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Chemical Dependency Research Working Group |
The steady state of blood plasma levels produced by an adequate daily dose of methadone normalizes the deranged physiological functioning of the endocrine and immune systems induced by heroin addiction (Dole, 1988). The following studies validate the medical safety of long term methadone treatment.
Studies of socially rehabilitated methadone patients in continuous treatment for over ten years, active heroin addicts and non-drug using healthy controls have shown that natural killer cell activity of the immune system was impaired for the heroin-addicted population. However, killer cell activity of the immune system was normal for the methadone patients and non-drug using healthy controls (Novick, Ochshorn, Ghali et al, 1989). All subjects and controls in this study were HIV negative therefore drug injection during heroin addiction can impair immune functioning independent of HIV infection.
Female menses which may have been interrupted while using heroin are restored to normal for the majority of opiate dependent women maintained on methadone (Kreek, 1992; Kreek, 1986). Therefore, women maintained on methadone are able to experience normal pregnancies. Human sexuality and fertility are seriously impaired while persons are dependent on heroin. Libido and fertility can be restored within a normal range of functioning for both male and female patients who are maintained on adequate doses of methadone. However, those who abuse alcohol, cocaine or other drugs may experience reductions in libido and disruptions in the reproductive system (Kreek, 1992). Women of child bearing age should be advised of this upon entering treatment.
Major medical problems effecting methadone patients are usually related to unhealthy life styles and unsterile injecting practices of the previous heroin addiction. Common medical problems include HIV infection, AIDS and drug-resistant TB; chronic liver disease resulting from either chronic alcoholism with cirrhosis or hepatitis usually contracted through use of contaminated needles to inject heroin and/or cocaine; and chronic illnesses presented at the time of admission to the program (Kreek, 1992; Kreek, 1986; Novick, Joseph, Croxson et al, 1990; Novick, Khan & Kreek, 1986). Upon entering methadone maintenance treatment these conditions can either be managed or treated, thus improving the patient's health (Kreek, 1992; Novick, Richman, Friedman et al, 1993).
A recent study of 110 methadone patients in treatment for 11 to 18 years showed that for most patients long term methadone treatment has facilitated social rehabilitation (e.g., employment, family stability, cessation of criminal activity, reduction or elimination of heroin addiction and polydrug use) and resulted in an overall improvement of their health (Novick, Richman, Friedman et al, 1993). Medical problems in this advancing age group of methadone patients are similar to those medical problems found in the general middle-aged and older populations (e.g., cardiac problems, cancer, etc.). Heroin addiction has either been completely eliminated or greatly curtailed with a reduced incidence of diseases related to the use of contaminated needles; reduction in the incidence of sexually transmitted diseases; improved endocrine and immune functioning; and less frequent abuse of cocaine and alcohol, although these drugs continue to pose significant problems for some patients.
HIV entered the heroin injecting population in New York City in the late 1970s. In the 1980s examination of stored blood collected in the 1970s from addicts and three deceased infants revealed the presence of HIV (Des Jarlais, Friedman, Novick et al, 1989; Novick, Khan & Kreek, 1986). Retrospective estimates indicate that by 1980, prior to the discovery of the HIV virus, about 35 percent of the heroin injectors in New York City were already infected. In the mid 1980s, prevalence of HIV infection among intravenous drug users increased to about 55 percent, and by 1990 the prevalence had leveled off to about 50 percent (Des Jarlais, Friedman, Novick et al, 1989; Marmor, Des Jarlais & Cohen, 1987).
Injecting and non injecting drug users, their sexual partners and their offspring are at high risk for contracting HIV. The prevalence of HIV infection among patients entering methadone maintenance treatment in New York City varies from about 21 percent to about 60 percent depending on the program and its geographic location (Joseph & Springer, 1990).
When properly administered, methadone maintenance treatment can be a highly effective intervention to reduce transmission of HIV among injecting heroin addicts and provide medical services and referrals. Evidence collected in Europe and the United States validates the findings of laboratory and clinical studies about the effectiveness of adequate methadone treatment in preventing transmission of HIV and in the treatment of infected individuals. Several independent studies have shown that successful methadone maintenance treatment reduces risk behavior to contract and transmit HIV.
Methadone programs are placed in a unique position to monitor HIV and other infectious diseases and provide clinical prevention and intervention. For example, AZT can be administered as well as medications for drug-resistant TB. Most importantly, clinics can offer AIDS prevention, counseling and referrals for services that exist in the community. Special methadone clinics and programs can be developed that serve patients infected with HIV (e.g., St. Claire's MMTP, Beth Israel AIDS program on 125th Street).
