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The Synthetic Opioid ProjectPharmacology, toxicology, and causation — sourced to primary literature.

What the science actually says about fentanyl

Pharmacology, toxicology, and causation for prosecutors, defenders, and civil counsel alike — sourced to primary literature, written by a board-certified toxicologist and a pharmaceutical chemist.

Read the standardsRequest a consultation
Published byVident Partners — expert witness referral, since 2005
Anchored byStephen L. Thornton, M.D., FACEP · Saadyah E. Averick, Ph.D.
References28 primary sources, every URL checked

The Synthetic Opioid Project is an independent reference on the pharmacology, toxicology, and forensic interpretation of fentanyl and the synthetic opioids following it — maintained by practicing experts and sourced to primary literature on every page. It takes no side in any case: prosecutors, defense counsel, and civil litigators are working from the same science, and this is where that science is written down plainly and completely.

Where this stands

The mortality curve is bending down. The litigation curve is not.

Synthetic opioids other than methadone — overwhelmingly illicitly manufactured fentanyl — were involved in 37,212 U.S. overdose deaths in the twelve months ending January 2026, according to CDC provisional counts. That is 54 percent of all 68,669 drug overdose deaths in the period, and it is roughly half the 75,390 recorded in the twelve months ending January 2023. The mortality curve is bending down. The litigation curve is not: federal fentanyl trafficking sentencings rose 135 percent between fiscal 2021 and fiscal 2025, thirty-one states and the District of Columbia now have drug-induced homicide statutes, and nearly three thousand civil actions remain pending in the national opioid MDL.

The science the record usually gets wrong

Almost every one of those matters turns on a scientific question that the record usually gets wrong. Whether a measured blood concentration means anything. Whether a reversal that worked proves the drug was survivable. Whether a defendant's product was the but-for cause of a death when four other substances were in the decedent, one of which naloxone cannot touch. Whether the analytical method used could even have detected what was actually in the supply. These are not rhetorical positions. They are answerable questions with a literature behind them, and the answers do not consistently favor either side.

The clinic and the bench

This Center is anchored by two complementary authorities from Vident Partners' expert network. Stephen L. Thornton, M.D., FACEP, is triple board-certified in Emergency Medicine, Medical Toxicology, and Addiction Medicine, serves as Medical Director of the Kansas Poison Control Center and as a faculty member at the University of Kansas School of Medicine, and has 95 peer-reviewed publications and more than 1,100 citations; he has been retained in 31-plus documented matters for both plaintiff and defense. Saadyah E. Averick, Ph.D., is a polymer and pharmaceutical chemist trained at Carnegie Mellon, with 92-plus peer-reviewed publications, an h-index of 38, and translational research in opioid countermeasures — long-acting naloxone nanoparticles and anti-fentanyl vaccine conjugates. A physician who treats the poisoning and a chemist who works on the molecule. The clinic and the bench.

The scale

What the record shows

Each figure below is reported with the source that produced it and the period it covers. Numbers describing a population are not findings about any individual case.

37,212

U.S. overdose deaths involving synthetic opioids other than methadone — principally illicitly manufactured fentanyl — in the 12 months ending January 2026 (CDC provisional reported count; predicted 37,607). That is 54% of all 68,669 drug overdose deaths in the period. Deaths are falling sharply from the peak of 75,390 in the 12 months ending January 2023 — back to roughly the 37,579 level of the 12 months ending January 2020 — but still more than six times the 5,766 recorded in the 12 months ending January 2015.[21]

3,605

individuals sentenced for federal fentanyl trafficking in fiscal year 2025 — up 135% from 1,533 in fiscal year 2021. The average sentence rose from 58 months to 79 months over the same period, 48% were convicted of an offense carrying a mandatory minimum, and the median base offense level corresponded to 400 grams to 1.2 kilograms of fentanyl.[22, 23]

31 states + D.C.

jurisdictions with drug-induced homicide laws as of May 1, 2024, up 33% from 24 states in 2018. Four — Arizona, Colorado, Florida, and Oklahoma — authorize a sentence of death for violation. Each state's causation and intent standards differ, which is precisely where expert testimony enters.[19, 20]

