Methadone Interactions: How Drugs & Alcohol Interact with Methadone

Clinical Reviewer

For more than 50 years, scientists have studied how methadone interacts with other substances. Many medications can be taken without issue while on methadone. However, some combinations increase the risk of respiratory depression, overdose and other serious or methadone side effects

Patients should always be honest with doctors about medications and medical conditions and tell their methadone clinic when they start new medications, even if there is no known interaction.

Mixing Methadone and Alcohol

Mixing methadone and alcohol can be dangerous and even life-threatening. 

Combining these substances has a synergistic effect (the combined effects are greater than the sum of their individual effects), which increases the risk of:

Recommendations for Alcohol When Taking Methadone

Patients that drink heavily before starting methadone are recommended to go to an inpatient detox or hospital to overcome the physical withdrawals from alcohol before starting methadone. Methadone can even be started at inpatient treatment and continued at an outpatient clinic after discharge, which is usually in 3-10 days.

Patients that start drinking heavily after already stabilized on methadone maintenance are also recommended to stay for 3-10 days in an inpatient facility for alcohol detox. Methadone can be continued during this stay, especially in a hospital setting.

Patients that drink occasionally while taking methadone should understand that this is dangerous. People are not typically able to recognize their slowed breathing to be able to seek help. And, a high percentage of methadone patients struggle with alcohol addiction. Alcohol addiction is just as life-destroying as opioid addiction and has its own painful and actually deadly withdrawal symptoms. Please consider following the recommendation to not drink alcohol while taking methadone. 

Mixing Methadone and Benzodiazepines

Taking benzodiazepines (“benzos”) with methadone has been shown to dramatically increase the likelihood of fatal overdoseBoth medications are “downers” and can slow down breathing to the point of death. It is especially dangerous to take these medications without a doctor’s oversight.

Methadone Should Not Be Mixed With Other Depressant Drugs

Methadone should not be mixed with alcohol, benzos or opioids

Benzodiazepines are also addictive. Patients that struggle with opioid use disorder are likely to become both physically dependent and mentally addicted to benzodiazepines too , which:

Recommendations for Benzodiazepines When Taking Methadone

Benzodiazepines should not be started while on methadone. Antidepressants are usually ideal alternatives to benzodiazepines and are generally safer and equally effective in treating anxiety and anxiety-related insomnia. Therapy and stopping illicit drug use also help with anxiety.

For those already taking benzodiazepines, methadone can still be started under medical supervision. Benzodiazepine requires a taper and stopping cold turkey can be life-threatening.

Methadone and Opioids

Methadone is a long-acting opioid. So, adding other opioids in addition to methadone increases the risk of opioid overdose, which is often fatal.

See also: Methadone Overdose

Using opioids also impacts your methadone treatment because:

Suboxone and Methadone

Suboxone is a partial opioid but also contains Naloxone, an opioid blocker. Taking methadone with Suboxone will cause intense opioid withdrawal symptoms within an hour after taking the Suboxone.

See also: Switching from Methadone to Suboxone and Suboxone Drug Interactions

Anesthesia and Methadone

Opioids are commonly used as anesthesia, though there are non-opioid options. Patients should always disclose methadone use to the anesthesiologists.

For most procedures, patients continue their normal methadone dose. For bigger procedures (ie. a hip replacement), the methadone dose may be lowered to allow more opioid receptors in the brain to open up for anesthesia pain blocking. It isn’t always necessary to alter the methadone dosing, so always check with the anesthesiologist.

Recommendations for Opioids When Taking Methadone

Taking additional opioids while taking methadone is not recommended.

If chronic pain is not well-controlled with methadone, talk to your methadone provider. Increased doses and other medications (like Gabapentin) may help, along with physical and mental therapies.

Methadone used to stop the use of other opioids.

Methadone and Gabapentin

Gabapentin has been studied in combination with methadone in the hope to improve treatment results. But, the data is not conclusive.

Gabapentin is an anticonvulsant but has depressive properties. It can increase the risk of slow or shallow breathing when mixed with a depressant like methadone.

In addition, gabapentin is addictive and causes physical dependence, meaning distressing withdrawal symptoms if stopped abruptly. Adding a gabapentin addiction on top of an opioid addiction can be a setback.

Recommendations for Gabapentin When Taking Methadone

Gabapentin should only be used with methadone as prescribed by the doctor. The medication is sometimes prescribed to methadone patients for anxiety or unmanaged pain or withdrawal symptoms.

