Psychological deficit in chewers of coca leaf

Sections

Introduction
TABLE 1 Distribution of studied sample by age, residence, literacy and relation to coca

Details

Author: J. C. H. NEGRETE , H. B. M. MURPHY
Pages: 11 to 18
Creation Date: 1967/01/01

Psychological deficit in chewers of coca leaf

J. C. H. NEGRETE
H. B. M. MURPHY
McGill University, Montreal, Canada

Introduction

The chewing of the leaves of the coca plant (Erythroxilum coca or Erythroxilum truxillense) is a habit affecting several million people of the Andean regions of South America. Dependence on it is known to be mild and since the habit usually disappears when users are given better social opportunities (e.g. in the army) there would be grounds for allowing it to die a natural death were there not the suspicion that it produced chronic brain damage. This suspicion has a long history and is based mainly on the fact that chronic users tend to look dull and apathetic [ 12] , [ 19] , but it has also for long been recognised that such apathy might be due to social conditions, malnutrition or physical exhaustion. Claims have been made that there is a specific delusional psychosis associated with the habit [ 5] and that an allegedly high incidence of epilepsy and degenerative stigmata in some groups of users [ 6] might be due to it, but there is no proof. There is no doubt that in the areas where the habit is mainly found one can also find much illiteracy (up to 90%) and low social achievement [ 6] , [ 16] , but which is cause and which is effect remains in question.

The main efforts at identifying the longer-term effects of coca have been those of Gutierrez Noriega in Lima, and with any simpler task his persistence and skill would undoubtedly have yielded the required answer by the time of his unfortunate death in 1950. But, as with many other psychotropic or habituating drugs, the effects appear to depend considerably on the personality of the user, the dose employed, and the degree of sensitisation developed. The average habitue takes between thirty and forty grams of the dried leaf per day, divided into two or four wads and chewed or sucked together with some form of alkali. This has been estimated to release between 250 and 350 mgm of cocaine, or very approximately 5 mgm per kilo of body weight per day, plus an unknown amount of other alkaloids [ 6] . Such dosage would customarily be expected to produce some psychomotor excitement and attention arousal in naive subjects, but without any disturbance of the sensorium, and is similar to what one would meet with other stimulants. The paradox is, however, that most coca users appear on the surface to be depressed rather than stimulated. When more of the leaf is consumed - 50 to 80 grams - then Gutierrez Noriega found that the physiological effects in chronic users were much the same as those produced in naive subjects by 2 to 4 mgm of cocaine per kilo body weight. Both groups, that is to say, showed rises in body temperature, pulse rate, blood pressure, B.M.R., bloodsugar level and muscle strength. Both groups also showed, on average, some euphoria and motor excitement, with increased speed but also increased inaccuracy in the test tasks, and although a few individuals showed a reversal of the latter effect, with depression and decreased speed, Gutierrez Noriega could not discover why the latter occurred or what connection it had to the apathy observed in habitual users.

Because of the obvious experimental difficulties, the foregoing investigations were not carried through to the point where the subjects could be said to have become habituated to the drugs, although it was found that repeated use induced sensitivity rather than tolerance, something which other workers had noted with cocaine. For evidence of longer-term effects, Gutierrez Noriega used a cross-sectional rather than a longitudinal approach, comparing five hundred long-term chewers with a group of non-chewers on a battery of non-verbal tests derived from Binet-Simon, Terman and Porteous originals [ 4] . The chewers performed less well than the controls and had an average I.Q. by this method of only 67, with the poorest scores tending to come from the longest users of the leaf. However, his two groups, though both drawn from the poorer parts of Lima, were not matched with regard to age, ethnicity, occupation, diet or social background and the investigators recognised that their results had thus no clear significance. Another researcher, Wolff, collected data on children which parallelled these findings. He reported, that is to say, that school children who had already started to chew coca performed less well on the Binet-Simon and showed less learning ability than their non-chewing schoolmates [ 19] . But once again there was no indication that the two groups were comparable initially, and although he suggests that performance improved when chewing was stopped he does not provide the evidence for this. Gutierrez Noriega, reviewing the general literature, therefore came to the conclusion that "in order to support such assumptions (regarding the adverse effects of coca) it would be necessary to perform psychological tests on large samples matched on social, ethnic and geographical levels".