2,927

civil actions still pending in In re: National Prescription Opiate Litigation, MDL No. 2804 (N.D. Ohio, Judge Dan A. Polster), out of 3,182 filed historically, per the Judicial Panel on Multidistrict Litigation report dated July 1, 2026. A related consultant MDL against McKinsey & Company (MDL 2996, N.D. Cal.) has 235 actions pending.[24]

$7.4 billion

value of the Purdue Pharma / Sackler national opioid settlement, signed by 55 attorneys general and now legally in effect — separate from the multistate settlements with distributors, pharmacies, and manufacturers. New York alone publishes allocations from those agreements totaling over $3 billion, including up to $1.1 billion from the three major distributors and up to $523 million from Teva.[25, 26]

9,950 kg + 61.1M pills

fentanyl powder and counterfeit fentanyl-containing pills seized by DEA in calendar year 2024 — approximately 29% and 24% below 2023 levels respectively. DEA's NFLIS forensic laboratory database has logged more than 1.2 million fentanyl reports since 1998, peaking above 182,000 in 2023 before falling to more than 152,000 in 2024.[1]

The standards

What the science actually says

Eight questions that decide synthetic opioid matters, answered from the primary literature. Every assertion carries a numbered citation to the source underneath it.

Why fentanyl kills

Fentanyl is a mu-opioid receptor agonist approximately 100 times more potent than morphine as an analgesic, with rapid onset and short duration, and it crosses the blood-brain barrier quickly. NIDA states that as little as 2 mg can be fatal. Death is respiratory. Opioid-induced respiratory depression is compounded, in some exposures, by skeletal muscle rigidity that stiffens the chest wall — what one review calls a "double whammy of a depressed respiratory drive and a mechanical restriction to breathing." Because the fentanyls are highly lipid-soluble, overdose deaths have been described occurring within five minutes, against more than thirty for heroin.[1, 2, 3, 4]

The reversal myth: renarcotization

Naloxone displaces fentanyl from the receptor, but it does not stay there. Naloxone's half-life in adults runs roughly 30 to 80 minutes; fentanyl's elimination half-life is 3 to 7 hours. When the antagonist clears before the agonist, respiratory depression can return — renarcotization. Clinical reference guidance instructs that patients who respond to naloxone be monitored 6 to 12 hours precisely because some opioids have a much longer half-life than the antidote, and notes that repeated doses are commonly required. Fentanyl respiratory depression is documented as harder to reverse than heroin's, often needing multiple or higher doses. A successful reversal is where the standard-of-care inquiry begins, not where it ends.[2, 3, 4, 5]

The remaining 6 standards

  1. The adulteration era: what naloxone cannot reverse
  2. Past fentanyl: the nitazenes
  3. The number is not the cause
  4. But-for causation in federal death-results prosecutions
  5. Drug-induced homicide is a different animal
  6. What Rule 702 now demands of the expert
Read the full standards →
Living impaired drivers have tested at 303 ng/mL of fentanyl. A postmortem number, standing alone, is not a cause of death.

Where it comes up

Matters that turn on this science

  • Federal 21 U.S.C. § 841(b)(1) "death results" prosecutions — but-for causation, for the government and for the defense
  • State drug-induced homicide, delivery-resulting-in-death, and felony-murder overdose prosecutions
  • Wrongful death and survival actions following a fatal or near-fatal overdose
  • Emergency department and EMS standard-of-care claims — naloxone dosing, post-reversal observation periods, and premature discharge
  • Correctional, jail, and detention overdose and withdrawal-management litigation
  • Hospital, surgery center, and pharmacy fentanyl diversion, substitution, and drug-tampering matters
  • Opioid prescribing, pill-mill, and DEA registration and administrative proceedings
  • Contested cause-and-manner-of-death determinations and postmortem toxicology disputes
  • Product liability and pharmaceutical formulation cases — transdermal patches, transmucosal products, and compounded preparations
  • Impairment and human-performance matters — drugged driving, workplace incidents, and industrial accidents
  • Sentencing disputes over drug quantity, purity, mixture weight, and analogue or fentanyl-related-substance classification
  • Insurance and benefits disputes turning on accidental versus intentional overdose, and on intoxication exclusions

The bar

What to require of an expert in these matters

The same standard applies to the experts who anchor this Center. It is published so counsel can hold anyone — including us — to it.