The information presented here is collected from the Treatment Improvement Protocol (TIP) on Pregnancy and Substance Abusing Women (Kandall, 1993) sponsored by the Center for Substance Abuse Treatment chaired by Janet Mitchell, M.D., M.P.H. of the Harlem Hospital Medical Center in New York City.
It is important for the health of the fetus that pregnant heroin users be placed in treatment during the first trimester of pregnancy (Kaltenbach & Finnegan, 1992). Since heroin is a short-acting drug with a half-life of four to six hours, the pregnant heroin addict will be subjected to periodic daily episodes of withdrawal resulting in fetal stress and risking intrauterine death. Methadone prescribed in adequate doses provides a relatively non-stressful environment in which the fetus can develop throughout pregnancy because of its long-acting duration (Kandall, 1993).
Entrance into methadone maintenance treatment during the first trimester of pregnancy is also associated with higher infant birth weights (Kaltenbach & Finnegan, 1992). There is evidence that methadone maintenance treatment, combined with prenatal services, promotes fetal growth, while continued use of heroin during pregnancy may result in infant morbidity (Kandall, 1993). The pregnant methadone-maintained patient may experience withdrawal symptoms and need an increase in the daily dose of the medication because of changes in metabolism and blood plasma levels of methadone, especially in the third trimester (Kaltenbach & Finnegan, 1992; Kandall, 1993).
Methadone maintenance with psychosocial counseling and prenatal care is recommended as the treatment of choice for opioid dependent pregnant women. The safety to the fetus of slow withdrawal from opiates has not been documented. Medical withdrawal of opioid dependent women (including methadone maintained women) is not recommended during pregnancy because of increased risk to the fetus of intrauterine death even under the most optimal circumstances such as close medical monitoring. Also, there are no research data that suggest withdrawal in one trimester is worse than in others, although some physicians have serious concerns of withdrawing a pregnant woman prior to 14 weeks and after 32 weeks of the pregnancy (Kandall, 1993).
Current research shows that doses below 60 mgs/day are "not effective and hence not appropriate" and "low dose policies for pregnant patients are often associated with increased drug use as well as reduced program retention." Methadone dose should be "individually determined by absence of subjective and objective abstinence symptoms and the reduction of drug hunger" (Kandall, 1993).
Most importantly, methadone dose may have to be increased or split (half in the morning and evening) to produce a beneficial effect during the later stages of pregnancy since greater plasma volume and renal blood flow during pregnancy can contribute to a reduced plasma blood level of methadone. Therefore, the pregnant woman's initial maintenance dose may be inadequate to prevent narcotic craving, and suppress symptoms of the abstinence syndrome resulting in the subsequent return to heroin use and relapse (Finnegan, 1993; Kaltenbach & Finnegan, 1992; Kandall, 1993). Pregnant methadone maintained patients should be counseled about the effects of pregnancy on their maintenance dose and the possibility of their needing a dose increase during pregnancy. It is most important that pregnant patients understand that the fetus will also feel it if they experience symptoms of the abstinence syndrome, so they will not resist a necessary increase in their dose. In addition to this pregnant patients should also be advised of the safety of methadone to the fetus and assured that dose has no relationship to the newborn being born drug dependent. The comfort of the mother and the fetus should be of paramount concern and understood by the mother.
Methadone maintenance is strongly encouraged for all pregnant opioid-dependent women (Kandall, 1993). It provides the following advantages:
Breast feeding of neonates is recommended if the pregnant woman maintained on methadone is HIV negative. Although minute traces of methadone have been found in mother's milk, they are of such low density as to be pharmacologically inert and do not cause physical dependency for the neonate. However, if the mother is HIV positive, breast feeding is not recommended since the HIV will be transmitted to the baby (Finnegan, 1993; Kaltenbach & Finnegan, 1992; Kandall, 1993).
Talwin, Nubain, Stadol and other agonist/antagonists should not be prescribed during pregnancy because of the dramatic withdrawal this class of drugs can precipitate thereby endangering the fetus. Narcan or any narcotic antagonist should never be given to pregnant substance-using women except as a last resort to reverse severe narcotic overdose. Administration of a narcotic antagonist, such as naltrexone to a pregnant opiate dependent woman could result in spontaneous abortion, premature labor and/or stillbirth. The long term effects and safety of clonidine in pregnancy are not known at the present time. Therefore, the drug should not be prescribed to pregnant opiate dependent women for withdrawal (Kandall, 1993).
