Methadone

What Kind of Drug Is It?

Methadone is a synthetic drug, meaning that it is made in a laboratory from chemicals. It behaves like an opiate drug in the brain. Opiates are drugs, derived from the opium poppy plant, that tend to decrease restlessness, bring on sleep, and relieve pain. The natural opiates—such as codeine, heroin, morphine, and opium—are known for their painkilling properties, but also for their addictive nature. Such substances encourage abuse because they induce euphoria, or feelings of extreme happiness or enhanced well-being.

Methadone works differently. Its slow onset and long-lasting impact lessen the chances that the user will get high from taking it. At the same time, it blocks the receptors in the brain that are stimulated by opiates, so those using methadone do not get high even if they take heroin or morphine too. (Entries on codeine, heroin, morphine, and opium are also available in this encyclopedia.) Methadone is best known as the medication prescribed to help opiate addicts end the destructive behavior associated with drug addiction.

People with opiate addictions often use drugs such as heroin and morphine more to avoid withdrawal symptoms than to achieve a high. Withdrawal is the process of gradually cutting back on the amount of a substance being taken until use can be discontinued entirely. Indeed, withdrawal from opiates—even prescription drugs such as OxyContin and Vicodin—can be difficult and challenging. Methadone eases all symptoms of opiate withdrawal, including anxiety and insomnia, a sleep disorder. Those who receive methadone treatment from trained, licensed doctors—and who follow the treatment schedule carefully—face little danger of overdose, infectious disease, or organ failure. When used properly, it is a medicine that helps users end their addictions and get on with their lives.

Official Drug Name: Methadone; Dolophine

Also Known As: Dolls, dollies, fizzies

Drug Classifications: Schedule II, opioid narcotic

When Methadone Is Abused

When used illegally or improperly, though, methadone is one of the most dangerous drugs on the street. According to the Drug Abuse Warning Network (DAWN), emergency room visits related to methadone overdose tripled between 1997 and 2001. Since then, methadone-related deaths and hospitalizations have continued to rise. Two factors have contributed to the spike in methadone-related emergencies. First, doctors are prescribing the drug more often as a painkiller. In that form, methadone is dispensed by pharmacies as pills and taken into homes. Sometimes it is either used improperly by the patient or sold on the street or to drug dealers.

The second possibility for methadone ER visits involves multi-drug use. Numerous drug deaths have occurred when people combine methadone with other painkillers, opiates, cocaine, tranquilizers, or alcohol. (Separate entries on these drugs are available in this encyclopedia.) The presence of other substances increases the likelihood that methadone will cause coma, breathing difficulties, and even death.

Since the beginning of the twenty-first century, drug enforcement agents have seized greater quantities of methadone that have been diverted or put into illegal use. Concern over this diversion has led to high-level government meetings and studies on how to keep this powerful pain reliever with many useful qualities out of the wrong hands.

Overview

Naturally occurring opiates are derived from the sticky sap of the opium poppy. Opium products have been used for many thousands of years, both for their pain-controlling properties and for the feelings of intense happiness and well-being they provide. From the ancient Egyptians to the celebrated British poets of the nineteenth century, opiate users have known of the plant's effects—and of its drawbacks. The latter includes addiction, tolerance, and death by overdose. In his book Illegal Drugs: A Complete Guide to Their History, Chemistry, Use and Abuse, Paul M. Gahlinger noted that the famous ancient Roman general Hannibal kept a fatal dose of opium in a ring on his finger and actually used it to kill himself in 183 bce.

Beginning in the nineteenth century, scientists worked with opium products, trying to isolate the painkilling qualities from the habit-forming qualities. They met with little success. In fact, all natural and synthetic opiate and opioid products on the market in the twenty-first century are still known to be addictive. Methadone is no exception. Users develop a dependence, or a physical need for the drug in order to ward off withdrawal symptoms. And they suffer withdrawal symptoms if they do not follow a careful program of specific directions for use.

Usage Grows in the 1940s and 1950s

Methadone was developed in Nazi Germany in 1939 because of wartime shortages of morphine. The German scientists called it Amidon and used it as a painkiller. At the end of World War II (1939–1945), the American pharmaceutical company Eli Lilly began clinical trials of the substance. Lilly called it "methadone." The drug has also been marketed as Dolophine, leading to nicknames such as "dolls" and "dollies." Methadone was found to be an effective, long-lasting painkiller and cough suppressant.

According to a report issued by the Substance Abuse and Mental Health Services Administration (SAMHSA), in 1950 researchers began using methadone to treat the many symptoms of withdrawal associated with heroin dependence. Heroin addicts typically need two to three "fixes" of the drug each day to ward off the wide range of symptoms that occur when the brain craves opiates. The desperate search to buy the illegal drug leads some addicts into criminal behavior, ranging from theft and burglary to prostitution and drug-dealing. People with opiate addictions feel trapped by their dependency. The desperation is sometimes described as a "monkey on the back."

Pharmacy Mix-ups

According to the Knight Ridder/Tribune Business News, several deaths have occurred in children because methadone has a name similar to methylphenidate, the generic name for Ritalin. (A separate entry on Ritalin and other methylphenidates is available in this encyclopedia.) In a few cases, children who were prescribed Ritalin to treat attention-deficit/hyperactivity disorder (ADHD) actually received methadone pills instead.

It is important to note that methadone is never prescribed for ADHD. Children should never be allowed to take Ritalin without having the tablets checked by a parent to be certain that the tablets are Ritalin, and not methadone. Anyone who has a prescription for Ritalin filled has the right to examine the product at the pharmacy counter and to double-check with the pharmacist that no one preparing the prescription has confused methylphenidate with methadone. Mistakes can be fatal.

Treating Addictions with Methadone

In 1964 a group of researchers discovered that heroin addicts could avoid the drug and live more normal lives if they received a daily dose of methadone. The methadone eased withdrawal symptoms and lessened cravings for heroin. Better yet, people taking methadone could not get high on heroin because methadone binds to the same brain receptors that heroin does.

Some problems remained. Methadone is itself an opioid, so it causes dependency too. Its side effects are identical to the natural opiates and include constipation, nausea, drowsiness, dry mouth, and the possibility of breathing problems. Researchers concluded that some people trying to wean themselves off heroin or other opiates by following a methadone treatment plan might have to take methadone for a very long time. The treatment was not foolproof, either. Many addicts returned to drug abuse, sometimes turning to cocaine to get high. Because methadone and cocaine work differently in the brain, methadone treatment does not help cocaine addicts stop using cocaine, nor does it block the effects of cocaine. (An entry on cocaine is available in this encyclopedia.)

Despite these drawbacks, methadone has remained the drug of choice for treatment of opiate dependency since the 1960s. It is not a "perfect cure," but it does provide a way for motivated people to straighten out their lives, hold jobs, and otherwise live more normally. The SAMHSA report stated: "Methadone is a medication valued for its effectiveness in reducing the mortality associated with opioid addiction as well as the various medical and behavioral morbidities associated with addictive disorders." In other words, even the U.S. government believes that methadone, when used properly, saves lives and cuts down on crime.

Methadone Clinics Open

In the late 1960s, the U.S. government began sponsoring methadone clinics in many parts of the country, especially the nation's largest cities. At methadone clinics, people line up to take their daily dose of the drug under the watchful eye of a nurse or other health care worker, and then leave. After a period of months, a patient who has followed the treatment program carefully might be allowed to carry one or two doses home. These doses are called "carries." Most patients use their "carries" as carefully as the doses given to them at the clinics, but some turn the "carries" over to illegal use. In addition, the drug is being prescribed more by doctors. Some patients sell their medications to others. In these ways, some of the drug makes its way on to the street illegally.

What Is It Made Of?

Methadone is not derived from the opium poppy plant. It is synthetic, or made from chemicals in a laboratory. Pure methadone is an odorless white powder that dissolves easily in water, juice, or alcohol. Hospitals also have solutions of methadone that can be delivered by injection.

Methadone takes effect slowly and stays in the brain for a period of twenty-four to thirty-six hours. During that time the user—assuming he or she uses no other drugs—will function normally, perhaps feeling a bit sluggish or groggy. Sleep cycles will be normal, but appetite may be lessened. Constipation is a troublesome side effect.

How Is It Taken?

In most clinics, methadone is dispensed in sugary liquids and swallowed by the patient. The drug can also be taken as a biscuit ("diskette") or in pill form. Very rarely, in a hospital or clinical setting, the drug is injected into a muscle. Methadone is not commonly used in post-surgical settings because other drugs such as morphine and fentanyl work faster to relieve pain. (Separate entries on morphine and fentanyl are available in this encyclopedia.) Rather, methadone is used for long-lasting pain, such as that resulting from cancer, back injuries, or severe arthritis.

In 2000 the federal government relaxed rules on prescribing methadone in pill form. Doctors who complete an eight-hour training seminar become certified to dispense methadone pills that vary in strength from 20 to 120 milligrams.

Methadone Chronology

1939      German scientists develop a synthetic opioid painkiller in response to wartime shortages of morphine. They call the new drug Amidon.

1947      American pharmaceutical company Eli Lilly begins trials of the painkiller. Lilly calls the drug methadone.

1950      Researchers begin using methadone to treat withdrawal symptoms in heroin addicts.

1964      Researchers in Lexington, Kentucky, conclude that a daily dose of methadone allows heroin users to avoid withdrawal symptoms while also being unable to experience a heroin high. The first methadone clinic opens in Lexington.

