Methadone use in the outpatient treatment of narcotic addicts


Methadone hydrochloride
The Philadelphia out-patient programme
Summary and discussion


Author: Walter R CUSKEY
Pages: 23 to 30
Creation Date: 1971/01/01

Methadone use in the outpatient treatment of narcotic addicts

Ph.D Walter R CUSKEY Associate in Community Medicine, Department of Community Medicine, Instructor, Department of IndustryWharton School of Finance and Commerce, University of Pennsylvania, Philadelphia, Pennsylvania

The synthetic narcotic methadone has recently become the centre of controversy involving physicians, law enforcement officials, and legislators. Both legally and pharmacologically a narcotic drug, capable of producing dependence and subjected to narcotic controls, it has nevertheless been shown to be of significant value in the rehabilitation of narcotic addicts. Its use has been shown to block the craving for other narcotics and to eliminate the need for largely ineffective total abstinence programmes. New results, reported here, suggest that methadone maintenance, on an ambulatory basis, can greatly reduce the need for costly, scarce inpatient treatment of addiction and enable rehabilitation programmes to treat a larger proportion of addicts. While not the only approach to the treatment of addiction, and while posing some hazards, methadone nevertheless is a drug of importance and deserves intensive further investigation-especially, as examined here, with regard to its potential for making possible changes in the organization of treatment resources.

Methadone hydrochloride

Methadone, a synthetic narcotic, was first synthesized by German chemists and introduced to clinical application at the end of the Second World War. The drug-known variously as methadone, dolophine, amidone, physeptone, miadone, butalgin, diadone, and polamidone-bears only a remote stereochemical resemblance to morphine; yet its pharmacological properties are qualitatively similar to those of the natural alkaloid.

Pharmacologic properties and actions

The most outstanding property of methadone is an effective analgesic activity of equal, or somewhat greater, potency than that of morphine; a dose of 7.5 to 10 mg provides the approximate analgesic equivalent of one 10 mg dose of morphine. While methadone generally produces relatively fewer hypnotic effects than do comparable doses of morphine, marked sedation is observed upon repeated administration, due possibly to a cumulative effect of the drug (1). In equianalgesic doses, its capacity for producing respiratory depression is equivalent to that of morphine.

While some peripheral vasodilatory properties may contribute to orthostatic hypotension, cardio-vascular effects, especially in the recumbent individual, are not prominent, and methadone does not interfere with cardio-vascular reflexes. Full analgesic doses do not modify cerebral oxygen consumption, although, since the drug depresses sensitivity to CO 2, there is some degree of CO 2 retention, resulting in dilatation of the cerebral vasculature and an elevation of cerebro-spinal fluid pressure ( [ 2] ).

Appreciable concentrations of methadone can be found in the plasma within ten minutes after subcutaneous injection. It is also well absorbed from the gastro-intestinal tract following oral administration. Like most narcotic analgesics, methadone is rapidly removed from the blood and localized in such tissues as the lungs, liver, kidney, and spleen; only a small fraction actually enters the brain. Methadone appears to be firmly bound to tissue protein, and the action of the drug in man can probably best be accounted for by assuming a gradual cumulative effect followed by low excretion.

Methadone undergoes extensive bio-transformation, chiefly in the liver. A considerable portion is excreted as metabolites into the intestinal tract by way of the bile, and a major fraction of the administered methadone appears in the urine and faeces as unknown bio-transformation products; less than 10 % of the drug is excreted unchanged ( [ 3] ).

As the hydrochloride (Methadone HCl, USP), methadone is a bitter white crystalline powder, soluble in water and ethanol, and incompatible with alkaline solutions. All conventional routes of administration may be used, although subcutaneous injection may cause local irritation. The oral analgesic dose for adults is from 5 to 15 mg, depending on the severity of pain and the response of the patient; parenteral dosage may be slightly lower.


Side-effects of methadone are similar to those caused by morphine, including lightheadedness, dizziness, drowziness, mental clouding, sweating, pruritus, nausea, and vomiting. As with morphine and meperidine, the side-effects more frequently occur after oral than after parenteral administration, and more often in ambulatory than in bed patients. The principal danger of overdosage is diminished pulmonary ventilation.

