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Buprenorphine: A New Tool in the Arsenal

Addiction to heroin and other opiates is a difficult disease to treat, due both to changes in brain chemistry that occur when the drugs are taken and to physical symptoms of withdrawal that occur when the drugs are stopped. The challenges of overcoming opiate addiction are exacerbated by the limited number of treatment slots available. And because of the highly regulated environment of opioid treatment, it has been mainly outside the realm of the primary care community—at least until now.

The principal medical treatment for opiate addiction in the United States is methadone, which must be administered at one of the Nation’s opioid treatment programs. There are 1,200 such programs nationally, but they have less than 20 percent of the needed treatment slots and treat only about 200,000 individuals per year. Individuals wishing to access treatment will find few programs in rural areas, and five States have none at all.1 Other barriers exist. For example, people newly admitted into treatment must visit the program site daily for the first few months, a requirement that can result in severe disruption to work and life and compound the effects of barriers to care such as poor transportation and lack of child care.

In October 2002, the Food and Drug Administration changed the landscape of addiction treatment by approving buprenorphine (byoo-pre-NOR-feen), the first medication for opiate dependence that can be prescribed in a primary care setting. This office-based approach was authorized by the Drug Addiction Treatment Act of 2000 (DATA 2000), which applies to certain controlled medications that may be useful in treating addiction.2 Buprenorphine, an opiate itself, is the first medication approved under DATA 2000 to treat the symptoms of withdrawal and block opioid craving. With buprenorphine, long waits for a methadone clinic slot and daily trips for treatment are no longer the only option for addicts seeking care. By increasing the potential number of treatment slots and allowing up to a month’s supply of the medication to be prescribed at once, this new approach to addiction therapy offers improved access to care for people addicted to opiates.

Opiate Use in the United States

Opiates, or opioids, are a class of drugs similar in chemical structure and effect to opium, a derivative of the Papaver somniferum (poppy) plant.3 The human body manufactures its own opiates as endorphins, enkephalins, and dynorphins. These chemicals work by activating opiate receptors located in the brain, spinal cord, and gastrointestinal tract. Exogenous opiates—those from outside the human body—work on the same receptors.

Opiates were used as early as 6,000 years ago for pain control as well as for their ability to produce euphoria. They continue to be used for the same reasons today, but when abused can be dangerous and even fatal. High doses can lead to confusion, hallucinations, and coma. Excessive doses can cause breathing to stop and—without immediate intervention—result in death.

The most common opiates used today include codeine, fentanyl, heroin, hydromorphone (Dilaudid), methadone, morphine, and oxycodone (OxyContin, Percocet). Opiates are used in the medical arena primarily for pain control, but they have a long history of recreational (i.e., nonmedical) use among Americans from all socioeconomic groups.4 More than 2.5 million people use prescription opiates—primarily oxycodone and hydromorphone—for nonmedical purposes each year.5,6 Three million people older than age 12 have used heroin at least once, and between 166,000 and 403,000 people use it annually.7,8

Opiate Abuse and HIV

The relationship between drug abuse and HIV/AIDS is complex. First, injection drug use is not the only way in which drugs contribute to the AIDS epidemic. Drugs taken by any route can affect sexual decision-making and lead to transmission.9 Second, not only heroin,10 but also other opiates, cocaine, amphetamines, and sedatives all may be abused through injection and spread HIV infection among those who share paraphernalia. Much remains to be learned about the specific role heroin and other opiates play in the spread of HIV, but the important lesson is that many HIV-positive injection drug users often became infected while “answering their drug hunger” and sharing syringes and paraphernalia, according to Terry Horton, M.D., Medical Director and Vice President of Phoenix House, a program that treats addicted patients in 10 States.

No one can precisely quantify the overlap between opiate addiction and HIV infection. Injection drug use was the HIV transmission category in approximately 26 percent of AIDS cases reported among adolescents and adults in 2001. The exposure category men who have sex with men and inject drugs accounted for another 5 percent of cases; heterosexual contact with an injection drug user accounted for an additional 6 percent.11 Given the number of cases for which an exposure category has not been reported and the relationship between the use of noninjected substances and HIV transmission, these numbers likely underestimate the number of HIV infections in which substance abuse played a role. Although not all abused substances are opiates, given that they are the most commonly injected drugs, the overlap between opiate use and HIV is clearly significant.

