Substance
What not to mix with Methadone
Opioid
Also calleddolophine, methadose, done
Long-acting — outlasts its own effects by many hours
Summary
Methadone is checked against 40 other substances — 12 dangerous, 4 unsafe and 7 caution.
Dangerous
12- Methadone and AlcoholMethadone stays in your body long after you stop feeling it, so drinking adds to a load you cannot feel. Do not combine, especially in the first two…
- Methadone and BenzodiazepinesTogether they slow breathing, on top of methadone's long, unfelt tail. Do not combine, especially early in methadone treatment.
- Methadone and CodeineCodeine adds slowed breathing on top of methadone's build-up, for very little extra effect. Do not combine. Keep naloxone nearby.
- Methadone and DXMTogether they slow breathing and strain the heart and liver, and DXM makes the opioid hit harder. Do not combine. Keep naloxone nearby.
- Methadone and FentanylYesterday's methadone is still active, and fentanyl on top of it is a common way people die, especially in the first two weeks of treatment. Do not…
- Methadone and GHB / GBLEach makes the other much stronger, fast and unpredictably, so people pass out quickly. Do not combine. Keep naloxone nearby, and put anyone who…
- Methadone and KetamineTogether they can cause vomiting and unconsciousness. Do not combine. Keep naloxone nearby, and put anyone who passes out on their side.
- Methadone and KratomMethadone is still fully active hours after you stop feeling it, so kratom lands on top of it. Do not combine. Keep naloxone nearby.
- Methadone and MXEMXE can make the opioid hit harder. Do not combine. Keep naloxone nearby.
- Methadone and OpioidsMethadone is still there whether you feel it or not, and it blunts other opioids, so people take more of them. Do not combine. Keep naloxone nearby.
- Methadone and PregabalinHigh risk of death or life-changing injury. Do not combine.
- Methadone and TramadolTramadol raises the seizure risk, and together they can slow breathing. Do not combine. Keep naloxone nearby.
Unsafe
4- Methadone and BuprenorphineBuprenorphine can throw anyone with methadone on board into withdrawal. Switching between them needs a prescriber and a taper.
- Methadone and CocaineBoth can disturb the heart's rhythm, and you would not feel it building. Avoid this combination.
- Methadone and DiphenhydramineEach makes the other stronger, raising the risk of memory loss, collapse and unconsciousness. Avoid this combination. Keep naloxone nearby.
- Methadone and MethamphetamineMeth hides how much the opioid is slowing you, and when it fades, everything you redosed hits at once, often as you fall asleep. Avoid this…
Caution
7- Methadone and AmphetaminesThe stimulant hides how much the opioid is slowing you; if it wears off first, breathing can stop. Take less of each than usual, do not use alone…
- Methadone and LithiumTogether they add sedation, and dehydration can push lithium levels up. Keep up water, and keep naloxone nearby.
- Methadone and MAOIsWith certain opioids, MAOIs have caused rare but severe and fatal reactions. Take less of each than usual, do not use alone, and keep naloxone nearby.
- Methadone and MephedroneThe stimulant hides how much the opioid is slowing you; if it wears off first, breathing can stop. Take less of each than usual, do not use alone…
- Methadone and Nitrous OxideEach makes the other stronger, so you can lose balance or pass out without warning. Take less of each than usual, do not use alone, and keep naloxone…
- Methadone and PCPPCP can lower your opioid tolerance, making an overdose more likely. Take less opioid than usual, do not use alone, and keep naloxone nearby.
- Methadone and SSRIsSome SSRIs raise methadone levels and can add to its effect on heart rhythm. Talk to whoever prescribes either, rather than stopping them.
Low / synergy
1Low / no synergy
16Checking more than one?
This page rates Methadone against one substance at a time. Combinations of three or more carry risks that no pair-by-pair list can show — the checker rates every pair at once and flags the whole-mix ones on top.
Open Methadone in the checkerOther opioids
All combinations →Educational information only, not medical advice. Absence of a documented interaction is not evidence of safety. Combination data from the TripSit drug combination chart, retrieved 2026-08-20.