Methadone, a long-acting opioid medication, is available as a liquid, a solid tablet (5 and 10 mg), a rapidly dissolving wafer or diskette (40 mg), or a powder. Liquid methadone is most commonly used for addiction treatment, while the 5 and 10 mg tablets are most often prescribed for pain management. FDA considers methadone safe and effective for both pain management and addiction treatment, although not all forms of methadone are FDA approved for both of these purposes. OTPs offer methadone maintenance treatment, including counseling, for people addicted to heroin and certain prescription drugs. Daily doses of methadone help normalize the body’s neurological and hormonal functions that have been impaired by the use of heroin or misuse or abuse of other short-acting opioids. When starting treatment, individuals go to an OTP daily to take their methadone dose under observation, although patients may receive a single take-home dose for a day that the clinic is closed for business. After a few months, they may become eligible for unsupervised take-home doses. The National Institute on Drug Abuse notes that 1 year is generally the minimum for methadone maintenance treatment, and that some individuals will benefit from treatment over several years. Buprenorphine and levomethadyl acetate (LAAM) are also FDA-approved medications for treating opioid addiction. When used for addiction treatment, methadone must be dispensed by an OTP that is certified by SAMHSA and registered with DEA. As of February 2009, about 1,200 OTPs were operating nationwide, but not all states have OTPs. (See fig. 1.) OTPs are operated by private for-profit organizations, private nonprofit organizations, hospitals, or government agencies. FDA approved methadone for treating pain in 1947, but from the early 1970s until the late 1990s the drug was primarily used for treating addiction. In the mid-1990s, various national pain-related organizations began to issue guidelines for treating and managing pain, including using opioids to treat both cancer and noncancer pain. For example, the practice guidelines issued by the Agency for Health Care Policy and Research informed physicians and other health care professionals about the management of acute pain in 1992 and cancer pain in 1994. In 2001, health care providers and hospitals were required to ensure that their patients received appropriate pain treatment when the Joint Commission, a national health care facility standards-setting and accrediting body, implemented pain standards for hospital accreditation. At first, methadone was prescribed more for the treatment of cancer pain, but it has been increasingly prescribed for the treatment of chronic noncancer pain. Methadone’s advantages include that it costs less than other opioids used to treat pain, and it comes in multiple forms. Unlike methadone’s use in addiction treatment where it generally must be dispensed by OTPs, when used to treat pain methadone may be prescribed by an appropriately licensed and registered practitioner and dispensed by licensed and registered retail pharmacies. Licensed and registered practitioners may also dispense methadone directly to patients for pain management, but DEA officials said that it is not a common practice. DEA, on behalf of the Attorney General of the United States, is the agency primarily responsible for enforcing the Controlled Substances Act. Under the act, controlled substances are classified into five schedules based on the extent to which the drug has an accepted medical use, and its potential for abuse and degree of psychological or physical dependence. Schedule II controlled substances—which include opioids such as morphine, oxycodone, and methadone—have a currently accepted medical use and a high potential for abuse, and may lead to severe psychological or physical dependence. DEA’s regulation of the manufacturing, distribution, dispensing, and prescribing of controlled substances, including Schedule II drugs, encompasses the following: Manufacturing. DEA limits the quantity of Schedule II controlled substances that may be produced by each manufacturer in the United States each year. DEA determines these quotas based on a variety of factors, including disposal and inventories. DEA also sets aggregate production quotas that limit the production of bulk raw materials used to manufacture Schedule II controlled substances. Distribution. DEA regulates transactions involving the sale and distribution of Schedule II controlled substances by manufacturers and wholesale distributors. Manufacturers and distributors are required to report their inventories of controlled substances to DEA, and these data are available for monitoring the distribution of controlled substances throughout the United States and identifying retail registrants that received unusual quantities of controlled substances. Dispensing and prescribing. Practitioners who dispense, administer, or prescribe controlled substances must obtain a valid registration. SAMHSA is the lead federal agency addressing substance abuse and mental health services. Its mission is to build resilience and facilitate recovery for people with or at risk for substance abuse and mental illness. SAMHSA’s resources and programs are designed to expand service capacity and improve service and infrastructure to address prevention and treatment gaps. SAMHSA directly supports state and local service systems and funds activities to improve practice