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Methadone Therapy for Opioid Dependence

LAURIE LIMPITLAW KRAMBEER, PH.D., WILLIAM VON MCKNELLY, JR., M.D., WILLIAM F. GABRIELLI, JR., M.D., PH.D. and ELIZABETH C. PENICK, PH.D.
University of Kansas Medical Center, Kansas City, Kansas

The 1999 Federal regulations extend the treatment options of methadone-maintained opioid-dependent patients from specialized clinics to office-based opioid therapy (OBOT). OBOT allows primary care physicians to coordinate methadone therapy in this group with ongoing medical care. This patient group tends to be poorly understood and underserved. Methadone maintenance therapy is the most widely known and well-researched treatment for opioid dependency. Goals of therapy are to prevent abstinence syndrome, reduce narcotic cravings and block the euphoric effects of illicit opioid use. In the first phase of methadone treatment, appropriately selected patients are tapered to adequate steady-state dosing. Once they are stabilized on a satisfactory dosage, it is often possible to address their other chronic medical and psychiatric conditions. The maintenance phase can be used as a long-term therapy until the patient demonstrates the qualities required for successful detoxification. Patients who abuse narcotics have an increased risk for human immunodeficiency virus infection, hepatitis, tuberculosis and other conditions contributing to increased morbidity and mortality. Short- or long-term pain management problems and surgical needs are also common concerns in opioid-dependent patients and are generally treatable in conjunction with methadone maintenance. (Am Fam Physician 2001;63:2404-10.)


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Opioid dependence is a chronic, often relapsing, disorder that contributes to major medical challenges such as human immunodeficiency virus (HIV)-related illnesses, hepatitis and other chronic diseases. 1-3 While opioid-dependent patients are generally treated within rehabilitation programs that specifically target their addiction, family physicians, with their emphasis on regular and ongoing health maintenance, have the opportunity to treat a patient's addiction as well as other medical concerns.4,5 Major issues in the medical management of opioid dependency are outlined in Table 1.

Epidemiology

Between 500,000 and 1 million Americans are believed to be opioid dependent at any point in time.2,6,7 Gender differences exist, with opioid-related disorders more prevalent in men than women by a ratio of up to 4:1.2,8 Opioid dependency is often linked to a history of drug-related criminal activity.2 Antisocial personality disorder is more prevalent in opioid-dependent persons than in the general population,2,8,9 and opioid-dependent persons frequently have coexisting mood disorders, especially depression.2,4,9

Methadone maintenance therapy in opioid-dependent patients reduces illicit narcotic use, risk of contracting and transmitting HIV, tuberculosis and hepatitis, and illegal activities.

Treatment Options for Opioid Dependence

Methadone is the most widely known pharmacologic treatment for opioid dependence and is effective in reducing illicit narcotic use,10-12 retaining patients in treatment and decreasing illegal drug use.11,12 Ongoing methadone maintenance decreases the risk of contracting and transmitting HIV, hepatitis B (HBV) and hepatitis C (HCV)13,14 and is considered a cost-effective intervention.15 Long-term methadone maintenance is more successful in averting relapse than shorter-term treatment.12

Alternatives to methadone therapy include levomethadyl (Orlaam), buprenorphine (Buprenex), naltrexone (Trexan) and Narcotics Anonymous (NA). Levomethadyl's efficacy lasts as long as three days, while methadone requires daily dosing. Thus, levomethadyl therapy is appropriate in patients who do not require intensive care, but it is less effective in those who need daily monitoring. Buprenorphine (available for investigational use only) demonstrates dose-response ceiling effects, a factor that may operate as a safeguard and limit the potential for abuse or diversion.16 Methadone produces better treatment retention rates than buprenorphine,17,18 although results of studies of its superiority in decreasing illicit narcotic use are mixed.17-19 In contrast to methadone, naltrexone produces no physical dependence but has poor patient compliance rates. NA, a nonpharmacologic intervention, is a self-help peer recovery group that provides social support.

