14 Psychopharmacology

IN THE WESTERN WORLD, THEN, BY THE 1970s, THERE COULD NO longer be any doubt that the attempt to control drugs through the crimino-legal system had failed; and though there was great reluctance to admit as much, there was more of an inclination to explore alternative possibilities. And science was at last beginning to help, by beginning to investigate the social effects of drugs.

d'Abernon: the effects of alcohol

The first tentative exploration of this territory was made in the First World War, when the d'Abernon Committee was set up to advise the Government on the effects of drink on the war effort. Drink taken during the day, Lloyd George believed, made workers slower and clumsier; and drink taken in the evening was apt to cause absenteeism 'the morning after'. To what extent, the d'Abernon Committee were asked to estimate, was the war effort thereby disrupted?

In their report, the Committee had to admit defeat. It was not merely that scientists had not provided them with the answers; scientists had not even asked the relevant questions. They had conducted a great deal of research into alcohol in the laboratory, but none into alcohol in the pub, the factory, or the home. Did the drunkenness caused by beer or wine differ from that caused by spirits? Did mixing drinks tend to produce drunkenness? How far did the dilution of a drink — whiskey with soda, say — modify its action? What was the effect of taking food in conjunction with alcohol? Did fatigue alter the effect of alcohol on performance of skilled movements? Was alcohol more injurious in dry than in moist climates? To what extent was alcoholism caused by physiological disturbances? And did the psychological effects of alcohol — cheerfulness for example — improve resistance to adverse physical circumstances such as cold? None of these questions had been put.

Nor, the report continued, had there been research into an aspect of drug-taking about which a misconception was firmly rooted in the public mind. It was widely assumed that alcohol, like other drugs, caused addiction. Yet the great majority of drinkers did not become addicts. There must, presumably, be something in an individual which predisposed him to addiction; but what? Again, the scientists had evaded the question. As a result there was 'an almost entire absence of reliable data regarding the psychology of the drunkard, though adequate information on this point is obviously essential in devising rational methods of treatment of the inebriate. Little is known of the progress of the drinker from occasional excess to chronic alcoholism. Are the occasional drinker and the habitual drunkard two distinct types, or is the former an early stage of the latter?'

The reason scientists had neglected applied research, the Committee suggested, was partly that they were reluctant to involve themselves in social, as distinct from academic, issues (sociology was not yet accepted as an academic discipline); and partly that they did not care to venture into unexplored territory — the choice of subjects for investigation had 'often been determined by the ease with which they could be put to the test, or by their bearing on some theoretical controversy, rather than their intrinsic and practical importance'. This was a shrewd criticism; and the guidelines which the Committee offered for the future were also sensible — that researchers should now begin to concentrate on finding out why people took drugs, and what effects the drugs had on the people who took them and on the community in general. But the Committee suffered from a limitation. Although it lacked the necessary evidence, there were some assumptions which, it felt, could safely be made. Most of them were little more than pious aspirations: 'the ordinary use of alcohol', its report advised, 'should not only be moderate, but should also be limited to the consumption of beverages of adequate dilution, taken at sufficient intervals of time to prevent a deleterious action on the tissues'. But one assertion, 'that alcohol is narcotic rather than stimulant in action', revealed that the Committee shared the orthodox view of the time that it was possible to categorise drugs as either narcotics or stimulants. And it based its classification not on everyday experience, but on research into the effects of alcohol on the body and the nervous system. Asked to examine alcohol's social effects, the Committee had castigated scientists for their reluctance to venture out of the laboratory. Yet its own diagnosis was derived from the lab, rather than the pub.

Louis Lewin: Phantastica

The most influential pharmacologist of the time, Louis Lewin, suffered from the same limitation. He was anxious to show that drugs had been one of the most important of man's discoveries, and could be one of the most valuable of man's allies, and he did his best to popularise mescaline — without success, though experiments by Rouhier in France and Beringer in Germany bore out his claims. In his Phantastica, published in 1924, he set out his creed.

If human consciousness is the most wonderful thing on earth, the attempt to fathom the depths of the psychological action of narcotic and stimulating drugs makes this wonder seem greater still, for with their help man is enabled to transfer the emotions of everyday life, as well as his will and intellect, to unknown regions; he is enabled to attain degrees of emotional intensity and duration which are otherwise unknown . . . By the exercise of their powers on the brain, they release marvellous stores of latent energy. They relieve the mentally tortured, massage the racking pains of the sick, inspire with hope those doomed to death, endow the overworked with new vitality and vigour such as no strength of will could attain, and replace for an hour the exhaustion and languor of the overworked by mental comfort and content.