Methadone and Antidepressants

Depressive symptoms have been shown to decrease in severity over the first eight months of methadone treatment. But, as high as 50% of methadone patients struggle with depression.

Generally, combining antidepressants with methadone is common and does not pose serious interactions.

However, there are many types of antidepressants that interact differently with the brain, and therefore, with methadone. 

For example:

Recommendations for Antidepressants When Taking Methadone

If depressive symptoms persist after stabilizing on methadone, SSRI medications are usually the first choice for depression treatment. Sertraline (Zoloft) or citalopram (Celexa) can be good options for those taking methadone. SNRI antidepressants like bupropion (Wellbutrin) have also been shown to be helpful for those taking methadone.

Antidepressants can be considered when tapering off methadone too.

Depression should also be treated with therapy — including Cognitive Behavioral Therapies (CBT), Mindfulness-Based Therapies and, if needed, trauma therapies. The cycle of addiction is unlikely to be successful without diagnosing and adequately treating underlying issues like depression.

Also, antidepressant medications should always be disclosed to a methadone provider since some antidepressants can impact dosing.

Methadone and Antipsychotics

While methadone has been shown to reduce the need for antipsychotics, the use of both methadone and antipsychotics can be helpful for some patients.
However, typical antipsychotics aren’t always as effective for substance use patients and some antipsychotics have shown to be risky when used with methadone.

Olanzapine (Zyprexa) is an antipsychotic that is commonly misused by those with opioid addiction, usually for sleep or anxiety. Without the oversight of a doctor, the risk of overdose from Olanzapine combined with opioids (including methadone) is high and life-threatening. There are safer ways to treat anxiety and sleep issues while on methadone.

The data on Quetiapine (Seroquel) use with methadone is inconclusive, though certainly indicates the potential of a dangerous interaction that has proven fatal.

Low doses of antipsychotics, such as chlorpromazine, fluphenazine and haloperidol may be a better consideration for patients on methadone continuing to experience psychotic symptoms.

Recommendations for Antipsychotics When Taking Methadone

Delaying the start of antipsychotic medications until a steady state has been reached with methadone is ideal when possible.
The doses of antipsychotic medications may be lower for those on methadone. And, the methadone dose may need to be higher, especially when psychotic symptoms are severe or chronic.

If your methadone clinic is not able to properly treat your mental health issues, seek outside psychiatric services instead of “living with it” or self-medicating!

Methadone and Other Interactions

Like most medications, drug interactions are possible with methadone.  To stay safe, disclose methadone use to all doctors and inform the methadone clinic of any changes to medication. 

Barbiturates are depressants that come with the same risks and recommendations as other depressants like alcohol or benzodiazepine — avoid mixing with methadone.

Mixing two depressants can slow body processes, including breathing, to the point the body cannot function.
Barbiturates aren’t prescribed very commonly. If a patient requires the medication for seizure, the methadone clinic can help assess and provide safe dosages.

If using barbiturates illicitly for sleep, your methadone clinic should be able to provide you with something safer that works better. For example, Mirtazapine is an antidepressant that has been shown to help methadone patients with sleep issues.

For more sleep tips, see: Withdrawal Insomnia

Stimulants like Adderall can be safe to use under doctor supervision, though aren’t recommended unless necessary.

Taking excessive Adderall and methadone can lead to a rare condition called serotonin syndrome. Symptoms of serotonin syndrome include excessive sweating, shaking, blurred vision, muscle spasm or stiffness, cramps or vomiting and can result in coma. It can also increase the risk of side effects like dizziness, drowsiness and difficulty breathing. Adderall is also addictive and causes physical dependence /withdrawals.

Because of these risks, methadone patients should never take Adderall without a prescription.

Methadone has been shown to help patients adhere to their HIV treatment, which helps the virus become undetectable. The two medications can be taken together safer, though there are known interactions that impact dosing. 

Impact on Methadone
Efavirenz (Sustiva / Stocrin), for example, was shown to require a methadone dose increase of 52% on average. Nevirapine (Viramune) required a 20% increase in methadone.
While methadone dosing should not increase unless symptoms of opioid withdrawal occur, an increased dose can cause serious issues if the HIV medication is missed or decreased. Stopping the HIV medication abruptly while maintaining the methadone dose could even cause opioid toxicity. It is important to keep the methadone clinic updated with any changes to HIV medications.