1970      The U.S. Controlled Substances Act places methadone on its list of Schedule II substances, recognizing that the drug has medical uses but also the potential for misuse and abuse.

2000      Prescriptions for the pill form of methadone rise sharply in response to abuse and illegal use of other opiate/opioid painkillers such as Vicodin and OxyContin.

2003      U.S. trials begin on the drug buprenorphine for use as an alternative to methadone.

The first week of methadone use for chronic pain can be difficult and dangerous. Doctors need to monitor patients carefully because the drug acts slowly on the pain and accumulates in the body. Patients must be watched for tolerance levels so that they are not given deadly doses. They must also be cautioned that methadone is not a "quick fix" for pain, and that taking an extra dose will not make the drug work any faster. Typically, patients will see little or no pain relief from methadone for the first twenty-four to forty-eight hours. After that, methadone works well for chronic pain, provided the user follows the directions and does not mix the medication with other drugs, except on the advice of a doctor.

Illegal Use

People also use methadone illegally as a recreational drug, which is a drug used solely to get high, not to treat a medical condition. People have been known to grind up methadone tablets and snort the powder or inject the drug. This can be extremely dangerous, even in the absence of other drugs or alcohol. Because methadone works so slowly, it does not provide the rush of euphoria that the user craves. This may entice the user to take more methadone, eventually leading to a deadly build-up of the drug in the body. It is often hours and sometimes even days before the poisonous effects of methadone become apparent, as the user first slips into a deep sleep, then into a coma, and then stops breathing.

Are There Any Medical Reasons for Taking This Substance?

Methadone is an effective means of taking control of an opiate habit. It lessens the withdrawal symptoms of opiate abuse and helps control—but does not eliminate—cravings for opiates. People driven to desperation in their search for illegal heroin or painkillers can resume a normal lifestyle if they follow a methadone treatment plan. Studies have shown that long-term use of methadone in the absence of other drugs and alcohol has no adverse effects on the heart or other internal organs.

Someone who stops using methadone suddenly will suffer the withdrawal symptoms typical of all opiates, including diarrhea, nausea, chills, muscle pains, anxiety, insomnia, sweating, and frequent yawning or sneezing. In order to quit using the drug without these symptoms, it is necessary to lower the dose slowly over a period of months. This allows the body to adjust its brain chemistry gradually. Again, patients must be highly motivated to stay with the program, as even small reductions in dosage can bring a mild onset of withdrawal symptoms.

An epidemic of illegal OxyContin abuse since 2000 has led more doctors to prescribe methadone for chronic pain. Methadone is very effective in this role, but patients must be aware that the full effects of the pain relief may take as much as a week to achieve. During that time, they must be careful to monitor sleep patterns and to be aware of how the drowsiness might affect them while driving or operating machinery. If the painful condition improves, patients must taper their use of methadone gradually to avoid withdrawal symptoms.

Drugs like methadone are not prescribed on an "as needed" basis. The kind of pain for which methadone is used is a crippling, ongoing, day-and-night pain that may never improve. For extremely sick cancer patients, methadone allows a quality of life that might be impossible otherwise. The drug does not cure the cancer or even slow its progress, but it can help patients manage the pain. The same holds true for other conditions such as chronic back pain and osteoarthritis.

Usage Trends

The amount of methadone dispensed in clinics for the treatment of opiate addiction has remained stable for decades. However, between 1999 and 2002, the number of doctor-generated prescriptions for methadone increased by 331 percent, according to a report by SAMHSA. Pills and biscuits account for almost all of this increase.

Researchers at SAMHSA acknowledged several reasons for the jump in prescriptions for methadone—and a related jump in methadone deaths. First, doctors began prescribing more methadone for pain, believing that its potential for abuse is less than that of oxycodone (OxyContin) and hydrocodone (Vicodin). Second, some doctors began prescribing methadone to patients who are trying to recover from oxycodone or hydrocodone habits. The SAMHSA researchers also suggested that some opiate addicts do not want to be seen visiting a methadone clinic and may be turning to their personal doctors for help in kicking their habits. Getting a prescription from a doctor, and having it filled at the local pharmacy, is far more anonymous than arriving at a clinic every morning. Some communities even fight expensive legal battles to keep methadone clinics out of their neighborhoods.

Methadone on the Streets

The increase in methadone prescriptions has led to an increase of the drug being sold on the street. Seizures of illegal methadone by drug enforcement agents increased 133 percent between 2001 and 2002. Deaths associated with methadone have grown sharply since the early 1990s. SAMHSA used data to show that between 1993 and 2002, methadone-related fatalities jumped 200 percent in the state of Washington. The report declared: "While overdose mortality was declining among [clinic] patients, such fatalities were rising in the overall population." DAWN statistics are quite similar. Between 1994 and 2001, DAWN reported a 230-percent increase in the number of emergency room patients being seen for methadone related problems or multi-drug problems with methadone in their systems.

According to the "Pulse Check" report in 2004, methadone addicts tend to be "white, middle-socioeconomic males older than 35." Florida, Pennsylvania, Ohio, Indiana, and Texas are among the states with the largest methadone problems. The availability of the drug in these states stems from patients in treatment centers who are saving their doses and selling them on the streets. "Pulse Check" authors noted that the cities of Tampa and St. Petersburg, Florida, in particular, have seen a "dramatic increase in emergency department episodes and deaths involving methadone."

Increased Abuse of Painkillers

The Join Together Web site published a survey by Kentucky's Louisville Courier-Journal that found 345 fatalities in that state from methadone overdoses between January of 2003 and May of 2004. In Kentucky during that same period, methadone surpassed OxyContin as "the most misused prescription drug in the region," according to the article.

The "2003 National Survey on Drug Use and Health" also determined that illegal use of methadone was on the rise among teenagers. The survey found that methadone use had increased 25 percent in just one year, part of a general increase in the abuse of prescription painkillers. Overall, methadone is becoming less associated with heroin addicts trying to go straight and more associated with the quiet epidemic of prescription painkiller use and abuse. The epidemic includes men and women of all races, ages, and economic levels.

Effects on the Body

Taken by mouth in pill, biscuit, or liquid form, methadone passes into the digestive system and from there is broken down in the liver. The liver releases the drug into the bloodstream, and it is carried to the brain and spinal cord, where it attaches to opiate receptors.

When no drugs are in the brain, opiate receptors take in endorphins and enkephalins, two brain chemicals that regulate feelings of well-being, overall motor coordination, breathing and coughing, and moods. Opiates replace these natural chemicals quickly and in such quantity that the user experiences a rush of pleasurable sensations and a calm drowsiness for hours afterward. This is the "high" that opiate users seek.

No "Rush" with Methadone

When methadone is introduced to the opiate receptors, it does not cause the rush of pleasure that other opiates and painkillers do. Its onset is slower, and it stays in the brain and body longer. Users may feel drowsy and relaxed. Any kind of pain will gradually cease, and it will not return as long as the user takes regular, carefully prescribed doses of the drug. As the dose of methadone leaves the brain and body—generally in about twenty-four to thirty-six hours—the user will begin to feel the discomfort of withdrawal unless a new dose is taken.

Alternative to Methadone

Beginning in the early twenty-first century, the U.S. Food and Drug Administration (FDA) approved trials on a drug called buprenorphine (marketed as Buprenex, Subutex, and Suboxone). A painkiller used in Europe to treat opiate addiction, buprenorphine works the same way as methadone without some of the complications of methadone treatment. The drug has similar effects on the body as methadone but it is not as addicting as other opiate or opioid-like drugs. In its Suboxone form, it contains naloxone, a drug that rids the body of opiates. Scientists are optimistic about the possibilities of Suboxone because grinding it up and snorting or injecting it will simply release the naloxone and cause withdrawal symptoms rather than a high.

In other parts of the body, methadone causes the same symptoms as other opiates and opioids. It inhibits the muscles in the bowels, leading to constipation, and works as a cough suppressant. If taken improperly, it can also affect breathing and lead to asphyxiation—the inability to breathe, which results in death.

Users may also experience nausea and loss of appetite, dry mouth that can lead to tooth decay and gum disease, and pinpoint pupils leading to sensitivity to light. Methadone may also lessen sexual function and desire.

At the end of methadone treatment, users must taper doses slowly to allow all the bodily systems to return to normal. A sudden end to methadone use brings on diarrhea, anxiety, insomnia, and flu-like symptoms.

Reactions with Other Drugs or Substances

Methadone becomes far more dangerous when combined with other drugs or alcohol. All types of tranquilizers, sedatives, antidepressants, and anti-anxiety drugs will increase the likelihood of breathing problems if taken along with methadone. The drug should not be combined with other painkillers, even over-the-counter medications like acetaminophen (Tylenol) and ibuprofen (Advil), unless supervised by a doctor.

In a 2004 report, the National Drug Intelligence Center revealed that in 65 percent of all emergency room visits related to methadone use, another drug was also present. Frequently the second drug was alcohol. When used together, methadone and alcohol magnify each others' effects. Drinking while taking methadone can lead to very poor motor control, vomiting and breathing problems, coma, and asphyxiation.

Illegal users of methadone sometimes combine it with cocaine as well. Cocaine causes a different sort of high in the brain, one that is unaffected by methadone. Users of cocaine and methadone find themselves in the difficult position of being addicted to two different substances at the same time, with a host of side effects unique to each substance.

