Public Health

Animal Tranquilizer ‘Xylazine’ Is Making the Fentanyl Crisis Even Worse

In recent years, the devastating impact of the fentanyl crisis has been felt by many Americans. The opioid epidemic, led by this potent synthetic drug, has claimed thousands of lives and shows no signs of abating. But now, a new threat lurks in the shadows, poised to exacerbate an already dire situation — a veterinary sedative known as xylazine.

First synthesized in the 1960s, xylazine is a non-opioid sedative, analgesic, and muscle relaxant used primarily in veterinary medicine for large animals such as horses1. However, it has started to creep into illicit drug markets, often used as an adulterant for opioids like heroin and fentanyl2. The rise of this trend is concerning, and it’s crucial to shed light on this development as it continues to evolve.

Chemical structure of xylazine. / PubChem

Xylazine, when used in humans, can induce effects similar to those of opioids — a deep sense of relaxation, sedation, and pain relief1. This might explain its allure for those entrenched in substance misuse, but these effects come at a steep price. Unlike traditional opioids, xylazine is not reversed by naloxone (Narcan), the standard emergency treatment for opioid overdoses3. This significantly complicates matters for first responders, who may be unaware that xylazine is present and find that their typical lifesaving interventions are ineffective.

Moreover, xylazine possesses several harmful side effects, including hypotension, bradycardia, respiratory depression, and, in some cases, even death4. Coupled with fentanyl — a substance already notorious for its fatal potency — the presence of xylazine is a ticking time bomb.

The issue of xylazine adulteration in the opioid supply is gaining recognition, yet its severity remains underestimated. According to a 2023 report in the New England Journal of Medicine, xylazine was found in more than 90% of illicit drug samples tested in Philadelphia in 20215. The report found that xylazine is typically found as an adulterant in polydrug mixtures, usually containing simulants like cocaine and amphetamines or opioids like heroin or fentanyl. Alarmingly, the report estimates that the number of xylazine-involved drug-poisoning deaths in the United States increased by 13 times from 2018 to 2021 (an increase from 250 to 3500 deaths).

This rapidly growing and evolving crisis calls for a broad, multi-faceted response involving policymakers, healthcare providers, researchers, and communities. Actions include tightening regulation of veterinary substances, amplifying harm reduction services, and research and development of new overdose drugs that work against xylazine.

The already formidable challenge of the fentanyl and opioid crises is deepened by the introduction of xylazine, adding another lethal layer to the issue. To protect those grappling with substance misuse, it’s crucial to adapt our strategies to this emerging reality. Through a combination of awareness, education, vigilance, and research, we can start to tackle the profound impact of xylazine on the opioid crisis.

  1. Ruiz-Colón, K.; Chavez-Arias, C.; Díaz-Alcalá, J. E.; Martínez, M. A. Xylazine Intoxication in Humans and Its Importance as an Emerging Adulterant in Abused Drugs: A Comprehensive Review of the Literature. Forensic Sci. Int. 2014, 240, 1–8.
  2. Kacinko, S. L.; Mohr, A. L. A.; Logan, B. K.; Barbieri, E. J. Xylazine: Pharmacology Review and Prevalence and Drug Combinations in Forensic Toxicology Casework. J. Anal. Toxicol. 2022, 46 (8), 911–917.
  3. National Institute on Drug Abuse. Xylazine. National Institutes of Health. (accessed 2023-05-25).
  4. Andrew McAward. Xylazine, an Emerging Adulterant. American College of Emergency Physicians. (accessed 2023-05-25).
  5. Gupta, R.; Holtgrave, D. R.; Ashburn, M. A. Xylazine — Medical and Public Health Imperatives. N. Engl. J. Med. 2023, 0 (0), null.
COVID-19 Public Health

COVID Disease Severity Lower Than Ever, Most People Infected Unaware of Status

As the omicron BA.5 subvariant has become dominant, many countries are heading into their third wave of Omicron cases. Japan reports its largest-ever surge in cases, recording over 200,000 new cases in one day.

Though omicron BA.5 has become the most dominant subvariant of COVID (accounting for 88% of new cases in the US) and is highly contagious, CDC data shows disease severity at its lowest point ever.

Intensive Care Unit (ICU) admission among hospitalized COVID-19 patients. (

Among hospitalized COVID patients, about 1 in 10 are admitted to the ICU as of July 2022. This figure was as high as 1 in 3 in March 2020, and 1 in 5 as recently as December 2021.

