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Program Profile: Methadone Maintenance Treatment

Evidence Rating: Effective - More than one study Effective - More than one study

Date: This profile was posted on June 13, 2011

Program Summary

A medication-assisted treatment for individuals with opioid dependence. The program is rated Effective. The methadone maintenance treatment intervention group had significantly lower HIV drug-risk behaviors (i.e. less reported needle use) than the comparison group who received psychologically enriched 180-day methadone assisted detoxification. The standard and minimal treatment group both reported less heroin use and had fewer positive urine tests at follow-up than the detoxification group.

Program Description

Program Goals/Target Population

Methadone maintenance treatment (MMT) is a medication-assisted treatment for individuals with opioid dependence. Methadone is a long-acting synthetic opioid analgesic that works as a pharmacologic intervention for patients in drug treatment and detoxification programs. MMT helps opioid-addicted patients alleviate withdrawal symptoms, reduce opiate cravings, and bring about a biochemical balance in the body in order to reduce the illicit use of opioids.


Program Components

Opioids, such as heroin or morphine, cause a release of excess dopamine in the body. Users become dependent on the drug because they need opiates to continuously occupy the opioid receptor in the brain. Methadone works by occupying this receptor and blocking the high that usually comes from illicit opioid drug use. This reduces the need and desire for users to seek and abuse opioids and diminishes the disruptive and uncontrolled behavior often associated with addiction. Subsequently, this allows patients to participate in normative activities, such as drug treatment programs or therapies.


Methadone can suppress narcotic withdrawal symptoms for 24 to 36 hours for patients. Single oral doses are administered daily under observation at a licensed clinic. Patients may receive take-home doses for a day that the clinic is closed. Patients may also become eligible for unsupervised take-home doses after some time under monitored treatment.


Dosage is determined by several factors related to the patient, such as opioid tolerance level, history of opioid use, age, and current medical status. During detoxification, an initial dose of 20–30 milligrams (mg) is usually prescribed to suppress withdrawal symptoms. For MMT, doses of 80–120 mg per day are generally sufficient to prevent opioid symptoms for 24 hours, reduce cravings, and block the euphoric effects of opioids. The amount of time in MMT will also vary by patient. In general, MMT takes a minimum of 12 months, but some patients may require continuous treatment that lasts over a period of several years.


In addition to administering medication, MMT also involves providing patients with comprehensive rehabilitation services. Services can include group therapy, individual therapy, medical services, and referrals to community-based agencies that can assist with health and mental health issues, HIV prevention and intervention services, education, housing, and employment.


Key Personnel

MMT is one of the most monitored and regulated medical treatments in the country. Therefore, methadone, when used in the treatment of opioid addiction, can only be dispensed by federally licensed opioid treatment program (OTP). OTPs must be certified by the Substance Abuse and Mental Health Services Administration (or SAMHSA) and registered with the Drug Enforcement Agency (or DEA).


Additional Information

One limitation to MMT is the possibility of patients abusing and overdosing on methadone. The number of methadone-associated deaths has been increasing in the last decade (Center for Substance Abuse Treatment, 2007). Yet part of this problem may be related to the increase in prescription methadone that, in addition to treatment for opioid dependence, can also be used in the treatment of chronic pain (Paulozzi, Budnitz, and Yongi, 2006). OTPs are subject to specific and strict regulations when using methadone to treat opioid-addicted patients. However, when methadone is prescribed to treat chronic pain, it is regulated under Federal and State laws that impose broad requirements for controlled substances in general but whose regulations are not as strict as they are for MMT use. Although it is unclear from the current data available how many methadone-related deaths are associated with MMT or chronic pain treatment, steps are being taken to prevent deaths related to methadone abuse and overdose that include educating practitioners, improving safety, and establishing prescription monitoring programs (GAO, 2009).

Evaluation Outcomes

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Study 1

Treatment Retention

Sees and colleagues (2000) found that treatment group members who received methadone maintenance treatment (MMT) remained in treatment significantly longer than comparison group members who received psychosocially enriched 180-day methadone-assisted (M-–180) detoxification. The median days in treatment for MMT participants were 438.5 days, compared to 174 days for M–180 participants.


Illicit Opioids

There were no significant differences between the groups on opioid use. Illicit opioid use rates were greater than 50 percent for both groups at all follow-up periods. When examining another index of heroin use (days of heroin use in the previous month, as reported on the Addiction Severity Index, or ASI), the results showed heroin use for both groups significantly decreased from the baseline, but the decrease was greater in the MMT group during the last 6 months of treatment.


