"The large contribution to mortality from oxycodone and methadone may be because of the long duration of action of methadone and OxyContin. Drug users may accidentally overdose by overlapping doses when the desired euphoric or analgesic effect is slow in coming. Abusers have learned to ingest and inject pulverized OxyContin pills, defeating the controlled-release mechanism and releasing dangerous amounts of the drug within a short time."

"Medications to help prevent relapse include:

"Methadone, which has been used for more than 30 years to treat heroin addiction. It is a synthetic opiate medication that binds to the same receptors as heroin; but when taken orally, as dispensed, it has a gradual onset of action and sustained effects, reducing the desire for other opioid drugs while preventing withdrawal symptoms. Properly prescribed methadone is not intoxicating or sedating, and its effects do not interfere with ordinary daily activities. At the present time, methadone is only available through specialized opiate treatment programs."

"Buprenorphine is a more recently approved treatment for heroin addiction (and other opiates). Compared with methadone, buprenorphine produces less risk for overdose and withdrawal effects and produces a lower level of physical dependence, so patients who discontinue the medication generally have fewer withdrawal symptoms than those who stop taking methadone. The development of buprenorphine and its authorized use in physicians’ offices give opiate-addicted patients more medical options and extend the reach of addiction medication."

"Naltrexone is approved for treating heroin addiction but has not been widely utilized due to poor patient compliance. This medication blocks opioids from binding to their receptors and thus prevents an addicted individual from feeling the effects of the drug. Naltrexone as a treatment for opioid addiction is usually prescribed in outpatient medical settings, although initiation of the treatment often begins after medical detoxification in a residential setting. To prevent withdrawal symptoms, individuals must be medically detoxified and opioid-free for several days before taking naltrexone. Naloxone is a shorter acting opioid receptor blocker, used to treat cases of overdose."

"In summary, data from studies conducted in Australia, Europe, Asia and the United States have, with few exceptions, found strong associations between participation in methadone treatment and reductions in the frequency of opioid use, fewer injections and injection-related HIV risk behaviors, and lower rates of HIV prevalence and incidence. Few randomized controlled trials have been conducted due to ethical concerns regarding the random assignment of individuals to no treatment or other potentially less effective treatment modalities. Despite this fact, the consistency of findings from the observational and case–controlled studies cited here provide a preponderance of evidence suggesting that sustained treatment of opioid-dependent injection drug users with methadone is associated strongly with protection from HIV infection."

"The wide international variation in the availability of opioid agonist treatment for opioid-dependent injection drug users, despite documented scientific evidence in support of its efficacy, highlights the impact of political and philosophical forces that determine the availability of this treatment. Few proven therapies for medical conditions are restricted in this fashion. Therefore, efforts to address the political and philosophical opposition to opioid agonist treatment are needed to meet the global needs to prevent HIV transmission."

"The unparalleled international epidemic of injection drug use as a major cause of global HIV transmission, coupled with the research evidence supporting the efficacy of methadone treatment in decreasing drug injection and HIV transmission, and the unique pharmacological properties and potential acceptance of buprenorphine and the buprenorphine/naloxone combination, mean that the world is poised for implementation and evaluation of these treatments as a method to stem the spread of HIV."

"The current narcotic treatment system is able to provide the most effective medical treatment for opioid dependence, opioid agonist maintenance, to only 170,000 of the estimated 810,000 opioid-dependent individuals in the United States."

"NTPs (Narcotics Treatment Programs) are the most highly regulated form of medicine practiced in the US, as they are subject to Federal, State, and local regulation. Under this regulatory burden, expansion of this system has been static for many years. This has resulted in a 'treatment gap', which is defined as the difference between the number of opiate dependent persons and those in treatment. The gap currently is over 600,000 persons and represents 75-80% of all addicts."

"The financial costs of untreated opiate dependence to the individual, the family, and society are estimated to be approximately $20 billion per year."

"Although a drug-free state represents an optimal treatment goal, research has demonstrated that this goal cannot be achieved or sustained by the majority of opiate-dependent people."