Paregoric and phenobarbital are recommended for neonatal withdrawal symptoms (Kandall, 1993). However, some physicians may prefer paregoric for treatment of neonatal opiate withdrawal symptoms (Neuspiel, 1993). Kaltenbach and Finnegan (1992) report that neonatal abstinence symptoms are not related to the mother's methadone dose. Finnegan (1993) indicates that treatment of the opiate withdrawal symptoms in neonates is an easily treatable condition when prescribing paregoric. If the mother is a polysubstance user, however, both paregoric and/or phenobarbital may be necessary to withdraw the neonate (Kandall, 1993). The proper drugs to use in withdrawing a neonate are dependent on the drugs used by the mother.
Methadone maintenance treatment, developed by Drs. Vincent Dole and Marie Nyswander in the 1960s at The Rockefeller University has been thoroughly researched and evaluated during the past thirty years. Several variables distinguish methadone as a preferable maintenance medication including, the lack of mood altering effects, the blocking of drug craving or hunger, the blocking of the effects of heroin, protection from overdose, no change in tolerance level, oral administration with a half life of 24 to 36 hours, and medically safe (nontoxic with minimal side effects). A small number of methadone patients are aberrant metabolizers and some medications may speed liver metabolism. These patients may need doses in excess of 120 mg/day.
For the long term heroin addict methadone maintenance treatment is truly a life saving medication. Thousands of once formerly considered intractable heroin addicts have been restored to productive lives. Methadone maintenance stabilizes a physiology deranged by illicit heroin use and normalizes endocrine and immune functioning and is the best prevention of HIV infection. Heroin addiction to be sure is a complex problem involving sociological and psychological factors, however because of the recent discoveries of the endogenous opioid receptor-ligand system the importance of biology can not be ignored. Methadone, therefore, acts as a normalizer for a deranged physiology in maintenance treatment and not a mood altering narcotic. Methadone maintenance is replacement therapy for the neurological deficits caused by heroin addiction. As such it is therapeutic, but not a curative. Communities should welcome methadone programs because they reduce addict-related crime and reduce morbidity and mortality related to the transmission of infection. The quality of life in a community is improved for all residents by the presence of a well administered methadone maintenance program.
Abdul-Quader, A.S.; Tross, S.; Friedman, S.R.; Kouzi, A.C. and Des Jarlais, D.C. Street recruited intravenous drug users and sexual risk reduction in New York City. AIDS 1990 4: 1075-1079.
Addiction Treatment Forum. A.T.F. dosage survey. Addiction Treatment Forum 1993 2(3): 1, 3, 5.
Ball, J.C.; Lange, W.R.; Myers, C.P.; Friedman, S.R. Reducing the risk of AIDS through methadone maintenance treatment. Journal of Health and Social Behavior 1988 29(3): 214-226.
Ball, J.C. and Ross, A. The Effectiveness of Methadone Maintenance Treatment. New York: Springer-Verlag, 1991.
Blix, O. Personal communication, 1990.
Blix, O. and Grondbladh, L. AIDS and IV heroin addicts: The preventive effect of methadone maintenance in Sweden. IV International Conference On AIDS, No. 8548. Stockholm, Sweden: 1988.
Borg, L.; Ho, A. and Kreek, M.J. Correlation of methadone blood levels from three laboratories with dosage and abstinence symptoms: A pilot study. In: Problems of Drug Dependence 1992. Proceedings of the 54th Annual Scientific Meeting of the Committee on the Problems of Drug Dependence (June, 1992). Keystone, CO: Committee on the Problems of Drug Dependence, 1992.
Brecher, E.M. Licit and Illicit Drugs. The Consumers Union Report. Boston: Little, Brown and Company, 1972.
Caplehorn, J.R.M. and Bell, J Methadone dosage and retention of patients in maintenance treatment. Medical Journal of Australia 1991 (February 4) 154: 195-199.
Cooper, J. Ineffective use of psychoactive drugs methadone is no exception (Editorial). Journal of the American Medical Association 1992 (January 8) 267(2): 281-282.
Courtwright, D.T., Joseph, H. and Des Jarlais, D.C. Addicts Who Survived: An Oral History of Narcotic Use in America, 1923-1965. Knoxville, TN: University of Tennessee Press, 1989.
Cushman, P. The major medical sequelae of opioid addiction. Drug and Alcohol Dependence 1980 5: 239-254.
