A New Psycho-biological Test to Detect Morphinedependent Users in the Work Environment

APPLIED PSYCHOLOGY: AN INTERNATIONAL REVIEW, 1!392,41(2) 175-184

A New Psycho-biological Test to Detect Morphine- dependent Users in the Work Environment

Miguel Navarro and J O S ~ M. Prieto Faculty of Psychology, Complutense University, Madrid, Spain

Cet article presente une methode psychobiologique qui facilite I’identification des morphinomanes dans un contexte organisationnel. Vingt- trois consommateurs habituels de drogues diverses (aussi bien d’htroi’ne que de drogues douces) et sept non droguCs ont servi de sujets pour cette etude. On leur a instille un antidote des dCrivts de I’opium (deux gouttes de naloxone dans un oeil et deux gouttes d’un serum salin dans I’autre) sans leur indiquer quel etait I’oeil critique. Les resultats disponibles temoignent d’une precision remarquable dans I’identification des morphinomanes qui sont detectes par le diamttre de la pupille resultant de I’effet de la naloxone. On a pris des photos avant et une demi-heure aprks I’instillation. L’anisocorie a ete mesurie sur la photo grice 1 une loupe lumineuse. Les analyses de sang et d’urine ont permis de confirmer le diagnostic en double aveugle. Le diametre de la pupille debouche aussi sur une classification par groupes tout 1 fait nette. . .

’This paper discusses a psychobiological methodology to assist in the identification of morphine-dependent users in the organisational milieu. Twenty-three consumers (with heroin as the basic drug), and seven non- addicts were the subjects of this study. They were instilled an opiate antagonist (two drops of naloxone in one eye and two drops of saline serum in the other), without knowing which eye it was. The available results show outstanding accuracy in the indentification of morphine addicts. The basis of differentiation is the difference in pupil size induced by naloxone. Photographs were taken before the instillation and 30 minutes afterwards. The measurement of anisocorie was obtained on the photographic paper with a light-equipped magnifier. Blood and urine analyses allowed us to confirm the diagnosis in a double-blind basis. Pupil diameter also favours a quite distinct classification by groups.

Requests for reprints should be addressed to Professor Miguel Navarro, Department of Psychobiology, Faculty of Psychology, Complutense University, Somosaguas, 28023 Madrid, Spain. Fax: 34-1-3943189.

Both authors express their acknowledgement to the Direccibn General de Trhfico and the Instituto Nacional de Toxicologia in Madrid since both governmental agencies provided formal support for this research.

This article was jointly accepted by the former editor Bernhard Wilpert and the present editor Michael Frese.

@ 1992 International Association of Applied Psychology

176 NAVARRO AND PRIETO

INTRODUCTION

This paper sets out a psychobiological methodology to assist in the identification of morphine addicts or multiple drug-users where heroin is the basis. In fact, heroin is a substance derived from morphine. The degree of purity of each dose as well as its frequency is of secondary relevance. It is important to personnel psychologists to identify in advance drug-users following a psychobehavioural model.

This article aids the personnel psychologist in assessing the applicability of findings accrued in the laboratory to resolving problems identified in the organisational milieu. The separation of basic and applied science may be self-defeating (Locke, 1986). Some applications of the available scientific advances may directly affect practices in organisational settings and may have far-reaching implications for human resources management.

DRUG-ADDICTION AND PERSONNEL DECISIONS

There has been a burgeoning of interest in the interface between job selection and drug addiction. Increased attention to this issue reflects changes both in the workforce and in the field of Work and Organisational Psychology. The increased use of drugs is one of the most impressive and easily documented of everyday events. Understanding the effects of this on working life and on employees' behaviour has become a real concern for Trade Unions as well as for Human Resources Departments. There has also been an increased interest in the available strategies to detect in advance those applicants who are regular drug consumers. Their organisation behaviour might be beyond their personal control. It seems that Personnel Departments are becoming more involved in detecting the presence of drug-addicts in the labour force in order to provide psycho- logical support and medical assistance.

The political and societal campaign against drug-users demands planned sets of action that must be carried out urgently to obtain information deemed damaging to living and working conditions. Public and private companies now pay considerable attention to this problem to achieve a safe and healthy environment for all workers. There is a socially constructed discrepancy between the actual and the desired state of affairs. The affected persons must be identified but at the same time their rights to privacy must be protected. Results are expected as a consequence of screening applicants or monitoring job holders for security or health reasons. In this way they can be transferred to other positions.