TABLE 1
Principles of Medical Management of Methadone Patients

Select appropriate patients and complete physical examination and psychiatric evaluation
Minimum age of 18 years (generally)
At least one year of physiologic dependence on a narcotic
Meets criteria for opioid dependence (see Table 2)
Achieve adequate steady-state dosing
Begin induction dosing phase
Establish maintenance-phase dosage
Avoid drugs that potentiate methadone dose or induce withdrawal
Evaluate need for detoxification or continued maintenance
Prevent relapse
Educate patient and family about potential for relapse
Encourage involvement in Narcotics Anonymous and Nar-Anon
Monitor patient for symptoms of opioid intoxication or drug-seeking behavior

Adjust dosage according to needs
Evaluate and treat medical conditions
Infectious disease
Reduce risk of contracting and transmitting disease
Educate family and involve them in preventive efforts
Pain management
Consider nonnarcotic agents first
Evaluate cross-tolerance in narcotic analgesia
Avoid narcotics that induce withdrawal

Appropriate Candidates for Methadone Therapy

Federal regulations stipulate that to be eligible for methadone maintenance therapy, patients must demonstrate at least a one-year history of physiologic dependence on a narcotic and meet the minimum age requirement of 18 years. However, an exception is available for patients between the ages of 16 and 18 who present with a documented history of at least two prior unsuccessful detoxification efforts and have parental consent.20 Specific criteria for opioid dependence are listed in Table 2. Identifying opioid dependence is relatively straightforward when patients are candid about their symptoms and actively request treatment of addiction. Unfortunately, not all patients are forthcoming about their condition.

To be eligible for methadone maintenance therapy, patients generally must be 18 years of age and have been physiologically dependent on a narcotic for at least one year.

The physician needs to be alert to signs of drug-seeking behavior or evidence of a recent relapse in a formerly addicted patient. Both of these situations warrant further assessment to establish whether current opioid dependence exists. Warning signs of possible drug seeking include a pattern of behavior in which a patient finishes narcotic prescriptions early, insists on replacement prescriptions and concurrently solicits prescriptions from multiple physicians. Evidence of a short-term relapse is perhaps best characterized by opioid intoxication (e.g., pupillary constriction, drowsiness, slurred speech, impaired attention or memory).2

Traditionally, methadone maintenance is managed through dedicated clinics, which provide dosing and a broad array of counseling and rehabilitative services. Methadone maintenance programs currently exist in
42 states, the District of Columbia, Puerto Rico and the U.S. Virgin Islands. These treatment programs are listed in the Narcotic Treatment Program Directory.21 Physicians can access this resource on the Internet to locate a nearby methadone clinic and obtain referral information for a prospective patient (Table 3). The cost of treatment in a methadone maintenance program averages $4,500 annually and is sometimes subsidized by private insurance or Medicaid.

Another treatment option is dispensing methadone through a general medical practice. In this circumstance, a physician provides methadone pharmacotherapy contingent on registration with the Drug Enforcement Administration, the U.S. Food and Drug Administration and the state methadone authority. Physicians and patients must comply with methadone maintenance program requirements. This is a useful treatment option for patients who have limited access to specialized clinics, especially those who live in rural areas. Nevertheless, the burden of the federal and state requirements make this option unpopular with physicians. Moreover, this form of treatment is as restrictive to patients as traditional methadone clinic care.

TABLE 2
Criteria for Opioid Dependence

At least three of the following symptoms must occur during a 12­month period:
Tolerance
Withdrawal
Opioid use in greater quantities or for longer periods of time than planned
Failed attempts to quit or cut back (at minimum, a wish to cut back)
Considerable time devoted to obtaining drug, using drug or recovering from use of drug
Interference with social, occupational or recreational activities
Ongoing use despite awareness of drug problem

Information from American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, D.C.: American Psychiatric Association, 1994:175-255.