Methadone should not be combined with medications that increase metabolism time in the liver. These include medicines for tuberculosis, such as Rifampin, and medicines for seizures and epilepsy, including Dilantin. Some antibiotics, and even over-the counter vitamins, can increase the level of methadone retained in the bloodstream. Methadone decreases the power of medicines prescribed for the human immunodeficiency virus (HIV), the virus that can lead to acquired immunodeficiency syndrome (AIDS). Methadone can worsen nausea, vomiting, and fatigue in patients with AIDS. Since people can be infected with HIV by sharing needles to inject heroin, some ill addicts might not be able to tolerate a methadone plan of treatment.

Treatment for Habitual Users

Habitual use of methadone is encouraged in people trying to kick an opiate habit. This is because proper use of methadone allows addicts to resume a normal life again. Studies from many countries show that heroin addicts who have lost jobs and contact with their families, and have fallen into criminal behavior, can turn their lives around as long as they adhere to a strictly supervised methadone plan. Sometimes recovering addicts take methadone for years. In other cases, the methadone doses are gradually decreased over a period of months until a full recovery is achieved.

However, many addicts who start a methadone treatment program will have difficulties following the plan. Some quit and go back to hard drugs. Others falter here and there, or become dependent on

another drug such as cocaine. Some combine methadone with other brain-altering drugs or alcohol. This greatly complicates the treatment process.

One researcher in a nationally published report by SAMHSA likened opiate addition to illnesses such as diabetes and extreme obesity. People with diabetes know that they have to manage their weight and watch what they eat. Some do, others do not. The ones who follow doctors' orders live longer than the ones who ignore the advice and carry on with their habits. The same holds true for obesity. People must be highly motivated to lose weight. Some are, some are not. The ones who make a commitment to change often live longer than the ones who do not change their lifestyles. Drug addicts are also suffering from a disease, and their willingness to fight the disease influences their ability to overcome it.

Most doctors realize that simply dispensing methadone tablets to people with a drug addiction will not end the cycle of abuse. Opiate addicts must also undergo talk therapy with counselors who are trained to offer strategies for combating drug use. Self-help groups such as Narcotics Anonymous can be helpful but might not be enough for those requiring methadone therapy. Most methadone clinics combine drug treatment with personal counseling.

In the News

How many ways can methadone kill? Newspapers reveal personal stories of tragic deaths.

• In 1999, an eight-year-old boy died following a mix-up in his prescription, having taken methadone instead of Ritalin (methylphenidate). It was one of six documented cases of confusion over the similar names for the two drugs.
• In 2001, an eight-year user of prescription methadone, a father with a young child, died in Ontario, Canada, after doctors refused to place him on a liver-transplant list. The man died of liver failure unrelated to his methadone use. A physician admitted that the victim was discriminated against because he used methadone.
• In 2002, a Fort Lauderdale, Florida, woman died in her home at age forty-one of a multiple-drug overdose, including prescribed methadone. She was being treated for an intensely painful back deformity.
• In 2002, a two-year-old boy died of methadone overdose in Sheffield, England, after drinking the sweetened liquid containing methadone that his mother had brought home from a clinic. His mother was high on heroin at the time.
• In 2002, a fifteen-year-old Toronto girl lapsed into a coma and stopped breathing many hours after drinking a beverage laced with methadone. Someone had spiked her drink without her knowledge.
• In 2004, a Colorado State University student died a month before his twenty-first birthday from a combination of alcohol and methadone. He collapsed on a street near the campus.

Self-Healing on the Street

Studies are being conducted of methadone abuse on the streets to see how the drug is used recreationally. Some researchers suggest that illicit methadone is used less for the high it produces and more as a self-treatment for withdrawal symptoms when other opiates are not available. Methadone is not a safe recreational drug. It is habit-forming. Anyone using it for any reason should be under the close supervision of a doctor.

Consequences

When used properly, methadone can literally save lives. Heroin users expose themselves to many deadly diseases, including HIV and hepatitis (a liver disease), when they share dirty needles. Heroin users are also prone to commit crimes or indulge in risky behavior. By stopping heroin use, the cycle of the desperate pursuit of the next "fix" ends. A thirty-one-year-old recovering heroin addict, quoted in the York Daily Record, said he rode a bus two hours each way from his home every day for his methadone treatments. Admitting he had been jailed "at least ten times," the man said that methadone "gives me the ability to get on with my day." While methadone treatment for drug abuse is not easy, quick, or always successful, it does offer hope to people who are harming themselves and others.

As a prescription painkiller, methadone use must be monitored very carefully for the potential of poisonous build-up in the body. Doctors prescribing it for pain need to be quite knowledgeable about how to adjust the doses and how to monitor patients for overdose. Patients must be aware that they need to take the medicine exactly as prescribed or face possibly fatal consequences. Doctors must be particularly careful when patients are taking any other medications, either prescription or over-the-counter drugs. When used as a prescription painkiller, methadone is typically a drug of last resort.

Any use of methadone with other drugs and alcohol in a recreational setting can be fatal. Failure to store the medicine properly can lead to poisoning in children. Crushing methadone pills and snorting or injecting them for recreational use can cause death, sometimes many hours or even a day or two after use. Methadone overdose generally causes the user to fall asleep, and the sleep then deepens into a coma that ends when the user's breathing stops.

Methadone is a habit-forming drug. Community leaders often fight against having methadone clinics in their neighborhoods because the clinics attract drug abusers who may have committed criminal acts. Anyone considering experimentation with methadone should keep in mind that those who really need the drug have very difficult lives with extremely challenging mental or physical illnesses.

The Law

Methadone is a Schedule II controlled substance, meaning that the U.S. government finds it to have some medical uses but also a high potential for abuse and addiction. Penalties for possession and sale of illegal methadone vary from state to state and can be quite harsh, since the drug carries so many potential dangers. Even a first conviction for possession or sale of illicit methadone can carry jail time. Second and third offenses can result in a lifetime in prison.

In 2000 the FDA relaxed some of the restrictions on the legal prescription of methadone. Still, doctors who prescribe the drug must attend training sessions to learn about methadone's profile, how to prescribe the drug safely, and how to monitor patients for life-threatening side effects. Doctors who finish the training are issued a special license to prescribe methadone. Needless to say, any doctor or pharmacist who issues methadone without the proper documentation can face prosecution as a criminal.

Methadone's dangerous side effects, its history as a substance used to help addicts, and its long-lasting effects on the body have all combined to bring its uses—both legal and illegal—under greater scrutiny.

For More Information

Books

Clayman, Charles B., ed. The American Medical Association Encyclopedia of Medicine. New York: Random House, 1989.

Gahlinger, Paul M. Illegal Drugs: A Complete Guide to Their History, Chemistry, Use and Abuse. Las Vegas, NV: Sagebrush Press, 2001.

Smith, D., and Richard Seymour. Clinician's Guide to Substance Abuse. New York: McGraw-Hill, 2000.

Periodicals

Babb, J. J. "Colorado State U. Student's Death Result of Alcohol, Methadone." America's Intelligence Wire (January 18, 2005).

"Cocaine Abuse by Methadone Patients Is a Growing Problem." The Addiction Letter (March, 1995): p. 1.

Dalrymple, Theodore. "An Official License to Kill." New Statesman (March 3, 2003): p. 30.

"Florida's Prescription Drug Deaths Now Exceed Those from Cocaine, Heroin." South Florida Sun Sentinel (November 13, 2002).

Gebhart, Fred. "Methadone-Related Deaths on the Rise, Report State Boards." Drug Topics (October 11, 2004): p. 65.

Hawaleshka, Danylo. "Too Many Deaths: As Ontario's Methadone Program for Drug Addicts Expands, So Do Fatalities." Maclean's (February 25, 2002): p. 44.

Henle, Mark. "Dartmouth College: New Hampshire Methadone Clinic Stymied by Zoning." America's Intelligence Wire (May 10, 2004).

Higgins, Michael. "Deerfield, Ill.-Based Walgreens Admits Giving Methadone to Brain-Damaged Boy." Knight Ridder/Tribune Business News (October 8, 2003).

Kinross, Ian. "Methadone Clients Denied Life-Saving Liver Transplants." Journal of Addiction and Mental Health (March-April, 2001): p. 3.

Patterson, Karen. "Beyond Methadone: New Hope for Heroin Addicts Comes in Tablet Form." Dallas Morning News (January 11, 2003).

Randerson, James. "Painkiller Linked to Rise in Overdose Deaths." New Scientist (March 6, 2004): p. 14.

Sadovsky, Richard. "Public Health Issue: Methadone Maintenance Therapy." American Family Physician (July 15, 2000): p. 428.

Schulte, Fred, and Nancy McVicar. "Rx for Death: Patients in Pain Overdosing in Alarming Numbers." South Florida Sun-Sentinel (May 12, 2002).

Smith, Sharon. "York County, Pa., Heroin Addicts Make Daily Trek for Methadone." York Daily Record (November 7, 2003).

Wainwright, Martin. "Boy, 2, Died from Mother's Methadone." Europe Intelligence Wire (October 8, 2002).

Wilson, Clare. "Fixed Up: When Nothing Else Works, Heroin Addicts Should Be Prescribed the Drug They Crave." New Scientist (March 30, 2002): p. 34.