Addiction Treatment and HIV/AIDS Care

Opiate addiction poses serious problems for people living with HIV disease as well as serious challenges for their care providers. Addiction severely limits daily function and poses health risks, apart from the effects of HIV. Addiction can increase the already daunting challenges of staying in care, navigating the fragmented health care and social services networks, and adhering to treatment regimens. The challenge of providing care to these dually diagnosed patients may be even more frustrating because of the inadequate number of treatment slots for addiction. In addition, up to now, the segregation of substance abuse treatment from primary care in the United States has challenged the dream of a truly seamless, effective, comprehensive care system.

For AIDS service organizations (ASOs), buprenorphine may prove to be a vital addition to a comprehensive treatment program. ASOs are ideal venues for treating HIV-infected people who are addicted to opiates because most of them already offer the mental health and social services essential to good addiction care. With buprenorphine, clients can receive coordinated HIV/AIDS care and addiction treatment in a single setting.

According to Dr. Horton, “substance abuse is a root cause of HIV [and] doctors must tend to the root cause.” He says that treatment can help people end high-risk behaviors that cause HIV transmission, thereby reducing the rate of HIV seroconversion among HIV-negative addicted patients.12,13 For the thousands of opiate-addicted patients already infected with HIV, effective addiction therapy should enhance comprehensive HIV/ AIDS primary care. According to Dr. Horton, HIV-positive addicted patients who are treated for substance abuse are more likely than those who are not to adhere to their HIV treatment regimens.

Research shows that buprenorphine is safe and effective in treating opiate abuse, and many physicians report good results in their patients. A multicenter study at several Department of Veterans Affairs (VA) Medical Centers, for example, demonstrated that the drug effectively reduced opiate cravings and abuse among participants.14 One of the study’s lead investigators was Laura McNicholas, M.D., Ph.D., Director of the VA Center for Excellence for Substance Abuse Treatment and Education and a psychiatrist at the Philadelphia VA Medical Center and the University of Pennsylvania. She observes that the VA has an extensive program for treating opiate-addicted veterans, but the increased prevalence of addiction has overwhelmed its resources and many clinics have long waiting lists. According to McNicholas, results from the VA’s buprenorphine trials are very encouraging: Participants had an “unbelievably good response.” Buprenorphine is “a very, very, very good option for a large number of opiate dependent patients,” she adds.

Other physicians have offered similarly positive experiences, some observing that addicted patients function better on buprenorphine than on methadone, which can cause sedation if inappropriately dosed. Dr. Horton noted how “remarkably lucid” his Phoenix House patients become once they start buprenorphine. He says that they are alert enough to participate actively in the program and engage in the community at large, critical goals of addiction therapy. And David A. Fiellin, M.D., a doctor at Yale and Chair of the American Society of Addiction Medicine’s Buprenorphine Training Subcommittee, found similar results, noting that, “patients on buprenorphine report they feel normal again.”

According to Yale’s Lynn Sullivan, M.D., buprenorphine helps addicts “stabilize and organize their often very chaotic lives.” She says that the drug can have dramatic effects on daily functioning and noted that HIV-positive addicts who take buprenorphine also do “a lot better in terms of their HIV.”

Buprenorphine Treatment Approaches

Buprenorphine is a new therapy in the United States, and many of the clinicians using it so far have been involved in the clinical trials that found that it safe and effective. Its potential is beginning to stir interest among AIDS service providers who recognize how important addiction treatment is for many of their clients. The HIV/AIDS Bureau (HAB) staff has undertaken several projects related to this new medication. At its annual clinical conference in Orlando, Florida, in June 2003, in collaboration with the Substance Abuse and Mental Health Services Administration and the American Osteopathic Association of Addictive Medicine, the agency sponsored training to qualify doctors to prescribe buprenorphine. HAB is currently planning a meeting in which experts in HIV, substance abuse, mental health, and primary care will discuss how to expand buprenorphine use in HIV treatment settings. Finally, the Special Projects of National Significance (SPNS) staff intends to develop a new initiative for fiscal year 2005 that would examine model demonstration projects for integrating buprenorphine treatment into HIV primary care settings.

ASOs that provide treatment to addicted patients may have at their disposal a variety of models for providing addiction care according to the severity of the addictive disorder. Whichever approach is taken, treatment should be offered as part of a multidisciplinary approach that may include mental health and social services, as appropriate. Several models for buprenorphine treatment—medical withdrawal or detoxification (“detox”) and maintenance therapy—are highlighted on page 5.