Recent changes in the Federal regulations advocate less restrictive alternatives, highlighting an increasing interest in providing care outside of traditional methadone clinics as a means of extending access to narcotic addiction treatment. Federal regulations established in 1999 endorse office-based opioid therapy (OBOT), in which primary care physicians provide methadone pharmacotherapy within comprehensive medical care for a segment of the methadone-maintained population.22

To practice OBOT, physicians must have training in addiction medicine, be affiliated with a methadone clinic or be monitored by the medical director of a methadone clinic. Physicians may incorporate up to 30 methadone-maintained patients into their practice. Eligible patients are referred exclusively from methadone clinics and must be stabilized and have achieved three years of successful methadone maintenance. The advantage of OBOT to patients is the fact that primary care physicians can dispense up to a 30-day supply of methadone, thus easing the scheduling demands characteristic of traditional methadone clinics.

Some research suggests that methadone treatment from a general medical practice is as effective as that provided in specialty clinics.5 Office-based methadone treatment is currently in operation in other countries.23

Methadone Dosing and Maintenance

The goals of the early induction dosages of methadone are to attenuate withdrawal symptoms, diminish opioid craving and arrive at a tolerance threshold, while preventing euphoria and sedation from overmedication.24-26 Initial daily dosages of 20 to 30 mg are usually safe and appropriate.24,25 Because of the long half-life of methadone, between four and 10 days are necessary to achieve steady-state maintenance dosing.

Subsequent induction dosages are adjusted on the basis of dose response, particularly an evaluation of abstinence symptoms. The maintenance phase of dosing is attained when the patient's dosage is satisfactory and effective for at least 24 hours. The length of the maintenance phase lasts as long as treatment benefits the patient. Periodic dosage increases are warranted in cases of patients who relapse or abuse other drugs. For example, because alcohol, barbiturates and sedative-hypnotics accelerate methadone metabolism, they foster withdrawal symptoms. In addition, patients sometimes need a dosage increase when taking prescribed medicines (e.g., rifampin [Rifadin], phenytoin [Dilantin], carbamazepine [Tegretol]) that speed methadone metabolism.3,25

Detoxification

Detoxification is indicated when a patient demonstrates consistent, long-term abstinence and possesses adequate supportive resources (e.g., productive use of time, a stable home life). Patient receptiveness to community resources for opiate addicts, such as NA, is a good sign. NA is a useful tool in relapse prevention. Local chapters of NA are listed in the telephone book. Further resources are provided in Table 3.

Methadone detoxification involves the induction of opioid withdrawal symptoms and typically refers to either a short- or a long-term process. Short-term detoxification does not exceed 30 days.20 Long-term detoxification lasts from 31 to 180 days. Gradual detoxification tends to be more successful than a sudden dose discontinuation.6 Detoxification is difficult for the physician to manage because some opiate withdrawal symptoms are subjective and thus are hard to accurately assess. The physician runs the risk of either overestimating or underestimating the intensity of withdrawal.

TABLE 3
Resources for Physicians, Patients and Family Members

Addiction Treatment Forum
www.atforum.com

American Methadone Treatment Association, Inc.
212-566-5555
www.americanmethadone.org

Methadone Awareness newsletter, published by Philadelphia chapter of National Alliance of Methadone Advocates (NAMA)
215-629-1510
Contact person Katharine Bolton: [email protected]

Methadone Information Exchange
www.mindspring.com/~methinfex

Nar-Anon Family Group Headquarters
310-547-5800
www.onlinerecovery.org/co/nfg

Narcotic Treatment Programs Directory
www.fda.gov/cder/compliance/ntpdir.pdf

The Authors

LAURIE LIMPITLAW KRAMBEER, PH.D.,
is adjunct assistant professor of psychiatry at the University of Kansas Medical Center and program director of the Kansas City Metro Methadone Program, operated by the Center's Department of Psychiatry and Behavioral Sciences in Kansas City, Kan.

WILLIAM VON MCKNELLY, JR., M.D.,
is professor of psychiatry at the University of Kansas Medical Center and medical director of the Kansas City Metro Methadone Program.

WILLIAM F. GABRIELLI, JR., M.D., PH.D.,
is professor and chairman of the Department of Psychiatry, University of Kansas Medical Center.

ELIZABETH C. PENICK, PH.D.,
is professor and director of the Division of Psychology, Department of Psychiatry and Behavioral Sciences, University of Kansas Medical Center.