Lewin was also well aware of the prevailing weakness of pharmacology; and he mocked those whose contribution had been simply to produce impressive-sounding terminology. 'Even today,' he wrote, 'we frequently meet with interpretations of the action of medicinal and poisonous substances which are merely pseudoscientific descriptions of their effects.' They reminded him of the scene in Molière's Malade Imaginaire when the examination candidate, asked the reason for opium's soporific action, replies 'because it is endowed with narcotic and soporific properties' — which so delights his examiners that they immediately pass him. But Lewin then proceeded to follow the same course himself. He had not received the formal academic recognition which his abilities as a researcher and a teacher merited — perhaps because he was a Jew, and not given to disguising his contempt for those rash enough to disagree with him. The easiest way in which he could obtain it, in his own time, was to provide the classification of drugs according to their pharmacological properties which had eluded earlier researchers. He decided that there were five categories:

1 Euphorica 'sedatives of mental activity, these substances diminish or even suspend the functions of emotion and perception'.
2 Phantastica — hallucinating substances.
3 Inebriantia — causing cerebral excitation followed by depression.
4 Hypnotica — sleep producing agents.
5 Excitantia — mental stimulants.

The trouble began when Lewin tried to squeeze all known drugs into the separate categories. His Euphorica were opium and its derivatives, and cocaine. Indian Hemp, however, was classified with the Phantastica, along with peyotl, the fly agaric, henbane, datura and caapi. In the Inebriantia section, alcohol was accompanied by chloroform, ether and benzine The Hypnotica included chloral, veronal, paraldehyde, potassium bromide and — remarkably, in view of the results of his own research into it — kava. And the Excitantia had to provide room for all the rest — a weird miscellany; including camphor, betel, kat, coffee, tea, kola, maté, coca, tobacco, arsenic, and mercury.

Lewin was not unaware of the inconsistencies, which he did his best to iron out by tortuous rationalisations. Some Hypnotica, he admitted, were capable of being Excitantia; the reason was that 'like all toxins, they act on the brain', producing a euphoric state. The fact that the American Indians used tobacco not as Excitantia, but as Phantastica, to produce visions, proved more troublesome to explain. The best he could do was suggest that the hallucinatory effects must have been due to the carbon monoxide which they inhaled, together wth the tobacco fumes, whenever they lit their pipes.

The book had other limitations. Well-versed though he was in the pharmacological literature, Lewin's reading outside it was less than comprehensive; he quoted Surgeon Crombie's statistics about the insanity caused by hemp drugs, unaware that they had been demolished in the report of the Indian Hemp Drugs Commission. But this was of little importance compared with the decision to try to classify drugs according to their effects. Not that his categories were accepted; but they gave rise to further futile attempts along the same lines. The basic premise remained, that it ought to be possible to think in terms of the chemical action of a drug, rather than of the reaction of the people who take it; leading to such pontifications as the argument that the St. Bernard dogs who found lost travellers in the snow ought not to have carried brandy in their little barrels, because brandy is a depressant.

Largely as a result of this fixation, pharmacologists could not come to grips with the most serious problem which drugs presented: addiction. They could not even accept the traditional premise, that addiction represented a failure of will power, because will power was not quantifiable. A favourite proposition in the 1920s, as Evelyn Waugh recalled in Brideshead Revisited, was 'it's something chemical in him'; applied to alcoholics, it became 'the cant phrase of the time, derived from heaven knows what misapplication of popular science'. The available research funds were channelled into the search for metabolic disfunction, or defects in the endocrine system. And although by the 1930s there was more of a disposition to admit the explanation might be psychological, research in that area continued to be hampered by lack of resources, and by the divisions among the psychologists themselves. The Freudians looked for the causes of addiction in unconscious conflicts; the Pavlovians preferred to regard it as another conditioned reflex — similar to that which B F Skinner induced in rats, so that when they experienced the joy of a certain type of electric shock, they would return to it again and again, sacrificing food, fighting and sex for the chosen form of stimulation.