In assessing the abuse liability of methadone and its cogeners in man, volunteer post-addicts who received subcutaneous methadone four times daily developed tolerance to the analgesic, nauseant, myotic, sedative, respiratory depressant, and cardio-vascular effects; tolerance to the constipating effect was not developed. Although tolerance to methadone develops more slowly than to morphine, especially with respect to the depressant effects, this may be related not so much to slow development of tolerance as to the cumulative effects of the drug. Marked sedation, with concommitant slowing of the EEG occurs during the first few days of experimental addiction, and the behaviour of the methadone addict is strikingly similar to that of the morphine addict ( [ 4] ).

Development of physical dependence upon the chronic administration of methadone can be demonstrated by drug withdrawal or by administration of the narcotic antagonist nalorphine. Subcutaneous administration of 10 to 20 mg of methadone in former narcotic addicts produces definite euphoria, persisting somewhat longer than that caused by morphine. As with other drugs, methadone has become a source of potential abuse, and many addicts now prefer the effects of the synthetic compound to those of the natural alkaloids ( [ 5] ). The over-all abuse incidence of methadone would seem to be somewhat lower at this point than that of morphine, but increasing numbers of addicts have added methadone to their list of abused drugs.

Therapeutic uses

The efficacy of methadone in the treatment of narcotic addiction has been well documented ( [ 6] ). Among the findings of numerous studies have been the observations that methadone produces a cross-tolerance, or blockade, to other narcotics while producing relatively few side-effects; that it is a long-acting drug, effective by the oral route; and that it markedly reduces drug craving in stabilized patients. On the basis of this knowledge, a large number of methadone maintenance programmes have been instituted in major cities throughout the United States and Canada. The widespread acceptance of this treatment method has also produced certain modification of the modality as first presented by Dole and Nyswander in 1965.

Research design

This study was designed first, to provide empirical data on patient-addicts currently under treatment for heroin addiction; and, second, to describe the effectiveness of the outpatient technique for detoxifying and maintaining addicts with methadone at the Narcotic Rehabilitation Clinic Program * of the West Philadelphia Community Mental Health Consortium located at Philadelphia General Hospital, in Philadelphia, Pennsylvania.

To accomplish these aims, data were analysed on admission of addicts to the Narcotic Rehabilitation Clinic Program between 30 March 1969 and 1 April 1970. During this period a total of 198 patients were admitted to treatment. Of the 198 new admissions 48 (24.2%) have terminated treatment and 20 (10.1%) have been successfully detoxified. As of 1 April 1970, a total of 310 patients were in active treatment at the Clinic: 196 patients (63.2%) on methadone maintenance; 104 (33.5%) on outpatient detoxification; and 10 (3.2%) on supportive counselling.

For descriptive purposes, we have grouped the attributes available for analysis into three groups: ( a) social characteristics; ( b) characteristics associated with hospital admission; and ( c) characteristics indicative of clinical improvement. No attempt has been made to compare the" detoxification" and the" maintenance" groups, but only to describe the characteristics of each group.

The Philadelphia out-patient programme

The rationale

During the development of a methadone programme in Philadelphia, applicants were interviewed who did not appear to require either high doses of methadone or prolonged maintenance treatment. Typically, these patients were either well integrated and highly motivated to give up heroin addiction, or they were only recently addicted and had decided not to regress further into the junkie life-style. Still other patients at least wanted to attempt detoxification before committing themselves to long term maintenance. Yet most of these patients had either tried the conventional treatment approaches and found them lacking, or were unable to obtain alternative treatment because of the dearth of facilities.

* The clinic is a unit of the West Philadelphia Community Mental Health Consortium and is located in Philadelphia General Hospital. The programme is financed through N.I.M.H. Support Grant: H-17 MH-16359-01.

