narcotic antagonist treatment of addict parolees by dr. charles savage

8/7/2019 Narcotic Antagonist Treatment of Addict Parolees by Dr. Charles Savage

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Narcotic Antagonist Treatment of Addict Parolees-

The Failure of an Effective Approach

Thomas E. Hanlon, 0. Lee McCabe, Charles Savage, and Albert A. Kurland

CONTEMPORARY TREATMENT APPROACHES for the chronic nar-

cotic abuser may be subsumed under two major models: maintenance and

abstinence. Prototypes of the maintenance model are the “British system” of le-

galized narcotics prescription and the “American system” of daily methadone

administration. Included under the abstinence model are various procedures

aimed at eliminating drug-seeking behavior and, ironically, establishing the goal of

treatment, i.e., abstinence, as a condition of continued participation from the very

outset. Procedures used in attempts at achieving the abstinence goal range from

traditional and behavior therapy to more exotic methods such as transcendental

meditation.One of the more recently applied abstinence methods is the narcotic antagonist

approach, the rationaleof which is anchored in learning theory/behavior modifica-

tion principles implemented through the use of a chemical agent. The apparently

sound theoretical basis for the application of this approach, together with promis-

ing early clinical trials, have produced not only an unusual amount of enthusiasm

and activity among scientists and clinicians in the tield but also a corresponding

supportive commitment from the United States Federal Government. The

massive expenditures of time, effort, and money to date not withstanding, there

are still unsettling questions which need to be answered before generalizations

about the efficacy of available narcotic antagonists can be made. In fact, our ownprevious work with these substances, as well as the pioneering efforts of other

investigators, have raised as many questions as they have answered.

Issues which appear to be of special relevance are the following: a) What spe-

cific therapeutic actions do antagonists have when placebo and programmatic ele-

ments are controlled? b) Must antagonists be administered daily, or can they be

effectively utilized on a “crisis-intervention” basis? c) Do so-called “pure” an-

tagonists such as naloxone have any significant side effects; particularly those

which might bias outcome in favor of patients not receiving active medication’? d)

On the other hand, are some secondary effects remedial, i.e., might not the best

antagonist be one with a slight agonistic property of its own? e) Do some types ofaddicts respond better to antagonist treatment than others? f) Is antagonist treat-

ment uniformly effective over diverse outcome criteria’?

From the Maryland Psychiarric Research Center and rhe V:! Hospital. Baltimore. Md.

Thomas E. Hanlon, Ph.D.: ChieJ’o/ Socioenvironmenral Research. and 0. Lee McCabe. Ph.D.:

Chief’?/ .4ddkrions Research, Maryland Psychiatric Research C‘enier, Charles Savage, M.D.: Chiei

oJ Psychiatric and Chiej’oj the Drug Dependenre Treatment L/nits. If.3 Hospital. Albert A. Kurland.

M.D.: Superintendent, Maryland Psychiatric Research Center. allof Baltimore. Md. 21228.

Supported by the Division of Research. National tnsfirure on Drug .4buse, NID.4 Grani D.3004IC.

and the Drug .4 buse .Administration oJlheSlatt,o/‘Mar~land.

Reprint requessrs should be addressed to Thomas E. Ha&on. Maryland P.yychiarric Reseawh

Center, Baltimore. Md. 21228.

L 1977 bv Grune & Strarron. Inc.

Comprehensive Psych/atry, Vol 18, No. 3 (May/June) 1977 21 1



212 HANLON ET AL.

Addressing itself to many of the above issues, the present study is the latest in a

series of studies on the effectiveness of narcotic antagonists in the treatment of

narcotic addict parolees newly released from the Maryland correctional system toa narcotic clinic in metropolitan Baltimore. It is the concluding report on the

“contingent” approach to the use of antagonists in this setting, offering a sum-

marization of all of our experiences to date.