That conclusion was written over twenty years ago and we still do not know whether the drug produces a psychological deficit or not. The present study was designed to re-open the matter and at the same time to respond to the call of a W.H.O. Expert Committee for more research into dependency-inducing drugs [ 1] .

The present study

As stated earlier, the main practical question regarding coca today is not whether it is associated with apathy and low social achievement, but whether it produces a form of psychological deficit which would prevent its habituees from being able to make use of improved social and educational opportunities when these are offered. The most serious interference of this sort would be that caused by brain damage, and it seemed natural, therefore, to look for specific evidence of such brain damage rather than simply for evidence of reduced striving or reduced intelligence. Furthermore since, as Gutierrez Noriega had stated, it would be necessary to investigate chewers and controls who would be as similar as possible in all respects except their use of coca, it seemed undesirable to work in either of the two main locations used by previous researchers, namely Lima and the Peruvian Andes. In Lima the coca chewer is sufficiently uncommon to be something of a deviant, so that the more ambitious or successful former cocausers abandon the habit and the remainder are thus an atypical residue. In the traditional Andes area it is the non-chewer who is the deviant, so that again it is difficult to match groups satisfactorily. We could have worked in some other part of Peru, but we preferred Northern Argentina despite the fact that the habit is confined to a small area there, our reason being that there were exceptional research facilities available, and that the population was divided more or less equally into chewers and non-chewers with no great pressure of opinion in either direction.

The population from which subjects and controls were drawn comprised the field labour force of a very large sugar plantation in Jujuy Province. In part the labourers are transient, coming each year at harvest time from the Bolivian highlands, and in part resident being either Argentinian-born or immigrants settled locally for many years. Coca chewers are found in both groups, and non-chewers also in both. The leaf is not grown locally, but it is imported from the Bolivian highlands and there is no legal penalty for its use so that habitues will admit to using it as readily as they will admit drinking alcohol. Migrant workers tend to come in groups from particular locations in Bolivia and to return each year, so that the sugar company has continuing records of them just as it has of the population resident on the plantation. These records are well kept and medical histories are often also available since the company has its own hospital and medical services. Thanks to them, and to the co-operation of the supervisory personnel, it was possible to be quite strict with respect to basic demographic criteria, and to match chewers and controls more closely than would normally have been the case.

The basic criteria for the sample were that subjects should be male, aged 25-49, employed in field work and not in the office, in the factory or in supervisory jobs, should come from a certain region of Bolivia and Argentina, have no history of mental disorder, head injury, epilepsy, diabetes, or other physical illness known to affect mental functioning, have no history of erratic or antisocial work practices, and no history of excessive drinking. The main purpose of these criteria was to eliminate irrelevant causes of psychological deficit, but the occupational restriction was to ensure as far as possible that performance on the tests was uninfluenced by unusual familiarity with office conditions or with machinery. Lists of potential subjects meeting these criteria were made out, supervisors were consulted regarding whether they were known to chew coca regularly or not, the company's managers of the relevant village stores were consulted regarding the amounts of coca leaf and alcohol purchased by different families, and from the shortened list thus obtained an attempt was made to match long-term chewers with non-chewers on the further variables of literacy and origin.

For the study, the operational definition of a "long-term chewer" was someone who had chewed an average of at least 200 grams of leaf per week over a period of not less than ten years. The intended definition of a "control" was someone who had never followed the habit at all, but in practice was someone never observed to chew the leaf when working, not known to purchase the leaf for his own use, and who denied having taken more than an average of about 10 grams per week.