Web Sites

"2003 National Survey on Drug Use and Health (NSDUH)." Substance Abuse and Mental Health Services Administration (SAMHSA).http://www.drugabusestatistics.samhsa.gov (accessed July 29, 2005).

"The DAWN Report: Trends in Drug-Related Emergency Department Visits, 1994-2001 At a Glance" (June, 2003). Drug Abuse Warning Network: Office of Applied Studies, Substance Abuse and Mental Health Services Administration.http://dawninfo.samhsa.gov/old_dawn/pubs_94_02/shortreports/files/TDR_EDvisits_glance_1994_2001.pdf (accessed July 31, 2005).

"Information Bulletin: Methadone Abuse Increasing" (September, 2004). National Drug Intelligence Center.http://www.usdoj.gov/ndic/pubs6/6292/6292t.htm (accessed July 28, 2005).

"Methadone" (April, 2000). Executive Office of the President, Office of National Drug Control Policy (ONDCP).http://www.whitehousedrugpolicy.gov/publications/factsht/methadone/index.html (accessed July 28, 2005).

"Methadone Abuse Surpasses OxyContin in Kentucky." Join Together.http://www.jointogether.org/sa/news/summaries/reader/0,1854,570886,00.html (accessed July 28, 2005).

"Methadone-Associated Mortality: Report of a National Assessment." Substance Abuse and Mental Health Services Administration.http://dpt.samhsa.gov/reports/methodone_mortality-03.htm (accessed July 31, 2005).

"Pulse Check: Drug Markets and Chronic Users in 25 of America's Largest Cities" (January, 2004). Executive Office of the President, Office of National Drug Control Policy.http://www.whitehousedrugpolicy.gov/publications/drugfact/pulsechk/january04/january2004.pdf (accessed July 28, 2005).

See also: Cocaine; Codeine; Fentanyl; Hydromorphone; Morphine; Opium; Oxycodone; Ritalin and Other Methylphenidates

METHADONE

OFFICIAL NAMES: Methadone, Dolophine

STREET NAMES: Fizzies, dollies, dolls

DRUG CLASSIFICATIONS: Schedule II, opioid narcotic analgesic

OVERVIEW

Methadone is a synthetic opioid narcotic, discovered in Germany in 1939. Its original name was Amidon, and it was used mainly as a pain reliever. After the conclusion of World War II, Eli Lilly and other American pharmaceutical companies began clinical trials of the medication, renamed methadone, and also began commercial production. Its original uses in the United States were for pain control and as a component of cough medicine.

While methadone works well as a pain control medication, its main use today is in the treatment of heroin addiction. Methadone itself is an addicting drug; its effects are much longer acting than heroin. Easier to administer on a once-daily basis, it is effective orally, which protects addicts from acquiring diseases such as HIV/AIDS, hepatitis B, and hepatitis C, obtained when they use dirty needles. Tolerance and dependence on methadone may develop in long-term users, and withdrawal symptoms, while less severe than among heroin users, are generally longer lasting.

CHEMICAL/ORGANIC COMPOSITION

Methadone is an odorless, white powder that dissolves easily in water and alcohol. In methadone treatment programs, it is often mixed with an insoluble matrix to form what are known as methadone biscuits. These biscuits stay in the stomach longer because it takes awhile for the stomach acids to break down the matrix. This is important because it allows more of the methadone to be absorbed, rather than passing quickly through the stomach when in liquid form.

INGESTION METHODS

Methadone is manufactured as tablets, diskettes (also known as biscuits), and liquid. People who use the drug illegally often inject either the liquid form or crushed and dissolved tablets. Methadone is detectable in a person's bloodstream seven to 10 days after use.

When used as a cough suppressant, methadone is taken in a liquid or tablet form in very small (1–2 mg) doses every four to six hours. For relief of moderate to severe pain, it is generally given as a tablet or as an intramuscular injection, 2.5–20 mg every three to four hours. When used in heroin detoxification and methadone maintenance programs, it is given as oral tablets, biscuits, or liquid, 20–120 mg every 24–48 hours.

THERAPEUTIC USE

The most well-known use of methadone is for treating heroin addiction. It is calculated that between 500,000 and one million Americans are addicted to heroin. Along with the obvious infectious risks to heroin users such as HIV/AIDS and hepatitis, heroin addicts often engage in criminal activity to obtain heroin, an illegal drug, to support their addiction. Methadone is an agonist, which means it fits into the brain's opiate receptors and blocks heroin. It reduces the intense cravings addicts experience when they try to give up heroin and enables them to participate in therapy and other aspects of their treatment. Methadone also reduces the need for addicts to commit crimes to obtain heroin and protects them from disease. Recent studies have found that persons in a methadone maintenance program were three to six times less likely than heroin users to become infected with HIV, even if they continue to use illegal drugs.

Methadone generally lasts about one day in the body, meaning that a person in a maintenance program has to take methadone at least once a day. Federal regulations require that to be eligible for enrollment in a methadone maintenance program, potential patients must be at least 18 years of age and demonstrate that they have had at least a one-year history of heroin (or other opiate) addiction. An exception is made for patients between the ages of 16 and 18 who can document a history of at least two unsuccessful detoxification trials.

Methadone maintenance programs are generally managed through methadone clinics, which also provide counseling and rehabilitation services. There are currently 42 states that have methadone maintenance programs, along with the District of Columbia, Puerto Rico, and the U.S. Virgin Islands.

The goal of a methadone maintenance program for people who are just coming off heroin is to decrease their withdrawal symptoms and their desire to use heroin. Initially, people starting in a methadone maintenance program will be given 30–40 mg of methadone a day, although there are addiction specialists who recommend higher initial doses such as 60–80 mg a day. In fact, most programs today are switching to the larger dose because research shows the larger dose is required for methadone to work effectively. Further into a methadone maintenance program, the dosages of the drug will be adjusted so that a person will not have cravings for heroin but also will not have any side effects from the methadone, such as sedation or euphoria.

Besides its use in treating illegal opiate addiction, methadone is occasionally used in other areas of medicine. All of the opiates, including methadone, are powerful pain control medications. Since pain is one of the most frequent, and least well-managed, aspects of cancer care, physicians often use multiple medications to try to control cancer pain. Methadone can be given in 20 mg tablets or by intramuscular injection every four to six hours to control moderate to severe cancer pain. Methadone is often used when there is a desire to let the patient sleep because of its high sedating properties.

Methadone can also be used to treat a common condition called restless leg syndrome. This condition generally affects middle-aged to older adults, although it is occasionally seen in adolescents. In restless leg syndrome, people complain of a strong, almost uncontrollable desire to move their legs, especially at night. In people who are unable to sleep because of this disorder, 10 mg of methadone, given at bedtime, often is effective at slowing or stopping the leg movements.

USAGE TRENDS

Scope and severity

The number of people entering methadone treatment programs to help them fight their heroin habit has steadily increased since methadone was first approved to treat heroin addiction. The latest statistics show that there are 170,000 admissions to methadone treatment programs throughout the United States every year.

Several major studies have been undertaken to gather data on opiate drug abusers who enter methadone treatment programs. The first of these was the Drug Abuse Reporting Program (DARP), which gathered data between 1969 and 1973. The second study, which examined patient characteristics of heroin addicts entering a methadone maintenance program, was the Treatment Outcomes Prospective Study (TOPS), which ran from 1979 to 1981. The most recent nationwide research, known as the Drug Abuse Treatment Outcomes Study (DATOS), collected data from 1991 to 1993.

There were many significant changes noted between the studies. In DARP, the earliest study, the patients entering methadone treatment programs had been, on average, addicted to heroin for at least nine years. In the 1990s, that number had increased to 13 years. Furthermore, the number of patients who had received previous treatment for heroin addiction increased from 50% in the 1960s to 75% in the 1990s. The proportion of addicts that had at least three prior treatment attempts increased from 13% in the 1960s study to 40% for the 1990s study. Use of other drugs such as cocaine among people entering methadone treatment programs increased from approximately 30% in the 1960s to 50% in the 1990s.

Age, ethnic, and gender trends

Based on data from these studies, there has been a significant change in the past three decades in the age, ethnic, and gender composition of methadone users. The proportion of women entering methadone treatment programs increased from 22% in the early studies to 39% in the most recent studies. The proportion of African Americans entering methadone programs decreased from 58% in the 1960s to only 28% in the 1990s, while the percentage

of Hispanics rose from 10% to 24% over that same time period. The percentage of whites entering methadone programs increased from 29% in the 1960s to 38% in the 1990s. Forty-six percent of the methadone program participants were between the ages of 35 and44. Only 20% were below the age of 30.

MENTAL EFFECTS

Methadone and all other opiates produce multiple effects on a user's psychological and mental status. These effects are generally dose-related, with more powerful effects seen at higher doses.

In order to influence a person's mental state, methadone, along with any other drug or substance, must first be able to cross what is known as the blood-brain barrier. The blood-brain barrier is an actual physical barrier, made up of tightly interspaced blood vessels that protect the brain from substances that might be harmful. The more effective a substance is at getting through the blood-brain barrier, the greater the effect it has on the person's mental status. Methadone and other opiates cross the blood-brain barrier quite easily.