Methadone use in the outpatient treatment of narcotic addicts 25

The rationale for this treatment is based upon clinical observations that indicate that methadone has the following therapeutic qualities : first, it produces few, if any, known debilitating effects from long-term administration; second, it markedly reduces or abolishes the drug craving which drives many detoxified patients to resume heroin addiction; third, the methadone patients achieve what is known as "tolerance" to methadone, and a "cross-tolerance" to heroin; and finally, patients look well, feel well, and behave normally under the influence of methadone. It was against this backdrop that an experimental "method for outpatient treatment" began to develop during 1967.

The selection process

Admission to the outpatient clinic depends on having been addicted to a narcotic and living within the geographic boundaries defined as the programme's catchment area. No other selection criteria are used. The outpatient clinic, located at a major city hospital, receives most of its referrals to the programme from informal communications on the street with addicts who are already in treatment. Only a small proportion of referrals come from physicians or agencies. Most patients seek treatment voluntarily even though they have been on a waiting list from four to six months before treatment begins.

The admission procedure consists of an intake interview with a social worker or ex-addict counsellor. The counsellor talks with the addict, and, when possible, with a member of his family, obtains a brief social and drug history, and schedules the patient for a complete physical check-up, including laboratory tests. Before the treatment process begins, a psychiatrist evaluates each patient, including psychological testing where indicated, and formalizes the procedures for the total rehabilitation process. The psychiatrist then refers the patient to either the detoxification programme or the methadone programme.

For example, of the 198 new patients admitted to treatment from 30 March 1969 to 1 April 1970, 14 (7.1%) began treatment on methadone maintenance, 176 (88.9%) began treatment on outpatient detoxification, and 8 (4.1 %) were admitted for supportive counselling only.

Patients with the greatest potential for successful rehabilitation are referred to the detoxification programme. A few "hard-core" addicts with long histories of multiple treatments and incarcerations and little chance of achieving abstinence are admitted directly to methadone maintenance. Patients may also be transferred to the maintenance programme when they fail to respond to the detoxification regimen. During the past year, for example, 62 detoxification patients have been transferred to methadone maintenance and have remained in treatment.

Detoxification programme

The detoxification programme is carried out in the following manner ( [ 7] ). Most patients begin treatment with methadone tablets at a dosage of 40 mg per day, which are dissolved in a liquid substance (orange juice) and taken orally. This dosage, when taken properly, will keep most persons from getting "sick" regardless of the size of their habits. Occasionally, patients with smaller habits (1-3 bags per day) start with 20-30 per day and patients with larger habits (over 7 bags per day) start with 50-60 mg per day. In general, however, most patients do well on a dosage of 40 mg per day. It is usually recommended that each patient take two 20 mg tablets every 12 hours, although some patients prefer 10 mg tablets every 6 hours.

New patients report to the clinic five days per week. On each daily visit the patient sees his counsellor, who is a social worker or trained ex-addict, for a 20-30 minute session. Besides individual counselling, the patient may receive group therapy. The main emphasis in this supportive counselling is on present and future behaviour, including such areas as drug abuse, employment, domestic relations, interpersonal relations, and general attitudes. The work role is strongly encouraged and assisted, when indicated, by job counselling or vocational training. After the counselling session, the patient receives a day's supply of methadone and leaves a urine specimen which is analysed for methadone, morphine, quinine, barbiturates, amphetamines, and cocaine.

When the patient has ceased, or almost ceased heroin use and has shown some progress toward emotional and social rehabilitation, the dose of methadone may be decreased in 10 mg intervals. The treatment is highly individualized, so that detoxification may occasionally be accomplished in a few weeks (30 days) or more typically in 4 to 8 months, or, in some instances, may even require a year or longer to complete the process. In the event of a relapse, the dosage is increased until re-stabilization occurs.

Certain aspects of the treatment can be viewed as a reward-punishment system. These include variation in the frequency of clinic visits, adjustment in dosage, the possibility of temporary suspension from treatment, and the verbal responses of the counsellor. Recalcitrant patients may be required to accomplish some task in a given time period (e.g. obtain a job, cease cheating, etc.) or face suspension for a period of time (usually 30 days). This reward-punishment system provides a concrete frame of reference for both the patient and his counsellor to judge over-all progress.