Physicians and psychologists in private companies and public agencies have been invited to look for new instruments that can detect minute signs

A PSYCHO-BIOLOGICAL TEST 177

of severe drug dependence in employees or civil servants. It is not fair play to impose formal check-ups to every individual worker, but a breakthrough may be possible if selection, classification or promotion procedures include circumstantial tests providing direct or indirect evidence. The considerable psychobiological literature on the behavioural and physiological effects of drugs has provided some cues for developing a general purpose test which may be helpful in finding an alternate solution.

THE EFFECT OF MORPHINE ON THE IRIS

Pupilar constriction, or rniosis, as a direct consequence of the regular consumption of morphine, was detected and studied some time ago (Frase, Nash, & van Horn, 1954; Martin & Frase, 1961). It is considered to be due to the action of the drug in the Edinger-Westphal nucleus.

This E-W nucleus is located pretectorially in the mesencephalon. It is part of the visceral component of the ocular motor nerve. The parasympathetic preganglionic fibres of the ciliar ganglion have their origin in this nucleus. Activation of the constricting muscle of the iris is under the control of such fibres (Lee & Wang, 1975; MacCrea, Eades, & Morgan, 1942; Murray & Tallarida, 1982; Warwick, 1954).

Local administration of morphine into the conjunctiva also shows this effect (Del Bianco, Fanciullacci, &. Sicuteri, 1980), which has also been described in humans (Nornof, Elliot, & Parker, 1968). Probably this is due to the inhibiting action that morphine has on noradrenergic neurotransmission of the radial muscle of the iris. This effect also appears in other structures in which the same neurotransmitter is released such as in the Locus Coeruleus (LC), among others. The LC is responsible for the noradrenergic innervation of the Limbic System, Cerebral Cortex, the Hypothalamus and the main troncocerebral nuclei in many animal species, including human (Aghajanian, 1978; Gold, Redmond, & Kleber, 1979).

An opiate antagonist, naloxone, has already received considerable attention. When locally administered in the eye, the naloxone cannot counteract the miosis which derives from an acute parenteral dose of morphine. However, the conjunctival instillation of naloxone reverses the local miosis induced by a drop of morphine in the non-addict’s eye. (Fanciullacci, Boccuni, Pietrini, & Sicuteri. 1980).

The instillation of naloxone may produce a dilatation of both pupils in a morphine-dependent individual. When it is instilled in only one eye of an addict then there appears a conspicuous difference in the size of the two pupils. This is an anisocoria.

The topical administration of naloxone to one eye leads to a miniature and local “withdrawal abstinence syndrome” that is limited to the tested eye exclusively.

.


Such experimental findings support the present psychobiological approach to discriminate between morphine-dependent addicts and non- addicts.

This phenomenon is quite specific when drops of opiate antagonists are instilled abruptly in the addict’s eyes. It is a consequence of the chronic action of morphine on multiple subtype opioid receptors in the Central Nervous System and in the periphery. However, the subtype of the underlying receptor in this effect has not yet been clearly identified (Holaday, 1985; Martin, 1981). The main purpose of this research was to apply a new test to measure the degree of naloxone-induced anisocoria in opiate-dependent subjects. This is a psychobiological technique to identify, mainly, morphine abusers within the organisational milieu.

METHOD

Subjects

The subjects were 30 volunteers, 25 males and 5 females between 17-26 years old. All the addicts studied were recruited from a private clinic for drug detoxification. The persons volunteering were informed as to the aims and purposes of the study, each of them signing a written consent to the instillation of the drugs studied into their eyes, and later collection of urine and blood samples.

The subjects comprising the control group were healthy persons recruited from outside the aforementioned centre. In an earlier question- naire, they had manifested that they had not previously taken drugs related with those studied (morphine, cocaine). The same process of informing and protocol was followed as in the previous group.

Both blood and urine samples were obtained to detect the presence of several drugs by means of solvent extraction homogeneous-enzymo- immuno-assay, gas chromatography, and mass spectography. The detec- tion limit for morphine, cocaine and benzodiazepine were 0.9 micro- gramdml. Accordingly, subjects were distributed as follows:

Control Group (n = 7): Non-addicts. No drugs or drugs’ metabolites were detected in their blood and/or urine samples.

Morphine Group ( n = 18): Opiate abusers. Only opiates or their metabolites were detected in their blood and/or urine samples.

Multi-Drug Group (n = 5) : Opiate addicts. In all cases opiates and, at least, other drugs’ metabolites (all of them were cocaine abusers and four of them were also benzodiazepine abusers), were detected in their blood and/or urine samples.