through grants and contracts. SAMHSA’s Center for Substance Abuse Treatment provides national leadership to expand the availability of effective treatment and recovery services for alcohol and drug problems, and to improve access, reduce barriers, and promote high-quality, effective treatment and recovery services for people with substance abuse problems and their families and communities. Under federal law and regulations, drugs must be approved by FDA before they can be marketed in the United States. The agency reviews new drug applications to determine whether they provide sufficient evidence that the drug is safe and effective for the proposed use. In approving a drug, FDA may require that the drug be dispensed only by a prescription by a licensed practitioner. Because some risks may not become known until after a drug’s approval and use in a wider segment of the population, FDA has certain postmarket oversight responsibilities once a drug is approved, such as assessing sponsors’ compliance with requirements for adverse event reporting. The agency compiles data from sponsor reports on adverse events, and voluntary reports submitted to its MedWatch program, a voluntary reporting program through which health professionals and consumers can report adverse reactions and other problems related to FDA-approved drugs. In addition, as of 2008, if FDA identifies postmarket safety concerns, the agency may take specific actions such as requiring drug manufacturers to make safety-related changes to a drug’s labeling and requiring drug manufacturers to implement a Risk Evaluation and Mitigation Strategy when necessary to ensure that the benefits of a particular drug outweigh the risks. Death investigations in the United States are typically conducted by a county, district, or state coroner system or a medical examiner system. These systems investigate deaths due to external causes, such as injury or poisoning; sudden and unexplained deaths; and deaths that occur under medical care. Most coroners are elected, and they may not be physicians. In contrast, medical examiners are usually appointed and are, with few exceptions, required to be physicians and are often pathologists or forensic pathologists. The registration of deaths varies by state. Death certificates can be completed by funeral directors, attending physicians, medical examiners, or coroners and contain such information as the deceased person’s age, sex, and race; the circumstances and cause of death; and the signature of the physician, medical examiner, or coroner. Each disease, abnormality, injury, or poisoning that the medical examiner or coroner believes contributed to the death generally is reported. The original records are filed in state registration offices. Statistical information is compiled in a national database through the National Vital Statistics System by CDC’s National Center for Health Statistics. From these data, monthly, annual, and special statistical reports are prepared for the United States and for cities, counties, states, and regions by various characteristics, such as sex, race, and cause of death. However, statistical data derived from death certificates can be no more accurate than the information provided on the certificate. For example, causes of death on the death certificate reflect a medical opinion that might vary among the individuals completing the certificates. Methadone is regulated as a controlled substance, under federal and state laws and regulations, when used for pain management and addiction treatment. When methadone is used for pain management, it is regulated under federal and state laws and regulations that apply to controlled substances generally and that do not impose requirements unique to methadone. For addiction treatment, however, federal and state laws and regulations impose additional requirements that are specific to the use of methadone. The use of methadone for pain management is regulated under federal and state laws and regulations that apply to controlled substances generally and that do not impose requirements unique to methadone. DEA has certain authorities, under the Controlled Substances Act, to regulate the use of methadone for pain management, as part of its oversight for controlled substances. For example, practitioners must register with DEA in order to dispense, administer, or prescribe Schedule II through V controlled substances. The Controlled Substances Act and implementing regulations also require that Schedule II controlled substances, including methadone, only be dispensed by pharmacists upon a written prescription, which must be issued for a legitimate medical purpose by registered practitioners acting in the usual course of professional practice. In addition, DEA uses its data on the distribution of methadone and other controlled substances to identify retail-level registrants, such as pharmacies, that receive and dispense unusual quantities of these drugs. Under these authorities, DEA may take action against practitioners that fail to prescribe or dispense controlled substances, including methadone, for legitimate medical purposes, one sanction of which is suspension or revocation of DEA registration. The use of methadone for pain management is also regulated under state law and regulations that apply to controlled substances generally. In the states we reviewed, some of these requirements were similar to provisions of the federal Controlled Substances Act.