"Of the various treatments available, Methadone Maintenance Treatment, combined with attention to medical, psychiatric and socioeconomic issues, as well as drug counseling, has the highest probability of being effective."

"Over the past two decades, clear and convincing evidence has been collected from multiple studies showing that effective treatment of opiate dependence markedly reduces the rates of criminal activity."

"Our results support the hypothesis that harm-reduction-based methadone maintenance treatment decreases the risk of natural-cause and overdose mortality. Furthermore, our data suggest that in harm- reduction-based methadone programs, being in methadone treatment is important in itself, independent of the pharmacologic effect of methadone dosage. To decrease mortality among drug users, prevention measures should be expanded for those who dropout of treatment."

"Methadone's half-life is approximately 24 hours and leads to a long duration of action and once-a-day dosing. This feature, coupled with its slow onset of action, blunts its euphoric effect, making it unattractive as a principal drug of abuse."

"Prolonged oral treatment with this medicine [methadone] diminishes and often eliminates opiate use, reduces transmission of many infections, including HIV and hepatitis B and C, and reduces criminal activity."

"Methadone maintenance treatment (MMT) has been shown to improve life functioning and decrease heroin use; criminal behavior; drug use practices, such as needle sharing, that increase human immunodeficiency virus (HIV) risk; and HIV infection."

A study reported in the March 8, 2000 edition of the Journal of the American Medical Association shows that traditional methadone maintenance therapy is superior to both short-term and long-term detoxification treatment as a method to treat heroin dependence.

The New England Journal of Medicine in Nov. of 2000 published a study comparing methadone with LAAM and buprenorphine. The authors concluded that "Levomethadyl acetate, buprenorphine, and high-dose methadone were all effective in treating opioid dependence and were supreior on multiple measures to low-dose methadone. The percentage of patients retained at 17 weeks compared favorably with rates reported elsewhere for these medications."

"As compared with patients taking low-dose methadone, those taking levomethadyl acetate had a significantly higher rate of continuous abstinence from opioids, and those taking high-dose methadone and buprenorphine had a trend toward a higher rate of continuous abstinence."

"In summary, levomethadyl acetate, buprenorphine, and high-dose methadone were more effective than low-dose methadone in reducing the use of illicit opioids. As compared with low-dose methadone, levomethadyl acetate produced the longest duration of continuous abstinence; buprenorphine administered three times weekly was similar to levomethadyl acetate in terms of study retention and was similar to high-dose methadone in terms of abstinence."

"The marginalization of medical care for opioid dependence and the stigma attached to this diagnosis and methadone maintenance treatment play an important role in untreated opioid dependence. Current federal regulations restrict the care of opioid-dependent patients to federally licensed narcotic treatment programs (NTPs) with little to no involvement by community-based physicians. Recent calls from federal and scientific bodies, including the Institute of Medicine, a National Institutes of Health consensus panel, and the Office of National Drug Control Policy, have recommended restructuring the regulatory processes involved in the treatment of opioid-dependent patients, including increased involvement of primary care physicians."

"Office-based methadone maintenance administered by appropriately trained primary care and specialist physicians has the potential to provide an alternative for selected patients to the current narcotic treatment system that would allow for greater physician involvement and perhaps increased quality of care. Potential benefits from this type of care include increased attention to comorbid medical and psychiatric conditions, decreased stigma associated with the diagnosis and treatment, decreased contact with active heroin users, and increased access to treatment. These benefits may increase patient satisfaction and enhance clinical outcomes."

"Our results demonstrate that methadone maintenance using weekly physician office-based dispensing is feasible, that treatment retention and patient and clinician satisfaction are high, and that illicit drug use does not differ significantly compared with continued treatment in an NTP. Stable patients demonstrated high functional status and low levels of health and social service use on transfer from an NTP to office-based care. The high level of patient and clinician satisfaction with office-based care and the outcomes observed with office-based treatment run counter to concerns regarding the potential quality of this type of care and the ability to identify a group of physicians interested in providing treatment for opioid-dependent patients."