If there is persistent failure to respond effectively to detoxification treatment, based on the judgement of the counsellor, three alternatives are available: ( a) transfer to methadone maintenance; ( b) temporary suspension from treatment; ( c) transfer to another treatment facility. The third alternative is rarely used, however, because of limited facilities available.

Methadone maintenance

Original use of the methadone maintenance modality required the addict-patients to be hospitalized for six to eight weeks. During in-patient treatment, the patient was stabilized on methadone and prepared psychologically and socially for re-integration into the community. Unfortunately, shortage of specialized hospital space and personnel experienced in treating narcotic addicts severely limited the use of a modality requiring in-hospital treatment. Since then, we have begun treating maintenance patients on an out-patient basis ( [ 8] ).

In the maintenance programme, instead of tapering off the methadone as in the detoxification programme, the medicine dosage is raised by 10 mg increments until a maintenance dose is reached. This maintenance dosage ranges from between 40 mg to 140 mg per day, depending on the tolerance level of the individual patient. As in the detoxification programme, the methadone is dissolved in a liquid solution (orange juice) and taken orally.

During the course of treatment, many patients will ask for and sometimes demand an increase in medication because their current dosage of methadone is not" holding them ". That is, in their perception, the amount of medicine they are getting has not kept them from experiencing some degree of physical discomfort (nausea, aches, dizziness, etc.). This perception sometimes arises from the fact that most addicts equate a feeling of strain with an insufficient amount of medication based on their previous experience with heroin. In the past, when a patient experienced problems in such areas as employment, domestic relations, interpersonal relations, heroin would be used as a mechanism for avoiding his problems.

In our programme, before a re-evaluation of the amount of methadone prescribed for a patient will be considered, the counsellor must confront the patient with the fact that he is willing to remain dependent on drugs as a means of avoiding painful situations and problems. Encounters of this nature are difficult for both patients and staff, but are therapeutically important to the successful rehabilitation of the addict-patient.

Observed clinical side-effects

Observations from the Philadelphia programme indicate that about 15% of the addict-patients develop minor side-effects from using methadone HCl. Among those side-effects observed were constipation, delayed menses, obesity, ankle oedema, occasional nausea, and impotence in males. Constipation is the most common side-effect observed. Several investigators reported sexual impotence in at least 25 % of the males studied in other methadone maintenance programmes around the coun try (9). The incidence of sexual impotence reported in the Philadelphia programme, about 10%, does not correspond with the findings reported elsewhere. However, clinicians are aware of its existence and deal with it in their counselling sessions with the patient.

Most of the side-effects noted diminish as the body develops tolerance to the pharmacologic action of methadone. Aside from these minor side-effects, no serious physical complications directly attributable to methadone have been observed.

Addict-patient profiles

The narcotic addicts reported in this study can be readily characterized as hard-core heroin addicts. All were heroin addicts and typically, they had begun using heroin while still in their teens, had been using heroin an average of 12.4 years, had undergone several formal treatment for their addictions, and had experienced non-medication detoxifications as the result of being incarcerated several times.

In spite of their addictions, the majority of addicts were married and living with their spouse and over half were legally employed at the time they began treatment. Indicative of geographic stability all of the addicts had been born in Pennsylvania. Most of these addicts were high-school drop-outs, however. The sex and race distributions were not representative of the Philadelphia population. Both males and whites were over-representated with most of the addicts being white males.


Characteristics of the addict-patient at time of admission to treatment



Percentage of total

1. White
159 53.0
2. Male
274 91.3
162 54.0
4. >12 years education
285 95.0
5. Married
197 65.6
6. Employed
165 55.0
7. State of birth (Penna.)
300 100.0
8. >Age 20 first addicted
210 70.0
9. History of prior treatment
223 74.3
10. History of criminal conviction
288 96.0
11. History of welfare
145 48.3

Urine surveillance

Urine laboratory surveillance to detect the use or abuse of dependence drugs has generally been accepted as a necessary adjunct to the proper management of any addiction detoxification or maintenance programme.

