Acupuncture in narcotic withdrawal: a preliminary report on biochemical changes in the blood and urine of heroin addicts

Sections

Abstract
Introduction
Material and methods
Results
Discussion
Acknowledgements
Bibliography

Details

Author: H.L. WEN,, W. K. K. HO, , K. P. FUNG, , H. K. WONG,, H.C. WONG,
Pages: 31 to 39
Creation Date: 1978/01/01

Acupuncture in narcotic withdrawal: a preliminary report on biochemical changes in the blood and urine of heroin addicts *

Y.H. NG, H.L. WEN, Neurosurgical Unit, Kwong Wah Hospital, Tung Wah Group of Hospitals, Howloon, Hong Kong
W. K. K. HO,
K. P. FUNG,
L. MA, H. K. WONG, Department of Biochemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong
H.C. WONG,
The Women's Treatment Centre, SARDA, Hong Kong

Abstract

Eight female heroin-addicted subjects were treated over a 10-day period by acupuncture and electrical stimulation (AES). Their plasma ACTH, cortisol and c-AMP levels were reduced after initial AES treatment. The reduction of c-AMP was significant the most of the three. The suppression of these compounds may be associated with the temporary relief of withdrawal symptoms on and after each AES treatment in the first three days. On the third day, ACTH, cortisol and c-AMP levels did not show significant changes after AES. This was presumably due to the disappearance of withdrawal symptoms and possibly to the stabilizing effect of the treatment. Both the ACTH and c-AMP levels were generally lower at the end of the treatment period. Results of the present investigation suggest that plasma c-AMP may be the best parameter by which to gauge the response of heroin addicts to AES.

Introduction

Acupuncture has been practised in China for more than 5,000 years. It has been used in the treatment of various illnesses but mainly for the relief of pain caused by various etiological factors. In 1972, acupuncture anaesthesia was reported in Foreign Language Press, Peking. Since then, it has generated interest in layman as well as in the medical profession.

The successful use of acupuncture, combined with electrical stimulation (AES), for the treatment of withdrawal symptoms has repeatedly been reported (Wen and Cheung, 1973a; Wen and Cheung, 1973b; Wen, 1975a; Wen, 1975b). It was found that subjects addicted to hard drugs (such as opium and heroin) show substantial improvements in respect to their withdrawal symptoms after 15 to 30 minutes of AES treatment. In view of this effect, it would be interesting to explore if there are any biochemical changes associated with this type of treatment and if there are, what functional roles these changes may play in the relief of withdrawal symptoms.

Reprinted from: Neuro.psychopharmacology: Proceedings of the 10th Congress of the College International of Neuro-Psychopharmacology, Pergamon Press, 1978.

Since both blood and urine are the most accessible physiological pools in the human body, we have attempted to examine (1) the blood levels of ACTH, cortisol, c-AMP, red cell cholinesterase activity, haemoglobin and white cells, (2) the urine levels of aldosterone, catecholamine, vanillyl mandelic acid (VMA), cortisol and c-AMP during the process of AES treatment.

Material and methods

Patient background

Eight female subjects, addicted to heroin, ranging in age from 16 to 34 years, made up the study-group. They were all Chinese admitted voluntarily to the Women's Treatment Centre (WTC) of the Hong Kong Society for the Aid and Rehabilitation of Drug Addicts (SARDA). The duration of addiction varied from five months to five years. Each of the subjects showed withdrawal symptoms when deprived of heroin. The method of heroin use in seven of the cases was inhalation, either by "shooting the anti-aircraft gun"* or by "chasing the dragon"*. Only one was a main-liner. Upon admission to the WTC, the subjects were given 10 mg of methadone, three times on the first day, 10 mg twice on the second day and 5 mg twice on the third day. On the fourth day, AES treatment began and no further methadone was given.