There are also HIV medications that don’t seem to require increased methadone dosing including etravirine (Intelence), atazanavir (Reyataz) and ritonavir (Norvir) combined with indinavir (Crixivan), saquinavir (Invirase) or fosamprenavir (Lexiva).

Impact on HIV Medication
Methadone has been shown to decrease the absorption of stavudine (Zerit), resulting in less effective HIV treatment that can lead to virus resistant to antiviral medications.
The interaction of methadone with zidovudine can cause symptoms that are easily confused with opioid withdrawal but are actually HIV medication toxicity.

Both physicians should be aware of all specific medications a patient takes. Certain HIV medications have been shown to require additional methadone. Other HIV medications may need an increased or decreased dosage if used with methadone. There are also HIV medication options that have not shown to interact with methadone that can be considered.

Some patients find the juice methadone is typically mixed with too acidic on an empty stomach. But, methadone can be taken with or without food.

Methadone and Vitamins
While studies have looked into the link between methadone patients and vitamins, there is no known interaction between vitamins and methadone. Those struggling with addiction tend to have low vitamin levels and taking a supplement may help overall health.

Methadone and Grapefruit
Grapefruit has been shown to modestly increase the response to methadone making the effects feel stronger. While it is not expected to cause issues, patients can consider avoiding grapefruit and grapefruit juice while on methadone.

Ready to Start Methadone?

Symetria doctors follow rigorous sourcing guidelines and cite only trustworthy sources of information, including peer-reviewed journals, court records, academic organizations, highly regarded nonprofit organizations, government reports and their own expertise with decades in the field.

Ali, S. F. (2012). P-03 – Olanzapine use and misuse among opiate dependent patients in a methadone treatment program. European Psychiatry27, 1.

Andersen, F. D., Simonsen, U., & Andersen, C. U. (2020). Quetiapine and other antipsychotics combined with opioids in legal autopsy cases: A random finding or cause of fatal outcome? Basic & Clinical Pharmacology & Toxicology128(1), 66–79.

BENMEBAREK, M. (2004). Effects of grapefruit juice on the pharmacokinetics of the enantiomers of methadone*1. Clinical Pharmacology & Therapeutics, 76(1), 55–63.

Bomsien, S., & Skopp, G. (2007). An in vitro approach to potential methadone metabolic-inhibition interactions. European Journal of Clinical Pharmacology, 63(9), 821–827.

Eibl, J. K., Wilton, A. S., Franklyn, A. M., Kurdyak, P., & Marsh, D. C. (2019). Evaluating the Impact of Prescribed Versus Nonprescribed Benzodiazepine Use in Methadone Maintenance Therapy: Results From a Population-based Retrospective Cohort Study. Journal of Addiction Medicine, 13(3), 182–187.

González, G., Desai, R., Sofuoglu, M., Poling, J., Oliveto, A., Gonsai, K., & Kosten, T. R. (2007). Clinical efficacy of gabapentin versus tiagabine for reducing cocaine use among cocaine dependent methadone-treated patients. Drug and Alcohol Dependence, 87(1), 1–9.

Gruber, V. A., & McCance-Katz, E. F. (2010). Methadone, Buprenorphine, and Street Drug Interactions with Antiretroviral Medications. Current HIV/AIDS Reports, 7(3), 152–160.

Kreek, M. J. (1984). Opioid Interactions with Alcohol. Advances in Alcohol & Substance Abuse, 3(4), 35–46.

Maremmani, I., Pacini, M., Lubrano, S., Perugi, G., Tagliamonte, A., Pani, P. P., … Shinderman, M. (2008). Long-Term Outcomes of Treatment-Resistant Heroin Addicts with and without DSM-IV Axis 1 Psychiatric Comorbidity (Dual Diagnosis). European Addiction Research14(3), 134–142.

Pacini, M., & Icro Maremmani. (2005, December). Methadone reduces the need for antipsychotic and antimanic agents in heroin addicts hospitalized for manic… Retrieved December 13, 2022, from ResearchGate website:

Palepu, A., Tyndall, M. W., Joy, R., Kerr, T., Wood, E., Press, N., … Montaner, J. S. G. (2006). Antiretroviral adherence and HIV treatment outcomes among HIV/HCV co-infected injection drug users: The role of methadone maintenance therapy. Drug and Alcohol Dependence, 84(2), 188–194.