Early in 1969, the Clinical Pharmacology-Toxicology Center at the Philadelphia General Hospital was asked to perform this function for the West Philadelphia Community Mental Health Consortium's Narcotic Addict Rehabilitation Programme (10). It was initially decided to adopt the Dole procedure presently in wide use, especially among the various New York City methadone programmes. Briefly, this method involves absorbtion of drugs from urine onto a cation exchange paper, ellusion into buffers at three different pH's, spotting on silica gel thin layer chromotographic plates, running the plates in a suitable solvent, and spraying with appropriate chromogenic stains to test for barbiturates, morphine, quinine, methadone, and the amphe-tamines. Since then, the Pharmacology-Toxicology Center has modified this procedure to include a test for cocaine in an effort to respond to the increasing problem of cocaine abuse in the Philadelphia area.

As indicated earlier, new patients report to the clinic five days a week and produce fresh urine for surveillance on each visit. Although the number of clinic visits is reduced as patients progress in the programme, these patients still visit the clinic on the average of four times per week. The approximately 1,000 urine specimens a week are screened for the presence of various drugs, provide each counsellor with immediate feed-back on the "cheating-behaviour" of each addict-patient of his case load. Since the initiation of this technique "cheating" has decreased substantially suggesting that immediate feedback of this kind of information may have rehabilitative value.

Our experience has been, for example, that over 60 % of maintenance patients initially "cheat" with heroin during the first few months of treatment. This eventually stabilizes, but even after twenty months of narcotic substitution therapy 30% of maintenance patients still "cheat" on occasion. However, during a recent 60-day evaluation, "cheaters" were analysed an average of 15.3 times and heroin (morphine and/or quinine) was detected an average of only 2.0 times. Stated differently, only 14.5% of the urines collected from the 30% of the "cheaters" were positive for heroin. This amount of heroin abuse is minimal when contrasted with those patients' previous incidence of heroin use.

Clinical improvements

In addition to urine surveillance, the research unit has developed a progress evaluation instrument-which is administered monthly to all active patients. During the third week of every month, each counsellor administers this form to every patient on his case load, and obtains information indicative of stability in daily living activities as to whether the patient lives with his spouse or has separated; whether he is working full time, part time, or has become unemployed, and the amount of his monthly income; whether he has been arrested in the last month and placed on probation, or has a case pending. This data is computer processed, analysed, and evaluated, and the results used to assess the clinical and social progress of each patient as well as the progress of the entire programme.

At the time of this evaluation, patients on both detoxification and maintenance programmes showed similar patterns of improvement, based on information such as weekly reporting, length of time in treatment, psychiatric interviews, employment status, and arrest record.

Clinical attendance

All of the patients were attending 1-5 times per week. Maintenance patients attend clinic on the average of four times per week and detoxification patients attend clinic on the average of three times per week.


Number of clinic visits per week



Number of visits



Number of visits



1 6 3.1 1 12 11.5
2 24 12.2 2 24 23.0
3 50 25.5 3 40 38.5
4 1
4 1 1.0
5 115 58.7 5 27 26.0
Total ..
196 100.0   104 100.0
(Mean: 4 visits)
(Mean: 3 visits)

Length of treatment

At the time of this evaluation, patients had been in treatment from 1-42 months. Maintenance patients remained in treatment on the average of 10.2 months and detoxification patients on the average of 9.4 months.


Length of treatment









81 41.3
32 30.7
18 9.2
25 24.0
22 11.2
16 15.4
43 21.9
12 11.5
32 16.3
19 18.4
Total ..
196 100.0   104 100.0
(Mean: 10.2 months)
(Mean: 9.4 months)

Psychiatric evaluation

All addict-patients are evaluated monthly by an ex-addict counsellor, social worker, or psychiatrist. Both groups showed clinical improvement, as judged by global ratings of mood, attitude, and emotional stability. Of the maintenance patients, 66.9% showed marked or moderate clinical improvements during the study period, as did 93.3 % of the detoxification patients.


Clinical improvement based on psychiatric interview




Clinical improvement





Marked improvement
96 49.0 58 55.8
Moderate improvement
35 17.9 39 37.5
Minimal or no improvement
65 33.1 7 6.7
196 100.0 104 100.0


The employment status of an addict-patient being treated with methadone is one of the major indices routinely cited as indicating the effectiveness of the modality. During the study period, 66.3 % of the maintenance patients and 58.6% of the detoxification patients held full-time or part-time jobs. The salaries ranged from $100 to $1,200 per month with a mean of $275.