D'Aunno, T. and Vaughn, T.E. Variations in methadone treatment practices. Journal of the American Medical Association 1992 (January 8) 267(2): 253-258.
Des Jarlais, D.C.; Friedman, S.R.; Novick, D.M. et al. HIV-1 infection among intravenous drug users in Manhattan. Journal of the American Medical Association 1989 261: 1008-1012.
Des Jarlais, D.C.; Joseph, H.; Dole, V.P. and Schmeidler, J. Predicting post-treatment narcotic use among patients terminating from methadone maintenance. Journal of Alcohol and Substance Abuse 1983.
Dole, V.P. Implications of methadone maintenance for theories of narcotic addiction. Journal of the American Medical Association 1988 (November 25) 260(20): 3025-3029.
Dole, V.P. Addictive behavior. Scientific American 1980 (December) 243(6): 138-154.
Dole, V.P. and Joseph, H. Long-term outcome of patients treated with methadone maintenance. Annals of the New York Academy of Sciences 1978 311: 181-189.
Dole, V.P. and Nyswander, M.E. Methadone maintenance A ten year perspective. Journal of the American Medical Association 1976 235(19): 2117-2119.
Dole, V.P. and Nyswander, M.E. Heroin addiction: Metabolic disease. Archives of Internal Medicine 1967 120: 19-24.
Dole, V.P. and Nyswander, M.E. A medical treatment for diacetylmorphine (heroin) addiction. Journal of the American Medical Association 1965 (August 23) 193(8): 646-650.
Dole, V.P., Nyswander, M.E. and Kreek, M.J. Narcotic blockade. Archives of Internal Medicine 1966 (October) 118:304-309.
Dole, V.P., Nyswander, M.E. and Warner, A. Successful treatment of 750 criminal addicts. Journal of the American Medical Association 1968 (December 16) 206: 2710-2711.
Finnegan, L.P. The success of methadone in the treatment of pregnant opiate dependent women. Presented at the Second European Symposium on Drug Addiction and AIDS. Sienna, Italy: October 1993.
Food and Drug Administration. FDA Regulations in the Federal Register, 21 CFR Parts 200 to 299. Washington, D.C.: U.S. Government Printing Office, 1993.
Gearing, F.R. Success and failures in methadone maintenance treatment of heroin addiction in New York City. In: Proceedings of the Third National Conference on Methadone Treatment, p 2-16. Rockville: US Public Health Service, #2172, 1970.
Gearing, F.R. and Schweitzer, M.D. An epidemiologic evaluation of long-term methadone maintenance treatment for heroin addiction. American Journal of Epidemiology 1974 100: 101-112.
General Accounting Office. Methadone Maintenance: Some Treatment Programs are Not Effective; Greater Federal Oversight Needed. GAO/HRD-90-104, 1990.
Gordon, N. Reaction-times of methadone treated ex-heroin addicts. Psychopharmacologia 1970 16: 337-344.
Gunne, L.M.; Gronbladh, L. and Ohlund, L.S. The street life and treatment response of 105 heroin addicted women. Presented at the Second European Symposium on Drug Addiction and AIDS, p 18. Sienna, Italy: 4-6 October 1993.
Hargreaves, W.A. Methadone dose and duration for maintenance treatment. In: Research on the Treatment of Narcotic Addiction: State of the Art. NIDA Research Monograph. Washington, D.C.: U.S. Government Printing Office (DHHS No. (ADM)97-1281)), 1983.
Hartel, D.; Selwyn, P.A.; Schoenbaum, E.E. et al. Methadone maintenance treatment and reduced risk of AIDS and AID-specific mortality in intravenous drug users. No. 8546. Stockholm, Sweden: IV International Conference on AIDS, 1988.
Hentoff, N. A Doctor Among the Addicts: The Story of Marie Nyswander. Chicago: Rand McNally and Company, 1969.
Himmelsbach, C. Clinical studies of morphine addictions. Nathan B. Eddy Memorial Award Lecture. In: Harris, L.S. (ed), Proceedings of the 49th Annual Scientific Meeting of the Committee on Problems of Drug Dependence. National Institute on Drug Abuse, Research Monograph Series 81. Rockville: U.S. Dept. of Health and Human Services, 1968.
Inciardi, J.A. Some considerations in the clinical efficacy of compulsory treatment: Reviewing the New York experience. In: Compulsory Treatment of Drug Abuse and Clinical Practice. NIDA Research Monograph No. 86, p 126-138. Rockville: 1988.