"This study has implications for future treatment of opioid dependence. First, the results support the feasibility of transferring stable patients from NTPs to the offices of trained primary care physicians and extends prior research inthis field.These findings, along with recent trials demonstrating the effectiveness of buprenorphine for untreated opioid-dependent patients in primary care settings, offer encouragement regarding the use of primary care offices to help expand access to treatment for opioid dependence."

"Prescription of methadone by primary care physicians can safely increase the availability of an important treatment modality, and at the same time improve health care for this difficult-to-reach population."

The Journal of the American Medical Association notes in an editorial in its March 8, 2000 edition that following the Scottish example, and allowing primary care physicians to dispense methadone, could provide a three- to five-fold increase in access, as well as reducing the cost per patient.

"Three primary scenarios characterize current reports of methadone-associated mortality: "1. In the context of legitimate patient care, methadone accumulates to harmful serum levels during the first few days of treatment for addiction or pain (that is, the induction period before methadone steady state is achieved or tolerance develops). "2. Illicitly obtained methadone is used by some individuals who have diminished or no tolerance to opioids and who may use excessive and/or repetitive doses in an attempt to achieve euphoric effects. "3. Methadone – either licitly administered or illicitly obtained – is used in combination with other CNS depressant agents (such as benzodiazepines, alcohol, or other opioids)."

"Taken together, the data confirm a correlation between increased methadone distribution through pharmacy channels and the rise in methadone-associated mortality. The data, thus, support the hypothesis that the growing use of oral methadone, prescribed and dispensed for the outpatient management of pain, explains the dramatic increases in methadone consumption and the growing availability of the drug for diversion to illicit use. Although the data remain incomplete, National Assessment meeting participants concurred that methadone tablets and/or diskettes distributed through channels other than OTPs most likely are the central factor in methadone-associated mortality."

The Treatment Outcome Prospective Study (TOPS)-a long-term, large-scale longitudinal study of drug treatment-found that patients drastically reduced heroin use while in treatment, with 10% using heroin or other narcotics weekly or daily after just three months in treatment.

Methadone treatment greatly reduces criminal behavior. The decline in predatory crimes is likely in part because methadone maintenance treatment patients no longer need to finance a costly heroin addiction, and because treatment allows many patients to stabilize their lives and return to legitimate employment.

In support of methadone as an effective treatment for heroin addiction, then-Drug Czar Barry McCaffrey issued the following statement: "Methadone is one of the longest-established, most thoroughly evaluated forms of drug treatment. The science is overwhelming in its findings about methadone treatment's effectiveness. The National Institute on Drug Abuse (NIDA) Drug Abuse Treatment Outcome Study found, for example, that methadone treatment reduced participants' heroin use by 70%, their criminal activity by 57%, and increased their full-time employment by 24%."

Methadone is cost effective. Methadone costs about $4,000 per year, while incarceration costs about $20,200 to $23,500 per year.

Methadone does not make patients "high" or interfere with normal functioning.

Methadone maintenance treatment helps clients to reduce high risk behaviors like needle sharing and unsafe sex.

In support of methadone as an effective treatment for heroin addiction, then-Drug Czar Barry McCaffrey quoted Drs. Adam Yarmolinsky and Richard A. Rettig, chairman and director of a recent National Academy of Sciences study of methadone treatment, who wrote: "Methadone treatment helps heroin addicts free themselves from drug dependency, a life of crime in support of their habit and the risk of adding to the AIDS population by sharing dirty needles ...[Methadone therapy] is more likely to work than any other therapy."

