Overdoses: A Comprehensive Guide for Prevention and Harm Reduction.
