Tox In Focus

Focused Clinical Reference

Vol. 02 · Cychlorphine · May 2026

Drug Quick Reference

Drug Class / Mechanism

Benzimidazolone synthetic opioid (orphine analogue)

Full mu-opioid agonist; ~10x fentanyl

Street Names

No established street name

Found unlabeled in counterfeit pills

Routes of Administration

Oral (counterfeit tablets)

Intravenous injection

Commonly Detected With

Fentanyl, carfentanil · Nitazenes, phenazolam

Metabolism

Presumed hepatic (CYP3A4, extrapolated)

Limited human PK data

Window of Detection

Not established

Not detected by standard IA

Control Status

Not CSA scheduled

CYCHLORPHINE

A next-generation orphine analogue emerging as a fentanyl successor

Cychlorphine (N-propionitrile chlorphine) is a benzimidazolone-class synthetic opioid roughly 10 times more potent than fentanyl, with a longer duration of action. A full mu-opioid agonist, it has been detected as the sole opioid in counterfeit hydromorphone and oxycodone tablets, placing patients at extreme risk of unrecognized lethal exposure. It represents a distinct pharmacological class with limited published human pharmacokinetic data.¹

Why This Matters Now

The Knox County (TN) Regional Forensic Center linked cychlorphine to 41 deaths across 11 counties from July 2025 to February 2026, and CFSRE confirmed fatal overdoses across 8 US states and 3 Canadian provinces, with spread to FL, NY, IL, TX, CA, and NV. It was the only opioid detected in 11 of 25 confirmed overdose deaths and has been co-detected with carfentanil, phenazolam, and nitazenes.²

⚠ Treat any counterfeit oxycodone or hydromorphone exposure as potential cychlorphine; standard screening will not detect it, so clinical suspicion is the primary diagnostic tool. Prepare now regardless of local detection rates.

Clinical Presentation

INTOXICATION

Profound sedation / coma

Miosis

Respiratory depression

Bradycardia

Hypotension

Apnea; death

WITHDRAWAL

Typical opioid pattern

Anxiety / agitation

Diaphoresis

Nausea / vomiting

Tachycardia

Hypertension

Important: Naloxone should be administered; cychlorphine is a mu-opioid agonist and naloxone is expected to reverse it. Given extreme potency (~10x fentanyl), use full doses and repeat aggressively; do not withhold based on unconfirmed claims of Narcan resistance.

UDT Considerations

Cychlorphine is not detected by standard opioid immunoassay panels, including extended fentanyl-analogue screens and point-of-care multi-panel tests. Confirmatory identification requires LC-MS/MS. Ask your reference laboratory whether orphine analogues (chlorphine, cychlorphine, spirochlorphine) are included in any expanded NPS or synthetic-opioid panel, and specify 'orphine analogue' or request the full CFSRE-aligned NPS panel when ordering.¹ A negative standard UDT does not rule out cychlorphine; treat clinically.³

Clinical Guidance

Administer naloxone at full dose and repeat aggressively; cychlorphine is a mu-agonist and naloxone is expected to reverse it.²
Treat any counterfeit pill exposure (especially fake oxycodone or hydromorphone) as potential cychlorphine; screening will not detect it.
Request LC-MS/MS with orphine-analogue coverage when confirming.¹
Report suspected cases to your state health department or CFSRE to support surveillance.¹
Maintain high clinical suspicion; presentation, not the screen, drives diagnosis.

Point-of-Care Testing Availability

Available strips

No point-of-care strip exists for cychlorphine or any orphine analogue.

Clinical use

Standard opioid IA panels, including fentanyl-analogue screens, do not detect it.

Limitations

LC-MS/MS is required; a negative UDT does not rule out exposure.

CYCHLORPHINE | Clinical & Program Guidance

Tox In Focus Vol. 02 · May 2026 · Page 2 of 2

Interpreting the Test Result

▲ If Testing Is Positive

Confirms cychlorphine exposure. LC-MS/MS detection confirms recent use; standard immunoassay would miss it.

Often the sole opioid. Cychlorphine has been the only opioid in counterfeit pills and in many fatal cases.

Does not change reversal. Give naloxone aggressively; it is expected to reverse a mu-agonist.

▼ If Testing Is Negative or Not Done

A standard UDT proves nothing. Routine and fentanyl-analogue panels do not include cychlorphine.

Confirm panel coverage. Ask the laboratory whether orphine analogues are on the panel.

Treat clinically. A negative screen does not rule out exposure; presentation guides care.

Metabolism & Urinary Markers

Cychlorphine analytes; human pharmacokinetics are limited.

Metabolite	Clinical Significance
Cychlorphine (parent)	Benzimidazolone mu-agonist; the LC-MS/MS target; limited human PK.
Presumed metabolites	Hepatic (CYP3A4 extrapolated); specific human urinary markers not established.

Key References

Center for Forensic Science Research and Education (CFSRE). Public alert: cychlorphine. January 2026.
Knox County Regional Forensic Center. Cychlorphine-associated deaths. 2026.
US Drug Enforcement Administration, Atlanta Field Division. Advisory: cychlorphine. April 2026.

DISCLAIMER: This document is intended for clinical reference and educational purposes only. It does not constitute medical, legal, or professional advice and should not replace independent clinical or programmatic judgment. Content reflects published data available at time of preparation. ToxiPharm LLC makes no warranties regarding completeness or applicability in all settings. | © 2026 ToxiPharm LLC | toxipharm.org