"Prior to the enactment of DATA 2000 [Drug Addiction Treatment Act of 2000], the use of opioid medications to treat opioid addiction was permissible only in federally approved Opioid Treatment Programs (OTPs) (i.e., methadone clinics), and only with the Schedule II opioid medications methadone and levo-alpha-acetyl-methadol (LAAM), which could only be dispensed, not prescribed. Now, under the provisions of DATA 2000, qualifying physicians in the medical office and other appropriate settings outside the OTP system may prescribe and/or dispense Schedule III, IV, and V opioid medications for the treatment of opioid addiction if such medications have been specifically approved by the Food and Drug Administration (FDA) for that indication. (The text of DATA 2000 can be viewed at http://www.buprenorphine.samhsa.gov/fulllaw.html [4].) "In October 2002, FDA approved two sublingual formulations of the Schedule III opioid partial agonist medication buprenorphine for the treatment of opioid addiction. These medications, Subutex® (buprenorphine) and Suboxone® (buprenorphine/naloxone), are the first and, as of this writing, the only Schedule III, IV, or V medications to have received such FDA approval and, thus, to be eligible for use under DATA 2000."

"Buprenorphine can be used for either longterm maintenance or for medically supervised withdrawal (detoxification) from opioids. The preponderance of research evidence and clinical experience, however, indicates that opioid maintenance treatments have a much higher likelihood of long-term success than do any forms of withdrawal treatment. In any event, the immediate goals in starting buprenorphine should be stabilization of the patient and abstinence from illicit opioids, rather than any arbitrary or predetermined schedule of withdrawal from the prescribed medication."

"A number of clinical trials have established the effectiveness of buprenorphine for the maintenance treatment of opioid addiction. These have included studies that compared buprenorphine to placebo (Johnson et al. 1995; Ling et al. 1998; Fudala et al. 2003), as well as comparisons to methadone (e.g., Johnson et al. 1992; Ling et al. 1996; Pani et al. 2000; Petitjean et al. 2001; Schottenfeld et al. 1997; Strain et al. 1994a, 1994b) and to methadone and levo-alpha-acetyl-methadol (LAAM) (Johnson et al. 2000). Results from these studies suggest that buprenorphine in a dose range of 8–16 mg a day sublingually is as clinically effective as approximately 60 mg a day of oral methadone, although it is unlikely to be as effective as full therapeutic doses of methadone (e.g., 120 mg per day) in patients requiring higher levels of full agonist activity for effective treatment. "A meta-analysis comparing buprenorphine to methadone (Barnett et al. 2001) concluded that buprenorphine was more effective than 20–35 mg of methadone but did not have as robust an effect as 50–80 mg methadone -- much the same effects as the individual studies have concluded."

"Buprenorphine and naloxone in combination and buprenorphine alone are safe and reduce the use of opiates and the craving for opiates among opiate-addicted persons who receive these medications in an office-based setting."

Researchers from Yale University "investigated the use of counseling and different frequencies of medication dispensing in primary care treatment with buprenorphine-naloxone. Neither the primary outcomes (the frequency of illicit opioid use, the percentage of opioid-negative urine specimens, and the maximum number of consecutive weeks of abstinence from illicit opioids) nor the proportion of patients who completed the study differed significantly among the three groups. Specifically, outcomes among patients receiving brief counseling combined with once-weekly medication dispensing did not differ significantly from outcomes among patients receiving either extended counseling or thrice-weekly medication dispensing. Patient satisfaction was significantly higher with once-weekly than with thrice-weekly medication dispensing, although because of the large number of statistical tests conducted, this may represent a chance finding."

According to research published in the New England Journal of Medicine, "Consistent with the findings of previous research with buprenorphine, the frequency of illicit opioid use decreased significantly from baseline to induction and was lowest during maintenance for all three groups. The mean percentages of patients who completed the 24-week study, which ranged between 39 and 48 percent, were similar to those found in previous studies, including one conducted in an office-based setting. Therefore, the majority of patients who entered this study either left treatment or were considered appropriate for transfer to a more structured treatment setting with methadone. Nonetheless, although we did not demonstrate the superiority of extended counseling or thrice-weekly medication dispensing over the relatively limited nurse-administered counseling and once-weekly dispensing, our findings support the feasibility of buprenorphine–naloxone maintenance in primary care."