Most users of methadone, especially new users, report feelings of well being and tranquility after taking the drug. How methadone produces these feelings is still being researched. Some scientists think that methadone and other opiates cause these effects by acting on a part of the brain known as the locus cerulus. This area of the brain is known to play a major role in feelings of pain, panic, fear, and anxiety. It is thought that by dampening the action of the locus cerulus, methadone and other opiates cause thoughts and feelings of tranquility and ease.

Methadone and opiates were first used for pain relief, and are still chiefly used in that area of medicine. It is important to remember that methadone and other opiates do not exert their pain control by altering a person's sensitivity to pain. Rather, methadone and other opiates interfere with the transmission of pain impulses from the nervous system to the brain. They accomplish this by a variety of methods. First, they decrease the transmission of nerve signals that conduct pain messages from various parts of the body to the spine. Secondly, they prevent production of neurochemicals that transfer this pain information to the spine. Finally, they mimic the actions of endorphins, which are the body's own pain-controlling chemicals. While methadone and other opiates work quite well to control pain, they do not affect touch, vision, or hearing.

Methadone also produces clouding of thoughts, drowsiness, and sleep in people who use it. It is thought that psychological effects seen in people who use methadone, including the inability to concentrate, apathy, and lethargy are related to methadone's pro-drowsiness effects, although researchers have yet to pinpoint the way in which methadone causes these effects. Methadone is often used by clinicians who specialize in addictive disorders to help heroin addicts resume a normal sleep cycle, since it is a powerful trigger at inducing sleep.

There are some reports by users that methadone use may cause hallucinations. While it is well known that heroin users often describe a dream-like mental state when using heroin, this effect is rarely seen in people who use methadone. The reason behind this is probably due to methadone's slower onset of action and reduced level of intensity. Likewise, while users of heroin and other harder narcotics sometimes report feelings of acute anxiety, especially when first using the drug, users of methadone rarely report these psychological effects.

PHYSIOLOGICAL EFFECTS

Methadone, like all opiates, is a chemically simple compound that has a variety of effects on those who take it. But while other opiates exert powerful euphoric effects on a person by acting very much like chemicals called endorphins and enkephalins, methadone produces only a mild (or no) euphoria, to which patients quickly become tolerate. Endorphins and enkephalins are naturally produced inside the brain. When released in the brain's reward system, they produce a mind reward and users feel good as a result. Methadone and other opiates mimic these natural brain chemicals, which is why they are so addicting.

Scientific research has shown that methadone and other opiates have specific areas, or sites, that they attach to in order to exert their influence on the brain and body. These sites, called receptors, are classified as mu, delta, and kappa, depending on what body functions they influence. Opiate activation of mu and delta receptors seems to influence mood, respiration, pain, blood pressure, and gastrointestinal functions. Kappa receptors appear to be more involved in the perception and aversion to pain. The degree of methadone's effect on these receptors can vary widely between individuals, however, there are certain effects that are almost universal.

Nausea is a side effect of all opiates. People who take opiates, including methadone, for a long period of time generally develop a tolerance for its nauseating effects. Vomiting, while common with other opiates such as heroin, is actually a rare side effect of methadone. These side effects are due to the stimulation by opiates of the part of the brain called the medulla, which controls nausea and vomiting.

Another important side effect of all opiates on the central nervous system is respiratory depression. This is caused by an inhibitory effect on the brain stem, which is the part of the brain that controls breathing and other involuntary bodily systems such as heart beat, etc. Like nausea and vomiting, people who take methadone and other opiates normally develop a tolerance to this side effect. However, even people who have taken methadone for a long period of time can develop major respiratory depression.

Cough suppression is another side effect of opiates. In fact, some opiates such as codeine are specifically marketed as cough suppressants. Other less common side effects of methadone include convulsions with very high doses, and a heavy feeling in the arms and legs. While not fully understood, it is thought that this side effect is due to the methadone causing increased blood circulation to the peripheral blood vessels of the body, especially to the arms and legs.

One of the most annoying physiological side effect of methadone use is a feeling of dryness in the mucous membranes of the mouth, eyes, and nose. This is caused by methadone reducing the secretion of saliva, tears, and mucous. Regular users of methadone refer to the dryness of the mouth as "cotton mouth," since the feeling is akin to having one's mouth stuffed full of cotton.

Methadone and all other opiates also have the unwanted physiological side effect of producing constipation. Generally, involuntary movements, or waves, of the muscles in the small and large intestines propel fecal matter through the intestines and out of the body. However, methadone and other opiates significantly slow these involuntary movements, and result in constipation. Even after long usage, many users of methadone will continue to report continued constipation.

A very visible physiological effect of methadone and all other opiates is the constriction of a person's pupils. The pupils, which are the black center of the eye, can be likened to lens on a camera. When pupils are wide open, then more light can pass through. When the pupils are constricted, very little light can pass through. Persons who are on methadone often have pupils that are quite small, making it very difficult for the person to see in anything but bright light.

There are other physiological effects of methadone for which there is no known mechanism. In women who use methadone, there can be changes seen in their menstrual cycle. It has been hypothesized that these changes are due to methadone's effect on the hormones that regulate menstruation, but this has not yet been proven.

Another side effect of methadone is a change in a user's sexual desire and function. One theory is that opiates decrease testosterone levels in both men and women; one small study of 29 methadone users found testosterone levels to be decreased by 40%. Methadone also inhibits sexual function by increasing the tone in the muscles surrounding the urethra and therefore causing a delay in orgasm in men.

It is generally thought that methadone is extremely dangerous for women who are pregnant. The fact is that there are no well-researched studies showing any adverse physiological effects for pregnant women who are using methadone for heroin withdrawal. However, while the risk for pregnant women may be minimal, there are very real physiological risks for their babies.

The first problem for the baby of a woman who is using methadone is a higher risk of low birth rate. Most studies show that babies born to women who are using methadone for heroin detoxification have a 25% greater risk of low birth weights than babies whose mothers were not using methadone. It is thought by some researchers that methadone itself somehow causes babies to be born underweight, but the majority of drug addiction specialists feel that the higher incidence of low birth weight seen among methadone users is due in fact to social factors such as poor nutrition, smoking, and poverty.

Babies who are born to mothers who are using methadone are at high risk of experiencing a syndrome known as the methadone withdrawal syndrome. This syndrome usually occurs within 48 hours of birth, but can be seen anytime during the first two weeks of birth. Symptoms are quite variable, but generally include irritability and sleep disturbances; prolonged sneezing; loud, shrill cries; watery stools; hyperactivity; poor weight gain; and aversion to bright lights.

Besides the classical withdrawal signs, there are other reported physiological problems in babies born to mothers who are using methadone. Some studies have reported that there is a higher rate of infant mortality and SIDS (sudden infant death syndrome) in babies who are born to methadone-using mothers. However, these studies were done in the 1970s, when there was a generally higher rate of infant mortality. Subsequent studies have failed to prove a definitive relationship between methadone use by pregnant women and a subsequent increase in death rates in their infant offspring.

Many physicians who do not treat opiate addicts on a regular basis believe that methadone inhibits and interferes with the functioning of a person's immune system. While it is true that some of the shorter acting opiates like heroin do inhibit a person's immune system, and thus make them more prone to infections, methadone does not inhibit the immune system. This is an important fact, especially in light of the fact that many ex-heroin users have HIV and AIDS. There are even some researchers who believe that methadone, by ways still unknown, may even help restore the functioning of the immune system in patients with HIV.

Harmful side effects

The harmful side effects of methadone, if taken in controlled conditions of a heroin detoxification program, are actually very small. The three main side effects of methadone use are tooth decay, constipation, and accidental overdose. Over half the users of methadone report problems with their teeth related to their methadone usage. Methadone use makes users more prone to tooth decay because methadone in a treatment clinic is generally given as a syrup-based mixture that has a high-sugar content, and is also acidic. Also, methadone itself inhibits the production of saliva in the mouth, which indirectly promotes the production of plaque. To help prevent tooth decay in methadone users, researchers are formulating water-based, sugar-free solutions of methadone, and promoting a low-sugar diet along with regular dental checkups for long-term users of methadone.

Chronic constipation is also another troublesome side effect of prolonged methadone use. As discussed previously, methadone significantly slows the involuntary movements of the small and large intestines. By consuming a high-fiber diet and plenty of water, chronic users of methadone can reduce, but not eliminate, the occurrence of constipation.

The third and most serious side effect of long-term methadone use is the danger of an overdose. Methadone is one of the most powerful opiates, and with its slow onset of action and long half-life, that is, the time it stays active in the body, it can cause overdose, even in chronic users. Early signs of methadone overdose include nausea and vomiting, drowsiness, reduced heart rate, and pinpoint pupils. Signs of a more severe overdose include breathlessness and convulsions, which may result in death. To help prevent a methadone overdose, people should follow the advice of the physician or treatment specialist who provides methadone to them, and they should not mix methadone with other drugs, especially tranquilizers or alcohol. All suspected cases of methadone overdose should immediately be taken to the nearest hospital emergency room.

Long-term health effects

The long-term health effects of methadone, if taken in the controlled conditions of a methadone maintenance program, are minimal. Through the study of thousands of patients, researchers have shown that while some physiological changes do occur in people taking methadone, problematic long-term health effects during prolonged treatment are very rare. In fact, the most important long-term side effect seems to be that there are significant improvements in the general health of heroin addicts who enter a methadone maintenance program.