After a pilot run with five chewers (excluded from the results), the main sample was selected by interviewing two or three long-term chewers, balancing these by controls of reportedly similar background, interviewing the next two or three chewers, and so on. When over half the series had been completed, it was realised that the exclusion of some heavy drinkers had disturbed the balance of the two groups, so that the controls were on average younger and more literate than the chewers. With the remaining subjects an attempt was made to correct for this, but it was not fully successful and a further distortion was produced when re-checking revealed that some of the controls were more habituated to the leaf than was permitted for their category. As a result the total sample, though still satisfactory, is less balanced than had been intended, as Table 1 shows.

TABLE 1 Distribution of studied sample by age, residence, literacy and relation to coca

 

Chewers

Controls

 

Age

 

Age

 
 

25-36

37-49

Total

25-36

37-49

Total

Migrant Bolivian workers:
           
Literate
9 4 13 15 3 18
Illiterate
10 3 13 4 1 5
 
-
-
-
-
-
-
  19 7 26 19 4 23
Local residents:
           
Literate
4 6 10 4 5 9
Illiterate
2 12 14 5 5 10
 
-
-
-
-
-
-
  6 18 24 9 10 19

The test battery

There is no reliable single method today of measuring psychological deficit deriving from brain damage, and although it is agreed that batteries of tests give much better results than any one test there is no agreement either on any particular battery or combination. This is not surprising, since the concept of brain damage is a very loose one and must relate injuries to almost any part of the cerebrum. For the present research we could not narrow the problem any further, since nothing has indicated that the coca alkaloids damage one particular part or system of the brain rather than another, if they damage it at all in the relevant dosage. As a result there was no one test or battery which was clearly the most suitable one for our task, although there are ample indications that some approaches are better than others. We therefore decided to construct our own battery, taking into consideration the recent work of Reitan [ 13] , Spreen [ 15] , and others, but also making allowance for our subjects' illiteracy. No effort was made to validate the battery as a whole, but its individual parts are all modelled on tests that have been well explored and results will be presented separately for each section. All instructions, etc., were naturally put into the local Spanish idiom, and some of the items were modified after the pilot run.

The battery comprised the following:

  1. A short verbal intelligence scale based on the Kent (9). From Reitan's work in Indiana [ 13] it was anticipated that this should discriminate least between the long-term chewers and the controls if the difference between them rested only with the coca habit and if an organic type deficit had been produced.

  1. An auditory memory test comprising two short stories modelled on the Wechsler memory scale [ 17] and scored by the number of elements correctly remembered. The score used was the mean for the two stories.

  2. A test of visual memory based on one published by Munn [ 11] but using playing cards instead of portraits. Five cards seen for 20 seconds one minute earlier had to be recognized from a spread of 25, and the score was the number of cards correctly recognized.

  3. Two figure-completion tests, namely exercises 3 and 5 of the Army Beta scale [ 8] , scored by subtracting the number of errors from an artificial total.

  4. Two tests of similarity recognition, exercises 7 and 10 of the Army Beta, scored as above.

  5. The Knox cubes [ 2] used as an attention test and scored for both immediate and delayed responses. For the measure of delayed response, which Milner has suggested is a particular effective single test of brain damage (personal communication), the subject had to tap on cubes which had been covered for a time after the examiner had signalled the order to be followed.

  6. The Seguin Form Board [ 14] , with 10 pieces, used as a test of manual ability of tactile and spatial memory, and of learning. Scoring was for the number of pieces correctly placed on the board in five minutes, first with the preferred hand, than with the other, and then with both hands together. Learning was measured by subtracting the score for the first hand from that when both hands were used.

  7. A block design test adapted from Wechsler's cards 1, 2 and 3 [ 18] , only four cubes being used. No time limit was imposed, and the basic score used was simply the number of designs correctly completed; but the time for completion or abandonment was also noted.

The form and and administration of these tests did not faithfully reproduce the instructions of the originals

since local conditions and the low education of the subjects had to be allowed for, but they were used, we believe, in the spirit of the originals and should therefore be able to yield the same types of inference.

