Two possible treatments for opioid use disorder are methadone or buprenorphine/naloxone (suboxone).

According to the National Alliance of Mental Illness(https://www.nami.org/About-Mental-Illness/Treatments/Mental-Health-Medications/Types-of-Medication/Buprenorphine/Buprenorphine-Naloxone-(Suboxone)):

Buprenorphine is known as a partial opioid agonist which means it partially works like an opioid and the effect is weaker than full agonists... The naloxone part of buprenorphine/naloxone is known as an opioid antagonist or “blocker”... This helps discourage people who are dependent on intravenous (IV) opioids from injecting buprenorphine/naloxone.

I'm curious why methadone (full opioid agonist) is not prescribed with naloxone to prevent misuse too?

  • it will depend on the pharmacological approach to treat the drug dependence, for instance, if the approach is a mechanism of substitution or to alleviate withdrawal symptoms then the use of methadone is appropriate; however if the mechanism is blocking pleasurable responses, a non-selective opioid antagonist such as naltrexone can be used; in therapeutics naloxone is more involved with cases of opioid-induced resperatory depression where it is rapidly reversed with IM injection of this competitive opioid antagonist however it is also possible to use methadone with naloxone – program Aug 5 at 13:44

The answer to this question lies within the clinical settings methadone and buprenorphine/naloxone are used in, and the forms in which they are provided to users as a result of how they are absorbed.

Methadone is provided by specially licensed clinics that require patients to come in daily to clinic to take methadone under direct observation. For the first 90 days they may have only one take home dose (typically their Sunday dose) each week. Only after they have a pattern of treatment compliance proven by random urine tox screens for 90 days, may they start to get a second take home dose. After 180 days, more take home doses may be provided at the clinics option. Take home doses are subject to random callback audits. Typically only those patients with very well established compliance and improved psychosocial function are allowed to take home 15-30 day supplies. Less than 15 days tends to be supplied as liquid, with a volume of up to 4oz per daily dose. Longer than 15 days tends to be provided as dry diskettes to be mixed with water. These diskettes contain insoluble material that can be dangerous if injected.

https://store.samhsa.gov/sites/default/files/d7/priv/pep15-fedguideotp.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/017058s019lbl.pdf

Methadone is rapidly and nearly completely absorbed via oral administration and does not undergo extensive first pass metabolism. It is thus is highly suitable for oral administration. The large volumes of liquid it is mixed with and the highly supervised conditions for use make misuse by injection all but impossible for the liquid, and only possible for the dry diskettes. These are rarely available on the street (see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2771323/).

Contrast this with buprenorphine/naloxone treatment. This is provided in office based settings by physicians who have taken a 8hr course or be board certified in addiction medicine or addiction psychiatry, and who have applied for a waver to treat opiate dependence with buprenorphine. NPs, PAs, ARNPs must take the 8hr course plus another 16 hr class to be waivered, They then can provide treatment for up to 100 patients. After a year they can apply to treat up to 275 patients. (disclosure: I have taken this training but did not apply as my practice environment at the time did not allow adequate monitoring for initial dosing). It is then usually prescribed for several days to a week at a time and may be rapidly advanced to a 30 day supply, the same as is common for other psychiatric medications. Buprenorphine/naloxone is thus provided under a much less structured and monitored environment. This dramatically increases treatment availability but does offer more opportunities for diversion. Experience in Europe suggests that most diversion and misuse was of buprenorphine alone not buprenorphine/naloxone.


Buprenorphine undergoes extensive 1st pass metabolism that dramatically reduces its availability when taken orally. Thus it is given as a tablet or film placed under the tongue to be absorbed through the oral mucosa. As such it cannot be provided as a dilute solution as methadone is but rather as a small pill or film. This can easily be dissolved in a small amount of water for injection. This is why it is provided with naloxone. Naloxone is poorly absorbed after either oral administration or through the oral mucosa. As such, if taken as intended little is absorbed and it has no effect. If injected however, it will overcome the effect of buprenorphine and produce strong opiate withdrawal. Naloxone is added to buprenorphine for diversion resistance not safety.


Methadone has relied on different mechanisms for diversion resistance. Naloxone could be added to methadone but there is little reason to do so. Only the dry diskette form can realistically be injected and little of this reaches the street due to the very controlled nature of methadone treatment. In contrast, the absorption characteristics of buprenorphine require distribution in a form that is amenable to injection and the medication is provided in a less controlled setting. Data from Europe suggested that buprenorphine alone not buprenorphine/naloxone was the primary form that was misused. Thus buprenorphine/naloxone became the standard form in use within the United States. Only patients with, for example, a true allergy to naloxone get buprenorphine alone. It is possible that if methadone was used under less controlled conditions for opiate addiction, and the dry diskette form of methadone became more widely used and diverted, the DEA might well push for inclusion of naloxone. Until then, there is little reason to do so.

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