The subjects of morphine and multi-drug groups had been regular abusers for approximately 3 years (38.3 k 2.98 months).


Materials

A Yashica TL Electro X camera was used with an automatic lens of 50mm f1.4 with llmm, 18mm, and 16mm extension tubes. A Starblitz lo00 Auto Macro-lite circular flash was mounted on the second camera covering the area around the focus. The camera was used at 1/125 a second with an exhibition of f8.

Procedure

Two drops ( 0 . 2 ~ ~ ) of naloxone at a concentration of 0.16% were instilled in one eye and two drops of saline serum in the other eye of each subject. They were not told which was which.

Each subject was placed at the end of a wooden structure holding the camera, ensuring a standard distance of 60cm between the film (Kodak Plus X) and the individual’s eyes. During a lapse of 5 minutes before administering the eye-drops, subjects were kept in a room with a constant light level. Three photographs were taken. The first photograph was shot just before instilling the solution. The second and third photographs were obtained after a 30-minute period.

Anisocoria was measured on the photographic paper with a light- equipped magnifier ( 7 X ) graduated in tenths of a millimetre. Afterwards the measurement obtained was compared and the difference was expressed in a coefficient resulting from the ratio:

Pupil diameter under saline serum Pupil diameter under naloxone 1 - = Index of anisocoria (1)

The biomedical analyst of blood and urine and the analyst who measured anisocoria worked independently without knowing each other’s results.

The person who instilled the drops kept secret the real identity of each subject by assigning them all a number.

Statistical Analysis Results were assessed by a normal distribution test (Kolmogorov- Smirnov). After this the data were analysed by a one-way ANOVA.

RESULTS There were no significant group differences in the degree of anisocoria of addict and non-addict subjects in the first pretest photograph.

In the second post-test photograph respective average indices of anisocoria in the morphine and multi-drug groups were observed: 0.547 (stan-


1 -

0.9 -

0.7 -

0.6 -

dard error of measurement, k0.06), and 0.292 (k0.059). In the third post-test photograph, the observed index of anisocoria in the morphine group was 0.523 (k0.049), and in the multi-drug group 0.241 (k0.031). By contrast, in the control group the average index in the second and third photograph was 0.013 (k0.0015). The degree of anisocoria was different among the morphine, multi-drug and control groups in the second and third photograph. The available data are illustrated in Fig. 1.

The control subjects showed no reaction to naloxone and none of the cases studied reported any ocular discomfort or other adverse signs.

0 Control

Morphlne

0 Multl-drug

DISCUSSION At the organisational milieu it is of great help to be able to identify morphine addicts who are under the effects of opiates but without withdrawal symptoms. In general, the most effective and most utilised methods for achieving these ends are:

.. T. .. -

0.5

0.4

0.3

0.2

0.1

0 - Pre-test 1 st Post-test 2nd Post-test 3rd

FIG. 1 Index of anisocorie. Before (pretest) and after (post-test) two drops of naloxone were instillated in one eye and two drops of serum saline were instillated in the other eye. The time elapsed between the pretest (1st) and the post-test (2nd and 3rd photography) was 30 minutes. Mean and f s.e.m. are: *P C 0.05, **P < 0.01 when compared to the control group (n = 7). (a) P < 0.05 when the morphine group (n = 18) and the multi-drug groups (n = 5 ) are mutually compared.


- Discovering a small amount of the drug carried by the addict - Detecting morphine or one of its metabolites in the addict's urine.

The development and application of the method for identifying morphine addicts which is studied in this paper offers certain advantages over the traditional approaches because:

1. It induces anisocoria by demonstrating the latent hypersensitivity present in the morphine addict's opioid receptors. It solves the problem of false positives which might occur with the traditional methods. Such would be the case with individuals undergoing temporary treatment with opiates (e.g. codeine), for the sake of their pain-killing effects or anti-tussive or anti-diarrhoea effects. Temporary treatment with opiates is prescribed with ever-growing frequency either in isolation or in combination with other drugs. Similarly, it is often the case when metabolites common with those of morphine are detected in urine tests: 10% of codeine undergoes a bio-transformation into morphine in the liver (Findlay, Jones, Butz, & Welch, 1978). For this reason an opiate consumer can be easily confused with a morphine addict under the available conventional approaches.

2. It provides a useful and alternative tool for carrying out screening of applicants and candidates at low costs. No great infrastructure or qualified staff are required for its application. The method could be applied in the work environment and others.

3. It facilitates the follow-up and checking process with addicts who are at different stages of detoxification, rehabilitation or reinsertion programmes in the organisation milieu. Also it excludes simulators when main- tenance programmes are set up with methadone.