REACTIONS WITH OTHER DRUGS OR SUBSTANCES

Methadone is mainly broken down, or metabolized, in the liver. Therefore, any other medications or substances that affect the functioning of the liver can change the rate of metabolism of methadone, either increasing or decreasing the amount in a person's bloodstream.

There are many drugs that increase the rate of the liver's metabolism. More commonly used medications that fall into this category include rifampin, which is used to treat tuberculosis, and dilantin, phenytoin, and carbamazepine, which are medications commonly used to treat seizures and epilepsy. Chronic alcohol abuse also speeds up the metabolism of the liver. Since all of these substances cause the liver to break down methadone faster then it normally would, one way to correct the problem would be to increase the dose of methadone or break down the dose into several smaller doses given throughout the day. This should only be done on a physician's advice.

Other medications that can slow down the metabolism of the liver, thereby causing a person to get a higher dose of methadone than they normally would, include Cimetidine, commonly used for upset stomachs, diazepam, a commonly used anti-anxiety medication, and fluvoxamine, a recently introduced antidepressant medication. Interestingly, alcohol, when used only occasionally, increases methadone levels as compared to decreasing methadone levels when it is used and abused on a chronic basis.

There are other well-known medications that can increase the level of a methadone in a person's bloodstream. Medications, including the common antibiotics, erythromycin and clarithromycin, along with vitamin E and the pain reliever ibuprofen, can all cause an increase in methadone levels by affecting the way methadone is carried in the bloodstream by plasma proteins. All the mentioned medications cause methadone to be "knocked away" from its plasma protein carriers, causing a great surge of methadone in the bloodstream. As with medications and substances that slow the metabolism of the liver, patients who are taking any other medications should discuss this with all the specialists involved in treating them for various problems so that they do not overdose on methadone.

Besides being affected by medications and substances that affect the liver's metabolism, methadone itself affects the liver's metabolism of certain substances. A significant number of people who are taking methadone for heroin addiction also are HIV positive and are taking anti-HIV medications such as Desipramine (DMI) and zidovudine (AZT). Through its actions on the liver, methadone decreases the metabolism of these medications. Because of this, certain troublesome side effects of DMI and AZT, including nausea, vomiting, and fatigue, can increase when a person is on both methadone and these anti-HIV medications.

TREATMENT AND REHABILITATION

Getting people off methadone, referred to as methadone detoxification, is a complex process. People who are on methadone to combat their heroin addiction often decide to stop using methadone when they and their counselors have decided that they are ready to live without drugs. However, there are times when, even though the patient is not truly ready to stop methadone, they feel they must stop for a variety of reasons such as getting a new job, moving to a new area, the societal stigma of being on methadone, or an upcoming or actual prison sentence. Whatever the reason, methadone detoxification must be done carefully.

Almost all people on methadone who decide to go off of it will have withdrawal symptoms such as anxiety, depression, nausea/vomiting, and difficulty sleeping. To help minimize these effects of methadone detoxification, a gradual reduction in the dose of methadone is done over a long period of time to help the person adjust to not having methadone in their body.

For short-term detoxification, a person would decrease and stop methadone in less then a month. It should be noted that people in short-term detoxification programs have a higher likelihood of returning to heroin abuse than do people in a long-term methadone detoxification program.

In a long-term detoxification program, people on methadone may spend up to six months gradually cutting back on the amount of methadone that they use. The entire detoxification program would take four months.

PERSONAL AND SOCIAL CONSEQUENCES

The personal and social consequences of drug abuse are wide-reaching. Consequences of drug abuse affect all people and all ages. The impact of drug abuse is a complete societal problem that leaves no person in this country, either directly or indirectly, untouched.

Opiate abuse, mainly heroin abuse, is the main reason people turn to methadone treatment programs. The consequences of opiate abuse can be staggering. People who are addicted to opiates generally have a variety of psychiatric, medical, and social problems. As compared to other persons their own age and sex, opiate addicts have a significantly higher incidence of anxiety, depression, schizophrenic-like symptoms, and other serious psychiatric disorders. Opiate abusers frequently suffer from multiple medical problems. Due to their high rate of injecting heroin to get high, opiate addicts have a very high rate of hepatitis B, hepatitis C, and HIV/AIDS.

People who are addicted to opiates also have a number of societal problems. Maintaining meaningful employment is almost impossible for a person addicted to opiates. Likewise, maintaining stable relationships or marriage, making and keeping friends, and functioning as a caring and dependable parent are almost impossible tasks for someone whose life revolves around the next high. Most opiate addicts have to steal in order to maintain their habit, so they are at very high risk of being jailed for drug-related crimes.

LEGAL CONSEQUENCES

The penalties for illegally using and distributing methadone are severe. Methadone is classified as a Schedule II substance. For illegal possession of methadone, the penalty (for first offenders) for possession of greater than 100 g is a fine of not more than four million dollars. The penalty for a second offense is a fine of no more than eight million dollars.

The penalties for trafficking illegal methadone are even more severe. For a first offense, the penalty can be up to 20 years in prison. For a second offense, the penalty can be up to 30 years in prison.

Legal history

Methadone began to be used as a treatment for heroin addiction in the 1960s. In 1963, Dr. Vincent Dole, an expert in metabolic disorders, and Dr. Marie Nyswander, a psychiatrist who had worked in the U.S. Public Health facility for heroin addicts in Lexington, Kentucky, began experimenting with several drugs to help addicts recover from their addiction. The doctors discovered that when heroin addicts were given methadone, their behavior radically changed. Suddenly, instead of focusing on getting more heroin, the focus of the addict's attention turned away from drugs and to pursuits in life they had had before they were addicted to heroin. Dr. Dole and Dr. Nyswander realized that once a heroin addict was given an adequate treatment dose of methadone, that person could remain on the same dose for a long period of time and function almost as well as they did when they were not addicts.

Within a year, Nyswander and Dole had developed a methadone maintenance treatment program. They based their program on the idea that heroin addicts suffer from a metabolic disorder much as a person with diabetes suffers from a metabolic disorder. They reasoned that just as insulin stabilizes a person with diabetes, methadone could stabilize a person with a heroin addiction. However, even though Nyswander and Dole viewed their program as a physical treatment for a physiological disorder, they also used intense psychological counseling services to help their patients get over their addiction. This new form of treatment for heroin addiction spread rapidly over the next few years, and by 1972 there were more than 800 methadone maintenance programs in the United States.

Federal guidelines, regulations, and penalties

Since the passage of the Harrison Narcotic Act in 1914 by the U.S. Congress, the federal government has been involved in the control of narcotics and the treatment of addicts. In terms of treatment of narcotic addicts, the federal government opened facilities in Lexington, Kentucky, and Fort Worth, Texas, between 1936 and 1939 to help deal with the rising number of opiate addicts in the United States.

After the development of methadone maintenance programs in the mid-1960s, the federal government, through the action of the 1966 Narcotic Addiction Rehabilitation Act, authorized the civil commitment of narcotic addicts, as well as giving federal finanical assistance to states and local authorities to develop a local system of drug treatment programs. The act required that these treatment programs include mandatory three-times-a-week counseling sessions; weekly urine tests; restorative dental services; and psychological counseling and vocational training.

In 1970, the Comprehensive Drug Abuse Prevention and Control Act was enacted into federal law. One purpose of the act was to clarify the ways in which medical personnel could legally dispense methadone to heroin addicts. In order to further clarify heroin treatment parameters, the Narcotic Addict Treatment Act of 1974 was passed, which set forth minimum standards for all methadone treatment facilities, as well as setting standard definitions for addicts. In the 1980s, these regulations were amended to allow younger patients (ages 16–18) to legally enter treatment programs. The regulations passed in the 1980s are still in effect today.

See also Heroin

RESOURCES

Books

Bray, R., and Mary Ellen Marsden. Drug Use in Metropolitan America. Thousand Oaks, CA: Sage Publications, 1997.

Lowinson, J., et al. Substance Abuse: A Comprehensive Textbook. Baltimore: Williams & Wilkins, 2001.

McDowell, D., and Henry Spitz. Substance Abuse: From Principles to Practice. Philadelphia: Taylor & Francis, 1999.

Smith, D., and Richard Seymour. Clinician's Guide to Substance Abuse. New York: McGraw Hill, 2000.

Other

"Drugs Used for the Treatment of Narcotic Addicts." Treatment Improvement Exchange. <www.treatment.org/taps/tap12/tap12part291.html>.

Federal Regulations of Drug Treatment. 1995. <http://books.nap.edu/books/0309052408/html/120.html>.

Edward R. Rosick, D.O., M.P.H.

Methadone

Definition

Methadone is a powerful narcotic drug in the same class as heroin. This class is known as the opioids.

Purpose

Methadone, formerly known as dolophine, is a psycho-active drug, meaning that it affects the mind or behavior. It belongs to the class of opioids, drugs that share some of the analgesic properties, and mimic the action of some of the body's naturally occurring chemicals called peptides, such as endorphins and enkephalines.

Methadone is used to relieve chronic pain in cancer patients and as a maintenance drug to control withdrawal symptoms in people undergoing treatment for opiate addiction.

