American Journal of Addictions, Volume 2, Number 3, Summer 1993. p194-201
REGULAR ARTICLES

Arthur Margolin, Ph.D., S.Kelly Avants, Ph.D

Patrick Chang, M.D. (China), Thomas R. kosten, M.D.

The rate of Cocaine abuse in some innercity Methadone programs is as high as 60% ^1,2. This condition seriously controverts the fundamental goal of Methadone maintenance – complete cessation of illicit drug use – upon which further treatment goals, such as psychosocial rehabilitation, are predicated. In addition, intravenous (TV) drug use – the predominant route for illicit drug use among Methadone patients – is a major route for the transmission of human immunodeficiency virus (HIV) and other infectious diseases. Given the limited success, to date, of psychopharmacologic treatments for Cocaine addiction³, and the urgency of the problem, there is a definite need to evaluate less conventional treatment modalities. The reported clinical success of acupunkture for the treatment of Cocaine addiction⁴, and its increasing popularity, directed our efforts toward an investigation of accupuncture intervention.

Acupuncture has been used in China for at least 2.000 years to treat a variety of disorders. The use of acupuncture for the treatment of drug addiction was discovered serendipitously in 1972 by Wen, a Hong Kong neurosurgeon conducting a series of studies on the analgesic properties of acupuncture. Heroin addicts where voluntered to be subjects reported that their opiate withdrawal symptoms were lessened on the days when they received the acupuncture treatments. Wen undertook a series of uncontrolled studies on the use of acupuncture in the treatment of opiate addiction and reported positive results^5,6.

Over the last 20 years, numerous studies have been undertaken investigating acupuncture for the treatment of various addictions, including opiates⁷, tobacco^8,9, and alcohol¹⁰. Many of these studies, particularly of alcohol and opiate dependence, report beneficial effects of acupuncture. Not infrequenly, however, investigations of acupuncture for the treatment of drug addiction suffer from problems of design ad assessment^11,12. In the current study, we used an objective primary outcome meansure, urine screens taken 3 times/week, a standardized diagnosis of Cocaine dependence.

Auricular acupuncture specifically for the treatment of Cocaine addiction has been employed for the last decade at Lincoln Hospital in the Bronx, NY. Over 8.000 Cocaine-abusing outpatients have received acupuncture treatments there, with 250 patients treated daily (D.Lipton, V.Brewington, and M.Smith, unpublished data). Urine samples are taken routinely, and published reports¹³ indicate that 40% of patients dependent on Cocaine gave a series of clean urine tests after weeks of treatment.

The mechanism by which acupuncture may constitute a treatment for Cocaine addiction is essentially unknown, although it has been conjectured that acupuncture, perhaps mediated by the release of endogenous opioids¹⁴, modulates neural circuits in the midbrain also affected by drugs of abuse¹⁵. Clinical reports^13,15 suggest that auricular acupuncture craving for Cocaine and facilitates patient participation in counseling and rehabilisation. Traditionel Chinese theories of acupuncture¹⁷, involving the rectification of chi deficiency or excess in various "organ" systems, have not been tested within Western biomedical frameworks.

To the best of our knowledge, this is the first study to investigate acupuncture in a sample composed wholly of Methadonemaintained, Cocaine-abusing patients. The literature contains only one controlled study of acupuncture for the treatment of cocaine addiction. In a study conducted at Lincoln Hospital, (D.Lipton, V.Brewington, and M.Smith, unpublished data), 150 Cocaine-dependent subjects were randomly assigned to receive either real or placebo acupuncture 6 days/week for up to 1 month. Urine sampled were taken after each treatment session. The authors report a positive finding for acupuncture insofar as subjects who received real acupuncture and remained in treatment for over 2 weeks had significantly lower levels of Benzoylecgonine in urine screens compared to the placebo group.

The purpose of the current study was twofold: 1) to evaluate acupuncture for the treatment of Cocaine dependence in Methadone-maintained patients: and 2) to compare the treatment response rates for acupuncture to those obtained previosly at our research center using pharmacotherapy with Disipramine or Amantadine. In the current study, treatment outcome was assessed in five domains: Treatment retention, Cocaine use, depression, self-representation, and cue-elicited craving. 