The overall program of research, which was superimposed on an ongoing ab-

stinence program,’ started several years ago with the introduction of the promis-

ing agent, naloxone (N-allylnoroxymorphone), a pure antagonist relatively free of

side effects. The scarcity and expense of naloxone at the time and the natural

reluctance on the part of most parolees to take medication daily prior to the

manifestation of need made the administration of naloxone contingent upon nar-

cotic drug use seem both economical and clinically appropriate. Early clinicalexperiences and subsequent pilot research2-4 were encouraging enough to prompt

a series of controlled clinical trials, the latest of which is herein reported.

MATERIALS AND METHODS’

Having volunteered for a six month narcotic antagonist treatment program, 154 newly paroled male

narcotic addicts were referred to an abstinence clinic employing daily urine monitoring and offering

weekly group psychotherapy. Upon referral, the parolees were randomly assigned to either a naloxone

or placebo treatment group and were administered medication under double-blind conditions whenever

unexcused absences or urinalysis results were indicative of opiate drug use. Ranging from l-4 tablets

per day, the equivalent of 500~2000 mg of naloxone, dosage was escalated on a one tablet per day basis

with continued evidence of opiate drug use and was discontinued only after four successive negativeurine specimens were obtained. Throughout the six month period, this procedure was repeated with

each subsequent deviation.

Criteria of treatment effectiveness included the number of unexcused absences, the number of

opiate positive specimens, length of participation in the program, reasons for termination, type and in-

cidence of side effects, and global community adjustment ratings for those remaining on the program

for the entire 6 months. The Minnesota Multiphusic Personality Inventory (MMPI) was administered

initial ly for descriptive and predictive purposes. Although its use as a criterion measure was curtailed

by lack of adequate group representation, the MMPI was also administered to study remainers at the

6 month evaluation point.

RESULTS

Of the 154 parolees referred to the study and assigned to the two treatment

conditions, 57 did not receive study medication for one reason or another and were

necessarily excluded from the naloxone-placebo comparison. Thirty-three of the

57 nonmedicated parolees completed the prescribed six month abstinence

program without a deviation in terms of unexcused absences or a positive urine

specimen. The remaining 24 nonmedicated parolees either refused medication or

absconded prior to the reception of medication.

Resulting sample sizes of parolees receiving medication were 55 for naloxone

and 42 for placebo. Descriptive characteristics for these parolees are presented in

Table 1.

Considering the total study sample of 97 parolees, the typical parolee was

single, black, in his mid twenty’s, and had completed a junior high school level of

education. He had experienced his first documented encounter with the law

enforcement system at age 17 and was subsequently involved in an average of four

more arrests, largely for drug-related reasons. The two subsamples showed no



NARCOTIC ANTAGONIST TREATMENT 213

Table 1. Demographic Characteristics of the Two Subsamples

Charactenstxs

Mean Age

Race

Black

White

Marital Status

Single

Married

Separated/Divorced

Mean Years of Education

Mean Age at First Arrest

Mean Number of Arrests

Naloxone PIWhO

Group GroupN = 55 N = 42

266 26.0

54 38

1 4

43 32

7 6

5 4

92 90

173 164

52 5.9

substantial differences with respect to the demographic characteristics in ques-

tion.

The MMPI profile for the study sample was similar in most respects to that

offered by Overall” as being the prototype for narcotic addicts. Its most salient

feature was the 4-9 ‘code type,’ considered by Marks and Seeman to be indica-

tive of a sociopathic-emotionally unstable personality with a high probability of

drug usage or addiction, and by Gilberstadt and Duker’ as characteristic of indi-

viduals who, though superficially friendly, outgoing, and likeable, tend to be self-centered, impulsive, and rebellious and to have a low standard of morality. The

initial MMPI profiles for the two subsamples are presented in Fig. 1. Although

there were no statistically significant differences between group means for any of

the validity or clinical scales shown, the overall profile for the placebo group

tended to have a slightly higher elevation. Completion and termination data for

the two subsamples and for the total sample are presented in Table 2.