"Because buprenorphine is a partial opioid agonist, it is thought to have some advantages over methadone and levomethadyl acetate, including fewer withdrawal symptoms and a lower risk of overdose. Buprenorphine is as effective as methadone if a sufficient dose is used. Like levomethadyl acetate, buprenorphine has the advantage of being long-acting; it can also be effectively administered three times per week."

The New England Journal of Medicine in Nov. of 2000 published a study comparing methadone with LAAM and buprenorphine. According to the report, "Most of the development and evaluation research on buprenorphine has been based on daily doses. Our study used thrice-weekly doses and found that outcomes were approximately equivalent to those with either daily methadone or thrice-weekly levomethadyl acetate. Thus, thrice-weekly buprenorphine may also offer greater convenience to patients and clinic staff."

The Danish National Board of Health reported in 2000 that "The Buprenorphine project was initiated in the City of Copenhagen during the autumn of 1998 and was evaluated this year. In conclusion the report points out that this type of substitution therapy is suitable for clients who have not previously been subjected to methadone treatment and which are resourceful. Furthermore, the report concluded that buprenorphine treatment may contribute by a significant percentage to the drug addict becoming drug-free and being able to revert to normal life through work, activation and education rather than any other kind of therapy."

In November 1997, the National Institutes of Health (NIH) convened a Consensus Panel on Effective Medical Treatment of Heroin Addiction. The panel of national experts concluded:

"• Vigorous and effective leadership is needed within the Office of National Drug Control Policy (ONDCP) (and related Federal and State agencies) to inform the public that dependence is a medical disorder that can be effectively treated with significant benefits for the patient and society.

"• Society must make a commitment to offering effective treatment for opiate dependence to all who need it.

"• The panel calls attention to the need for opiate-dependent persons under legal supervision to have access to MMT. The ONDCP and the U.S. Department of Justice should implement this recommendation.

"• The panel recommends improved training of physicians and other health care professionals in diagnosis and treatment of opiate dependence. For example, we encourage the National Institute on Drug Abuse and other agencies to provide funds to improve training for diagnosis and treatment of opiate dependence in medical schools.

"• The panel recommends that unnecessary regulation of MMT and all long-acting agonist treatment programs be reduced.

"• Funding for MMT should be increased.

"• We advocate MMT as a benefit in public and private insurance programs, with parity of coverage for all medical and mental disorders.

"• We recommend targeting opiate-dependent pregnant women for MMT.

"• MMT must be culturally sensitive to enhance a favorable outcome for participating African American and Hispanic persons.

"• Patients, underrepresented minorities, and consumers should be included in bodies charged with policy development guiding opiate dependence treatment.

"• We recommend expanding the availability of opiate agonist treatment in those States and programs where this treatment option is currently unavailable."

According to the National Institutes of Health (NIH), "Methadone maintenance treatment is effective in reducing illicit opiate drug use, in reducing crime, in enhancing social productivity, and in reducing the spread of viral diseases such as AIDS and hepatitis."

"The unnecessary regulations of methadone maintenance therapy and other long-acting opiate agonist treatment programs should be reduced, and coverage for these programs should be a required benefit in public and private insurance programs."

"The safety and efficacy of narcotic agonist (methadone) maintenance treatment has been unequivocally established."

According to the NIH, "All opiate-dependent persons under legal supervision should have access to methadone maintenance therapy..."

"Substitution (or replacement) therapy such as methadone maintenance therapy, which has been widely credited with controlling HIV transmission among injection drug users in many countries, is illegal in Russia, and the 2003 amendments to the drug law did not change this. Methadone is classified as "illicit" by the terms of the three United Nations conventions on drug control, though most countries that are signatories to the conventions have methadone programs that are successful in substituting injected heroin with noninjected methadone. In this case, neither the SDCC nor the Ministry of Health seems necessarily disposed to review the status quo. Dr. Golyusov of the Ministry of Health said that he is concerned by first-hand accounts from drug users that methadone is more addictive or "harder to get off" than heroin and that other countries' experiences have been "contradictory.""