Acupuncture treatment

The technique of AES treatment consisted of cleansing the concha of both ears with an alcohol cotton-wool swab. Then, a sterile, half-inch stainless-steel acupuncture needle, gauge 30, was inserted on each side of the ear, subcutaneously for about 3 mm. The needles were then connected to an electrical stimulator (Biopulse Generator, Biopulse Co. Ltd., Hong Kong), which ran on a 12 volt battery. The frequency used was 125 Hz. On the average, only 5 to 6 volts were required by the subject. Some subjects may need more depending on the duration of their addiction, the quantity of drug they have taken and the method used.

When the intensity of electrical stimulation was increased, the subject felt vibration passing through the needles in each concha, much like the buzzing of a mosquito. Too much current would produce pain, headache, nausea, vomiting and, sometimes, even skin-burns. It was advisable to ascertain whether the subject felt the current "tickling" the ear. If so, stop at this point. Usually, after 5 or 10 minutes, they could not feel the current any more and then, the intensity should again gradually be increased. The duration of treatment was 30 minutes, three times a day. On the fourth to the tenth day after admission, the subjects received AES treatment three times per day. Figure 1 summarizes the scheme of treatment after admission to the clinic.

*Bulletin on Narcotics, XXII:2, 9 (1970) (editor's note).

FIGURE 1 Post admission treatment scheme of heroin addicts.

Full size image: 21 kB, FIGURE 1 Post admission treatment scheme of heroin addicts.

Sampling procedure

Blood samples were obtained from subjects between 9:00 and 10:00 a.m. by venepuncture and collected in tubes, containing either heparin or EDTA as anticoagulants. The blood obtained in this manner was immediately cooled in an ice-bath. Plasma was separated from the blood cells by low-speed centrifugation (3,000 g) and was frozen at - 20 °C until needed.

Urine from individual subjects was collected in 3 litre bottles over a 24-hour period. No preservative was added. All urine samples were stored at 4 °C for no more than four days prior to the tests.

Radio-immunoassay

The aldosterone, cortisol, ACTH and c-AMP levels in either the urine or plasma were determined by using commercially available radio-immunoassay kits from the New England Nuclear Corporation, Worcester, Mass., USA (for aldosterone and cortisol) or the Radiochemical Centre, Bucks., UK (for ACTH and c-AMP). The procedures used in this study were essentially those recommended by the manufacturers. Radioactive counting was carried out, using either a Nuclear Chicago Mark I (Des Plaines, I11., USA) liquid scintillation counter or a gamma counter of a similar make. All samples were counted to a statistical margin of error of less than 1 per cent, at a 95 per cent confidence level.

Chemical analysis

Urine catecholamine and vanillyl mandelic acid (VMA) levels were determined by the methods of Weil-Malherbe (1971) and Wootton (1974), respectively. Red blood cell cholinesterase activity was measured by the decrease of pH during the incubation of freshly lyzed red blood cells with acetylcholine chloride at 25 °C (Demetriou et al., 1974). Blood haemoglobin was determined by the method of Makarem (1974) after converting the haemoglobin to cyanmethaemoglobin.

Statistical analysis

In the present study, data on individual subjects were pooled and presented as the mean plus or minus one standard deviation. The large standard deviation associated with all the urine values as well as those of the plasma ACTH, cortisol and c-AMP was probably a reflection of the inherent problems connected with the sampling procedure. Specifically, an increase of variation might be due to (1) the controlling of urine volumes from individual to individual, during the course of AES treatment; (2) the variation of circadian rhythm from subject to subject even though precautions were taken to obtain the blood samples within a fixed period of the day; (3) a change in environmental factors, such as temperature from day to day and (4) the alteration of the subjects' temperaments from one day to the next. In view of the possibility of these factors affecting the precision of our results we took a less rigid statistical criterion to evaluate the changes of chemical levels in both urine and plasma, during the course of the AES treatment. The Student's t-test was used to evaluate the significance of the difference in plasma concentrations, before and after AES, in the compounds tested. Except in borderline situations, a p 0.05 was considered to be different.