The chi square value for the seemingly differential completion rate in favor of

placebo noted in the table was found to be 3.27 (3.84 needed for significance at the

0.05 level for 1 df). Considering the reasons for termination, this rate must be

viewed as a negative rather than a positive reflection of the pharmacological action

-- Nalorone

- PkWhO

100

90

Fig. 1. In i t i a l MMPI prof i les for the Naloxone (N =

43) and Placebo (N = 38) subsamples.

L F Kti5 DH~WMIP~P~SCM~S,

MMPI SCALES



214 HANLON ET AL.

Table 2. Completion and Termination Data for the Total and Two Subsamples

Disposition

Completed

Terminated

Absconded

Refused Further

Medication

Institutionalized

Transferred to

Maintenance

NSlOXO” e Placebo

Group Group

N = 55 N = 42

20 (36%) 23 (55%)

35 (64%) 19 (45%)

11 (20%) 7 (17%)

16 (29%) 8 (19%)

7 (13%) 1 (2%)

1 (2%) 3 (7%)

Total

Sample

N = 97

43 (44%)

54 (56%)

18 (19%)

24 (25%)

8 (8%)

4 (4%)

of naloxone, including, ironically, its antagonistic effect. Data relating to thelength of program participation are consistent with completion rates. The average

length of participation for the naloxone group was found to be 3.7 months vs. 4.8

months for the placebo group, most of this one month differential being accounted

for by the shorter participation of naloxone patients once medication was begun.

Results of urine monitoring procedures, in terms of unauthorized absences and

the provision of either a QNS or opiate positive urine specimen, are presented in

Table 3. Since the results of such procedures prior to the reception of medication

were uninfluenced by specific treatment effects, only data occurring after the

initiation of treatment were examined for comparative purposes. Also, to insure

meaningfulness of the information involved, only those individuals who remainedin the program for at least one month after their first dosage reception were in-

cluded in the analysis of results. Comprising at least 75% of their respective sam-

ples, 41 naloxone and 37 placebo subjects were thus selected.

Again reflecting the relative retention rates of the two treatments, those

parolees receiving placebo tended to remain longer in treatment and to attend the

clinic, providing an analyzable urine specimen, at least as reliably as those receiv-

ing naloxone. They were, however, providing positive urine specimens at a signifi-

cantly higher rate (the proportional difference of 0.11 vs. 0.07 significant at p <

.OOl). This result was largely accounted for by eight placebo cases whose rates

were above that of 39%, the highest for the naloxone group, and was consistentwith earlier reported findings of the relative effects of daily administered naloxone

vs. placebo.8

In view of the causal relationship involved, the amount of medication dispensed

in the contingent approach can be considered as another indication of the extent of

narcotic drug use, i.e., the greater amount, the greater the narcotics use. On the

average, treatment for both the naloxone and placebo groups was begun shortly

after one month of abstinence program participation. Although there was an

Table 3. Resultsof Urine Monitoring Procedures After the Initiation of Medication

Group

Numberof

Days Active

PercentageofUnexcused

Absences and

ONS Specimens

Number ofAnalyzable

Specimens

Provided

Percentageof Positive

Specimens

Percentageofuncoopara-

tive

Days

Naloxone (N = 41)

Placebo (N = 37)-

98 21% 73 7% 25%

114 22% 90 11% 27%




average of three contingent interventions for both treatment groups, the mean

number of days medication was dispensed overall was 19 days for naloxone and 25

days for placebo, with average daily dosages being 757 mg and the equivalent of

1068 mg, respectively (total mg dispensed/total days of administration). Analysis

of individual dosage schedules revealed that patients administered naloxone

tended to moderate their narcotic drug intake when they were placed on the

maximum dosage of 2000 mg. Whereas approximately one-third of the patients in

both treatment groups were administered the maximum dosage at one time or

another during the course of treatment, the average number of days this dosage

was utilized in the treatment of these cases was only 5 days for naloxone vs. 22

days for placebo. This result was not explainable in terms of relative absence or

dropout rates since these were found to be equivalent in the two treatment groups

at the 2000 mg level.

