Mixing Methadone and Xylazine (tranq)

Q: How dangerous is Methadone with Xylazine?

Dangerous: High risk of death or life-changing injury. Do not combine.

Q: Is it safe to mix Methadone and tranq?

MixSafe lists tranq under Xylazine. That combination is rated "Dangerous". Methadone is still active long after it stops feeling like anything, and xylazine adds heavy sedation and slowed breathing on top of that load. Naloxone wears off sooner than methadone does, and does nothing for the xylazine.

Dangerous

Xylazine adds heavy sedation on top of methadone that is still active long after you stop feeling it.

Do this

Do not combine. Keep naloxone nearby, and put anyone who won't wake on their side.

Where the risk isTap for why

In an emergency, call 911911 Never Use Alone Poison Control

What to do

Say what was taken and how much.Responders need it, and in most US states Good Samaritan laws protect both of you from drug possession charges when you call for an overdose.
Unresponsive: put them on their side, tilt the head back, and stay until help arrives.Never leave someone alone to “sleep it off”.
Give naloxone (Narcan) if you have it.It is sold over the counter in every US state and does no harm if opioids turn out not to be involved.
Never Use Alone 1-800-484-3731Stays on the line and sends help if you stop responding.
Full steps: what to do if it is already happeningOverdose signs, the recovery position, what to say on the call, and whether you can be charged for making it.
Poison Control 1-800-222-1222Free and 24/7, for “is this bad?” before it becomes an emergency.

What “Dangerous” means

High risk of death or life-changing injury. Do not combine.

How the ratings work

The longer explanation

Methadone is still active long after it stops feeling like anything, and xylazine adds heavy sedation and slowed breathing on top of that load. Naloxone wears off sooner than methadone does, and does nothing for the xylazine.

Sources (6)

Choi S, Irwin MR, Kiyatkin EA. Xylazine effects on opioid-induced brain hypoxia. Psychopharmacology. 2023link.springer.com
Watkins JM et al. Xylazine exacerbates fentanyl-induced respiratory depression and prevents rescue by naloxone in mice. Psychopharmacology. 2026pmc.ncbi.nlm.nih.gov
What You Should Know About Xylazine. CDCcdc.gov
Friedman J et al. Xylazine spreads across the US. Drug Alcohol Depend. 2022pubmed.ncbi.nlm.nih.gov
QT prolongation with methadonepmc.ncbi.nlm.nih.gov
Methadone Safety: A Clinical Practice Guideline From the American Pain Society and College on Problems of Drug Dependence, in Collaboration With the Heart Rhythm Societysciencedirect.com

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Other names

Methadone: dolophine, methadose, done; Long-acting — outlasts its own effects by many hours
Xylazine: tranq, tranq dope, zombie drug, anestesia de caballo, rompun, medetomidine; Animal sedative cut into fentanyl, as is its stronger cousin medetomidine — naloxone reverses neither

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Related combinations

Methadone with

What not to mix with Methadone →

Xylazine with

What not to mix with Xylazine →

All combinations →

Can you mix Methadone and Xylazine (tranq)?

MixSafe rates mixing Methadone and Xylazine as "Dangerous" — high risk of death or life-changing injury. Do not combine. Source: MixSafe research. Educational information, not medical advice.