Question 20: Can methadone and buprenorphine be abused?

Answer: Both methadone and buprenorphine can be diverted from their intended recipients. This diversion occurs in countries that provide these medications via supervised dispensing (e.g., pharmacies) and by prescription. Oftentimes, this diversion is by individuals who are seeking a therapeutic benefit (e.g., unobserved treatment). Other times, this diversion results in abuse. The extent of these two types of diversion varies, although most studies note that the benefits of providing the treatment outweigh the risks associated with diversion. For instance, the efficacy of methadone has been demonstrated over the past 40 years (O’Connor and Fiellin, 2000). The provision of methadone and buprenorphine treatment was associated with a 75-percent decrease in fatal heroin overdoses in France (Lepere, Gourarier, Sanchez, et al., 2001; Auriacombe, Fatseas, Dubernet, et al., 2004).

In studies that have compared death rates from heroin overdose among those who are untreated and those who receive methadone, deaths are higher among untreated opioid-dependent individuals (Capelhorn, Dalton, Haldar, et al., 1996,; Zanis and Woody, 1998).

Research Highlights

Methadone Abuse

Methadone can be diverted for oral or intravenous use (Fiellin and Lintzeris, 2003; Green, James, Gilbert, et al., 2000). Some diverted methadone can result in fatal overdoses; however, the rate of overdose among patients enrolled in methadone maintenance is low. A meta-analysis revealed a relative risk of death of 0.25 (95% CI: 0.19-0.33) for patients receiving methadone maintenance (Capelhorn et al., 1996). A study of nearly 10,000 individuals inducted onto methadone determined that the mortality rate was 7.1 deaths per 10,000 inductions (95% CI: 1.8± 12.4). In this same study, 51 percent of methadone-related deaths occurred in people who were not registered in methadone maintenance (Zador and Sunjic, 2002).

In addition, while methadone may be detected in drug-related deaths, it is often not the causative agent. In one study in the west of Scotland, during the period 1991–2001, methadone alone was judged to be the causative agent in only 29 percent (56) of drug-related deaths (Seymour, Black, Jay, et al., 2003).

Similarly, with the increased use of methadone as a treatment for chronic pain, the majority of methadone-related deaths in Australia and the United States are believed to be associated with the use of this medication for pain treatment instead of treatment of opioid dependence (Center for Substance Abuse Treatment, 2004).

Buprenorphine Abuse

As a partial agonist, buprenorphine has less potential for abuse than most full agonists. However, there is a reinforcing effect that subjects can experience with buprenorphine administration, especially via the injection route. This reinforcement is less likely if the subject has recently used a full agonist compound; in fact, buprenorphine can lead to a painful and uncomfortable precipitated withdrawal under this scenario. In addition, the development of a tablet that combines buprenorphine with naloxone, in a 4 to 1 ratio, has demonstrated decreased abuse potential and the ability to precipitate withdrawal in patients who are receiving a full opioid agonist (Mendelson, Jones, Welm, et al., 1999).

When the buprenorphine/naloxone combination tablet is taken sublingually, as prescribed, naloxone is poorly absorbed, and the patient receives a buprenorphine effect. However, if the tablet is dissolved and injected, the naloxone will antagonize the buprenorphine, resulting in a range of reactions, including blockade of opioid effects and precipitation of an immediate withdrawal. In this way, the combination gives the therapeutic benefit but greatly reduces opportunities for abuse by injection.


Auriacombe M, Fatseas M, Dubernet J, Daulouede JP, Tignol J. French field experience with buprenorphine.American Journal on Addictions 2004;13(Suppl 1):S17-28.

Capelhorn JR, Dalton MS, Haldar F, Petrenas AM, Nisbet, JG. Methadone maintenance and addicts' risk of fatal heroin overdose. Substance Use and Misuse 1996;31:177-96.

Center for Substance Abuse Treatment. Methadone-Associated Mortality: Report of a National Assessment, May 8-9, 2003. CSAT Publication No. 28-03. Rockville, MD: Center for Substance Abuse Treatment, Substance Abuse and Mental Health Services Administration, 2004.

Fiellin DA, Lintzeris N. Methadone syrup injection in Australia: a sentinel finding? Addiction 2003;98:385-386.

Green H, James RA, Gilbert JD, Harpas P, Byard RW. Methadone maintenance programs–a two-edged sword?American Journal of Forensic Medicine & Pathology 2000;21(4):359-61.

Lepere B, Gourarier L, Sanchez M, Adda C, Peyret E, Nordmann F, et al. Reduction in the number of lethal heroin overdoses in France since 1994. Focus on substitution treatments. Annales de Medecine Interne 2001;152:5-12.

Mendelson J, Jones RT, Welm S, Baggott M, Fernandez I, Melby AK, et al. Buprenorphine and naloxone combinations: the effects of three dose ratios in morphine-stabilized, opiate-dependent volunteers.Psychopharmacology 1999;141(1):37-46.

O'Connor PG, Fiellin DA. Pharmacologic treatment of heroin-dependent patients. Annals of Internal Medicine2000;133:40-54.

Seymour A, Black M, Jay J, Cooper G, Weir C, Oliver J. The role of methadone in drug related deaths in the west of Scotland. Addiction 2003;98(7):995-1002.

Williamson PA, Foreman KJ, White JM, Anderson G. Methadone-related overdose deaths in South Australia, 1984-1994. How safe is methadone prescribing? Medical Journal of Australia 1997;166(6):302-05.

Zador DA, Sunjic SD. Methadone-related deaths and mortality rate during induction into methadone maintenance, New South Wales, 1996. Drug & Alcohol Review 2002;21(2):131-36.

Zanis DA, Woody GE. One-year mortality rates following methadone treatment discharge. Drug & Alcohol Dependence 1998;52:257-60