Meth Address correspondence to Laurie Limpitlaw Krambeer, Ph.D., Department of Psychiatry and Behavioral Sciences, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160-7341. Reprints are not available from the authors.

REFERENCES

  1. Dole VP. What is "methadone maintenance treatment"? J Maintenance Addict 1997;1:7-8.
  2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, D.C.: American Psychiatric Association, 1994:175-255.
  3. Neshin S. HIV and other infectious diseases. In: Parrino MW. State methadone treatment guidelines. Rockville, Md.: U.S. Department of Health and Human Services, Public Health Service, Substance and Mental Health Services Administration, Center for Substance Abuse Treatment. Treatment improvement protocol (TIP) series, 1993; DHHS publication no. (SMA) 93-1991:95-118.
  4. Sullivan E, Fleming M. A guide to substance abuse services for primary care clinicians. Rockville, Md.: U.S. Department of Health and Human Services, Public Health Service, Substance and Mental Health Services Administration, Center for Substance Abuse Treatment, 1997; DHHS publication no. 97-3139:1-48.
  5. Byrne A, Wodak A. Census of patients receiving methadone treatment in a general practice. Addict Res 1996;3(4):341-9.
  6. Nadelmann E, McNeely J. Doing methadone right. Public Interest 1996;Spring(N123):83-93.
  7. National Institute on Drug Abuse. Heroin abuse and addiction. Rockville, Md.: U.S. Department of Health and Human Services, National Institutes of Health, National Institute on Drug Abuse 2000. Research report series; NIH publication no. 00-4165.
  8. Maxmen JS, Ward NG. Substance-related disorders. In: Essential psychopathology and its treatment. 2d ed. New York: Norton, 1995:132-72.
  9. Mason BJ, Kocsis JH, Melia D, Khuri ET, Sweeney J, Wells A, et al. Psychiatric comorbidity in methadone maintained patients. J Addict Dis 1998;17:75-89.
  10. Aszalos R, McDuff DR, Weintraub E, Montoya I, Schwartz R. Engaging hospitalized heroin-dependent patients into substance abuse treatment. J Subst Abuse Treat 1999;17:149-58.
  11. Abbott PJ, Moore B, Delaney H, Weller S. Retrospective analyses of additional services for methadone maintenance patients. J Subst Abuse Treat 1999;17:129-37.
  12. Sees KL, Delucchi KL, Masson C, Rosen A, Clark HW, Robillard H, et al. Methadone maintenance vs 180-day psychosocially enriched detoxification for treatment of opioid dependence: a randomized controlled trial. JAMA 2000;283:1303-10.
  13. Stenbacka M, Leifman A, Romelsjo A. The impact of methadone on consumption of inpatient care and mortality, with special reference to HIV status. Subst Use Misuse 1998;33(14):2819-34.
  14. Stark K, Bienzle U, Vonk R, Guggenmoos-Holzmann I. History of syringe sharing in prison and risk of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus infection among injecting drug users in Berlin. Int J Epidemiol 1997;26(6): 1359-66.
  15. Barnett PG. The cost-effectiveness of methadone maintenance as a health care intervention. Addiction 1999;94(4):479-88.
  16. Walsh SL, Preston KL, Bigelow GE, Stitzer ML. Acute administration of buprenorphine in humans: partial agonist and blockade effects. J Pharmacol Exp Ther 1995;274:361-72.
  17. Fischer G, Gombas W, Eder H, Jagsch R, Peternell A, Stuhlinger G, et al. Buprenorphine versus methadone maintenance for the treatment of opioid dependence. Addiction 1999;94:1337-47.
  18. Kosten TR, Schottenfeld R, Ziedonis D, Falcioni J. Buprenorphine versus methadone maintenance for opioid dependence. J Nerv Ment Dis 1993;181: 358-64.
  19. Oliveto AH, Feingold A, Schottenfeld R, Jatlow P, Kosten TR. Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone. Arch Gen Psychiatry 1999;56:812-20.
  20. Code of Federal Regulations. Food and drugs. Human services, part 291--drugs used for treatment of narcotic addicts. U.S. Government Printing Office via GPO Access; cite 21CFR291.505:157-78.
  21. U.S. Food and Drug Administration. FDA narcotic treatment programs directory. Rockville, Md.: U.S. Department of Health and Human Services, Public Health Service, Food and Drug Administration, 1995.
  22. Code of Federal Regulations. Food and drugs. Human services, part 291--narcotic drugs in maintenance and detoxification treatment of narcotic dependence. U.S. Government Printing Office via GPO Access; cite 21CFR291.
  23. Matheson C, Bond CM, Hickey F. Prescribing and dispensing for drug misusers in primary care: current practice in Scotland. Fam Pract 1999;16(4):375-9.
  24. Kauffman JF, Woody GE. Matching treatment to patient needs in opioid substitution therapy. Rockville, Md.: U.S. Department of Health and Human Services, Public Health Service, Substance and Mental Health Services Administration, Center for Substance Abuse Treatment. Treatment improvement protocol (TIP) series, 1995; DHHS publication no. (SMA) 95-3049:1-46.
  25. Payte JT, Khuri ET. Principles of methadone dose determination. In: Parrino MW. State methadone treatment guidelines. Rockville, Md.: U.S. Department of Health and Human Services, Public Health Service, Substance aand Mental Health Services Administration, Center for Substance Abuse Treatment. Treatment improvement protocol (TIP) series, 1993; DHHS publication no. (SMA) 93-1991:47-58.
  26. Martin J, Payte JT, Zweben JE. Methadone maintenance treatment: a primer for physicians. J Psychoactive Drugs 1991;23(2):165-76.
  27. Janiri L, Mannelli P, Persico AM, Serretti A, Tempesta E. Opiate detoxification of methadone maintenance patients using lefetamine, clonidine and buprenorphine. Drug Alcohol Depend 1994;36(2):139-45.
  28. Batki SL, Selwyn PA. Substance abuse treatment for persons with HIV-AIDS. Rockville, Md.: U.S. Department of Health and Human Services, Public Health Service, Substance Abuse and Mental Health Services Administration, Center for Substance Abuse Treatment, treatment improvement protocol (TIP) series, 2000; DHHS publication no. (SMA) 00-3410:23-68.
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  30. Diamantis I, Bassetti S, Erb P, Ladewig D, Gyr K, Battegay M. High prevalence and coinfection rate of hepatitis G and C infections in intravenous drug addicts. J Hepatol 1997;26(4):794-7.