Examination procedure

Subjects were seen by appointment in the village medical dispensary, having been told that this was an enquiry into their nutritional state, that they would be compensated for lost time, and that it was a physician who would see them. The examining psychiatrist (J.C.N.) identified himself as working for an international organization in order to avoid any suspicions orre sistance which might arise from identification with the employers or with the government, but the subjects also knew that his work was approved of both by management and by the local union representatives, and there were no refusals. The interview started with a general review of health, diet habits, occupational history, leisure time activities and family history. Questions about coca were inserted among other topics to avoid too great attention being focussed on it, and although by the end of the series it was well realized within the community that the enquiry had coca use as one of its main objectives, this did not lead to recognizable efforts at disguising a history of the habit. On the contrary, chewers were apt to answer "Yes, I chew; I work hard" reflecting the belief in their own minds that the habit enabled men to work harder and hence was socially approved, at least for manual labourers.

After these preliminaries a brief physical examination was carried out to uncover any sensory or motor defect which could handicap the subject with the tests, or any signs of neurological abnormality which might relate to an irrelevant cause of cerebral defect. The battery of tests was then given, always in the same order and at a single sitting. Chewers were not asked and, as far as could be judged, did not themselves decide to alter their normal chewing habits for the occasion, in this respect being similar to cigarette smokers in other societies. All chewers had taken coca the day they were seen but only two of them were chewing at the time of the interview. None of the controls had chewed that day, as far as could be ascertained.

We would have liked to have kept the testing quite separate from the sample selection and history taking, but finance and organization did not permit this, so that, as will be realized from the above description, the examiner knew whether an individual belonged to the experimental or control categories. Since we entered the research with the expectation that there might be no difference between the two groups this should not of itself have induced any bias, but a careful watch was kept for anything that might imply or encourage examiner bias. None was found.

Results

First impressions of the examiner were that no significant differences would be found. In co-operation, attention to the task and in general attitude the two groups could not be distinguished, and a simple averaging of crude scores similarly yielded no difference. However, more elaborate analysis after the whole series was ended contradicted that and showed indubitably that the chewers had performed less well than the controls at almost all points, when due allowance was made for age, degree of literacy, and background.

Figure I presents the complete data, expanded to show each test and each demographic category of the sample separately, and following the order in which the tests were actually given. This expanded presentation has been thought preferable to a summarized form since each test tends to be affected by different variables and since the two groups were not fully matched. The Kent-type test of verbal intelligence, as was to be expected from the work of Reitan and others, yields no significant differences. With the measure of delayed attention using the Knox cubes it is only the chewers in the younger age groups that score singificantly less well than the controls. With all the other tests and ratings, however, it can be seen that the controls score better than the chewers in not less than six out of the eight demographic categories, the differences being particularly marked in the two pairs of tests from the Army Beta, and in the measure of learning on the sorting test.

Evidence for some type of psychological impediment or deficit affecting the chewers seems indubitable, therefore, and we can discover no reason to think that this is due to some extraneous factor. Analysis by age using much finer categories than those presented does not reduce the total difference, and neither does allowance for different grades of literacy. The diet of each subject was enquired into but this yielded no reason for suspecting greater dietary deficiencies in the one group than in the other. Culturally, although there are differences between the transients and the more permanent residents, there were none within each group which would distinguish the habitues from the others. The fact that coca chewing is associated with lower mental performance is thus unquestionable; what is questionable is the nature of the relationship between the two. The choice of subjects and choice of tests for this research were geared to exploring chronic brain damage, but there are two immediately obvious possibilities which could yield the same results. One is that the habit is favoured by people who already possess some degree of mental deficiency, perhaps because it permits them to forget that limitation. The other is that performance was affected by a temporary coca intoxication rather than by any long-term effect.

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Fig. I. Comparative test scores of coca-chewers and of non-chewers, by title of test, age of subjects, literacy and residence. (Chewers are indicated by the black columns, controls by the shaded ones.)