  1. ABMS board certification in medical toxicology — granted through ABEM, ABP, or ABPM after a two-year ACGME-accredited fellowship. This is a defined subspecialty credential, not a self-designated title such as "toxicology consultant."
  2. Current clinical practice in the relevant setting: poison center medical direction, an active bedside toxicology consultation service, or emergency medicine, so the opinion reflects how these patients actually present now rather than how they presented a decade ago.
  3. Separate addiction medicine credentialing where tolerance, withdrawal, medication-assisted treatment, or treatment adequacy is genuinely at issue — tolerance is frequently the pivotal fact and it is a distinct body of knowledge.
  4. For analytical questions, a doctoral-level chemist with hands-on LC-MS/MS and GC-MS method development and validation experience, able to explain limit of detection, limit of quantitation, matrix effects, and why an unreported substance may simply never have been in the assay's scope.
  5. A peer-reviewed publication record in the specific question at issue — synthetic opioid pharmacology, overdose reversal, adulterant toxicology, or postmortem interpretation — rather than general toxicology output. Ask for the citation list and read three of them.
  6. Demonstrated fluency in postmortem redistribution and specimen provenance. A qualified expert asks which blood was drawn — peripheral or cardiac — and how long after death, before offering any concentration-based opinion.
  7. A documented, verifiable testimony history on both sides of the "v.", with prior Daubert and Frye challenges disclosed and their outcomes stated. An expert retained only ever by one side is a liability under cross-examination.
  8. Willingness to state the limits of the science on the record — including that a concentration alone does not establish cause of death, and that published lethal-dose figures are population heuristics, not individualized findings. This is now what Rule 702(d) affirmatively requires.

Anchor experts

A physician who treats the poisoning. A chemist who works on the molecule.

Stephen L. Thornton, M.D., FACEPStephen L. Thornton, M.D., FACEPMedical Director, Kansas Poison Control Center · Associate Professor, University of Kansas
Triple Board-Certified: Emergency Medicine, Medical Toxicology, Addiction Medicine

A triple board-certified physician leading the Kansas Poison Control Center, with 95 peer-reviewed publications, 1,100+ citations, and 31+ documented expert witness cases for both plaintiff and defense.

Medical toxicologyEmergency medicine standard of careFentanyl and synthetic opioidsDrug and alcohol impairmentFull profile, publications and testimony history →
Saadyah E. Averick, Ph.D.Saadyah E. Averick, Ph.D.Biotechnology, Pharmaceuticals, & Materials Science Expert
Ph.D. Chemistry, Carnegie Mellon · 92+ Publications · h-index 38 · 4,700+ Citations

A prolific polymer chemist and pharmaceutical scientist with 92+ peer-reviewed publications and 4,700+ citations. Deep expertise in drug delivery systems, biomaterials, and protein–polymer bioconjugates. Holds multiple U.S. patents in biomaterials, bioconjugates, and opioid countermeasure technologies. Peer reviewer for the NIH, NSF, and DoD/DoW.

Pharmaceutical drug delivery and formulationPolymer chemistry and bioconjugation (ATRP)Opioid overdose countermeasures and naloxoneFentanyl vaccine developmentFull profile, publications and testimony history →

Profiles, publication lists, and testimony histories are maintained on each expert’s Vident Partners page. Appearing here is not an endorsement of any opinion an expert may offer in a particular matter.

In the directory

Related expert witness specialties

These specialty pages live in the Vident Partners expert directory. This Center does not duplicate them.

Medical & Healthcare

Medical Toxicology

Expert directory →

Forensic & Criminal

Forensic Toxicology

Expert directory →

Medical & Healthcare

Pharmacology

Expert directory →

Medical & Healthcare

Addiction Medicine

Expert directory →

Medical & Healthcare

Emergency Medicine

Expert directory →

Medical & Healthcare

Pathology / Forensic Pathology

Expert directory →

Writing

Published, and in preparation

Already published in Vident Partners Insights.