Thirty-two subjeckts, 14 men and 18 women, gave informed written consent and participated in this study. All subjects were enrolled in an inner-city Metadone program and were referred to this study by their counselors after providing at least four consecutive urine screens positive for Benzoylecgonine in the month prior to entering the study. All subjects meet DSM-UI-R criteria for Cocaine dependence. Twenty eight subjects used Cocaine by IV route of administration, two by smoking, and two intranasally. The subjects' mean age was 34 ± 7.9 years; 17 subjects were white; 13 were black; and 2 were Hispanic. Their mean yearly income was $5,357 ± $2,658. The average daily Metadone dose was 65.2 ± 18.1 mg. Subjects used an average of 3.5 ± 3.1 grams of Cocaine/week in the month prior to entering the study. They had been using Cocaine for an average of 13.4 ± 7.7 years and had been using opiates for a mean of 15.6 ± 8.0 years. Sixteen subjects (50%) were HIV-positive, in symptomatic remission. Eleven of these patients were takeing Azidothymidine (ATZ). Subject screening included a physical examination, electrocardiogram, blood chemistry, and full blood count. Patients with plateler counts below 50,000 or T-cell count below 200 were excluded from participation in the study. Patients currently taking psychotropic medication were also excluded from the study.

Patients were treated for 8 weeks. During the first 6 weeks, subjects received treatment 5 days/week. For the last 2 weeks, treatments were given 3 times/week, on Monday, Wednesday, and Friday. The treatment protocol employed in this study was developed by Michael Smith, M.D.¹⁸, and is currently used at the Substance Abuse Clinic of Lincoln Hospital, Bronx, NY. Needles were inserted into the ear cancha bilaterally at five locations: (1) "sympathetic", located in the deltoid fossa at the junction of the infra-antehelix crus and the medial border of the helix; (2) "lung", located in the center of the cavum concha; (3) " liver", located in the posterior to upper portion of the helix crus; (4) "shen men", located in the inferior corner of the bifurating point of the antihelix; and (5) "kidney", located in the lower border of the infra-antihelix crus. Neddles were inserted to a depth of 2 mm and left in place for 30 minutes. The acupuncture needles (Seirin Co., Ltd.) were stainless steel, disposable needles, sterilized with ethylene oxide gas, and individually packaged in sterile containers that were opened by the acupuncturist immediately before insertion. Acupuncture treatments were provided by PC, an trained acupuncturist (Canton School of Traditionel Medicine, China; NADA certification).

Each acupuncture session adhered to the following format:

1. Subject sits in a comfortable reclining chair.
2. Subject cleans ears with a pad saturated with 70% Isopropyl alcohol.
3. Acupuncture inspects ears, cleans further with alcohol if needed.
4. Acupuncturist inserts five needles into each ear.
5. Subject sits quiely for 50 minutes.
6. Acupuncturist or subject removes needles and disposes of them in a "sharps" box.

All Tretments were given between 10 a.m. and noon, after the patients had received their daily Methadone dose between 6 a.m., and 10 a.m. Patients were treaded in groups of three or four, seated in the same room.

Patients with a documented history of Cocaine abuse were referred to the study by a counselor in the Methadone program, and an interwiew was scheduled with one of the researchers. After a determination that the patient met entrance criteria, the study was explained and informed consent was obtained. During a subsequent pretreatment assessment session, the patient completed the Beck Depression Inventory and the Selves Questionnaire. After completing these questionnaires, subjects participated in the pretreatment cue-reactivity session. Immediately following the cue-reacivity session, subjects received their first acupuncture treatment. Treatments lasted for 8 weeks. At the end of the 8 weeks, a cuereactivity session identical to the pretreatment session was administered and subjects again completed the Beck Depression Inventory and the Selves Questionnaire.

Cocaine us was determined by urine toxicology screenings. Urine samples were collected from subjects 3 times/week and analyzed on-site for Benzoylecgonine, using the Abbott TDx method. The test's range was 300-5.000ng/ml. A reading greater than 300 was regarded as positive. Depression was assessed using the Beck Depression Inventory¹⁹. Self-representation was assessed using the modified Selves Questionnaire²⁰. As modified, this questionnaire asks subjects to describe their "ideal" self and their "addict" self. In the current study, these data were quantified by asking subjects to rate, on a scale from 0 (not at all) to 4 extremely), the extent to which they "felt like" their addict self and their ideal self during the previous week. Craving in response to Cocaine cues was assessed by showing subjects a 2-minute video of people using Cocaine, follow by in vivo exposure to, and handling of, Cocaine-related paraphernalia matched to the subject´s preferred route of administration. At baseline and after Cocaine-cue exposure, subjects verbally rated their current desire for Cocaine on a scale of 0 (no crawing) to 10 (maximum craving), and their current aversion to using Cocaine. also on a scale of 0 (no aversion) to 10 (maximum aversion).

