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Issue

#14

August 2026

Scheduling Xylazine Out of the Supply Did Not Remove Alpha-2 Agonists From It.

A quasi-experimental study published August 4 analyzed NFLIS data across all US states from 1999 to 2025 and found that state xylazine scheduling laws were not associated with a statistically significant reduction in xylazine drug reports (ATT 2,872.3 per 100,000; 95% CI, -2,024.6 to 7,769.2; p=.250). At the same time, xylazine scheduling was significantly associated with an increase in medetomidine reports (ATT 1,536.5 per 100,000; 95% CI, 211.1 to 2,861.9; p=.023). Drug-checking surveillance in Philadelphia tracks the same substitution curve in real time: medetomidine rose from approximately 29% to roughly 90% of drug supply samples between May 2024 and March 2026 while xylazine fell to approximately 28%.

Medetomidine is a more potent alpha-2 agonist than xylazine. A Chicago CDC/EIS cluster investigation published the same week documented 12 confirmed cases of medetomidine-involved opioid overdose from a single-week surveillance window. The clinical presentation was distinctive: persistent altered mental status despite naloxone administration, marked hypertension, and bradycardia in 75% of confirmed cases. Confirmed and probable cases showed significantly higher odds of hospital admission (OR 3.2; 95% CI, 1.4-7.3) and ICU admission (OR 4.0; 95% CI, 1.4-11.8) compared to suspected opioid overdoses without confirmed medetomidine exposure.

From a testing standpoint, the implication is direct: a urine drug screen that includes xylazine but not medetomidine cannot distinguish a medetomidine-adulterated sample from a clean one. The two compounds are structurally related veterinary alpha-2 agonists; commercial immunoassay cross-reactivity data for xylazine panels against medetomidine are not established. Definitive detection requires LC-MS/MS with explicit medetomidine targets. Sources: Zhu & Oh, Int J Drug Policy 2026; Gressick et al., J Med Toxicol 2026.

◷  Upcoming Deadline

DEA Scheduling: Comment Period Closing

August 17 Is the Last Formal Comment Date on DEA Cannabis Rescheduling. Here Is Why Drug Testing Programs Should Be Paying Attention.

The DEA's proposed rule to move marijuana from Schedule I to Schedule III under the Controlled Substances Act is now at post-hearing brief stage. Interested parties have until August 17 to submit post-hearing briefs, the final formal input before DEA issues a ruling. This is not a done deal: the administrative law judge hearing phase has included objections, and the timeline for a final rule remains uncertain. But the direction of travel matters for drug testing programs now, not later.

If marijuana is rescheduled to Schedule III, the downstream effects on testing policy could include: changes to federal workplace drug testing frameworks under SAMHSA mandatory guidelines (which currently follow Schedule I classifications), pressure to revisit THC cutoff thresholds and medical review officer guidance in DOT-regulated industries, and arguments from defense counsel in drug court proceedings about the legal status of the substance being tested. None of these changes are automatic on rescheduling; each requires subsequent regulatory action. The practical effect is a period of policy uncertainty during which existing standards remain in force but face legal challenge.

For drug court programs and OTPs: rescheduling does not eliminate THC testing authority or change the interpretation of positive results under your current court orders, treatment contracts, or state regulations. Monitor for any state-level legislative or regulatory follow-on after a federal ruling. Source: DB Recovery Resources.

PLOS MEDICINE  ·  2026  ·  COHORT STUDY / 49,727 PATIENTS

Methadone vs. Buprenorphine in OUD With Comorbid Chronic Pain: What a 49,727-Patient Medicare Cohort Shows

A new cohort study in PLOS Medicine followed 49,727 Medicare patients initiated on either methadone or buprenorphine for opioid use disorder, with comorbid chronic pain as the defining inclusion criterion, for up to one year. The study addresses a question that comes up at virtually every OTP and CTC: for a patient whose OUD is intertwined with chronic pain, does the choice of agent matter for pain outcomes, treatment retention, or both? The brief does not summarize which agent performed better on primary outcomes, so pull the full text before citing comparative findings in clinical conversations.

What makes this study notable beyond its size is the population: Medicare patients with documented chronic pain are a reasonable analog for the OTP/CTC patient mix, where musculoskeletal pain, neuropathy, and injury-related chronic pain coexist with OUD in a majority of patients. Prior evidence on this question has been limited to smaller, often clinic-specific samples. This cohort gives clinicians a real-world outcomes comparison at scale.

[Authors TBD on full publication]. Pain and treatment outcomes after initiating methadone vs. buprenorphine in OUD with comorbid chronic pain. PLOS Medicine. 2026. doi:10.1371/journal.pmed.1004846. [Primary Data; Cohort Study; 49,727 Medicare patients]

Also From ToxiPharm This Week

Tox Pearl #14: A Negative Xylazine Result No Longer Means What It Used To. One-page clinical reference on the testing gap created by medetomidine substitution.