Joseph, H. Substance abuse and homelessness within the inner cities. In: Lowenson, J.H.; Ruiz, P.; Millman, R.B. and Langrod, J.G. (eds). Substance Abuse, A Comprehensive Textbook. Baltimore: Williams and Wilkins, 1992.
Joseph, H. The criminal justice system and opiate addiction: A historical perspective. In: Leukefeld, C.G.; Times, F.M. (eds), Compulsory Treatment of Drug Abuse: Research and Clinical Practice, NIDA Research Monograph 86 (ADM 88-1578). Rockville: U.S. Department of Health and Human Services, 1988.
Joseph, H. and Appel, P. Historical perspectives and public health issues. In: Parrino, M. (Chair/Editor) State Methadone Maintenance Treatment Guidelines. Rockville: U.S. Dept. of Health and Human Services, 1992.
Joseph, H. and Appel, P. Alcoholism and methadone treatment: Consequences for the patient and the program. American Journal for Drug and Alcohol Abuse 1985 11(1&2): 37-54.
Joseph, H. and Des Jarlais, D.C. Methadone Patients in Conventional Society (unpublished internal report of the Research Bureau). New York: NYS Office of Alcoholism and Substance Abuse Services, 1980.
Joseph, H. and Dole, V.P. Methadone patients on probation and parole. Federal Probation 1970 June: 42-48.
Joseph, H and Springer, E. Methadone maintenance treatment and the AIDS epidemic. In: The Effectiveness of Drug Abuse Treatment: Dutch and American Perspectives, p 261-274. Malabar, Florida: Robert E. Krieger, 1990.
Kaltenbach, K. and Finnegan, L.P. Methadone maintenance during pregnancy: Implications for perinatal and developmental outcome. In: T. Sonderegger (ed), Perinatal Substance Abuse: Research Findings and Clinical Implications. Baltimore: John Hopkins University Press, 1992.
Kandall, S. R. (consensus panel chair). Improving Treatment for Drug-Exposed Infants. Treatment Improvement Protocol (TIP) Series 5, # (SMA) 93-2011. Rockville, MD: U.S. Department of Health and Human Services (DHHS), Center for Substance Abuse Treatment (CSAT), 1993.
Kreek, M.J. Methadone treatment (Special Presentation). Staten Island, NY: 30th Anniversary of Methadone Maintenance Treatment, 1993.
Kreek, M.J. The addict as patient. In: Lowenson, J.H.; Ruiz, P.; Millman, R.B. and Langrod, J.G. (eds), Substance Abuse A Comprehensive Textbook. Baltimore: Williams and Wilkins, 1992.
Kreek, M.J. Summary of Presentation at 1988 meeting of the Committee for the Problems of Drug Dependence. NIDA Notes 1988 Fall: 12, 25.
Kreek, M.J. Tolerance and dependence: Implications for the pharmacological treatment of addiction. In: Harris, L.S. (ed), Problems of Drug Dependence. Proceedings of the 48th Scientific Meeting of the Committee of the Problems of Drug Dependence, 1986. DHHS No. (ADM)87-1508. Rockville, MD: National Institute on Drug Abuse.
Kreek, M.J. Multiple drug abuse patterns and medical consequences. In: Meltzer, H.Y. (ed), Psychopharmacology: The Third Generation of Progress (Chapter 172), p 1597-1604. New York: Raven Press, 1987.
Kreek, M.J.; Garfield, J.W.; Gutjahr, C.L. et al. Rifampin-induced methadone withdrawal. New England Journal of Medicine 1976 294: 1104-1106.
Kreek, M.J. Medical complications in methadone patients. Annals of the New York Academy of Sciences 1978 311: 110-134.
Kreek, M.J. Medical safety and side effects of methadone in tolerant individuals. Journal of the American Medical Association 1973 (February 5) 223(6): 665-668.
Kreek, M.J.; Dodes, L.; Kane, S.; Knobler, J. and Martin, R. Long-term methadone maintenance therapy: Effects on liver function. Annals of Internal Medicine 1972 (October) 77(4): 598-602.
Loimer, N.; Schmid, R.; Grunberger, J.; Jagsch, R.; Linzmayer, L. and Presslich, O. Psychophysiological reactions in methadone maintenance patients do not correlate with methadone plasma levels. Psychopharmacology (Berl) 1991 103(4): 538-540.
Marmor, M.; Des Jarlais, D.C. and Cohen, H. Risk factors for infection with human immunodeficiency virus among intravenous drug abusers in New York City. AIDS 1987 1: 39-44.