The preferred and recommended model is to offer maintenance therapy with buprenorphine. The early stage of treatment, when the illicit substance is stopped and opiate replacement medication is initiated, carries the risk of withdrawal. This induction stage requires close monitoring to find the correct maintenance dose and keep the patient safe. Once a patient is on a stable dose, ongoing medical management is typically less difficult. Doctors at both Montefiore Medical Center and Yale offer maintenance therapy with buprenorphine, and they have developed useful approaches for ensuring patient safety and treatment effectiveness.

Montefiore, for example, operates a number of Federal Community Health Centers (CHCs) that offer primary care to a population that includes many opiate addicts. Marc N. Gourevitch, M.D., M.P.H., an addiction specialist at Montefiore and Albert Einstein College of Medicine, says that during the “earlier, trickier phase of starting buprenorphine,” CHC doctors may collaborate with staff at methadone clinics operated by Montefiore and Einstein. Once patients are stable, the CHC physicians can provide ongoing care with buprenorphine.

At Yale, Dr. Sullivan is designing a protocol to provide comprehensive medical care to HIV-positive opiate addicts. She recommends “mentored clinical experience” with a knowledgeable colleague as a way for physicians who lack experience to gain proficiency in treating addiction. She herself learned to treat addiction by working with her colleague Dr. Fiellin, who is an expert on addiction therapy and the author of some of the leading articles on buprenorphine.

Meanwhile, Dr. Fiellin is conducting research to determine the optimal level of mental health and social services for addicts on buprenorphine. He says that private physicians must select patients carefully and focus on those with limited psychiatric comorbidity. Addicts with serious psychiatric disorders require intensive services beyond what most community physicians can provide and should be treated in specialized settings.

One of these settings may be a residential facility such as Phoenix House. Before buprenorphine was available, Phoenix House offered a program of in-hospital medical withdrawal or detoxification followed by residential treatment. But it was so difficult for patients to negotiate the “chasm of withdrawal,” Dr. Horton found, that retention was poor. Most patients experienced significant withdrawal symptoms and dropped out before starting residential treatment; many who made it as far as treatment left, also due to protracted withdrawal symptoms. This “chasm” disappeared when the program launched a new approach, in which addicted patients start with buprenorphine detox in the residential setting in which they live for the duration of the 1- to 2-year program. Following detox, clients receive no further opiates. Residential treatment includes drug abuse counseling, education, and job training as well as psychiatric and medical treatment. For those who need it, HIV care is provided as well.

Dr. Horton reports that while the number of Phoenix House patients treated with buprenorphine so far is small, only 13 percent of those prescribed the drug have dropped out of detox. Some patients experience nausea or malaise for about 36 hours after their final buprenorphine dose, but most still manage to complete detox. Historically, detox has enjoyed only marginal success in keeping addicts off illicit opiates, Dr. Horton notes. It is too early to know how many addicts will complete the full program and remain drug-free, but he is optimistic that buprenorphine will help his patients undergo “core behavioral changes” and become “tax-paying, employed, sober citizens.”

Barriers to Treatment

DATA 2000 spells out certain rules and requirements for physicians who want to treat opiate addiction in their offices and clinics.15 For example, they must receive 8 hours of special training (a list of DATA 2000–qualifying physician trainings is maintained at Physicians must also apply for a special license and be able to refer patients for psychosocial services, as needed. More fundamentally, most physicians lack experience treating addiction, and as of this writing, guidelines have not yet been published.

According to unofficial reports, about 3,000 doctors have been trained to use buprenorphine, but only 1,000 have prescribed. Vigorous efforts are underway to train more physicians. Thus far, however, doctors have not been enrolling in numbers large enough to meet the need, according to Montefiore’s Gourevitch. He is hopeful, however, that more community physicians will embrace buprenorphine when they realize that “opiate addiction is now a medical disease that they can address.” Ongoing research provides insights into physician perspectives on addiction treatment. In a study sponsored by the Maryland State Medical Society, Yngvild Olsen, M.D., of Johns Hopkins University, is investigating the willingness of physicians to use buprenorphine. Preliminary results indicate that physicians view buprenorphine as a valuable tool but want to learn more about it. They also expressed the need for more counseling resources and a system for networking with peers who have experience in addiction therapy.