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Narcotics Anonymous (NA)
818-773-9999
www.na.org

National Alliance of Methadone Advocates (NAMA)
www.methadone.org

National Clearinghouse for Alcohol and Drug Information (NCADI)
800-729-6686
www.health.org

Substance Abuse & Mental Health Services Administration (SAMHSA) Treatment Facility Locator
800-729-6686
http://findtreatment.samhsa.gov/

SAMHSA homepage: http://www.samhsa.gov

National Institute on Drug Abuse (NIDA)
www.nida.nih.gov/DrugPages/Heroin.html

 

Fentanyl

 


 

Molecular structure of fentanyl
  • Fentanyl is a powerful synthetic opiate analgesic similar to but more potent than morphine. It is typically used to treat patients with severe pain, or to manage pain after surgery. It is also sometimes used to treat people with chronic pain who are physically tolerant to opiates. It is a schedule II prescription drug.
  • In its prescription form, fentanyl is known as Actiq, Duragesic, and Sublimaze. Street names for the drug include Apache, China girl, China white, dance fever, friend, goodfella, jackpot, murder 8, TNT, as well as Tango and Cash.
  • Like heroin, morphine, and other opioid drugs, fentanyl works by binding to the body's opiate receptors, highly concentrated in areas of the brain that control pain and emotions. When opiate drugs bind to these receptors, they can drive up dopamine levels in the brain's reward areas, producing a state of euphoria and relaxation. Medications called opiate receptor antagonists act by blocking the effects of opiate drugs. Naloxone is one such antagonist. Overdoses of fentanyl should be treated immediately with an opiate antagonist.
  • When prescribed by a physician, fentanyl is often administered via injection, transdermal patch, or in lozenge form. However, the type of fentanyl associated with recent overdoses was produced in clandestine laboratories and mixed with (or substituted for) heroin in a powder form.
  • Mixing fentanyl with street-sold heroin or cocaine markedly amplifies their potency and potential dangers. Effects include: euphoria, drowsiness/respiratory depression and arrest, nausea, confusion, constipation, sedation, unconsciousness, coma, tolerance, and addiction.
285171since 6/17/06