Auto-suggestion

The break-through to a better understanding of the effect of drugs can be traced to an experiment undertaken in 1933 — though it was to be many years before its significance was appreciated. In the Quarterly Journal of Medicine in 1933 two London cardiologists, William Evans and C. Hoyle, described how they had given out pills which their patients, suffering from angina, assumed were pain-killing, but which were actually made from bicarbonate of soda. Over a third of the patients reported that their pain had been satisfactorily relieved.

It had long been known that people could be fooled by the fairground quack's coloured water, and come back for more. But it had been taken for granted they must be gullible souls, who only imagined they were better, or who perhaps had only imagined they were ill. This could hardly account for so high a proportion of angina patients reacting to a placebo, as if it had been the real thing. And by this time, there was a widely-publicised alternative explanation. From his experience as a chemist in Troyes, Emile Coué had become convinced that what cured many of his customers was not his medicines, but their belief in them; a conviction which he was able to test by giving them placeboes.

At the time, Evans and Hoyle's paper aroused only mild curiosity; and Coué's fame, though world-wide, turned out to be transitory. The imagination could be stimulated, he had suggested, with the aid of a simple formula; 'every day, in every way, I get better and better'. It was a reversion to ritual; and in a ritual-starved civilisation it caught on, throughout Europe and America, as well as in France, with people intoning it in the bath or on the bus. But his basic proposition, that the formula's function was simply to help bring the imagination into play — just as a drug might — was not grasped. It was assumed that he was calling for an exercise of the will. The ritual became a music-hall joke and, like many another craze of the twenties, Couéism soon became only a mildly absurd memory.

After the Second World War, however, research began at last to broaden its base. The psychologists did not compose their differences, but they managed to establish a measure of common ground, leading to acceptance of the proposition that there are addiction-prone individuals — or, rather, that some people are more addiction-prone than others, and are therefore more likely to become addicts if nudged in that direction by any of a variety of forces.

At first sight this was not far removed from the earlier idea that addicts lacked will power. But there was one essential difference. It had been believed that the addict could extricate himself if he really wanted to, by an effort of will. The new theory came closer to regarding addiction as a neurosis. There was no point in telling an addict to pull himself together, because the fact he had become an addict itself revealed that he was incapable of such self-discipline.

The reasons why one individual was more addiction-prone than his neighbour proved difficult to pin down. It was easy enough to show with the help of statistics that the Italians, in proportion to the amount of wine they drank, were far less likely to become alcoholics than the French; not so easy to determine why. Longterm monitoring projects began to turn up clues; they revealed, for example, that alcoholics were more likely to come from homes where there had been parental conflict. But there were scores of similar environmental possibilities to be considered, as well as interactions between them. All that could be claimed with assurance was that — as Howard Jones put it, in his study of alcoholism — addiction was not 'the invariable result of particular kinds of personality constellation', but 'the solution found when problems of adjustment arise because certain types of personality are confronted by certain types of environmental stress'.

This research therefore, though it contributed to a better understanding of the drug problem, did little to assist either prevention or cure. For a time it was hoped that new institutions, specialising in the treatment of drug addicts, would be the answer. Even hardliners like Anslinger approved, because they wanted it to be demonstrated that addicts could learn, or be taught, self-control. The first such establishment was opened in Lexington, Kentucky, in 1935, subjecting heroin addicts to a rigorous course designed to dry them out and refit them for society; and by 1953, Anslinger was able to boast that of the 18,000 patients who had been through it, two-thirds had not returned. This should, he felt, give everyone confidence that the system worked. That confidence was soon shattered. Follow-up studies of those two-thirds, to find how they were faring, revealed that the great majority had relapsed. Lexington's success rate, it was estimated, was only around three per cent. Other institutions, more sympathetic in their approach, were to do a little better; but not much. As Brecher sadly noted in his Licit and Illicit Drugs, 'no effective cure for heroin addiction has been found'.

One reason for the failure of institutional treatment emerged when a few doctors began to study placebo effect in its own right. They found that the pharmacological content of a drug was not necessarily the determining factor in the patient's reaction to it. For example, when Dr Stewart Wolf — one of the pioneers of such studies in America — gave a woman an emetic, telling her it was a medicine designed to stop her feeling sick, not merely did she stop feeling sick, but her stomach juices, which were being monitored, reacted as if they were dealing with an anti-emetic — in other words, to her mental picture of what the drug's effects should be, rather than to the drug.