Results

The plasma ACTH and cortisol levels of the addicted subjects revealed changes before and after AES on the fourth day after admission (figures 2 and 3). ACTH reduction was minus 32 per cent (0.1 p0.2) and cortisol minus 32 per cent (0.05 p0.1). Neither presented much change before and after AES on Day 7 and on Day 10, ACTH showed a reduction to 10 pg/ml. In normal subjects, ACTH reduction after AES treatment was minus 33 per cent (0.2 p0.3) and cortisol minus 36 per cent (0.3 p0.4). The plasma c-AMP (figure 4) on Day 4 showed post AES a significant reduction of minus 56 per cent (0.01 p0.02). On Day 7, no change was noted but an over-all reduction of c-AMP level to 5 p mole/ml was observed on Day 10. In the normal subjects, c-AMP showed changes after AES to plus 25 per cent (0.6 p0.7).

The haemoglobin, white blood cell count and red blood cell cholinesterase activity of the person addicted to heroin and the control showed no remarkable changes during AES treatment.

Urine aldosterone, cortisol, catecholamine and c-AMP all showed changes after Day 4, and then gradually increased slightly on Day 7. After that, they started to decline and fluctuate (figure 5 - A, B, C, E). In view of large standard deviations associated with the mean values, the above trend could not be regarded as significant.

FIGURE 2 - Plasma ACTH levels of heroin addicts and normal controls during AES treatment.

Full size image: 27 kB, FIGURE 2 - Plasma ACTH levels of heroin addicts and normal controls during AES treatment.

Urine VMA level showed a gradual increase from 2.5 mg/day to 4.25 mg/day on Day 7 (figure 5 - D). After that, it started to go down and then stabilized at 3.4 mg/day.

Discussion

The biochemical basis of drug addiction and the mechanism of acupuncture with electrical stimulation (AES) in ameliorating withdrawal symptoms are, by and large, still unknown. In the present investigation, we evaluated a number of biochemical parameters in both the blood and the urine before and after AES treatment in subjects who were addicted to heroin. Based on our findings, AES appears to have little effect on the haemoglobin, white blood cell and red blood cell cholinesterase level either in heroin addicted or in normal control subjects.

FIGURE 3 - Plasma cortisol levels of heroin addicts and normal controls during AES treatment.

Full size image: 24 kB, FIGURE 3 - Plasma cortisol levels of heroin addicts and normal controls during AES treatment.

On the other hand, initial AES treatment was effective in reducing the plasma ACTH, cortisol and c-AMP levels in the addicted subjects. This was most significant with c-AMP. Similar but statistically insignificant reductions of ACTH and cortisol were also observed in the normal controls, however in the case of c-AMP, there was actually an increase after treatment with AES.

The different effects of AES treatment on addicted and normal subjects may be due to the fact that heroin addiction has altered the normal neural and/or hormonal physiology of each of the addicted individuals and, consequently, they may become more sensitive to AES. Renault et al. (1972) have demonstrated that an elevation of the plasma cortisol level in methadone-maintained subjects usually precedes the appearance of withdrawal symptoms. In this connexion, the suppression of ACTH and cortisol levels after initial AES treatment may be taken as an indication of how this technique can avert and ameliorate withdrawal symptoms.

The effect of AES seems to wear off after three days of treatment (i.e., Day 7 on the treatment scheme). On the seventh day, both ACTH and cortisol showed little change (figures 2 and 3) before and after AES. This phenomenon may be explained by the fact that, during the first three days of AES treatment, the subjects were not given substitute drugs and this could have brought on the withdrawal symptoms. In support of this contention which was observed clinically, one to two days after the initial AES treatment, subjects often showed signs of withdrawal. Because of this, more frequent and longer periods of AES treatment were needed to satisfy the subjects, craving for heroin. However, after the first three days of AES treatment, there was no evidence of clinical symptoms or signs of withdrawal pains. Apparently, by this time, AES had somehow stabilized the subjects' condition and accordingly additional AES might have little effect in inducing biochemical and hormonal changes.

FIGURE 4 - Plasma c-AMP levels of heroin addicts and normal controls during AES treatment.

Full size image: 24 kB, FIGURE 4 - Plasma c-AMP levels of heroin addicts and normal controls during AES treatment.