4. It might help to pick out drug-mixers who are consuming opiates as a basal drug due to the difference in pupil size in the first photograph between the cocaine consumer and the control group.

The neurobiological mechanism associated with this effect on pupillary anisocoria might involve a complex process both presynaptically and post- synaptically in the sympathetic postganglionic fibre of the radial muscle in the iris.

One of the functions of the endogenous opioid system in adrenergic neurotransmission is to modulate the flow of noradrenaline (Hughes, 1975; Langer, 1982). This would explain how the strong action of morphine on the opioid receptor of the radial muscle causes a sympathetic inhibitory effect. It allows the parasympathetic postganglionic fibre to take exclusive control of the size of the pupil, contracting the sphincter muscle of the iris.

This opioid receptor, placed so peripherally, confirms the hypothesis of Martin (1981) about the existence of multiple opioid receptors in the


central nervous system and in the periphery. Different behavioural, neuro- hormonal (Navarro, Leza, Lkasoain, & Lorenzo, 1991; Olson, Olson, & Kastin, 1990), and immune (Dougherty, Pellis, & Dafny, 1990) effects are involved.

Similarly, the action of morphine on the opioid receptor results in adaptive intra- and extra-cellular mechanisms, known as the tolerant and dependent state of the receptor. Tolerance could result from a dissociation between the binding site of the receptor morphine, in proportion to the degree of tolerance. One result of this is that it prevents an inhibitory effect on noradrenergic flow, except at very high dosages. The non-dissociated receptors show lower tolerance and a compensatory hyperexcitability (Way, Loh, & Shen, 1969). It manifests itself extra-cellularly by intact circuits and, intra-cellularly , by raising the signal for neural transmission (Wuster, Schulz, & Hen , 1985). Probably it involyes an increase in the availability of calcium and hyperactivity of adenylate cyclase (Nathanson & Redmond, 1981). For opiate abuse, the postsynaptic events appear to be of great relevance (Aghajanian, Sprouse, & Rasmussen, 1987).

Thanks to this latent postsynaptic hyperexcitability, the neuron main- tains a normalised activity, thereby providing the explanation for the size of the pupil in the dependent state very similar to that of the normal state (see Fig. 2).

This neural supersensitivity can be demonstrated by suddenly interrupt- ing the administration of morphine andor by administering an opiate antagonist. It induces withdrawal symptoms, which induce a sudden increase in neurotransmitter release; and, hence, the rise of the signal transmitted. It produces a mydriasis in the eye treated with naloxone and therefore anisocoria, compared to the eye treated with saline.

CONCLUSION The methodology described in this article might prove rather useful as a complementary psychobiological test for the screening of rnorphine- dependent applicants or for the monitoring of job-holders, along with traditional tests, bearing in mind that it has certain peculiar characteristics which make it highly specific. It may become a single or a routine testing procedure to determine whether a person is heroin-dependent.

Manuscript received April 1990 Revised manuscript received July 1991

This article was jointly accepted by the former editor Bernhard Wilpert and the present editor Michael Frese.

A PSYCHO-BIOLOGICAL TEST I83

A

n

B

FIG. 2 Hypothetical mechanism explaining the action of morphine in pupil diameter. Panel A : illustrates the baseline state of the noradrenergic neuron centre of radial muscle of the eye in a normal subject. The left side shows opioid receptors (small triangles) and presynaptic noradrenaline receptor (small square). The centre shows the noradrenaline released (Black circles) and the postsynaptic noradrenergic receptor. The right side shows the resulting pupillary response. Panel E: illustrates the acute effects of opiates (small black triangles) inhibiting the neurotransmitter. The number of circles is reduced and the pupil diameter is also decreased. Panel C illustrates the neuron after substance abuse with opiates. In this compensated stare, the activity of adenylate cyclase is increased (shadowed region) and other extracellular phenomena (the curved arrow with the + sign) do occur. Noradrenaline increases by tolerance, producing a "normalised" effect in the pupillary diameter in response to chronic inhibition generated by the opiates. Panel D: shows the neuron after a precipitated withdrawal in which the neuron is "reset" by an opiate antagonist (naloxone). The neuron comes back to approximately its baseline state. However, the response becomes increased because the whole system is already hyperexcited; the consequence is a remarkable increase in pupillary diameter. Thereafter. there is a prominent difference in pupil sire between the eye instillated with naloxone and the eye instillated with saline serum.

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A New Psycho-biological Test to Detect Morphinedependent Users in the Work Environment