Nationwide Public Health Alert Issued Concerning Life-Threatening Risk Posed by Cocaine Laced with Veterinary Anti-Parasite Drug

Date: 9/21/2009
Media Contact: SAMHSA Press
Telephone: 240-276-2130

Nationwide Public Health Alert Issued Concerning Life-Threatening Risk Posed by Cocaine Laced with Veterinary Anti-Parasite Drug

The Substance Abuse and Mental Health Services Administration (SAMHSA) is alerting medical professionals, substance abuse treatment centers and other public health authorities about the risk that substantial levels of cocaine may be adulterated with levamisole – a veterinary anti-parasitic drug. There have been approximately 20 confirmed or probable cases of agranulocytosis (a serious, sometimes fatal blood disorder), including two deaths, associated with cocaine adulterated with levamisole. The number of reported cases is expected to increase as information about cocaine adulterated with levamisole is disseminated.

“SAMHSA and other public health authorities are working together to inform everyone of this serious potential public health risk and what measures are being taken to address it,” said SAMHSA Acting Administrator Eric Broderick, D.D.S., MPH.

Levamisole is used in veterinary medicine and is currently approved for use in cattle, sheep and swine as an anti-parasitic agent. Although it was once used in human medicine in the past for treating autoimmune diseases and cancer, it is no longer an approved drug for human use.

Ingesting cocaine mixed with levamisole can seriously reduce a person's white blood cells, suppressing immune function and the body's ability to fight off even minor infections. People who snort, smoke, or inject crack or powder cocaine contaminated by levamisole can experience overwhelming, rapidly-developing, life threatening infections. Other serious side effects can also occur.

According to the Drug Enforcement Administration and State testing laboratories, the percentage of cocaine specimens containing levamisole has increased steadily since 2002, with levamisole now found in over 70 percent of the illicit cocaine analyzed in July. In addition, a recent analysis in Seattle, Washington found that almost 80 percent of the individuals who test positive for cocaine also test positive for levamisole.

According to the SAMHSA alert substance abuse treatment providers, clinicians, outreach workers, and individuals who abuse cocaine need to be aware of the following:

A dangerous substance, levamisole, is showing up with increasing frequency in illicit cocaine powder and crack cocaine. Levamisole can severely reduce the number of white blood cells, a problem called agranulocytosis. THIS IS A VERY SERIOUS ILLNESS THAT NEEDS TO BE TREATED AT A HOSPITAL. If you use cocaine, watch out for:

* high fever, chills, or weakness
* swollen glands
* painful sores (mouth, anal)
* any infection that won’t go away or gets worse very fast, including sore throat or mouth sores -skin infections, abscesses -thrush (white coating of the mouth, tongue, or throat) -pneumonia (fever, cough, shortness of breath).”

SAMHSA is working with the U.S. Centers for Disease Control and Prevention (CDC), the Drug Enforcement Administration, the Food and Drug Administration, the Office of National Drug Control Policy, and other federal and international organizations, as well as state agencies to monitor the levamisole issue. CDC will be publishing a case report analysis in the Morbidity and Mortality Weekly Report (MMWR) and will be working with state health departments to systematically collect information on cocaine-associated agranulocytosis cases. Information from this effort will be used to guide treatment and prevention initiatives to address this public health concern.

Individuals are encouraged to report suspected and confirmed cases of agranulocytosis that are associated with cocaine abuse to their respective state health departments. Cases can also be reported to local Poison Control Centers (1-800-222-1222), these centers may also provide assistance in clinical management and additional reporting.

For further medical/technical information, contact Nicholas Reuter, SAMHSA ([email protected]).