Employment status as of 4 January 1970









Working full- or part-time
130 66.3 61 58.6
Not working
66 33.7 43 41.3
196 100.0 104 100.0

Most of the patients who remained unemployed after being treated with methadone have stopped stealing and other deviant forms of obtaining money. This treatment has permitted most of them to live within the limits of public assistance or to live within their spouses' or families' incomes.


As with most narcotic addicts, multiple arrests were common among these 300 addict-patients prior to treatment. Of these 300, 94.6% reported that they had been arrested prior to treatment with an average of 5.8 arrests.

Under treatment, however, 95.5% of the maintenance patients reported they had not been arrested and 93.5% of the detoxification patients also reported no arrests. Since treatment, mean numbers of arrests for both groups was only 1.0.


Arrest since beginning treatment









10 4.5 6 6.5
186 95.5 98 93.5
196 100.0 104 100.0

Summary and discussion

This report describes the properties of methadone as an effective analgesic, and its side-effects on the body. It also describes the West Philadelphia Community Mental Health Consortium's Narcotic Addiction Rehabilitation Program at Philadelphia General Hospital, and shows the efficiency of this out-patient technique in stabilizing and maintaining narcotic addicts with methadone.

At the time of this evaluation, the 300 patients in both the detoxification and maintenance programmes at the Narcotic Addiction Rehabilitation Program showed similar patterns of improvement, based on information such as weekly reporting, length of time in treatment, psychiatric evaluation, employment status, and arrest history.

  1. All of the patients, detoxification and maintenance, attended clinic regularly and remained in treatment for an extended period of time. Maintenance patients attended clinic on the average of four times a week, and remained in treatment on the average of 10.7 months. Detoxification patients attended clinic on the average of three times a week and remained in treatment on the average of 9.4 months.

  2. The monthly psychiatric evaluation indicated that both groups showed clinical improvement as judged by global ratings of mood, attitude, and emotional stability. Of the maintenance patients, 66% showed marked or moderate clinical improvement, as did 99.3 % of the detoxification patients.

  3. Almost two-thirds of all addict patients were gainfully employed: 66% of the maintenance patients and 58.6% of the detoxification patients had full-time or part-time jobs. The salaries ranged from $100 to $1,200 per month, with an average of $275.

  4. Of the 300 patients, 94% reported that they had been arrested prior to treatment, with an average of 5.8 arrests. Under treatment, however, almost 95% of both maintenance and detoxification patients reported no arrests. The mean number of arrests for both groups under treatment was only 1.0.

These findings suggest several theoretical, practical, and clinical advantages for utilizing an out-patient detoxification and maintenance programme in the treatment of narcotic addicts. Of primary clinical importance is the fact that rehabilitation occurs in the community with all of its normal stress and temptations. The ability to cope with these problems has much greater poignancy and relevance to patients than a limited and artificial ability to cope with the environment of an institution. Furthermore, certain types of behaviour can occur in the community which would be intolerable in an institution, including sexual intercourse, aggression, and drug abuse. In most hospital or therapeutic communities, any of these behaviours are grounds for immediate discharge and termination of treatment. By contrast, in an outpatient clinic, these behaviours become topics for therapeutic discussion, and, in fact, may represent essential learning experiences for both the patients and the staff. Treatment does not have to be terminated.

Secondly, out-patient treatment avoids the difficulties of re-entry into the community. After extended institutionalization, re-entry is traumatic, and often results in relapse to drugs. The chief benefit of the out-patient modality for the patient is that even during the detoxification or maintenance process, he can begin to learn new, or re-establish old, non-addict social patterns. This time can also be utilized to engage in ego-building experiences such as meaningful family and peer relationships and re-establish himself in educational and occupational roles.

Thirdly, some addicts do not seek treatment for fear of jeopardizing their jobs, their school attendance, or their maternal roles. They will, however, accept treatment in an out-patient clinic where they can continue their normal activities. As a rule, this group has an excellent prognosis for successful treatment.

