Principles of Drug Addiction Treatment: A Research-Based Guide (Third Edition)
Opioid Addiction


Methadone is a long-acting synthetic opioid agonist medication that can prevent withdrawal symptoms and reduce craving in opioid-addicted individuals. It can also block the effects of illicit opioids. It has a long history of use in treatment of opioid dependence in adults and is taken orally. Methadone maintenance treatment is available in all but three States through specially licensed opioid treatment programs or methadone maintenance programs.

Combined with behavioral treatment:  Research has shown that methadone maintenance is more effective when it includes individual and/or group counseling, with even better outcomes when patients are provided with, or referred to, other needed medical/psychiatric, psychological, and social services (e.g., employment or family services).

Further Reading:

Dole, V.P.; Nyswander, M.; and Kreek, M.J. Narcotic blockade. Archives of Internal Medicine 118:304–309, 1966.

McLellan, A.T.; Arndt, I.O.; Metzger, D.; Woody, G.E.; and O’Brien, C.P. The effects of psychosocial services in substance abuse treatment. The Journal of the American Medical Association  269(15):1953–1959, 1993.

The Rockerfeller University. The first pharmacological treatment for narcotic addiction: Methadone maintenance. The Rockefeller University Hospital Centennial, 2010. Available at

Woody, G.E.; Luborsky, L.; McClellan, A.T.; O’Brien, C.P.; Beck, A.T.; Blaine, J.; Herman, I.; and Hole, A. Psychotherapy for opiate addicts: Does it help? Archives of General Psychiatry  40:639–645, 1983.


Buprenorphine is a synthetic opioid medication that acts as a partial agonist at opioid receptors—it does not produce the euphoria and sedation caused by heroin or other opioids but is able to reduce or eliminate withdrawal symptoms associated with opioid dependence and carries a low risk of overdose.

Buprenorphine is currently available in two formulations that are taken sublingually: (1) a pure form of the drug and (2) a more commonly prescribed formulation called Suboxone, which combines buprenorphine with the drug naloxone, an antagonist (or blocker) at opioid receptors. Naloxone has no effect when Suboxone is taken as prescribed, but if an addicted individual attempts to inject Suboxone, the naloxone will produce severe withdrawal symptoms. Thus, this formulation lessens the likelihood that the drug will be abused or diverted to others.

Buprenorphine treatment for detoxification and/or maintenance can be provided in office-based settings by qualified physicians who have received a waiver from the Drug Enforcement Administration (DEA), allowing them to prescribe it. The availability of office-based treatment for opioid addiction is a cost-effective approach that increases the reach of treatment and the options available to patients.

Buprenorphine is also available as in an implant and injection. The U.S. Food and Drug Administration (FDA) approved a 6-month subdermal buprenorphine implant in May 2016 and a once-monthly buprenorphine injection in November 2017.

Further Reading:

Fiellin, D.A.; Pantalon, M.V.; Chawarski, M.C.; Moore, B.A.; Sullivan, L.E.; O’Connor, P.G.; and Schottenfeld, R.S. Counseling plus buprenorphine/naloxone maintenance therapy for opioid dependence. The New England Journal of Medicine 355(4):365–374, 2006.

Fudala P.J.; Bridge, T.P.; Herbert, S.; Williford, W.O.; Chiang, C.N.; Jones, K.; Collins, J.; Raisch, D.; Casadonte, P.; Goldsmith, R.J.; Ling, W.; Malkerneker, U.; McNicholas, L.; Renner, J.; Stine, S.; and Tusel, D. for the Buprenorphine/Naloxone Collaborative Study Group. Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone. The New England Journal of Medicine 349(10):949–958, 2003.

Kosten, T.R.; and Fiellin, D.A. U.S. National Buprenorphine Implementation Program: Buprenorphine for office-based practice. Consensus conference overview. The American Journal on Addictions 13(Suppl. 1):S1–S7, 2004.

McCance-Katz, E.F. Office-based buprenorphine treatment for opioid-dependent patients. Harvard Review of Psychiatry 12(6):321–338, 2004.

Treatment, not Substitution

Because methadone and buprenorphine are themselves opioids, some people view these treatments for opioid dependence as just substitutions of one addictive drug for another (see Question 19). But taking these medications as prescribed allows patients to hold jobs, avoid street crime and violence, and reduce their exposure to HIV by stopping or decreasing injection drug use and drug-related high-risk sexual behavior. Patients stabilized on these medications can also engage more readily in counseling and other behavioral interventions essential to recovery.


Naltrexone is a synthetic opioid antagonist—it blocks opioids from binding to their receptors and thereby prevents their euphoric and other effects. It has been used for many years to reverse opioid overdose and is also approved for treating opioid addiction. The theory behind this treatment is that the repeated absence of the desired effects and the perceived futility of abusing opioids will gradually diminish craving and addiction. Naltrexone itself has no subjective effects following detoxification (that is, a person does not perceive any particular drug effect), it has no potential for abuse, and it is not addictive.

Naltrexone as a treatment for opioid addiction is usually prescribed in outpatient medical settings, although the treatment should begin after medical detoxification in a residential setting in order to prevent withdrawal symptoms.

Naltrexone must be taken orally—either daily or three times a week—but noncompliance with treatment is a common problem. Many experienced clinicians have found naltrexone best suited for highly motivated, recently detoxified patients who desire total abstinence because of external circumstances—for instance, professionals  or parolees. Recently, a long-acting injectable version of naltrexone, called Vivitrol, was approved to treat opioid addiction. Because it only needs to be delivered once a month, this version of the drug can facilitate compliance and offers an alternative for those who do not wish to be placed on agonist/partial agonist medications.

Further Reading:

Cornish, J.W.; Metzger, D.; Woody, G.E.; Wilson, D.; McClellan, A.T.; and Vandergrift, B. Naltrexone pharmacotherapy for opioid dependent federal probationers. Journal of Substance Abuse Treatment 14(6):529–534, 1997.

Gastfriend, D.R. Intramuscular extended-release naltrexone: current evidence. Annals of the New York Academy of Sciences 1216:144–166, 2011.

Krupitsky, E.; Illerperuma, A.; Gastfriend, D.R.; and Silverman, B.L. Efficacy and safety of extended-release injectable naltrexone (XR-NTX) for the treatment of opioid dependence. Paper presented at the 2010 annual meeting of the American Psychiatric Association, New Orleans, LA.

Comparing Buprenorphine and Naltrexone

A NIDA study comparing the effectiveness of a buprenorphine/naloxone combination and an extended release naltrexone formulation on treating opioid use disorder has found that both medications are similarly effective in treating opioid use disorder once treatment is initiated. Because naltrexone requires full detoxification, initiating treatment among active opioid users was more difficult with this medication. However, once detoxification was complete, the naltrexone formulation had a similar effectiveness as the buprenorphine/naloxone combination.