War On Drugs Has Failed

'Global war on drugs has failed,' key panel says

Commission criticizes US approach and argues that governments should end the criminalization of drug use

Image: Soldiers carry bundles of marijuana towards a bonfire for incineration during the destruction of a plantation in Amata, Mexico.
Tomas Bravo  /  Reuters, file
Soldiers carry bundles of marijuana towards a bonfire for incineration during the destruction of a plantation in Amata, on the outskirts of Culiacan in Mexico's northwestern state of Sinaloa on Nov. 30.
msnbc.com staff and news service reports msnbc.com staff and news service reports
updated 12 minutes ago 2011-06-02T09:50:43

The global war on drugs has failed and governments should explore legalizing marijuana and other controlled substances, according to a commission that includes former heads of state, a former U.N. secretary-general and a business mogul.

A new report by the Global Commission on Drug Policy argues that the decades-old worldwide "war on drugs has failed, with devastating consequences for individuals and societies around the world." The 24-page paper was released Thursday.

"Political leaders and public figures should have the courage to articulate publicly what many of them acknowledge privately: that the evidence overwhelmingly demonstrates that repressive strategies will not solve the drug problem, and that the war on drugs has not, and cannot, be won," the report said.

The 19-member commission includes former U.N. Secretary-General Kofi Annan and former U.S. official George P. Schultz, who held cabinet posts under U.S. Presidents Ronald Reagan and Richard Nixon.

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Others include former U.S. Federal Reserve chairman Paul Volcker, former presidents of Mexico, Brazil and Colombia, writers Carlos Fuentes and Mario Vargas Llosa, U.K. business mogul Richard Branson and the current prime minister of Greece.

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Instead of punishing users who the report says "do no harm to others," the commission argues that governments should end criminalization of drug use, experiment with legal models that would undermine organized crime syndicates and offer health and treatment services for drug-users in need.

"Vast expenditures on criminalization and repressive measures directed at producers, traffickers and consumers of illegal drugs have clearly failed to effectively curtail supply or consumption," the report added. "Apparent victories in eliminating one source or trafficking organization are negated almost instantly by the emergence of other sources and traffickers."

The commission called for drug policies based on methods empirically proven to reduce crime, lead to better health and promote economic and social development.

"Arresting and incarcerating tens of millions of these people in recent decades has filled prisons and destroyed lives and families without reducing the availability of illicit drugs or the power of criminal organizations," the report said. "There appears to be almost no limit to the number of people willing to engage in such activities to better their lives, provide for their families, or otherwise escape poverty. Drug control resources are better directed elsewhere."

'Alternatives'
The commission is especially critical of the United States, saying it must change its anti-drug policies from being guided by anti-crime approaches to ones rooted in healthcare and human rights.

"We hope this country (the U.S.) at least starts to think there are alternatives," former Colombian president Cesar Gaviria told The Associated Press by phone. "We don't see the U.S. evolving in a way that is compatible with our (countries') long-term interests."

Story: Why it's so hard to win war against US oxycodone epidemic

The office of White House drug czar Gil Kerlikowske said the report was misguided.

"Drug addiction is a disease that can be successfully prevented and treated. Making drugs more available — as this report suggests — will make it harder to keep our communities healthy and safe," Office of National Drug Control Policy spokesman Rafael Lemaitre said.

That office cites statistics showing declines in U.S. drug use compared to 30 years ago, along with a more recent 46 percent drop in current cocaine use among young adults over the last five years.

The report cited U.N. estimates that opiate use increased 34.5 percent worldwide and cocaine 27 percent from 1998 to 2008, while the use of cannabis, or marijuana, was up 8.5 percent.

Meanwhile, TIME reported that Southeast Asia's so-called Golden Triangle narcotics zone "has reinvented itself — and is more dangerous than ever."

It said that poppy cultivation in Burma increased 76 percent last year to about 639 tons. Cultivation has also grown in Thailand and Laos, the magazine reported.

"We are worried about the prospects of further expansion in 2011," Gary Lewis, East Asia and Pacific representative for the U.N. Office on Drugs and Crime, told TIME. "The international community has taken its eye off the ball on drug production and trafficking in Southeast Asia."

The Associated Press and msnbc.com staff contributed to this report