Mortality among hospitalized COVID-19 patients. (

Similarly, mortality among hospitalized COVID patients has decreased appreciably from 1 in 5 in March 2020 to 1 in 40 in July 2022.

These decreases in COVID disease severity follow the emergence of the omicron variant in November 2021 and its ever-growing share of new infections. The omicron variant, while of high concern and contagion, does not appear to be of proportionally high consequence compared to earlier variants.

The most common symptoms of COVID include cough, fever, and chills. Many report symptoms resembling a common cold with symptoms like upper respiratory congestion. Most people (56%) who are infected with the omicron variant are not aware of their positive status according to a recent Cedars-Sinai study.

Multiple factors could explain omicron’s lower severity, including widespread vaccination or immunity gained from prior exposure and infection. It is also possible that omicron has mutations that decrease severity while favoring infectivity.

Immunotherapy Public Health

How Bacteriophages Could Save Humanity from Antibiotic Resistance

“Thanks to penicillin… he will come home!” pronounced a Life magazine advertisement published in 1944. At this time, penicillin, the first true antibiotic drug, had just been discovered and made commercially available.

Antibiotics are drugs that prevent or treat bacterial infections. Before the advent of penicillin, the leading causes for death were bacterial infections resulting in pneumonia, tuberculosis, diarrhea, and enteritis, causing one third of all deaths in the United States. Since then, the idea of deaths by bacterial infection have largely faded into the past—until the evolution of antibiotic-resistant bacteria has now threatened this status quo.

In antibiotic or antimicrobial resistance, antibiotics are no longer effective against bacteria that have evolved to survive it, particularly using beta-lactamase enzymes. This resistance is further accelerated by excessive, unnecessary use of antibiotics, mainly in industrial livestock production and over-prescription. This increased use contributes to the evolutionary pressure on microbes to develop resistance to antibiotics.

Alexander Fleming, who discovered penicillin, was receiving the Nobel Prize in medicine and physiology when he ominously predicted antibiotic resistance: “It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them.” Fleming himself was hesitant of widespread antibiotic use, recognizing its resistant capabilities from the year they were released. In 2019, the CDC reported more than 2.8 million antibiotic-resistant infections in the US.

Antibiotics have very specific mechanisms of action to target bacteria. For example, penicillin binds to an enzyme on the bacteria and removes it, which breaks an important barrier in the cell. If one certain bacteria has a mutated enzyme, the antibiotic will be rendered ineffective, and that mutation will become prevalent in that bacterial species.

A key difference between bacteria and most other organisms is their ability to transmit genes to nearby bacteria in a process called horizontal gene transfer. This is why bacterial resistance has quickly become an epidemic as it spreads quickly and efficiently. Unfortunately, it would take almost a decade to modify the antibiotics necessary to combat these “superbug” bacteria.

Bacteriophages, meaning “bacteria eaters,” are viruses that only infect bacteria. Most are lytic, meaning that when infecting a host, they inject their genes into the host, utilize the host to rapidly replicate, and destroy the cell walls by bursting through, essentially creating a “phage-producing factory” from a bacteria. A small number are lysogenic, which means they coexist with bacteria.

Consequently, bacteriophages have provoked the interest of researchers as a potential replacement for traditional antibiotics, which are obtained from fungi. While there are a little over 100 known traditional antibiotic drugs to fight the near-infinite supply of bacteria in the world, estimates show that there exist about 10 phages for each bacterium. This indicates that there may be many more potentially therapeutic bacteriophages than traditional antibiotics. Bacteriophages are the most abundant “organism” in the biosphere, either living harmoniously with bacteria in the lysogenic cycle or destroying about 40% of the ocean’s bacteria every day, amounting to 10²³ phage infections in only one second.

Though, phages have drawbacks as potential antibiotic therapies. For one, they are extremely specific. While a single traditional antibiotic can target a multitude of bacteria, bacteriophages target one bacteria. A working solution for this is the use of “phage cocktails,” which combine multiple natural and synthetic bacteriophages to more effectively treat patients.

Also, phages are not entirely shielded from bacterial resistance. Bacteria can fight back with certain immune responses, specifically CRISPR Cas  systems. However, unlike antibiotics, phages are continually adapting and responding to such defensive systems. This continual mutation of phages poses a risk for FDA approval, but some researchers are working on machine learning  systems to predict these changes.

Still, bacteriophages show promise as an alternative therapy to traditional antibiotics. Scientists hope that phages will become an alternative defense against bacteria that could help ease antimicrobial resistance.