Published

Fentanyl: A Brief Introduction

Saadyah Averick, PhD · April 21, 2026

Published

The key differences in Federal vs. State prosecutions for Fentanyl sales

Arie S. George · April 7, 2026

Published

The Status of Daubert in Federal Practice

Arie S. George · March 9, 2026

Published

The Status of Daubert Across the States

Arie S. George · March 24, 2026

Planned for this Center. These are commissioned outlines, not published pages — there is nothing to read yet, and we would rather say so than link you somewhere that does not exist.

Not yet published

Primer

How Fentanyl Kills, Step by Step

Receptor, respiration, chest wall, dose. The pharmacology in plain language, with every figure traced to a primary source.

Not yet published

For Litigators

The Number Is Not the Cause: Reading a Postmortem Fentanyl Report

Sampling site, redistribution, tolerance, and co-intoxicants — the four questions to ask before anyone quotes a concentration.

Not yet published

The Law

Burrage, a Decade On: What But-For Causation Still Requires

The holding, the independently-sufficient-cause carve-out, and how circuits have handled polysubstance deaths since 2014.

Not yet published

The Supply

After Xylazine: Medetomidine, Nitazenes, and the Tests That Miss Them

What is now in the drug supply, what standard panels cannot see, and what that means for causation and intent.

Questions counsel ask

Answers, with the citation attached

Does a high postmortem fentanyl concentration establish cause of death?

No, not standing alone. Postmortem redistribution can raise measured fentanyl well above in vivo levels — up to ninefold in one patch study — and depends heavily on whether cardiac or peripheral blood was drawn. A two-year county review found living impaired drivers at concentrations up to 303 ng/mL, overlapping the postmortem range almost entirely. Concentration is one input alongside tolerance, co-intoxicants, scene findings, and autopsy.[11, 12, 13]

What exactly does Burrage require in a federal death-results case?

Where the distributed drug is not an independently sufficient cause of death, the twenty-year enhancement under § 841(b)(1) applies only if that drug's use was a but-for cause of the death or serious bodily injury. A jury instruction permitting conviction on a "contributing factor" theory is error. The death-results element must be submitted to the jury and proven beyond a reasonable doubt.[14, 16, 17]

How can someone die after a naloxone reversal that visibly worked?

Naloxone's half-life in adults is roughly 30 to 80 minutes; fentanyl's elimination half-life is 3 to 7 hours. When the antagonist clears first, respiratory depression can recur — renarcotization. Standard guidance is to monitor a responder for 6 to 12 hours for exactly this reason, and repeat naloxone dosing is commonly required. Whether that observation happened is often the whole standard-of-care question.[2, 3, 5]

Does naloxone reverse xylazine or medetomidine?

No. Both are alpha-2 adrenergic agonists, not opioids, and NIDA states plainly that naloxone and nalmefene do not reverse xylazine's effects. Naloxone is still indicated because these adulterants almost always accompany fentanyl. Clinically this changes the picture; forensically it changes both causation analysis and any intent analysis premised on what the defendant knew was in the product.[7, 8, 9]

Which expert do I need — a medical toxicologist, a forensic toxicologist, or a chemist?

A medical toxicologist is a physician who addresses clinical causation, tolerance, treatment, and standard of care. A forensic toxicologist is a laboratory scientist who addresses analytical methodology, chain of custody, and specimen interpretation. A pharmaceutical or synthetic chemist addresses the molecule, formulation, synthesis route, and countermeasure science. Complex fentanyl matters frequently require two of the three, and the pairing should be deliberate.[27, 28]

Will routine toxicology testing catch the newer adulterants?

Frequently not. Common five-panel urine screens do not detect xylazine or medetomidine, and immunoassays used for conventional opioids are largely ineffective for most nitazenes; widely used fentanyl test strips do not detect nitazenes either. Confirmatory LC-MS/MS with an appropriate target panel is required. A negative screen is evidence about the assay's scope before it is evidence about the decedent.[8, 10]

References

Every figure in this Center, traced to its source

28 primary sources

Each URL was checked before publication and is rechecked whenever a page in The Synthetic Opioid Project is revised. The numbered markers throughout this Center link straight to the entry they rest on.

View the full reference list →

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