A potential barrier to making buprenorphine available to some patients is that physicians—whether working as solo practitioners, within a clinic, or as part of a large medical group—are permitted to treat no more than 30 patients with an opiate replacement medication at a time. In-office treatment for opiate addiction is new, so the 30-patient limit may yet to have much practical effect. The 30-patient limit could become a problem in communities with limited access to medical care and large physician group practices.

In fact, one major group practice already has voiced concerns about the 30-patient cutoff. Kaiser Permanente, the country’s largest nonprofit health plan, is organized as eight medical groups serving a total of 8.1 million members. Each group can treat a maximum of 30 patients for opiate addiction. Steve Cole, Kaiser’s Director of Public Policy and Government Relations, is working to overturn the limit. “The law treats our medical groups—the largest of which has 3,500 physicians—the same way it treats a two-person practice. It restricts our ability to treat patients,” he said.

John Avery, Director of Public Policy for the National Association of Drug and Alcohol Abuse Counselors, expresses a similar concern: “From a health care standpoint, if someone specializes in addiction, you shouldn’t limit his or her practice.”

The cap could also prove problematic for veterans. According to Dr. McNicholas, the VA treats addicts in 38 opiate replacement programs that together maintain 4,234 slots. Although the total number of veterans with opiate addiction is unknown, nearly 22,600 people diagnosed with opiate dependence were treated in VA substance abuse settings in 2000. For VA facilities, the 30-patient limit applies to each doctor, rather than to the system. Still, according to Dr. McNicholas, because a limited number of VA doctors treat addiction, the cap could become a hindrance.


Buprenorphine offers both a safe alternative to methadone and the opportunity to treat hundreds of thousands of opiate addicted patients in the primary care setting. For HIV/AIDS clinical care providers, buprenorphine is an important new tool that has the potential to reduce the number of new HIV infections and treat the full spectrum of disease of our growing population of opiate addicts with HIV. For addicted patients themselves, buprenorphine offers a route out of addiction and the possibility of a getting on with a normal life. As Dr. Sullivan says, once addicts are treated, they can “start creating their lives.”


1 Clark HW. Office-based practices and opioid-use disorder. N Engl J Med. 2003;349(10):928-31.
2 U.S. Food and Drug Administration. Subutex and Suboxone approved to treat opiate dependence. FDA Talk Paper. 2002. Available at:
3 Rehman Z, Khoromi S, Douglas JE. Opioid abuse. March 2003. Available at:
4 Fiellin DA, Rosenheck RA, Kosten TR. Office-based treatment for opioid dependence: reaching new patient populations. Am J Psychiatry. 2001;158(8):1200-04.
5 National Institute of Drug Abuse. Research Report Series—Prescription Drugs: Abuse and Addiction. Available at:
6 National Institute on Drug Abuse. NIDA InfoFacts. Available at: nationtrends.htm.
7 Schoener EP, Hopper JA, Pierre JD. Injection drug use in North America. Infect Dis Clin N Am. 2002;16(3):535-51.
8 Substance Abuse and Mental Health Services Administration, Office of Applied Studies. Overview of Findings from the 2002 National Survey on Drug Use and Health.NHSDA Series H-21, DHHS Pub. No. SMA 03–3774. Rockville, MD: Author; 2003. Available at: 2k2nsduh/Overview/2k2Overview.htm.
9 Schoener EP, Hopper JA, Pierre JD. Injection drug use in North America. Infect Dis Clin N Am. 2002;16(3):535-51.
10 Substance Abuse and Mental Health Services Administration, Office of Applied Studies. Treatment Episode Data Set. 1998. Available at:
11 Centers for Disease Control and Prevention. HIV/AIDS Surveillance Report. 2001;13(2):31-2. Tables 22 and 23.
12 Comacho LM, Bartholomew NG, Joe GW, et al. Maintenance of HIV risk reduction among injection opioid users: a 12 month post treatment follow-up. Drug Alcohol Depend. 1997;47(1):11-8.
13 Fiellin DA, O’Connor PG. Office-based treatment of opioid-dependent patients. N Engl J Med. 2002;347(11):817-23.
14 Fudala PJ, Bridge P, Herbert S. Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone. N Engl J Med. 2003;349(10):949-58.
15 Fiellin and O’Connor, 2002.


A Primer on Opiate Addiction

What Is Opiate Addiction?