HIV Risk Behaviors

The level of HIV drug-risk behaviors reported by MMT participants was significantly lower than those reported by M–180 participants; however, there were no significant differences on measures of sex-risk behaviors. The analysis also showed that there was a significant group-by-assessment interaction on reported injection of heroin, meaning the MMT group had significantly less needle use during months 6 through 12.


Psychosocial Functioning

There were no significant differences between groups on measures of psychiatric problem areas, family functioning, employment, or legal status.


Cocaine Use

At each assessment, only 30 percent to 50 percent of study participants in both groups were abstinent from cocaine. Although M–180 participants had significantly lower cocaine use rates at certain follow-up periods (month 4–7 and 9–12), the difference between the groups was confounded by the fact that cocaine users were more likely to drop out of M–180 treatment. After additional analysis, the significant difference in cocaine use between groups disappeared, suggesting the initial difference was observed because of the higher probability of cocaine users dropping out of M–180 treatment.


Alcohol Use

There were no significant differences between the groups on measures of alcohol use.


Study 2

Gruber and colleagues (2008) found that there were a number of significant differences found when comparing the 21-day methadone detoxification group to the 6-month methadone maintenance with minimal counseling (MM minimal) and to the methadone maintenance with standard counseling (MM standard). However, there were no significant differences on any outcome measures between the MM minimal and MM standard groups.


Treatment Retention

There were no significant differences between the three groups in retention rates.


Heroin Use

At baseline, all three groups urinalyses were 87.5 percent to 100 percent opiate positive, and their self-reported heroin use averaged 18–19 days of the previous month. During months 1–6, 78 percent to 96 percent of the 21-day methadone detoxification group had opiate-positive test results, and they reported heroin use an average of 15.5–18.4 days in each follow-up month. In contrast, the MM minimal group had a significantly greater reduction from baseline in opiate-positive urine tests (65 percent to 85 percent of participants had positive results) and self-reported heroin use (an average of 5.8–8.1 days per month) during the follow-up periods. The MM standard group also had significantly greater reduction in opiate-positive urine tests (59 percent to 77 percent of participants tested positive) and self-reported heroin use (an average of 4.2–6.1 days per month) compared to the 21-day detoxification group. The comparisons remained significant when the 8.5 month follow-up assessment was included.


Alcohol Use

Compared to the 21-day detoxification group, the MM minimal group and MM standard group had significantly greater reductions from baseline in self-reported days of alcohol use during months 1–6. The comparisons remained significant when the 8.5 month follow-up assessment was included.


Cocaine Use

There were no significant differences between the three groups in cocaine-positive urine tests or self-report days of cocaine use during months 1–6 or when the 8.5 month follow-up assessment was included.


Other Outcomes

There were no significant differences between the three groups in outcome measures from the ASI or the Beck Depression Inventory (or BDI).

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Evaluation Methodology

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Study 1

Sees and colleagues (2000) used a randomized controlled trial to compare outcomes of patients with opioid dependence treated with methadone maintenance treatment (MMT) to patients who received an alternative treatment (psychosocially enriched 180-day methadone-assisted [M–180] detoxification). More than 850 patients were initially screened to determine if they were eligible to participate in the study. Patients were eligible if they met the Diagnostic and Statistical Manual Mental Disorders, Third Edition, Revised (DSM–III–R) criteria for a diagnosis of opioid dependence and had an initial urine screening test result of positive for an opioid (other than methadone) and negative for methadone. Patients were excluded if they had a medical condition that contraindicated methadone treatment, had a psychiatric condition that would interfere with treatment, were enrolled in a substance abuse treatment program already, or were younger than 18 years. After the initial screening process, 179 patients were left for randomization.


Ninety-one patients were randomly selected to receive standard methadone maintenance (treatment group), and 88 received the 180-day methadone detoxification (comparison group). The treatment group was 57 percent male, and 46 percent white, 34 percent African American, 9 percent Hispanic, and 7 percent “other,” with an average age of 39.4 years. The comparison group was 60 percent male, and 52 percent white, 26 percent African American, 17 percent Hispanic, and 5 percent “other,” with an average age of 39.4 years. There were no significant differences between the two groups, except that comparison group members were more likely to be diagnosed as having an alcohol abuse or dependence disorder.