Of the 32 patients enrolled, 16 (50%) completed the study. Of the 16 completers 14 (44%) of all enrolled; 88% of completers attained abstinence from Cocaine use, defined as providing urine samples negative for benzoylecgonine during at least the last 2 weeks of the study. The mean number of weeks abstinent for these 14 subjects was 4.8 (± 2.1), with a range of 2-8 weeks (median = 4.7 weeks). Subjects who dropped out completed a mean of 10 (median = 6.5) treatment sessions.

Sixty-one percent of women (11/18) and 36% of men (5/14) who entered the study completed the entire 8-week course of acupuncture treatment. All 11 of the women and 3 of the 5 men (60%) who completed the study attained abstinence. Among the HIV-positive patients, 6 of the 16 (38%) completed the study; of these 6 individuals, 5 (83%) attained abstinence.

Individuals who completed treatment and attained abstinence did not significantly differ from those individuals who did not complete the study on any of the following characteristics: age, race income, HIV-status, Methadone dosage, number of years using Heroin, number of years using Cocaine, amount of Cocaine used pretreatment, pretreatment Beck depression scores, selfrepræsentations, craving to drug cues, and aversion to drug cues.

Significant differences between the two groups were found for gender and for presence of children. Subjects who attained abstinence were more likely to be female than male (c = 5.0; P<0.02), and were more likely to have children than to be childless (Fisher´s Exact Test, P<0.01). Having children thus had a differential impact on women and men; a greater proportion of women with children (71%) than men with children (25%) attained abstinence (Fisher´s Exact Test, P<0.04).

Paired t-tests were performed on each of the remaining dependent measures for the 14 patients who successfully completed the 8-week treatment. Table 1 presents the means and standard deviations (SDs) for each of the dependent measures. Beck depression scores decreased significantly from pretreatment (M = 14.8) to post-treatment (M = 9.0), (t[13] = 4.15; P<0.001). Post-treatment, subjects also indentified less with their "addict" self-representation (M_pre = 2.4; M_post = 0.5; t[3] = 6.32; P<0.001), and had a greater indentification with a nondrugusing, "ideal" self-representation (M_pre = 1.1; M_post = 3.3; t[13] = 5.94; P<0.001). Baseline craving also significantly decreased at posttreatment (pretreatment baseline = 2.8; posttreatment = 0.64; t[13] = 2.90; P<0.01; and baseline aversion to Cocaine significantly increased (M_pre = 5.9; M_post 9.5; t[13] = 3.22; P<0.01). Graving in response to Cocaine cues also decreased significandy post-treatment (M_pre 0 6.0; M_post = 9.9; t[13] = 3.55; P<0.01).

There were no reported or observed adverse effects of the acupuncture treatments. Some subjects were light-headed after treatment, an effect that seemed to subside after a few minutes. After their first treatment, some subjects reported feeling "high". This response to treatment usually did not recur.

There was no apparent interaction between acupuncture and Methadone. Patients were asked at the middle and end of the study if they were experiencing any symptoms of being under- or overmedicated; none were reported, nor were there any spontaneous patient requests for increased or decreased Methadone dose during the course of the study.

Of the 14 subjects who successfully completed the study, there were 10 who were abstinent at the 6-month follow-up; one subject had died from a non-drug-related illness; and three subjects had relapsed to Cocaine use.

A double-blind, 12-week randomized clinical trial of Amantadine 300 mg daily (n = 33), Desipramine 150mg daily ( n = 30), and Placebo (n = 31) for the treatment of Cocaine-dependence in Methadone-maintained patients was recently undertaken at this same facility²¹. The results from this study were compared with those of the current study on abstinence and retention rates. With respect to the subjects in the acupuncture study, subjects in the pharmacotherapy study met a number of the criteria propounded for historical controls²²; (1) they were recruited from the same clinic; (2) similar subject eligibility requirements were employed; (3) subjects in both studies were assessed using primary measures of reduction in Cocaine use, verified by urine screens and treatment retention; (4) both studies were performed in the same organization by the same personnel. There were two primary differences between the studies.  

TABLE 1. Changes in affect, self-representation, and cue reactivity for patients who completed treatment.

 Note: Values are means ± SD. Signifiance levels determined by Student t-test p < 0.01

First, the pharmacotherapy study lasted 12 weeks, 4 weeks longer than the acupuncture study. Second, subjects in the pharmacotherapy study were somewhat less severely addicted that subjects in the acupuncture study. They had been using Cocaine for an average of 7.6 years and opiates for an average of 9.3 years. They spent an average of $211 (± $262) per week on Cocaine in the month before entering the study. Table 2 presents abstinence and retention rates for patients receiving acupuncture, Amamtadine, Desipramine, and placebo.