Addiction—the inability to control drug use—can result from sustained use of heroin or another drug. Research suggests that addiction is rooted in an interplay of genetic, chemical, and physiologic factors. Compared with other drugs of abuse, the chemical properties of opiates play a larger role in addiction than do genetics and psychosocial factors. Opiates induce euphoria and produce changes in brain chemistry that reinforce the user’s urge to use the drugs. Dependence is established quickly. Most addicts who try to decrease or stop opiate use experience protracted withdrawal.

Alan Leshner, former Director of the National Institute on Drug Abuse (NIDA) at the National Institutes of Health, considers addiction a neurological disease, not “a voluntary behavior.” According to Leshner, drugs like heroin “‘highjack’ the brain’s normal pleasure and motivational systems, moving drug use to the highest priority in the individual’s motivational hierarchy. . . These brain changes, then, are responsible for the compulsion to seek and use drugs that we have come to define as addiction.”1 Addiction is “more than just a lot of drug use,” he noted. Rather, it is “a state of compulsive, uncontrollable drug use” that becomes the center of the user’s life, “even in the face of negative social consequences or health consequences.”2

Standard Treatment

Methadone, long the drug of choice to treat opiate addiction, is administered through detoxification (“detox”) and maintenance therapy. With detox, methadone is used briefly, and then all opiates are discontinued, whereas in maintenance therapy, methadone is continued indefinitely. Although some experts object to maintenance therapy because it continues addicts on an opiate, this approach has proven more effective than detox in keeping addicts from using illegal substances.3

The use of a legal opiate to substitute for an illicit opiate is based on the principle of cross-tolerance: The legal medication occupies receptors previously occupied by the illicit opiate, thereby preventing withdrawal.4 Methadone therapy is thought to reduce drug craving by supplying a chemical that is needed by brains altered through addiction, much as insulin therapy reduces high blood sugar levels by supplying a chemical needed by people with diabetes. Because methadone is long acting and taken orally, it usually engenders less euphoria than heroin and other short-acting opiates do, thus allowing addicts to function better without the drug cravings, highs, and lows associated with heroin.5

1 Leshner AI. Treatment, education, and prevention: adding to the arsenal in the war on drugs. Hearing before the Senate Committee on the Judiciary. 14 Mar 2001.
2 Leshner AI. Interview with Bill Moyers. Moyers on Addiction: Close to Home. Broadcast March 29, 1998. Transcript available at PBS Online, .
3 Lubran R. Substance Abuse and Mental Health Services Administration, Center for Substance Abuse Treatment, private communication, 26 Aug 2003.
4 Rehman Z, Khoromi S, Douglas JE. Opioid abuse. March 2003. Available at:
5 Fiellin DA, Rosenheck RA, Kosten TR. Office-based treatment for opioid dependence: reaching new patient populations. Am J Psychiatry. 2001;158(8):1200-4.


New Report: SPNS Information Technology Initiative

Given the increasingly complex nature of HIV treatment—and the challenge of reaching underserved populations—information technology (IT) promises to be a powerful new tool HIV care delivery. Yet IT has not been sufficiently evaluated in the HIV clinical setting. To address this need, the Special Projects of National Significance (SPNS) Information Technology Initiative is evaluating the impact of existing IT tools and interventions on the delivery and quality of HIV care. Six grantees have been funded in the 4-year initiative, which began in October 2002 and will continue through September 2006. A report on the initiative is available online at


Buprenorphine 101

Two formulations of buprenorphine have been approved by the Food and Drug Administration:1

Suboxone does not induce analgesia or euphoria; instead, under certain circumstances, it can block and reverse the actions of opioid agonists (i.e., activators). Naloxone has no effect if Suboxone is taken as intended, but if it is injected in an attempt to cause a high, it can lead to withdrawal. Therefore, Suboxone is less likely than methadone or even buprenorphine alone to be sold or otherwise diverted for illicit use.2,3

Buprenorphine is a Class C medication, which means that insufficient research exists to understand its effects on the human fetus when used by pregnant mothers.4 It does pass through breast milk, so mothers taking the drug should not breast feed. The most common side effects of buprenorphine include cold symptoms, headaches, sweating, sleeping difficulties, nausea, and mood swings.5 Although the risk of serious respiratory distress is lower than with full opioid agonists, buprenorphine has been associated with deaths from respiratory arrest, especially when combined with alcohol or other sedatives. The estimated monthly cost of buprenorphine is between $150 and $300.6

A Safe Alternative

Buprenorphine is a partial agonist–partial antagonist medication, meaning that it works by both activating and blocking opioid receptors.7 The antagonist (or blocking) property provides a “ceiling effect” on buprenorphine’s ability to control pain and induce euphoria. Up to a certain dose, buprenorphine’s agonist (or activating) property predominates, and each dose increase is accompanied by an increase in the intensity of the drug’s analgesic and euphoric effects. Beyond a ceiling dose, however, the antagonist property of buprenorphine predominates. At that point, the effects of the drug level off and cannot be further enhanced—even with additional buprenorphine.