Fourthly, the maintenance and detoxification of patient-addicts without an in-patient phase provides a research laboratory not previously available. It becomes possible to study the processes out of addiction, the adjustment to conventional roles, the frequency of relapse during the process of treatment, etc.

Finally, out-patient treatment is comparatively inexpensive and has minimal space requirements. The cost is about $1,000 to $1,500 per patient per year. This amount would cover only about a month of hospitalization, or about three months in a therapeutic community. Organized properly, out-patient clinics with proportionately smaller numbers of professional and support staff than required in an in-patient unit would have the capability of dispensing medication, providing counselling, and giving medical, vocational and educational services to a larger number of patients on a daily basis. In addition, most of the patients are gainfully employed during the treatment, are paying their taxes, and are paying a clinic fee.

The author is committed to the efficacy of ambulatory techniques in the treatment of narcotic addiction, and believe these techniques will be an important answer to the increasing incidence of narcotic abuse in the United States.



Isbell, H., Wikler, A., Eisenman, Anna J., Daingerfield, Mary and K. Frank, "Liability of addiction to 6-dimethylamino-4-4-diphenyl-3-heptanone (methadone, 'amidone', or '10 820') in man ", Archives of Internal Medicine, 82:362-392, 1948.


Jaffee, Jerome H., "Narcotic analgesics" in The Pharma-cologic Basis of Therapeutics, Third Edition, L. S. Goodman and A. Gilman. New York: McMillan, 247-284, 1965.


Way, E. L. and Adler, Terrine K., "The pharmacologic implications of the fate of morphine and its surrogates", Pharmacologic Review, 12:383-446, 1960.


Jaffee, Ibid., p. 253.


Isbell, Ibid.


See, Dole, V. and Nyswander, M., "A medical treatment for diacetylmorphine (heroin) addiction ", Journal of the American Medical Association, 193(8):646-650, 1965; Dole, V. and Nyswander, M., "Rehabilitation of heroin addicts after blockade with methadone ", New York State Journal of Medicine, 66:2011-2017, 1966; Dole, V., Nyswander, M. and Kreek, M., "Narcotic blockade ", Archives of Internal Medicine, 118:304-309, 1966; Freedman, A., Fink, M., Sharoff, R. and Zaks, A., "Cyclazocine and methadone in narcotic addiction ", Journal of the American Medical Association, 202:191-194, 1967; Brill, L. and Jaffee, J., "The relevancy of some newer American treatment approaches for England ", British Journal of Addictions, 62:375-386, 1968; Dole, V., Nyswander, M. and Warner, A., "Successful treatment of 750 criminal addicts ", Journal of the American Medical Association, 206:2708-2711, 1968; Wieland, W., "Methadone maintenance treatment of heroin addiction: beginning treatment on an outpatient basis ", Read before the annual meeting of the American Psychiatric Association, Boston, May 12, 1968; Jaffee, J., Zaks, M. and Washington, E., "Experience with the use of methadone in a multi-modality program for the treatment of narcotics users ", International Journal of the Addictions, 4(3):481-490, 1969; Cuskey, W. R., Chambers, C. D., Wieland, W. F., "Predictors of attrition during the outpatient detoxification of opiate addicts ", Bulletin on Narcotics, Volume XXII, Number 4, October 1970.


Wieland, W., "Methadone maintenance treatment of chronic narcotic addiction ", New Physician, 18:210-211, 1969.


Wieland, W. and Chambers, C., "Two methods of utilizing methadone in the out-patient treatment of narcotic addicts ", read before the Second National Conference on Methadone Treatment, New York City, October 26-27, 1969.


Scrigner, C. B., Associate Professor of Psychiatry, Tulane University School of Medicine, and Bloom, W. A., Assistant Professor of Psychiatry, Tulane University School of Medicine, "Guidelines for using methadone in the outpatient treatment of narcotic addicts", unpublished monograph, page 5, 1970.


Muantongchin, M., Becker, S. R. and Taylor, W. J. R., "Detection of abuse-potential drugs in urine ", Federation Proceedings, 26:677, 1970.