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Clinical Toxicology Intelligence

Issue

#10

July 2026

Medetomidine Withdrawal Begins Within 4 to 6 Hours. COWS Will Not Catch It. Buprenorphine Alone Will Not Treat It.

Medetomidine is an α2-adrenergic agonist found with increasing frequency in the illicit fentanyl supply. Its active enantiomer is dexmedetomidine, the same compound used for ICU sedation. DEA law-enforcement seizure reports rose from 247 in 2023 to over 8,000 in 2025, and the DEA named medetomidine explicitly in its May 2026 public safety advisory alongside xylazine, nitazenes, and cychlorphine. In some regional samples, it is now appearing more frequently than xylazine.

Regular use produces physiologic α2-receptor dependence. When the drug is stopped, the result is rebound sympathetic activation: agitation, tremors, hypertension, tachycardia, diaphoresis, and severe nausea and vomiting that is often refractory to standard antiemetics. Onset is typically 4 to 6 hours after the last dose, substantially earlier than opioid withdrawal. The clinical picture can look like moderate opioid withdrawal on COWS, but the vital sign abnormalities are disproportionate to the score, and buprenorphine induction does not resolve the autonomic symptoms.

First-line management is α2-agonist replacement: oral or transdermal clonidine, often at doses above labeled recommendations. When nausea and vomiting prevent enteral therapy or enteral therapy fails, IV dexmedetomidine is required, at infusion rates that can exceed standard ICU sedation protocols. Concurrent opioid withdrawal and any other substance withdrawal must be treated separately on top of the α2-agonist regimen. Two 2026 publications from emergency medicine and pharmacy describe the clinical presentation and management in detail, and the case series and management data are new enough that most OTPs and emergency departments have not had time to update their protocols.

Zimmerman DE, et al. Presentation and management of acute medetomidine withdrawal. Am J Health Syst Pharm. 2026. doi:10.1093/ajhp/zxag141  ·  Lynch MJ, et al. Emergence of medetomidine in the illicit drug supply. Ann Emerg Med. 2026;87(6):709-716.  ·  DEA Public Safety Advisory, May 12, 2026.

Comment Period Closes: July 31, 2026

7-OH Kratom Temporary Scheduling: Comment Period Closes July 31. Effective Date Expected August 2026.

The DEA's July 1 Notices of Intent to temporarily place concentrated 7-hydroxymitragynine (7-OH) and three synthetic analogs into Schedule I carry a 30-day public comment period closing July 31. The temporary scheduling order is expected to take effect in August 2026 barring a hearing request that substantially delays the timeline. Natural kratom leaf preparations remain outside federal scheduling.

For OTPs, drug courts, and testing programs: the clock is running. If your program uses mitragynine immunoassay testing, now is the time to confirm what your laboratory reports for kratom-positive specimens, how your MRO or program will handle a Schedule I classification, and whether your policy language distinguishes enhanced products from leaf kratom. Standard immunoassays do not make that distinction analytically; LC-MS/MS with 7-OH quantitation is required.

Update: July 15, 2026

DEA Marijuana Rescheduling Hearing Concluded July 15. Watch for Post-Hearing DEA Guidance on Rulemaking Timeline.

The DEA administrative hearing on proposed marijuana rescheduling from Schedule I to Schedule III concluded on July 15 per the court-ordered schedule. The hearing closed the evidentiary record; a final rule requires separate DEA action and additional rulemaking. For drug testing programs, a Schedule III classification does not automatically change federal workplace testing mandates or program-level marijuana prohibitions. Watch for post-hearing DEA guidance indicating the projected rulemaking timeline.

RETROSPECTIVE SURVEILLANCE STUDY + COMMENTARY

Xylazine Positivity Is Rising Nationally in Fentanyl-Positive UDT Specimens. Concentration Is Falling. Both Findings Matter.

A retrospective cross-sectional analysis of 42,307 fentanyl-positive urine drug test specimens (LC-MS/MS, March 2023 through September 2025, Millennium Health co-authors) found that xylazine co-detection rates are rising in both the East and West: from 11.1% to 19.6% in the East, and from effectively zero to 13.5% in the West. At the same time, xylazine concentrations in co-positive specimens are falling in the East (median: 61.8 to 24.0 ng/mg creatinine). The paired JAMA Network Open commentary interprets this as xylazine diluting into a larger fraction of the fentanyl supply rather than retreating from it.

The study also found xylazine 79% less likely in the West than the East in adjusted analysis, and strongly associated with heroin co-positivity and higher fentanyl concentrations, suggesting the distribution pattern remains tied to specific supply networks even as geography expands. A companion systematic review (PMID 42417934, Forensic Sci Med Pathol. 2026) confirms fentanyl co-detection in 98 to 100% of fatal xylazine intoxication cases.

Sugarman OK, Marks C, Whitley P, et al. Xylazine-fentanyl positivity and concentration in urine drug tests. JAMA Netw Open. 2026;9(7):e2622473. PMID 42424081.  ·  Childerhose JE. Using urine drug testing to track xylazine-fentanyl copositivity. JAMA Netw Open. 2026;9(7):e2622481. PMID 42424085.