COVID-19 Public Health

Recovered Patients of Severe COVID-19 Infection 233% More Likely To Die Within Year Than Negative Counterparts

Research published by University of Florida scientists in Frontiers in Medicine reported that patients (aged 18-65) who recovered from severe COVID-19 infection were 233% more likely to die within 12 months than COVID-19-negative counterparts.


The study analyzed 13,638 patients in the University of Florida Health system over a 12-month period, including positive (mild, severe) and negative cases. A severe case was defined as one requiring hospitalization within 30 days of a positive COVID-19 test. The 12-month risk of mortality was adjusted for age, sex, race, and comorbidities–meaning these factors did not affect the data.


Survival curve showing probability of survival over time following mild, severe, and lack of COVID-19 illness. / Mainous 2021

Patients aged 18 to 65 who recovered from an initial episode of severe COVID-19 had a 233% increased incidence of mortality in a 12-month period compared to negative counterparts. Recovered patients aged over 65 also had increased mortality compared to negative counterparts, but to a lesser extent.

The difference in 12-month mortality between COVID-negative and mild COVID patients was not statistically significant.

Only 20% of the deaths in the 12-month period were attributed to cardiovascular or respiratory conditions.


These results show that those who recover from severe COVID-19 infections are much more likely to die within 12 months of recovery compared to those with mild or no infection. This reveals that the increased risk of death from COVID-19 is not limited to the initial episode of infection, indicating that the biological and physiological insult from severe infection is significant. This is further demonstrated by the unexpectedly low portion of deaths caused by cardiovascular or respiratory conditions.

Arch G. Mainous III, Ph.D., first author of the study and University of Florida College of Medicine faculty member, said in a statement to the University of Florida Health Newsroom that “patients may feel that if they are hospitalized and recover from COVID-19 then they have beaten COVID-19. Unfortunately, having a substantially increased [risk] of death in the next year after recovery from a severe episode of COVID-19 shows that this is not the case. Preventing severe COVID-19 should be our primary focus.”

The study mentions that nearly all hospitalizations and severe infections are preventable. Pfizer and Moderna’s COVID-19 vaccines prevent severe infection in more than 95% of cases.

Mainous hopes that the data, which he described as devastating, will “make everyone rethink the impact of COVID-19.”

Public Health

Study Shows Reddit’s Potential as an Early Warning System for New Designer Drugs

In a new study, researchers demonstrated the use of data mining of social networks like Reddit to predict increased use of novel psychoactive substances (NPS).

Reddit is a social network and media aggregator divided into subreddits pertaining to certain topics, like college football, art, movies, and world news. Niche subreddits exist for many topics, including specific drugs.

Users on subreddits like r/ResearchChemicals discuss designer drugs (including analogs) and other newly discovered substances. Analogs are two drug compounds that have similar molecular structures and/or effects. Sometimes, an analog of an illegal drug has similar effects and properties to its illegal counterpart but has yet to be made illegal.

Under the Federal Analogue Act, compounds “substantially similar” to controlled substances are meant to be treated as if they were the controlled substances themselves. However, designer drugs are often overlooked or may take years for federal authorities to address.

Reddit post on “research chemicals” subreddit discussing novel psychoactive substances.

Researchers from Florida Atlantic University, the University of Florida, and New York University gathered and analyzed data on mentions of newly discovered NPS on Reddit. They found that users mentioned certain NPS months to years before the substances became prevalent in toxicology reports. Such reports are conducted to identify a culprit substance when a patient has overdosed or is subjected to a toxic exposure.

The study mentioned that NPS mentioned on Reddit before any exposures were recorded include:

  • Carfentanil
  • U-47700
  • Eutylone
  • Flualprazolam
  • N-ethylpentylone
  • Isotonitazene
  • Brorphine

Carfentanil, for example, was first mentioned on Reddit in February 2013–almost 4 years before its first reported exposure in October 2016.

Reddit mentions of N-ethylpentylone peaked 5 months before the number of reported cases. (Barenholtz et al, 2021)

The study found that seven of the eight analyzed NPS were mentioned on Reddit before there were any reported cases of the substances in toxicology reports.

Five of the eight analyzed NPS peaked in Reddit mentions months before the substances peaked in reported exposures.

The researchers posit that these data mining methods could prove to be a useful tool for early detection of NPS trends by public health authorities and legislatures.

This article is based on the following works:

– Barenholtz et al. (2021, August 5). Online surveillance of novel psychoactive substances (NPS): Monitoring Reddit discussions as a predictor of increased NPS-related exposures.