Of the 43 patients completing the prescribed treatment course, data on a locally

devised community adjustment scale” were available for 36 patients, or 18 from

each of the two treatment groups. Consisting of an average of IO-point ratings of

abstinence and occupational, residential and interpersonal adjustment, this scale

was completed by a social worker after an interview with the parole agent

responsible for the supervision of the addict in the community. As in earlier

studies in the same setting, the mean adjustment rating for the total sample of

study completers at six months was approximately 7.0, indicative of “good overall

adjustment,” with at least half of the sample demonstrating either no, or only

slight (“chipping”), narcotic drug use. Mean adjustment ratings for the naloxone

and placebo subsamples were almost identical.

Side effect information was also in agreement with past experiences with na-

loxone. Somatic complaints were reported for a total of 26 patients, 16 of whom

were receiving naloxone and 10 placebo. Accounting for the only significant

difference in terms of side effects between drug or placebo, gastrointestinal

distress (nausea, vomiting, and/or upset stomach) occurred in ten naloxone cases

vs. only one placebo case. Although severe untoward reactions necessitating the

termination of treatment did not occur, two naloxone patients refused further

medication after experiencing gastrointestinal problems and one after

unelaborated complaints of sickness, and three placebo patients refused further

medication after respective complaints of rash, loss of appetite, and general ma-

laise.

DISCUSSION AND OVERVIEW

Narcotic antagonists have been used for several years in the treatment of addic-

tion, yet rarely has their use been put to controlled test. Originally, there seemed

to be a universally held assumption that except for side effects, which until the

introduction of naloxone had been the antagonists’ principal drawback, there was

little question as to their utility. More recently, this assumption has beenchallenged, both in clinical practice and in studies, such as the currently reported

one, designed to isolate their pharmacological contributions beyond the mere

palliative value of pill taking.

For a period of time, investigative efforts centered on the search for a “pure”

antagonist, i.e., one that would demonstrate little or no action of its own other



216 HANLON ET AL

than the theoretically crucial opiate blocking effect. Unfortunately, it is now be-

coming apparent that a pure antagonist may not necessarily be the best an-

tagonist; at least, results of controlled studies on contingently and dailyadministered antagonists 4*8.‘”tend to support the conclusion that with the less mo-

tivated patient, effectiveness as an antagonist often precludes satisfactory treat-

ment outcome. There is little reason to doubt that a pure antagonist successfully

blocks the euphoric and analgesic effects produced by opiates, theoretically reduc-

ing an individual’s incentive to use narcotics while medicated. Rather than inhibit-

ing the drug-taking behavior of the typical less motivated addict, however, the

principal effect of such an agent appears to be that of reinforcing avoidance of

medication and indulgence in otherwise uncooperative behavior.

In the present employment of contingent administration, one-half of the na-

loxone patients (27 of 55) either refused to continue to take medication or ab-sconded prior to the 6-month termination point. Although obviously contributory

in both instances, the relative extent to which this noncompliance was the result of

the narcotic antagonistic property of naloxone or of its contingent method of

administration could not be determined on the basis of available evidence. Besides

the narcotic blocking effect, other deterrent influences on continued treatment in-

volvement were undoubtedly operating in the situation. Naloxone, for example,

was not exactly pleasant to take, inasmuch as one out of every five patients com-

plained of gastrointestinal distress at one point or another during treatment. Also,

because of the relatively large dosage of naloxone required to achieve blockade,

the consumption of as many as four large, bitter pills by the addict parolee was attimes required. Considering these aversive circumstances, an increase in termina-

tion rate would not be unexpected. Should aversive and/or artifactual effects have

less bearing on the acceptance of the newer antagonist, naltrexone,” controlled

studies of this agent which are currently underway will hopefully offer more speci-

fic information on the relationship between blocking effect and retention in treat-

ment.

Another matter relating to retention in the present study bears consideration.