Martin, W.R.; Wilker, A.; Eades, C.G. et al. Tolerance and physical dependence on morphine in rats. Psychopharmacology 1963 4: 247-260.
McLellan, T.A.; Arndt, T.O.; Metzger, D.S.; Woody, G.E. and O'Brien, C.P. The effects of psychosocial services in substance abuse treatment. Journal of the American Medical Association 1993 (April 21) 269(15): 1953-1959.
Newman, R.G. and Cates, M. Methadone Treatment in Narcotic Addiction: Program Management, Findings and Prospects for the Future. New York: Academic Press, 1977.
Neuspiel, D. Personal communication, 1993.
Novick, D.M.; Joseph, H.; Croxson, T.S. et al. Absence of antibody to human immunodeficiency virus in long-term, socially rehabilitated methadone maintenance patients. Archives of Internal Medicine 1990 (January) 150: 97-99.
Novick, D.M.; Ochshorn, M.; Ghali, V. et al. Natural killer activity and lymphocyte subsets in parental heroin abusers and long-term methadone maintenance patients. Journal of Journal of Pharmacology and Experimental Therapeutics 1989 250: 606-610.
Novick, D.M.; Khan, I. and Kreek, M.J. Acquired immunodeficiency syndrome and infection with hepatitis viruses in individuals abusing drugs by injection. Bulletin of Narcotics 1986 38: 15-25.
Novick, D.M.; Richman, B.L.; Friedman, J.M.; Friedman, J.E.; Fried, C.; Wilson, J.P.; Townley, A. and Kreek, M.J. The medical status of methadone maintenance patients in treatment for 11-18 years. Drug and Alcohol Dependence 1993 33: 235-245.
Nyswander, M.E. The Drug Addict As A Patient. New York: Grune & Stratton, 1956.
Parrino, M.W. Overview: Current treatment realities and Future Trends. In: Parrino, M.W. (Chair & Editor), State Methadone Maintenance Treatment Guidelines (The Purple Book). Rockville, MD: U.S. Department of Health and Human Services, Center for Substance Abuse Treatment; 1992.
Payte, J.T. and Khuri, E. Principles of methadone dose determination. In: Parrino, M.W. (Chair & Editor). State Methadone Maintenance Treatment Guidelines (The Purple Book). Rockville, MD: U.S. Department of Health and Human Services, Center for Substance Abuse Treatment; 1992.
Payte, J.T.; Khuri, E.; Joseph, H. and Woods, J. Methadone patients and the treatment of pain. In: Methadone Treatment Is Recovery: A Manual for Methadone Maintenance Treatment, Part 1. New York: Chemical Dependency Research Working Group, NYS Office of Alcoholism and Substance Abuse Services, 1994.
Randall, J. Personal communication, 1994.
Schuster, C. Methadone maintenance: An adequate dose is vital in checking the spread of AIDS (Director's Column). NIDA Notes 1989 Spring/Summer: 3.
Stimmel, B.; Goldberg, J.; Cohen, M. and Rotkopf, E. Detoxification from methadone maintenance: Risk factors associated with relapse to narcotic use. In: Kissen, B.; Lowenson, J.H. and Millman, R. (eds), Recent Developments in the Chemotherapy of Narcotic Addiction. New York: New York Academy of Sciences, 1978.
Simpson, D.D. Treatment for drug abuse follow up outcomes and length of times spent. Archives of General Psychiatry 1981 38: 875-880.
Tennant Jr., F.S. Inadequate plasma concentrations in some high-dose methadone maintenance patients. American Journal of Psychiatry 1987 144: 1349-1350.
Tong, T.G.; Pond, D.M.; Kreek, M.J. et al. Phenytoin-induced methadone withdrawal. Annals of Internal Medicine 1981 94: 349-351.
Unterwald, E.M.; Horne-King, J. and Kreek, M.J. Chronic cocaine alters brain mu opioid receptors. Brain Research 1992 584: 314-318.
Watters, J.A. and Price, R.H. The relationship of treatment policy to client retention. In: Appel, P., Treatment Issue Report #56 (unpublished internal report). New York: New York State Division of Substance Abuse Services, 1985.
Weber, R.; Ledergerber, B.; Opravil, M. and Luthy, R. Cessation of intravenous drug use reduces progression of HIV infection in HIV+ drug users. Presented at the VI International Conference on AIDS. San Francisco: 1990.
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Last Update: March 15, 2001 |
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