Study participants were assessed at baseline and every month for 12 months. Urine specimens were analyzed using an enzyme-multiplied immunoassay technique. The specimens were analyzed for the presence of cocaine, heroin, amphetamines, barbiturates, benzodiazepines, tetrahydrocannabinol, and methadone.


The primary outcome measures of interests were opioid use and cocaine use. Opioid and cocaine use was coded as negative if the study participant reported no opioid or cocaine use in the last 30 days, and if the urine screening test result was negative for opioids other than methadone and negative for cocaine. The Addiction Severity Index (ASI) was also administered monthly to participants and assessed functioning in employment, drug use, alcohol use, legal, family, and psychiatric problem areas. The Risk of AIDS Behavior (or RAB) scale was also administered at 6 months and at 12 months to assess drug use and sexual behaviors that increase the risk for HIV infections over a 6-month period. The Treatment Services Review (TSR) was used to assess treatment services received in the past week. Treatment retention was measured as the number of days between study enrollment and the last day a participant received any psychosocial services.


In both groups, study participants were given an initial methadone dosage of 30 milligrams per day (mg/d), which was increased to 80 mg/d within the first 3 treatment weeks. The maximum methadone dosage was 100 mg/d, reached by day 44 of the study.


The study used an intent-to-treat analysis model that included all collected data in the analyses; complete-case-only analyses were not used. Retention in treatment was tested using Kaplan–Meier survival estimates and Wilcoxon signed rank test to compare groups. A treatment group by assessment generalized linear model was used to compare groups on other measures.


Study 2

Gruber and colleagues (2008) used a randomized prospective trial to assess the benefits of transferring patients to 6 months of methadone maintenance, with either standard or minimal counseling, compared to keeping them in 21-day outpatient methadone detoxification. Patients were from a public hospital’s 21-day outpatient methadone detoxification program. They were eligible for the study if they had a DSM–III–R diagnosis of opioid dependence, were between the ages of 21 and 59 years, and expressed willingness to receive 6 months of methadone treatment.


There were 111 eligible participants who were randomized into one of three outpatient methadone treatment conditions:


·         A usual care group consisting of 21-day methadone detoxification (n= 39)

·         6 months of methadone maintenance with minimal counseling (minimal MM), followed by a 6-week methadone detoxification (n= 35)

·         6 months of methadone maintenance with standard counseling (standard MM), followed by a 6-week methadone detoxification (n= 37)


The detoxification group was 74.4 percent male, and 40.5 percent white, 27 percent African American, 18.9 percent Hispanic, 8.1 percent Asian/Pacific Islander, and 5.4 percent Native American. The minimal MM and standard MM groups were 54 percent male, and 41.6 percent white, 32 percent African American, 20.8 percent Hispanic, 2.7 percent Asian/Pacific Islander, and 2.7 percent Native American. The only significant difference between the three groups was age: the standard MM group was younger (average age of 40.2 years) than the minimal MM group (42.6 years) and the detoxification group (43 years).


Methadone doses in each group ranged, from 60 mg to 90 mg.


The outcome measures were collected at baseline (before randomization) and at each of the seven monthly follow-ups. Monthly urine samples were analyzed for opiates, methadone, cocaine, amphetamines, barbiturates, benzodiazepines, and phencyclidine. Study participants were also asked to self-report the frequency and amount of heroin and cocaine use on each day of the past week. The ASI was administered to assess addiction problem severity in the past 30 days. The Beck Depression Inventory (or BDI) was used to assess symptoms of depression experienced in the past week. The TSR was used to assess treatment services received in the past week.


Outcomes were compared using parallel models that included treatment condition; assessment month (months 1–6, or months 1–8.5); and the interaction of condition-by-time. General estimating equations were used to adjust for the dependency inherent in repeated measures.

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According to the White House Office of National Drug Control Policy (2000), methadone maintenance therapy (MMT) has a cost–benefit ratio of 4:1. This means that for every $1 spent on MMT, $4 is accrued in economic benefit.
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Evidence-Base (Studies Reviewed)

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These sources were used in the development of the program profile:

Study 1
Sees, Karen L., Kevin L. Delucchi, Carmen Masson, Amy Rosen, H. Westley Clark, Helen Robillard, Peter Banys, and Sharon M. Hall. 2000. “Methadone Maintenance vs. 180-Day Psychosocially Enriched Detoxification for Treatment of Opioid Dependence: A Randomized Controlled Trial.” Journal of the American Medical Association 283(10):1303–10.