It is desirable that we should be able to distinguish between these initial possibilities, and fortunately this can be done. Where both recent dosage and duration of use vary, the three possibilities we are considering would seem to predict different results, as follows:

Hypothesized cause

Predicted effect

Adverse selection:
Results correlate neither with recent dose nor with duration of use.
Acute intoxication:
Results correlate with recent dosage; not with duration of use.
Chronic process:
Results correlate with duration of use; not with recent dosage

We did not know the amount of leaf chewed on the day of the test, but we knew when the subjects regarded themselves as having started the habit and we knew also, both from the subjects and from outside sources, estimates of their recent consumption. There is no detectable relation between heavy recent consumption and poorer test scores, so that recent intoxication is probably not the important variable, There is a relationship, however, between duration of chewing and certain test scores, as Figure II shows. This relationship is not accountable on the basis of age, and therefore it seems highly probable that we are dealing with a chronic, cumulative process rather than with acute temporary intoxication or with a selective factor. Moreover, if coca had tended to attract the less intelligent from among the studied population, we would have expected this to show itself in the Kent-type intelligence test rather than in the measures focusing on possible brain damage, and we have seen that the reverse is the case. Why only four measures of deficit should show the effect is unclear, but it might be that they come closest to measuring the most affected functions.

On Figure II, an unexpected finding was that in the older age group the subjects who had chewed least performed better on attention than the controls. Because of the few cases involved this could be an accident, but there is another weak trend in the data pointing in a related direction. This is that the chewers with the higher levels of recent consumption tend to score somewhat better than those with about the same age and duration of chewing whose recent consumption has been less. The difference is slight, but one is reminded of Gutierrez Noriega's finding that chronic chewers, when given 50 to 80 grams of leaf (a high single dose in the view of our subjects) showed on average improved attention, improved speed and decreased accuracy. Unfortunately there is no evidence of increased speed in our chewer sample, rather the reverse; and those with heavy recent consumption are no faster than the rest. Accordingly, there is nothing in our data to suggest that the deficit shown by the habitues was due to recent doses of coca agitating their minds, but there is a slight suggestion that such recent doses may in some individuals partially correct for the deficit which long-term use of the drug appears to produce.

Discussion

The foregoing findings highlight two paradoxes, both remarked on by previous observers and both contributing to the confusion of earlier opinion regarding the habit. One is that a plant whose main active agent is a renowned stimulant should show a retardant or depressant effect on regular consumers. The other is that so clear a degree of psychological deficit should be present Fig. II. Test scores related to duration of coca-chewing, for two age groups of subjects. in persons whom neither the examiner nor their work supervisors could recognize as different from the nonhabituated controls. Consideration of these two paradoxes is instructive.

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The discrepancy between test performances and performance in daily life is the easier to explain. The tests were designed to ferret out weaknesses of a particular kind, not to assess general social functioning. The work, the social environment, the possibilities for advancement and the general set of expectations surrounding the coca chewers investigated were such that opportuities for applying intelligence were limited and a decline in that intelligence was likely to remain obscured. Moreover, even if such decline were observable, individual variation was such that it was likely to go unrealized unless special attention was paid. The examiner's initial impressions were that the chewers and controls would not show any significant difference in their mean performance and it took statistical analysis to reveal this. Outside of the testing situation the same can be shown to be true. On superficial examination the family histories of the two groups appeared indistinguishable, but Figure III shows that in one important respect the chewers had definitely a poorer record, something which we are now investigating. (The social aspects of coca chewing in the studied sample will be the subject of a further report.) Unless signs of deficit are correctly looked for, therefore, they can be easily missed.

Fig. III. Child mortality in families of coca-chewers and controls, analysed by age of father and background of family. (Note: Questions covered the number of children the subject had, and whether he was officially married or not.)