In opiate addiction treatment, methadone blocks the opioid receptors of the brain that bind opiates such as heroin. The blocking of these receptors leads to two major effects:

• because these chemical receptors remain blocked by methadone for up to 24 hours, even if a person addicted to heroin takes heroin after the administration of methadone, this person is not likely to feel the same effects of the heroin as he or she previously felt;
• because the action of methadone is associated with slower and less intense withdrawal symptoms than those of heroin, the patient can experience milder opiate effects while the addiction is being treated and avoid the unpleasant withdrawal symptoms associated with heroin.

Methadone has also been shown to reduce cravings for heroin while not altering a person's mood.

Precautions

Methadone magnifies the effects of alcohol and other central nervous system depressants, such as antihistamines, cold medicines, sedatives, tranquilizers, other prescription and over-the-counter (OTC) pain medications, barbiturates, seizure medications, muscle relaxants, and certain anesthetics including some dental anesthetics. Alcohol and other central nervous system depressants should not be taken or consumed while methadone is being taken.

Methadone is a powerful narcotic. It can cause some people to feel drowsy, dizzy, or light-headed. People taking methadone should not drive a car or operate machinery.

Intentional or accidental overdose of methadone can lead to unconsciousness, coma, or death. The signs of methadone overdose include confusion, difficulty speaking, seizures, severe nervousness or restlessness, severe dizziness, severe drowsiness, and/or slow or troubled breathing. These symptoms are increased by alcohol or other central nervous system (CNS) depressants. Anyone who feels that he or she, or someone else, may have overdosed on methadone, or a combination of methadone and other central nervous system depressants, should seek emergency medical attention for that person at once.

Description

A typical adult dosage for methadone is 5-20 mg as an oral solution, 2.5-10 mg as an oral tablet or injection, every four to eight hours as necessary for pain. When used for detoxification, methadone is initially given in a dose of 15-100 mg per day as an oral solution. This dose is then decreased until the patient no longer requires the medication. The injection form of methadone is only used for detoxification in patients who are unable to take the medication by mouth.

Preparation

No preparation is generally necessary prior to the intake of methadone as a pain reliever. In cases of maintenance treatments, it is important to be sure that the patient is not currently intoxicated by alcohol, heroin, other opioids, or taking other central nervous system depressants.

Aftercare

Patients receiving methadone should be monitored for adverse reactions to this drug, and/or possible accidental overdose.

Risks

Methadone can interfere with or exacerbate certain medical conditions. For these reasons, it is important that the prescribing physician be informed of any current case, or history of:

• alcohol abuse
• brain disease or head injury
• colitis
• drug dependency, particularly of narcotics
• emotional problems
• emphysema, asthma, or other chronic lung disease
• enlarged prostate
• gallstones or gallbladder disease
• heart disease
• kidney disease
• liver disease
• problems with urination
• seizures
• underactive thyroid

Side effects

The most common side effects of methadone include:

• constipation
• dizziness

• drowsiness
• itching
• nausea
• urine retention
• vomiting

Less common side effects of methadone include:

• abnormally fast or slow heartbeat
• blurred or double vision
• cold, clammy skin
• depression or other mood changes
• dry mouth
• fainting
• hallucinations
• hives
• loss of appetite
• nightmares or unusual dreams
• pinpoint pupils of the eyes
• redness or flushing of the face
• restlessness
• rigid muscles
• ringing or buzzing in the ears
• seizure
• severe drowsiness
• skin reaction at the site of injection
• stomach cramps or pain
• sweating
• trouble sleeping (insomnia)
• yellowing of the skin or whites of the eyes

Normal results

Normal results after the administration of methadone to treat chronic pain is the alleviation of that patient's pain, at least to the point where the pain is bearable.

Normal results of methadone treatment to control heroin addiction, is that the patient reduces heroin intake almost immediately upon starting methadone treatments, followed by complete abstinence, usually within two weeks after starting treatment.

KEY TERMS

Analgesic— Any agent that relieves pain.

Central nervous system (CNS) depressant— Any drug that tends to reduce the activity of the central nervous system. The major drug categories included in this classification are: alcohol, anesthetics, anti-anxiety medications, antihistamines, antipsychotics, hypnotics, narcotics, sedatives, and tranquilizers.

Endorphins— Any of several opiate peptides naturally produced in the brain that bind to certain neuron receptors and have the effect of relieving pain.

Enkephalines— Peptide produced by the body that have analgesic properties.

Morphine— Morphine is the naturally occurring opioid in the opium poppy, Papaver somniferum. It is a powerful narcotic analgesic, and its primary clinical use is in the management of moderately severe to severe pain. After heroin, morphine has the greatest potential for addiction of all narcotic analgesics.

Narcotic— Any drug that produces insensibility or stupor and/or generally causes effects similar to those caused by morphine.

Opiate— Any narcotic analgesic derived from a natural source, such as morphine from the opium poppy.

Opioid receptors— Receptors located in the brain and various organs that bind opiates or opioid substances.

Opioids— One of the major classes of semi or fully synthetic psycho-active drugs that includes methadone.

Psychoactive drugs— Any drug that affects the mind or behavior. There are five main classes of psychoactive drugs: opiates and opioids (e.g. heroin and methadone); stimulants (e.g. cocaine, nicotine), depressants (e.g. tranquilizers, antipsychotics, alcohol), hallucinogens (e.g. LSD), and marijuana and hashish.

Receptor— A molecular structure on the surface that selectively binds a specific substance resulting in a specific physiological effect.

Resources

PERIODICALS

Sadovsky, Richard. "Methadone Maintenance Therapy." American Family Physician July 15, 2000.

ORGANIZATIONS

National Alliance of Methadone Advocates (NAMA). 435 Second Avenue, New York, NY, 10010. (212) 595-6262. 〈http://www.methadone.org/〉.

National Clearinghouse for Alcohol and Drug Information. 11426-28 Rockville Pike, Suite 200, Rockville, MD 20852. (800) 729-6686. 〈http://www.health.org/〉.

Methadone

Definition

Purpose

Description

Recommended dosage

Precautions

Side effects

Interactions

Resources

Definition

Methadone is classified as an opioid (an analgesic that is used for severe pain). In the United States, methadone is also known as dolophine, methenex and methadose.

Purpose

Methadone is used in the long-term maintenance treatment of narcotic addiction . Both heroin and methadone are opioids ; as such, methadone and heroin bind to the same places in the brain . Methadone, however, is the opioid of choice for the treatment of narcotic addiction since it is longer lasting and patients don’t experience the “high” associated with the drug of abuse . In opioid maintenance therapy, a person addicted to heroin receives methadone instead of heroin. Essentially, the person is switched from an opioid that gives a “high” to an opioid that does not. The dose of methadone may then be decreased over time so that the person can overcome his or her opioid addiction without experiencing withdrawal symptoms, or, after a person has received methadone for a period of time, he or she may choose to go through detoxification with clonidine . In the United States, methadone treatment is associated with a significant reduction in predatory crime, improvement in socially acceptable behavior and psychological well-being.

Methadone may also be prescribed for pain relief, but in these cases, the physician must note this use on the prescription.

Description

Methadone has been used successfully to treat narcotic addiction for over twenty years in the United States. Methadone is the only FDA-approved agent in its class for the maintenance treatment of narcotic addiction.

Methadone for maintenance treatment is dispensed in methadone clinics. The program needs to be registered with the Drug Enforcement Agency. For admission to methadone treatment in clinical programs, federal standards mandate a minimum of one

year of opiate addiction as well as current evidence of addiction. Pregnant, opiate-addicted females can be admitted with less than a one-year history and AIDS patients are routinely accepted. New patients must report daily, take medication under observation, and participate in recommended psychosocial treatments.

Some studies have shown that more than 50% of patients in methadone clinics do not abuse drugs in the first month of treatment. After ten months, however, the success rate drops to approximately 20%. Moreover, major depression is a powerful predictor of relapse in methadone treatment. If the patient has dual addictions (alcoholism along with the heroin addiction, for example), management of the other addiction increases the success rate of the methadone therapy. Proper psychiatric and psychological treatment can considerably improve methadone treatment outcome.

In the cases of pregnant women who are addicted to heroin, detoxification (discontinuing the opioid altogether) is associated with a high rate of spontaneous abortions in the first trimester and premature delivery in the third trimester. Therefore, pregnant women can be in methadone maintenance programs if they are at risk of returning to drug dependence. These women should receive the lowest effective dose, receive appropriate prenatal care, and be warned about risks of returning to drug abuse, as well as the dangers associated with withdrawal effects of metha-done. Methadone is associated with lower birth weights and smaller head circumference, but it has never been shown that this has any impact on the infants’ further development.

Methadone is available in 5-, 10-, and 40-mg tablets and a solution.

Recommended dosage

The initial dose of methadone is 20 mg daily with additional 10 mg given four to eight hours later. After achieving initial dosing of about 40 mg daily, the dose should be increased since there is evidence that the relapse rate is significantly lower in patients on 80-100 mg daily rather than 40-50 mg daily. The stabilization to maintenance dosing requires one to three months.

The minimum effective dose is 60 mg daily. Patients on lower maintenance doses have recently been studied and have shown shorter treatment retention and have continued heroin use. If patients are stable on methadone for six months or longer, their methadone dose should not be increased by 33% or over, as this sudden increase in dose is associated with an increase in craving for the drugs that were previously abused. Some heroin patients need to be on doses up to 180 mg daily to provide adequate maintenance and to prevent relapse.