Study 2
Gruber, Valerie A., Kevin L. Delucchi, Anousheh Kielstein, and Steven L. Batki. 2008. “A Randomized Trial of 6-Month Methadone Maintenance With Standard or Minimal Counseling Versus 21-Day Methadone Detoxification.” Drug and Alcohol Dependence 94:199–206.
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Additional References

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These sources were used in the development of the program profile:

Center for Substance Abuse Treatment. 2007. Summary Report of the Meeting: Methadone Mortality. Washington, D.C.: U.S. Department of Health and Human Services, Substance Abuse and Mental Health Services Administration.

Corsi, Karen F., Wayne K. Lehman, and Robert E. Booth. 2009. “The Effect of Methadone Maintenance on Positive Outcomes for Opiate Injection Drug Users.” Journal of Substance Abuse Treatment 37:120–26.

Fiellin, David A., Patrick G. O’Connor, Marek Chawarski, Juliana P. Pakes, Michael V. Pantalon, Richard S. Schottenfeld. 2001. “Methadone Maintenance in Primary Care: A Randomized Controlled Trial.” Journal of the American Medical Association 286(14):1724–31.

Government Accountability Office (GAO). 2009. Methadone-Associated Overdose Deaths: Factors Contributing to Increased Deaths and Efforts to Prevent Them. Washington, D.C.

Mattick, Richard P., Courtney Breen, Jo Kimber, and Marina Davoli. 2009. “Methadone Maintenance Therapy Versus No Opioid Replacement Therapy for Opioid Dependence (Review).” Cochrane Database of Systematic Reviews, Issue 3.

Millson, Peggy, Laurel Challacombe, Paul J. Villeneuve, Carol J. Strike, Benedikt Fischer, Ted Myers, Ron Shore, and Shaun Hopkins. 2007. “Reduction in Injection-Related HIV Risk After 6 Months in a Low-Threshold Methadone Treatment Program.” AIDS Education and Prevention 19(2):124–36.

Office of National Drug Control Policy (ONDCP) Drug Policy Information Clearinghouse. 2000. Methadone. Rockville, Md.

Paulozzi, Leonard J., Daniel S. Budnitz, and Xi Yongli. 2006. “Increasing Deaths From Opiod Analgesics in the United States.” Pharmacoepidemiology and Drug Safety 15:618–27.

Strain, Eric C., George E. Bigelow, Ira A. Liebson, and Maxine L. Stitzer. 1999. “Moderate- vs. High-Dose Methadone in the Treatment of Opioid Dependence: A Randomized Trial.” The Journal of the American Medical Association 281(11):1000–1005.

U.S. Food and Drug Administration. 2006. Dolophine Hydrochloride CII (Methadone Hydrochloride Tablets, USP). Washington, D.C.
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Related Practices

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Following are practices that are related to this program:

Opiate Maintenance Therapy for Dual Heroin–Cocaine Abusers
A medication-assisted treatment for opioid dependence, including methadone, buprenorphine, and Levo-Alpha-Acetymethadol (LAAM). The overall goals are to help opioid-addicted patients alleviate withdrawal symptoms, reduce or suppress opiate cravings, and reduce the illicit use of opioids (such as heroin). The practice is rated Effective for achieving higher sustained heroin abstinence for dual heroin–cocaine abusers, but No Effects for cocaine abstinence for dual abusers.

Evidence Ratings for Outcomes:
Effective - One Meta-Analysis Drugs & Substance Abuse - Heroin/opioids
No Effects - One Meta-Analysis Drugs & Substance Abuse - Cocaine/crack cocaine
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Program Snapshot

Age: 18+

Gender: Both

Race/Ethnicity: Black, American Indians/Alaska Native, Asian/Pacific Islander, Hispanic, White, Other

Geography: Suburban, Urban

Setting (Delivery): Inpatient/Outpatient, Other Community Setting

Program Type: Alcohol and Drug Therapy/Treatment, Individual Therapy

Targeted Population: Alcohol and Other Drug (AOD) Offenders

Current Program Status: Active

Valerie A. Gruber
Department of Psychiatry
University of California, San Francisco, San Francisco General Hospital
1001 Potrero Avenue, Ward 93
San Francisco CA 94110
Phone: 415.206.3943
Fax: 415.206.6875