Pilot trial of gabapentin for the treatment of benzodiazepine abuse or dependence in methadone maintenance patients. (2016). Retrieved December 13, 2022, from The American Journal of Drug and Alcohol Abuse website:

Stein, M. D., Kurth, M. E., Anderson, B. J., & Blevins, C. E. (2020). A Pilot Crossover Trial of Sleep Medications for Sleep-disturbed Methadone Maintenance Patients. Journal of Addiction Medicine, 14(2), 126–131.

Weschules, D. J., Bain, K. T., & Richeimer, S. (2008). Actual and Potential Drug Interactions Associated with Methadone. Pain Medicine, 9(3), 315–344.

All content is for informational purposes only. No material on this site, whether from our doctors or the community, is a substitute for seeking personalized professional medical advice, diagnosis or treatment. Never disregard advice from a qualified healthcare professional or delay seeking advice because of something you read on this website.

Still Have Questions?

Leave a Reply

Your email address will not be published. Required fields are marked *




    1. Using both methadone and Zofran (Ondansetron) together increases the risk of developing an electrical conduction abnormality in your heart called Long QT syndrome, or QT prolongation. Having this condition, in and of itself isn’t a problem, it’s just something that needs to be monitored by routine EKGs. This is because if the QT prolongation worsens, it can cause a rare issue of ventricular arrhythmia, which can be life-threatening. Greater QT prolongation is seen in higher doses of methadone (i.e. over 120mg), with higher doses of Zofran over longer periods of time, and with other risks.

  • I’m a 65 y/o male on 170mg of methadone. I notified the P.A. 6 months ago that the liquid burned, caused wheezing and difficulty swallowing. I wanted to try the 40mg dispersible tablets but she said they were very strict because it’s easier to divert. I’ve had a negative pulmonary test and upper GI in a week. I have not had a dirty urine since after starting. Are all clinics this strict on the tablets?

    1. Not to my knowledge, but every clinic is different. The tablet form is easier to divert if it is not already dissolved in water when it is dispensed to you. You should try asking your methadone clinic if they can dissolve the dispersible tablets in liquid in front of you, as a means of decreasing the risk of diversion.

    1. You will feel more sedation if you were to take Zolpidem while on methadone compared to if you were only taking one or the other. It is possible to use both medications together safely, but caution must be taken, because if your dose of one or the other is too strong for you, it can lead to increased sedation, respiratory depression, and possibly even overdose. Since you are on a low dose of both methadone and Zolpidem, the overall risk of you having any complications is low. In general, the higher the amount of methadone and Zolpidem you are taking, the higher the risk. If you are also taking other sedating medications, such as benzodiazepine (i.e. Alprazolam or Clonazepam), or if you drink alcohol, then your risk gets even higher.

    1. Taking Prozac while on methadone will impair the metabolism of each, which means they will stay in your body longer and cause increased blood concentrations of each. This can cause increased sedation, respiratory depression, overdose, and even cardiac arrhythmias. The increased Prozac concentration increases the risk for serotonin syndrome (a rare but potentially life-threatening condition when there is too much Serotonin in your body). If you were to suddenly decrease your Prozac dose, this would cause a decrease in the methadone levels in your bloodstream and can cause you to feel opioid withdrawal symptoms. Alternatively, if you suddenly had Prozac added or increased Prozac dose, this can cause an increased concentration of methadone in your bloodstream, which can cause increased opioid side effects (i.e. constipation, drowsiness/sedation) and may require a decrease in your methadone dose if that occurs. In order to reduce all of these risks, it’s very important that any dose adjustments are made in smaller-than-usual increments, and that you inform your physicians promptly if you are experiencing any abnormal symptoms when adjusting the dose of one of those medications.

  • I have been on Suboxone various doses from 16mg to 6mg but still have craving for opioids. Would I benefit from Methadone?

    1. If still experiencing cravings while on 16mg of Suboxone, it’s reasonable and acceptable to increase the Suboxone as high as 24 mg daily. I would rarely go higher than 24mg daily. That being said, methadone can be more effective at controlling cravings than buprenorphine. However, there is more patient responsibility required with methadone due to more strict government regulations regarding methadone compared to Suboxone, and potentially more side effects, so methadone isn’t the always the most appropriate choice for everyone.

  • 1 2 3
    What To Read Next
    Do you live in Illinois or Texas?

    Symetria has addiction treatment clinics across the state. You can likely get scheduled TODAY — medications or therapy.

    Hi there — Most people want to know costs/insurance upfront. Would you like to check your policy now?