Methadone Interactions – The Dangers Of Mixing Different Drugs

Last Updated: June 24, 2020

Authored by Olivier George, Ph.D.

Reviewed by Michael Espelin APRN

Being a substance prescribed to many drug addicts, Methadone hydrochloride has the potential to be abused alongside other dangerous drugs. As a result, there are many hazardous interactions that should be taken into account to reduce their frequency and severity.

Can one shoot methadone? Although it is a slow-acting drug, thanks to which it became a widespread addiction treatment medication, some individuals inject this substance in order to achieve faster and more intense onset of drug effects. This kind of use increases the risk of dangerous interactions when the opiate is consumed alongside other substances.

Severe Interactions

  • Gabapentin and methadone interaction – taking any opioid with gabapentin will lead to respiratory depression, sedation, irregular heartbeat, and, finally, death. People who take gabapentin therapy are more likely to abuse opioids, which is another reason to discourage combining these medications. Opioids increase the body’s uptake of gabapentin, which is the mechanism behind the interaction of these medications. A study that included 550 participants found that this dangerous combination substantially increased the risk of death. A significant proportion of all methadone deaths are related to this drug interaction.
  • Tramadol and methadone interaction – patients who take these medications are more likely to experience hypoglycemia, a dangerous metabolic disbalance that may result in death, when untreated. People with diabetes are even more likely to experience dangerous interaction effects due to their health condition. As a result, the co-occurring use of Methadose and tramadol should be strongly discouraged.
  • Methadone and Suboxone interaction – taking Subutex and methadone is generally not as dangerous as the previous two interactions, but it may cause an extremely irregular heartbeat. The risk increases for people who have cardiac diseases (especially the so-called QT syndrome) and electrolyte disturbances due to chronic/severe vomiting and diarrhea. Does suboxone block methadone? Buprenorphine won’t block or reduce the opioid effects, and dangerous synergic effects may seriously endanger one’s health. Can you take Dolophine after suboxone? When changing medications, always consult a medical professional who will estimate the necessary amount of time between the two therapies. Methadose buprenorphine combination is prescribed seldom, if ever, in cases with various comorbid mental illnesses and under close supervision.
  • Methadone and oxycodone interaction – respiratory depression and failure happen more frequently in patients who take these substances together when compared to controls. It has been found that oxycodone use in patients who are being treated for heroin addiction is a highly likely outcome, with 19% of methadone patients testing positive for oxycodone. Mixing methadone and oxycodone is potentially life-threatening, and individuals who experience even mild Methadose-oxycodone interaction effects should consult a medical professional immediately.
  • Adderall and methadone interactions – it has been found that 4.7 % of patients who reported a history of stimulant-abuse also reported the use of illicit methadone. These drugs have the exact opposite effects, which means that the stimulant effects of Adderall are likely to mitigate the adverse impacts ostensibly.  In severe cases, this drug interaction will result in cardiac arrest, heart failure, and death.

methadone drug interactions

Serious Interactions

  • Xanax and Dolophine interaction – both benzodiazepines (Xanax) and opioids inhibit the activity of the central nervous system while having different biochemical pathways. This leads to serious interaction, which may result in an overdose. Moreover, Xanax is one of the most widely abused drugs, which makes it more likely for a comorbid overdose to appear. Methadone and benzos should never be mixed to avoid the damaging drug interaction effect, which means that the same precautions mentioned for Methadose-Xanax combination go for methadone and valium interaction.
  • Ativan and methadone interaction – this methadone drug interaction may result in dizziness, loss of coordination, and, when substantial doses are ingested, to respiratory depression.

Moderate Interactions

  • Methadone and heroin interaction – these drugs generally don’t have dangerous interactions. A Dolophine heroin combination is in no way safe, and patients receiving treatment for opiate addiction should refrain from combining these two drugs. Heroin and methadone may not interact as severely as some other combinations, which doesn’t mean that there aren’t indirect dangers. Patients who are receiving treatment for their opioid addiction may resort to consuming more heroin to get the desired effect. Needless to say, this type of compulsive consumption will lead to overdose. Heroin and methadone co-consumption is also indicative of serious opiate addiction, which warrants systematic and efficient treatment.
  • Methadone-alcohol interaction – while the co-ingestion of these substances should be vehemently discouraged, a Journal for Drug and Alcohol Abuse didn’t find a significant interaction- while both drugs will impede cognitive and motor performance, their effects on the individual’s health are additive, and not interactive. However, alcohol should never be consumed alongside heroin addiction treatment medication.
  • Methadone and morphine interaction – does methadone block morphine? It appears that methadone decreases tolerance to morphine by increasing the endocytosis of mu-opioid receptors. This doesn’t mean that these medications should be consumed together; quite the contrary, combining them is dangerous, and a medical professional should be consulted even in cases of moderate drug interactions.
  • Grapefruit juice and Methadose – grapefruit juice will inhibit cytochrome P450, the main enzyme involved in the metabolism of opiates. As a result, grapefruit increases the bioavailability of these drugs, increasing the risk of overdose for vulnerable groups of patients.

grapefruit juice

Methadone Drug Interactions Outcome And Treatment

Acute symptoms of medication interactions are generally treated in primary care units, after which medical professionals can turn to solve the underlying polysubstance abuse issues.

Nevertheless, rehab for methadone is possible, especially when treated in a highly structured context, with the help of highly experienced professionals. Not only do the addictive properties of this drug require expert assistance, but the withdrawal effects resulting from sudden cessation of use also require intense treatment. How long does methadone withdrawal last? It may take anywhere from 12 to 72 hours to eliminate this drug from one’s system. Moreover, this medication will remain for two weeks in the body after quitting use, which means that it will be detectable on tests. Some patients are false positive for methadone, who previously consumed cyamemazine or levomepromazine.

Taking methadone 10 mg pill with one Xanax may result in mild alterations, while more severe abuse of these medications is much more likely to result in an overdose.

The risk further increases for sensitive groups, which is, for instance, the case with pregnancy and Dolophine consumption.

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Published on: May 14th, 2018

Updated on: June 24th, 2020

About Author

Olivier George, Ph.D.

Olivier George is a medical writer and head manager of the rehab center in California. He spends a lot of time in collecting and analyzing the traditional approaches for substance abuse treatment and assessing their efficiency.

Medically Reviewed by

Michael Espelin APRN

8 years of nursing experience in wide variety of behavioral and addition settings that include adult inpatient and outpatient mental health services with substance use disorders, and geriatric long-term care and hospice care.  He has a particular interest in psychopharmacology, nutritional psychiatry, and alternative treatment options involving particular vitamins, dietary supplements, and administering auricular acupuncture.


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  • Stacy
    So I have a situation. I’m on the Methadone but need to get off the Fentanyl. I was wondering if Tramadol would work in small.doses.Night time is when the methadone wears off and I don’t want to use anymore. Need help