Though not statistically significant, seven of the parolees administered naloxone,

as opposed to only one administered placebo, were subsequently terminated from

treatment because of the commission of a new offense. (One of the naloxone caseswas incarcerated on the day he was first placed on medication.) Disquieting to

some extent because of its implication, this finding was not generally explainable

in terms of any discernible underlying pattern of reaction to naloxone.

In evaluating any addiction treatment program, retention in program, i.e.,

simply whether a patient remains in the program or not, is a misleading criterion

without consideration of the extent of narcotic drug use. Results illustrativeof this

were obtained from a recently concluded study* of the daily use of naloxone in a

“partial blockade” dosage as well as from the present study. Although as a group

the placebo patients in both of these controlled studies tended to remain in treat-

ment for longer periods of time than those administered naloxone, they were,nevertheless, deviating more in terms of narcotic drug use. Interestingly, the

possibility that contingent administration might in itself have therapeutic value

was also illustrated. Whereas, in the earlier study, one of every two patients

administered daily placebo produced positive urine specimens at least 40% of the




time, only one of every four patients administered contingent placebo in the

present study deviated to this extent. Reflecting this difference in response to daily

and contingent administration, the average deviation rates for the respectiveplacebo samples were 28% vs. 11%. Although somewhat higher with daily

administration, narcotic positive rates for naloxone were less disparate under the

two conditions, uniformly ranging below the 40% level and averaging less than

10%.

Improved placebo effectiveness under contingent conditions was at least

partially responsible for the lack of any substantial naloxone-placebo differences

in the present study. Though statistically significant, the 4% differential in the 7%

vs. 11% narcotic positive rates for naloxone and placebo, respectively, was princi-

pally due to the deviations of only a few of the placebo cases. It might be argued

that for most patients, i.e., at least three out of four, the contingent administrationof placebo was associated with relatively cooperative behavior (attending the clinic

and providing a specimen at least 80% of the time) and positive outcome. Also,

these patients tended to remain relatively longer in treatment over the 6 month

period, and of course, experienced little or no “side effects.” Understandably, it

would be difficult to convincingly demonstrate the worth of any pharmacologically

active agent under such circumstances.

As mentioned, 33 parolees, or slightly more than 20% of the original 154 refer-

rals, did not demonstrate sufficiently deviant behavior during the 6-month ab-

stinence program to require the prescription of medication. These individuals

were identifiable as a group prior to program participation. Though configurally

similar, their mean MMPI profile was found to be significantly lower than that for

the remaining referrals on nine of the ten clinical scales examined. As further in-

dication of the relative stability of this subgroup, their mean community adjust-

ment rating at the 6-month evaluation point was 8.7, revealing good to excellent

global adjustment.

As also noted, another subgroup of initial referrals not included in the con-

trolled study was comprised of 24 parolees who either absconded prior to the the

reception of medication or refused to take medication during their participation in

the abstinence program in spite of evidences of deviation. These parolees were

indistinguishable in terms of pretreatment descriptive measures from those ac-

cepting medication who were thereby included in the study. On posttreatment

assessment, however, the relatively unfavorable status of 12 parolees refusing

medication who were available for evaluation at six months was revealed in a

mean community adjustment rating of 4.2 indicative of poor overall adjustment,

including fairly consistent narcotic drug use.

Except for preliminary findings by Resnick and his coworkers’2 that bear rep-

lication, efforts at the prediction of treatment response in the area of drug addic-

tion have been notoriously unrewarding. Meaningful analyses of the differences

between responders and nonresponders in the present instance were precluded by

the small number of successfully concluded cases.

The findings of the present study relating to the effectiveness of placebo again

highlight the importance of controlled research in the evaluation of any new treat-

ment procedure. Prior to this controlled examination of the contingent use of na-

loxone in an ongoing abstinence program, results of pilot research conducted at



218 HANLON ET AL.

the clinic had been especially encouraging. In this initial work, criteria of effective-

ness, including clinic attendance, the extent of narcotic drug use, and final disposi-

tion at six months, were viewed in relation to already established baseline resultswith a sample of patients processed through the same clinic over a five year period

before the introduction of antagonist treatment. Comparative findings indicated

longer program involvement, less narcotic drug use, and less reinstitutionalization

with contingently administered naloxone. In view of presently reported results,

however, it appears likely that placebo reactivity was to a large extent responsible

for these initial favorable impressions.