Sustained abstinence rates (for at least the last 2 weeks of the study) for subjects who completed treatment were significantly better for patients receiving acupuncture (88%; 14/16) than for patients receiving Amantadine (20%; 5/25) (c ²=17.9; P<0.001), Desipramine (36%; 8/22) (c ²=9.9; P<0.01), or placebo (15%; 4/27) (c ²=21.8; P<0-0.01). However, we also found a significantly poorer retention rate for subjects who received acupuncture (16/32; 50%) that for subjects who received Amantadine (76%; 25/33) (c ²=4.6; P<0.03) or placebo (87% 27/31) (c ²=10.0; P<0.01). The retentionrate for Desipramine (73%; 22/30 was marginally better than the acupuncture retention rate (c ²⁼3.6; P<0.06). The overall abstinence rate (treatment retention rate multiplied by abstinence rate) was significntly better for acupuncture (44%) than for Amantadine (15%) (c ² = 6.4; P<0.01) or placebo (13%) (c ² = 7.3; P<0.01) but failed to reach statistical significance for Desipramine (26%) (c ²=2.0; P=0.16).

TABLE 2 Comparison of acupuncture, Desipramine, Amantadine, and placebo on retention in treatment and abstinence from Cocaine (%)

Note: Abstinence is defined as providing Cocaine-free urines for at least the last 2 weeks of the study. Ss = subjects. See text for pairwisecomparison P values.

We conducted a preliminary investigation of acupuncture for the treatment of Cocaine dependence in patients maintained on Methadone. Fifty percent of the subjects completed the study. Of those who completed treatment, 88% attained abstinence, yielding an overall abstinence rate of 44%. A post-hoc comparison of recention and abstinence rates in the curent study with our previous study of Amantadine and Desipremine for Cocaine dependence showed poorer retention, but higer abstinence rates for completers recieving Amantadine, Desipramine, or placebo.

The higet abstinence rates with acupuncture may be due to several possible treatments effects. For example, in the acupuncture study, patients came to the clinic daily for an hour-long treatment, during which time they sat quietly in a relaxing environment. During treatments, subjects frequency seemed to enter a somnolent state; some actually fall asleep. This "relaxation" component was not a treatment condition in the pharmacotherapy study. Patients in that study had psychotherapy once weekly. In addition, there was no control condition in the acupuncture study, and the study was not "blind". Unblinded studies in addiction traditionally have better response rates than blind, controlled studies. Due to such factors as selection bias and demand characteristics³.

In the pharmacotherapy trial, retention in treatment was excellent, and abstinence rates were modest. In the amupuncture study, the retention rate was lower, but the patients who remained in treatment did extreamely well. The fact that the drop-out rate was higher in the acupuncture study than in the pharmacotherapy study may be due to several factors. It takes less effort for patients to ingest a pill with their daily Mathadone dose, that it does to receive an hour-long treatment several times a week. Subjects who were deciving no benefit from the acupuncture treatments may have simply decided it was not worth the effort to continue in the study. No subject reported dropping out of the study because of an adverse response to acupuncture treatments. The drop-out rate of 50% found in the current study with Cocaine-dependent patients was the same as that found for the group receiving auricular acupuncture in Bullock´s study of acupuncture for the treatment of alcoholism¹⁰.

Subjects who attained abstinence in this study exhibited decreased Beck Depression Inventory scores, at shift in self-representation away from "addict" and toward desired "non-addict" self-schemata, decreased craving, and increased aversion to Cocaine cues. We found similar results with treatment responders in a previous pharmacotherapy study using Bupropion²⁰. These changes may therefore be concomitants of abstinence from Cocaine abuse rather that specific effects of acupuncture. This suggests that such divergent treatment modalities as acupuncture and antidepressant therapy can be associated with similar cognitive-effective shifts in newly abstinent subjects. Future studies could examine the longer-term consequences of each treatment modality.

Whereas women in this study responded well to auricular acupuncture, the men had a significantly lower abstinence rate. This is consistent with previous research that found femal Cocaine abusers to be more responsive to treatment than male Cocaine abusers^23,24. These findings may be particularly relevant in the case of auricular acupuncture because pregnancy is not a contraindication to this treatment modality. It is therefore one of the few treatments for Cocaine addiction, other than psychotherapy, that could be offered to pregnant women who abuse Cocaine.

In view of the widespread use of acupuncture in the treatment of drug addiction and the relative success of the current study, it is our opinion that this procedure warrants further controlled investigation as a treatment for Cocaine addiction in opiate-dependent populations.

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