In addition to ACTH and cortisol, the c-AMP level was significantly reduced in addicted subjects during the initial AES treatment. Since c-AMP is suspected of playing a significant role in both neural transmission (Greengard, 1976) and hormonal response (Jost and Rickenbery, 1971), the drop in plasma c-AMP level after AES may reflect a neural and/or hormonal role of this compound as a link with the effect of AES in the treatment of withdrawal symptoms.

Acknowledgements

We wish to thank the Lee Foundation, Singapore and Mr. Lee Wing Tat and Mr. Ko Fook Son, Hong Kong, for financial support; The Society for the Aid and Rehabilitation of Drug Addicts, Hong Kong, its Chairman and the various members of his staff for the use of their facilities. We are also grateful to Mr. K.K. Au and Mr. Y.T. Lee for their technical assistance.

FIGURE 5 - Comparison of the levels of the various compounds assayed in the urine of heroin addicts during AES treatment. A, c-AMP; B, catecholamine; C, cortisol; D, VMA and E, aldosterone.

Full size image: 27 kB, FIGURE 5 - Comparison of the levels of the various compounds assayed in the urine of heroin addicts during AES treatment. A, c-AMP; B, catecholamine; C, cortisol; D, VMA and E, aldosterone.

Bibliography

Acupuncture Anaesthesia, Foreign Language Press, Peking, 1972.

Demetriou, J.A., P.A. Drewes and J.B. Gin. Enzymes. In: Clinical chemistry - principles and technics. R.J. Henry, D.C. Cannon and J.W. Winkelman, Ed., pp. 917-922, Harper & Row, Hagerstown, Md., 1974.

Feldman, S., N. Conforti and I. Chowers. Complete inhibition of adrenocortical responses following sciatic nerve stimulation in rats with hypothalamic islands. Acta Endocrinologica, 78: 539-544, 1975.

Greengard, P. Possible role for cyclic nucleotides and phosphorylated membrane proteins in post-synaptic actions of neuro-transmitters. Nature, 260: 101-108, 1976.

Grizzle, E., F. Dallman, L.F. Schramm and D.S. Cann. Inhibitory and facilitatory hypothalamic areas mediating ACTH release in the cat. Endocrinology, 95: 1450-1461, 1974.

Acupuncture in narcotic withdrawal 39

Jost, J.P. and H.V. Rickenberg. Cyclic AMP. Ann. Rev. Biochem., 40: 741-774. 1971.

Li, C.H. and D. Chung. Isolation and structure of an untriakontapeptide with opiate activity from camel pituitary glands. Proc. Natl. Acad. Sci. U.S., 73: 1145-1148, 1976.

Makarem, A. Hemoglobins, hemoglobin derivatives and hemoglobin binding proteins. In: Clinical chemistry - principles and technics. R.J. Henry, D.C. Cannon and J.W. Winkelman Ed. pp. 1131-1135, Harper & Row, Hagerstown, Md., 1974.

Renault, P.F., C.R. Schuster, R.L. Heinrich and B. van der Kolk. Altered Plasma corticol response in patients on methadone maintenance. Clinical Pharmacology and Therapeutics, 13: 269-273, 1972.

Weil-Malherbe, H. The chemical estimation of catecholamines and their metabolites in body fluids and tissue extracts. In: Methods of biochemical analysis, suppl, vol., D. Glick, Ed., pp. 127-132, John Wiley, New York, 1971.

Wen, H.L. and S.Y.C. Cheung. Treatment of drug addiction by acupuncture and electrical stimulating. Asian J. of Med., 9: 138-141, 1973 a.

Wen, H.L. and S.Y.C. Cheung. How acupuncture can help addicts. Drugs and Society, 2: 18-20, 1973 b.

Wen, H.L. The role of acupuncture in narcotic withdrawal. Medical Progress, May: 15-16, 1975 a.

Wen, H.L. Experience in the treatment of drug addiction by electrical acupuncture. Mod. Med. Asia, 11: 23-24, 1975 b.

Wootton, I.D. Microanalysis in medical biochemistry. Churchill Livingstone, Edinburgh, 1974.