By contrast, heroin and methadone are full agonists: They have purely activating effects on opioid receptors and therefore lack buprenorphine’s ceiling effect. As a result, methadone is effective for addicts who require an extremely high dose of opioids to avoid withdrawal. Although the ceiling effect makes buprenorphine ineffective for addicts who require high doses, it does confer some safety advantages over methadone because it less likely to result in dependence or cause breathing to stop.8 The net result for most addicts is that buprenorphine is as effective as methadone in treating opioid addiction—but safer.9

1 Food and Drug Administration. Subutex and Suboxone approved to treat opiate dependence. Press release. 8 Oct 2002. Available at: 2002/ANS01165.html.
2 Fudala PJ, Bridge P, Herbert S. Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone. N Engl Med. 2003;349(10): 949-58.
3 Clark HW. Office-based practices and opioid-use disorder. N Engl J Med. 2003;349(10):928-31.
4 Mosby’s Drug Consult. 2003. Available at: http:// 549/top?sid=209449253.
5 McClellan MB. Two drugs for opioid dependence. JAMA. 2002;288(21):2678.
6 Clark, 2003.
7 Fudala et al., 2003.
8 Substance Abuse and Mental Health Services Administration, Center for Substance Abuse Treatment. About Buprenorphine Therapy. Available at: about.html.
9 Raisch DW, Fye CL, Boardman KD, et al. Opioid dependence treatment, including buprenorphine/naloxone. Ann Pharmacother. 2002;36(2):312-21.



Buprenorphine and HIV/AIDS Drugs

Because active drug use is associated with poor adherence to antiretroviral medication regimens, addiction therapy appears to improve clinical outcomes in HIV-positive addicts.1 Experts overwhelmingly agree that treating drug addiction in people who are HIV-positive can improve outcomes for both diseases.

Some information regarding drug interactions between buprenorphine and antiretroviral drugs is available, but more research is needed. Unlike methadone, which increases the concentration of AZT in the body and therefore carries a risk of toxic effects, buprenorphine does not result in AZT toxicity.2 Research does indicate, however, that some protease inhibitors may increase concentrations of both methadone and buprenorphine.3 Of the protease inhibitors studied, ritonavir had the most potent effect, followed by indinavir and saquinavir. Providers are therefore advised to exercise caution when prescribing methadone or buprenorphine to patients on protease inhibitors.

1 Cohn JA. HIV-1 infection in injection drug users. Infect Dis Clin N Am. 2002;16(3):745-70.
2 McCance-Katz EF, Rainey PM, Friedland G, et al. Effect of opioid dependence pharmacotherapies on zidovudine disposition. American J Addict. 2001;10(4):296-307.
3 Iribarne C, Berthou F, Carlhant D, et al. Inhibition of methadone and buprenorphine N-dealkylations by three HIV-1 protease inhibitors. Drug Metab Disposition. 1998;26(3):257-60.


Glossary: Substance Abuse

Substance Abuse is the continued use of a substance even though it may cause physical, psychological, or social harm or result in significant impairment or distress at work, school, or home.

Tolerance is the need to increase the amount of substance taken in order to achieve a desired effect or to avoid an undesirable effect.

Withdrawal is the constellation of symptoms that emerges if the substance is not taken or if too little is taken. Opioid withdrawal may cause fever, high blood pressure, increased heart rate, nausea, vomiting, abdominal pain, and irritability.

Addiction refers to the behaviors associated with drug use and the inability to control drug use despite consequences. Drug craving, drug seeking, and relapse are the major characteristics of addiction.

Dependence describes the physiological changes that occur with drug use, changes that result in the need to take increasing amounts of the drug to avoid withdrawal.

Sources: Adapted from American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (4th ed.). Washington, DC: Author; 1994. pp. 175–94. Rehman Z et al. Opioid abuse. 19 Mar 2003. Available at: topic1673.htm.


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