Precautions

Methadone should not be used in patients who have had hypersensitivity to methadone. Patients who experience an allergic reaction to other opioids, which may include a generalized rash or shortness of breath, such as morphine, hydromorphone, oxymorphone, or codeine may try methadone. They are less likely to develop the same reaction since methadone has a different chemical structure. Methadone should be administered carefully in patients with pre-existing respiratory problems, history of bowel obstruction, glaucoma, renal problems, and hyperthyroidism.

As stated, pregnant women can be in methadone maintenance programs if they are at risk of returning to drug dependence. Methadone is associated with smaller birth weights and smaller head circumference.

KEY TERMS

Benzodiazepines —A group of central nervous system depressants used to relieve anxiety or to induce sleep.

Glaucoma —A group of eye diseases characterized by increased pressure within the eye significant enough to damage eye tissue and structures. If untreated, glaucoma results in blindness.

Maintenance treatment —The period of treatment beginning after the initial introduction of the treatment medication. During this period, the dose of medication can be either increased or decreased, depending on the program and needs of the patient.

MAO inhibitors —A group of antidepressant drugs that decrease the activity of monoamine oxidase, a neurotransmitter found in the brain that affects mood.

Naloxone —A drug that combines competitively with opiate receptors on the nerve cells and blocks or reverses the action of narcotic analgesics.

Neurotransmitter —A chemical in the brain that transmits messages between neurons, or nerve cells.

Side effects

Most adverse effects of methadone are mild and seen only in the beginning of therapy. Initially patients may develop sedation and analgesia. It takes about four to six weeks for tolerance to these effects to develop. Tolerance to constipation and sweating may take longer to develop.

A few patients who are on larger doses of methadone may experience respiratory problems. These patients also may experience unwanted cardiac effects.

A small number of patients report a decrease in libido, impotence, and premature, delayed, or failed ejaculation. There are a few reports of occasional menstrual irregularities in female patients on methadone.

Interactions

Life-threatening interactions with other drugs have not been identified. One of the initial side effects of methadone could include dizziness and sedation, and these effects are worsened if the patient is also taking other narcotics, benzodiazepines , or is consuming alcohol.

Monoamine oxidase inhibitors (MAOIs), such as Parnate (tranylcypromine ) and Nardil (phenelzine ), should be avoided by people taking methadone. Medications such as naltrexone and naloxone should never be used concurrently with methadone. People must stop taking methadone for seven to 10 days before starting naltrexone or naloxone.

See alsoAlcohol and related disorders; Decrease concept of chemical dependency; Opioids and related disorders.

Resources

BOOKS

Albers, Lawrence J., M.D., Rhoda K. Hahn, M.D., and Christopher Reist, M.D. Handbook of Psychiatric Drugs. 2001–2002. Laguna Hills, CA: Current Clinical Strategies Publishing, 2001.

Kay, Jerald. Psychiatry: Behavioral Science and Clinical Essentials. Philadelphia: W. B. Saunders Company, 2000.

PERIODICALS

Curran, Valarie H. “Additional Methadone Increases Craving for Heroin: A Double-Blind, Placebo-Controlled Study of Chronic Opiate Users Receiving Methadone Substitution Treatment.” Addiction 94 (1999): 665-74.

Strain, Eric. “Moderate-vs High-Dose Methadone in the Treatment of Opioid Dependence.” Journal of the American Medical Association281 (1999): 1000-5.

Ajna Hamidovic, Pharm.D.

Methadone

Definition

Methadone is classified as an opioid (an analgesic that is used for severe pain). In the United States, methadone is also known as dolophine, methenex and methadose.

Purpose

Methadone is used in the long-term maintenance treatment of narcotic addiction . Both heroin and methadone are opioids; as such, methadone and heroin bind to the same places in the brain . Methadone, however, is the opioid of choice for the treatment of narcotic addiction since it is longer lasting and patients don't experience the "high" associated with the drug of abuse. In opioid maintenance therapy, a person addicted to heroin receives methadone instead of heroin. Essentially, the person is switched from an opioid that gives a "high" to an opioid that does not. The dose of methadone may then be decreased over time so that the person can overcome his or her opioid addiction without experiencing withdrawal symptoms, or, after a person has received methadone for a period of time, he or she may choose to go through detoxification with clonidine . In the United States, methadone treatment is associated with a significant reduction in predatory crime, improvement in socially acceptable behavior, and psychological well-being.

Methadone may also be prescribed for pain relief, but in these cases, the physician must note this use on the prescription.

Description

Methadone has been used successfully to treat narcotic addiction for over twenty years in the United States. Methadone is the only FDA-approved agent in its class for the maintenance treatment of narcotic addiction.

Methadone for maintenance treatment is dispensed in methadone clinics. The program needs to be registered with the Drug Enforcement Agency. For admission to methadone treatment in clinical programs, federal standards mandate a minimum of one year of opiate addiction as well as current evidence of addiction. Pregnant, opiate-addicted females can be admitted with less than a one-year history and AIDS patients are routinely accepted. New patients must report daily, take medication under observation, and participate in recommended psychosocial treatments.

Some studies have shown that over 50% of patients in methadone clinics do not abuse drugs in the first month of treatment. After ten months, however, the success rate drops to approximately 20%. Moreover, major depression is a powerful predictor of relapse in methadone treatment. If the patient has dual addictions (alcoholism along with the heroin addiction, for example), management of the other addiction increases the success rate of the methadone therapy. Proper psychiatric and psychological treatment can considerably improve methadone treatment outcome.

In the cases of pregnant women who are addicted to heroin, detoxification (discontinuing the opioid altogether) is associated with a high rate of spontaneous abortions in the first trimester and premature delivery in the third trimester. Therefore, pregnant women can be in methadone maintenance programs if they are at risk of returning to drug dependence. These women should receive the lowest effective dose, receive appropriate prenatal care, and be warned about risks of returning to drug abuse, as well as the dangers associated with withdrawal effects of methadone. Methadone is associated with lower birth weights and smaller head circumference, but it has never been shown that this has any impact on the infants' further development.

Methadone is available in 5-, 10-, and 40-mg tablets and a solution.

Recommended dosage

The initial dose of methadone is 40 mg daily administered in single or divided doses. After achieving initial dosing of about 40 mg daily, the dose should be increased since there is evidence that the relapse rate is significantly lower in patients on 80-100 mg daily rather than 40-50 mg daily. The stabilization to maintenance dosing requires one to three months.

The minimum effective dose is 60 mg daily taken at once or in divided doses. Patients on lower maintenance doses have recently been studied and have shown shorter treatment retention and have continued heroin use. If patients are stable on methadone for six months or longer, their methadone dose should not be increased by 33% or over, as this sudden increase in dose is associated with an increase in craving for the drugs that were previously abused. Some heroin patients need to be on doses up to 180 mg daily to provide adequate maintenance and to prevent relapse.

Precautions

Methadone should not be used in patients who have had hypersensitivity to methadone. Patients who experience an allergic reaction to other opioids, which may include a generalized rash or shortness of breath, such as morphine, hydromorphone, oxymorphone, or codeine may try methadone. They are less likely to develop the same reaction since methadone has a different chemical structure. Methadone should be administered carefully in patients with pre-existing respiratory problems, history of bowel obstruction, glaucoma, renal problems, and hyperthyroidism.

As stated, pregnant women can be in methadone maintenance programs if they are at risk of returning to drug dependence. Methadone is associated with smaller birth weights and smaller head circumference.

Side effects

Most adverse effects of methadone are mild and seen only in the beginning of therapy. Initially, patients may develop sedation and analgesia. It takes about four to six weeks for tolerance to these effects to develop. Tolerance to constipation and sweating may take longer to develop.

A few patients who are on larger doses of methadone may experience respiratory problems. These patients also may experience unwanted cardiac effects.

A small number of patients report a decrease in libido, impotence, and premature, delayed, or failed ejaculation. There are a few reports of occasional menstrual irregularities in female patients on methadone.

Interactions

Life-threatening interactions with other drugs have not been identified. One of the initial side effects of methadone could include dizziness and sedation, and these effects are worsened if the patient is also taking other narcotics, benzodiazepines, or is consuming alcohol.

Monoamine oxidase inhibitors (MAOIs), such as Parnate (tranylcypromine ) and Nardil (phenelzine ), should be avoided by people taking methadone. Medications such as naltrexone and naloxone should never be used concurrently with methadone. People must stop taking methadone for seven to 10 days before starting naltrexone or naloxone.

See also Alcohol and related disorders; Disease concept of chemical dependency; Opioids and related disorders

Resources

BOOKS

Albers, Lawrence J., M.D., Rhoda K. Hahn, M.D., and Christopher Reist, M.D. Handbook of Psychiatric Drugs. 2001–2002. Laguna Hills, CA: Current Clinical Strategies Publishing, 2001.

Kay, Jerald. Psychiatry: Behavioral Science and Clinical Essentials. Philadelphia: W. B. Saunders Company, 2000.

PERIODICALS

Curran, Valarie H. "Additional Methadone Increases Craving for Heroin: A Double-Blind, Placebo-Controlled Study of Chronic Opiate Users Receiving Methadone Substitution Treatment." Addiction 94 (1999):665-74.

Strain, Eric. "Moderate-vs High-Dose Methadone in the Treatment of Opioid Dependence." Journal of the American Medical Association 281 (1999):1000-5.

Ajna Hamidovic, Pharm.D.