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For the other paradox there is not so satisfactory an explanation, but there are certain obvious alternatives. One possibility, the closest to that which we set out to test, is that progressive brain damage eventually outweighs the drug's stimulant effect. Another is that the effect is psychological rather than organic, with the habit inducing withdrawal or detachment from the environment so that the subjects have less interest in applying themselves to the test situation, and less practice in facing problems. (No difference was observed between the chewers and controls in their application to the test tasks, and that is against this hypothesis, but it is not sufficient to disprove it.) Yet a third type of mechanism is possible, however, and this has some external evidence in its favour. Repeated experience with a drug can induce changes in the body's reaction to it, changes which can be progressive but which at the same time can be latent in the sense that they do not demonstrate their presence and have no effect on functioning until a fresh dose of the drug is introduced. The obvious examples of such a mechanism are antibody formation and anaphylactic shock, and it might be that something of this kind occurs when former users of the drug take a fresh dose. Either a different part of the brain could have become sensitized, or there could be a form of systemic or antibody reaction which had depressant effects.

There are studies which can be interpreted as supporting each of the latter alternatives. The first was by Zapata Ortiz who showed that cats can sometimes exhibit a depressive reaction when given large doses of cocaine, a reaction which had an inhibitory or catatonic character that was nevertheless different from the paralysis induced by excessive doses [ 20] . Later, Zapata Ortiz with Guttierez Noriega showed that this inhibitory reaction could sometimes be induced by doses of no more than 5 mgm per kilo body weight, if the animal had received repeated administration of the drug for not less than two months [ 7] . At the same time the normal excitatory effect of the cocaine disappeared. During this period of inhibition there was especially an abolition of the nociceptive reflexes, with no rise in blood pressure, tachycardia, etc., in response to painful stimuli. The authors' suggested explanation, if we have understood them correctly, is that excitatory and inhibitory reactions are closely allied, so that what may produce the first may also, with very little change, produce the second. If such a mechanism also applies in humans it could be an explanation for the depressant or retardant effect we are investigating, and if there were also a suppression of reaction to pain this could explain the drug's continuing attraction to users after its stimulant effect had disappeared.

But no one has pursued this hypothesis further, as far as we are aware, and in the meantine Montesinos and his colleagues from the same centre have been pursuing an alternative explanation [ 10] . They point out that cocaine taken by mouth is broken down by saliva and gastric juices, and suggest that it is then further broken down in the blood stream and the liver by a cocaine esterase, the principal metabolites being benzoylecgonine and ecgonine. If either of the latter should prove to have a depressant or inhibitory action in humans (something which we do not think has yet been demonstrated) then it would seem very possible that the depressive effects observed in chronic coca chewers were due to an increased efficiency at converting the cocaine into one of these metabolites.

In the data from the present research there is no real evidence proving or disproving any of these hypothesized explanations. If the leaf permitted its habitues to detach themselves from their everyday worries and concerns, or if it reduced awareness of pain as the inhibitory hypothesis would suggest, then we would have an explanation for the persistence of the habit, whereas with what we may call the brain damage and metabolite hypotheses this persistence is difficult to explain. Analysis of the times taken in the various tests and observation of behaviour during testing do not support the inhibition and detachment hypotheses, however, but rather are against them, since the chewers showed no difference here from the controls. Also, if the inhibition hypothesis were true then we would have expected greater inhibition with higher recent doses of the drug, whereas the reverse seemed tentatively to be the case. No one appears to have been able to demonstrate signs of brain damage on post-mortem, however, unless one counts the work of Bravetta and Invernizzi who gave sufficient cocaine to kill their animals [ 3] , and no one appears either to have demonstrated any psychopharmacological action on the part of the cocaine metabolites. So support for the alternative hypotheses is also lacking.

The one definite result of this investigation is that coca must be assumed to have an adverse effect on the brain until it is proved otherwise. Regarding future research, some of the above questions might be resolved by investigating former chewers during periods of proven abstinence, and by the use of known antagonists of cocaine. Of particular value would be information on the degree to which long-time chewers with psychological deficit can be retrained to overcome that deficit. However, all such work would have some point only if the coca chewers were provided with social opportunities which called for them to use their intelligence. Without that, the degree of psychological deficit which we have demonstrated must remain relatively unimportant.