With some individuals in the present study, there did appear to be reinforce-

ment value in the taking of antagonist medication. Although the evidence was not

overwhelming, the capacity of naloxone to attenuate the narcotic drug intake of

those addict parolees remaining in the abstinence program was at least demon-strable. It was principally in terms of treatment acceptance and dispositional data

that naloxone, in the dosages and contingent schedules employed, failed to demon-

strate its expected potential. Considering the generally low level of motivation in

the population in question, however, there is reason to doubt the utility of any

presently known narcotic antagonist administered under similar conditions.

Present results, therefore, do not discount the potential usefulness of naloxone in

other settings or under other conditions.

Granted an innumerable array of causative factors, compulsive narcotic use ap-

pears to be partially attributable to diffuse psychophysiological discomfort, the

alleviation of which is a significant reinforcer. The failure of chemotherapeutic in-tervention to deal directly with such discomfort will inevitably result in limited ap-

plicability and effectiveness. It is primarily for this reason that antagonists do not

seem to offer substantial rehabilitative promise for the typical parolee or street

addict. For many such individuals, there is simply no incentive or reward in the

taking of a chemical that denies them the relief they obtain from narcotics. Thus

viewed, antagonists can be expected to be no more effective in alleviating chronic

narcotics use than disulfiram (Antabuse) has been in alleviating chronic alcohol

use.

Considering the above, it seems advisable to supplement the search for pure and

longer-acting narcotic antagonists by further concentration on the development ofantagonists with non- or minimally addicting agonistic properties that are more

acceptable from the side effect standpoint than those that are presently available.

Judiciously used during the early stages of treatment, such agents would be more

likely to sustain the participation of less motivated addicts in therapeutic environ-

ments to which they might not otherwise be attracted.

SUMMARY

The results of a controlled study of the contingent administration of naloxone to

newly released addict parolees were viewed in relation to the goals of the narcotic

antagonist approach to the treatment of addiction. Program participation and nar-cotic usage data on 97 addict parolees, 55 of whom were assigned to naloxone and

42 to placebo, revealed that although demonstrating a capacity to attenuate nar-

cotic drug intake, the use of naloxone in contingent dosages ranging from 500 to

2000 mg was associated with a relatively high dropout rate during a prescribed 6-




month treatment course. In view of the population and methodology employed,

the unfavorable outcome result could not be regarded as discounting the potential

usefulness of naloxone in other settings and under other conditions. Implications

and possible causes of the findings of the study, including a surprising amount of

placebo effectiveness under contingent conditions, were discussed and conclusions

drawn regarding limitations of the antagonist approach for the less motivated ad-

dict.

ACKNOWLEDGMENTS

The authors wish to express appreciation to Dr. Ralph Jacobsen. Deputy Medical Director of I-ndo

Laboratories, Inc.. a subsidiary of E. I. Dupont De Nemours & Co.. for furnishing supplies of na-

loxone: to Friends Medical Science Research Center, Inc., for providing administrative support and

physical facilities; to Dr. Robert J. Kokoski and his statf at the Drug Abuse Laboratory. Catonsville.

Maryland, for the processing of specimens; to the staff of the Friends Experimental Outpatient Nar-

cotic Clinic for their continued cooperation: and to Vasilios Frankos for his suggestions and help.

REFERENCES

I. McCabe OL, Kurland AA, Sullivan I>:

Paroled narcotic addicts in a veritied abstinence

program: Results of a five-year study. Int J Ad-

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2. Kurland AA, McCabe OL, and Hanlon

TE: Contingent naloxone treatment of the nar-

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4. Hanlon TE, Kurland AA, McCabe OL:

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narcotic antagonist treatment of addict parolees by dr. charles savage

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