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's half-life runs anywhere from 8 to 59 hours and it accumulates in tissue, so the dose you took is still substantially present long after…
- Methadone and BenzodiazepinesAdditive respiratory depression against methadone's long, invisible tail. The combination is well documented in methadone-treatment mortality data…
- Methadone and CodeineAdditive respiratory depression on top of methadone's accumulating baseline, for very little added effect.
- Methadone and DXMCNS depression, difficult breathing, heart issues, hepatoxic, just very unsafe combination all around. Additionally if one takes DXM, their tolerance…
- Methadone and FentanylMethadone accumulates over days and stays active far longer than it feels active. Fentanyl on top of a methadone dose from yesterday is a common and…
- Methadone and GHB / GBLThe two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is…
- Methadone and KetamineBoth substances bring a risk of vomiting and unconsciousness. If the user falls unconscious while under the influence there is a severe risk of vomit…
- Methadone and KratomMethadone's effects outlast its own high by many hours, so kratom taken later in the day lands on top of methadone that is still fully active…
- Methadone and MXEThis combination can potentiate the effects of the opioid
- Methadone and OpioidsUsing heroin or oxycodone on top of methadone is dosing into an opioid load that is still there whether or not you feel it. Because methadone blunts…
- Methadone and PregabalinHigh risk of death or life-changing injury. Do not combine.
- Methadone and TramadolConcomitant use of tramadol increases the seizure risk in individuals taking other opioids. These agents are often individually epileptogenic and may…
Unsafe
4- Methadone and BuprenorphineBuprenorphine displaces methadone from the receptor and replaces it with less activity, so this precipitates withdrawal in anyone with a meaningful…
- Methadone and CocaineBoth prolong the QT interval, and methadone's QT effect is dose-dependent and associated with a roughly four-fold rise in sudden cardiac death…
- Methadone and DiphenhydramineBoth substances are CNS depressants, potentiating each other strongly and unpredictably, raising the chances of memory loss, severe ataxia, and…
- Methadone and MethamphetamineA stimulant masking opioid sedation is how people miss the point at which they are overdosing. Methamphetamine's long duration means the opioid is…
Caution
7- Methadone and AmphetaminesStimulants increase respiration rate, which can allow for a higher dose of opiates normal . If the stimulant wears off first then the opiate may…
- Methadone and LithiumNo direct pharmacokinetic interaction, but additive sedation and any dehydration or reduced kidney perfusion can raise lithium levels. Note that…
- Methadone and MAOIsCoadministration of monoamine oxidase inhibitors (MAOIs) with certain opioids has been associated with rare reports of severe and fatal adverse…
- Methadone and MephedroneStimulants increase respiration rate allowing a higher dose of opiates. If the stimulant wears off first then the opiate may overcome the patient and…
- Methadone and Nitrous OxideBoth substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While…
- Methadone and PCPPCP can reduce opioid tolerance, increasing the risk of overdose
- Methadone and SSRIsSeveral SSRIs inhibit the enzymes that clear methadone, raising levels from an unchanged dose, and some independently prolong the QT interval that…
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.