In his Drugs and Human Relations, published in 1970, Dr Gordon Claridge set out the evidence which had been accumulating to show the extent to which it is not the drug, but the expectation of the drug taker, which determines reactions. In a trial where one group took barbiturates, while a matched group were given placeboes, the barbiturates proved to be more effective sedatives only when the members of the group which was taking them were expecting sedation. Where they did not know what to expect from the pills, the reaction was the same whether they took the placebo or the drug. An experiment which Claridge himself undertook on behalf of the British army in 1961, to find out how the tranquilliser meprobamate affected soldiers' reactions, had a similar result. Although there was no significant difference between the reactions of those who took the drug, and those who took the placebo, both performed their set laboratory tasks less well than a third group who had not been given pills at all. The fact of taking pills, in other words, led to a deterioration in performance. 'Although none of the subjects was told what to expect', Claridge observed, 'most of them clearly associated drug taking with "being drugged", or being made less efficient in some way'.

It was not simply the lay public who could be deceived by placeboes. Doctors had been inclined to think they would not be good subjects in such tests, because they would know from training and experience how to recognise a drug's effects. But when in the late 1960s the members of the staff of the Department of Psychological Medicine in Glasgow University who had volunteered for tests were given pills which might be either amphetamines or placeboes, and were invited to guess which they had taken, their replies were scarcely more accurate than if they had decided by spinning a coin. One psychiatrist of several years' standing recognised his symptoms as coming from dexamphetamine. According to Claridge, 'during the next few hours he became more "high", and the following morning announced that participation in the experiment had considerably enhanced his enjoyment of a party the previous evening'. It had then to be broken to him that he had taken a placebo. Other members of the staff, equally convinced that they had taken placeboes, found that they had in fact taken amphetamines.

In search of reality

At first sight, such evidence may seem hard to reconcile with the accounts of the effects of the vision-inducing drugs. It is conceivable that Huxley knew enough about mescaline, when he took it, for his imagination to take over; but not that Hofman could have known what was going to happen when he took LSD. Another experiment described by Claridge provides a clue. In it, one of the subjects who thought he had taken LSD described what he saw:

. . . a lot of strange shapes and brilliant colour, after images, as if I looked through pebble finished glass, particularly this morning. Especially this morning colours were more brilliant than I have ever experienced. Voices were at times somewhat in the distance, along with a feeling of being in a real situation, a dream kind of state, time is distorted, goes rather slowly, and an hour is only 10 to 15 minutes when I look at my watch . . .

'A perfect description of the LSD state!', Claridge commented

— but the subject had in fact had a placebo. The mind, in other words, is capable of duplicating any drug experience; but this is not the same as saying that the drug is irrelevant. LSD is obviously a highly potent substance, capable of inducing striking changes in perception. What it cannot do is produce more than is already within the mind's own capability. The drug is essentially the trigger mechanism. That is why at different times, or in different cultures, reactions to the same drug have been so very different. Take, for instance the passage

Shivering I rose from my seat, incapable of rest, when that heavenly and harp-like voice sang its own victorious welcome . . . a chorus of elaborate harmony displayed before me as in a piece of arras-work, the whole of my past life — not as if recalled by an act of memory but as if present and incarnated in the music; no longer painful to dwell upon, but the details of its incidents removed, or blended in some hazy abstraction, and its passion exalted, spiritualised, and sublimed

This, too, might have been written about an LSD 'trip'; it is, in fact, de Quincey's description of the effects of laudanum. Jean Cocteau reacted similarly to opium. All of us, he claimed, carry something folded up within us like those Japanese flowers made of wood which unfold in water

opium plays the same role as the water. None of us carries the same kind of flower. It is possible that a person who does not smoke may never know the kind of flower that opium might have unfolded within him.

On other writers, however, the opiates have had the opposite effect. For William Burroughs, they diminished awareness so that they could only, he felt, be a hindrance to the artist; whereas cannabis gave him what he needed: 'unquestionably this drug is very useful to the artist, activating trains of association that would otherwise be inaccessible'. Others, again, have derived their inspiration from tobacco, about whose effects J. M. Barrie wrote in terms ordinarily applied only to a loved one.

An attempt to account for these variations was made by William James in his Varieties of Religious Experience, where he recalled the effect ether had had on him. He had found no reason, he wrote, to change the impression he had formed at the time.

It is that our normal waking consciousness, rational consciousness as we call it, is but one special type of consciousness, whilst all about it, parted from it by the flimsiest of screens, there lie potential forms of consciousness entirely different. We may go through life without suspecting their existence; but apply the requisite stimulus, and at a touch they are there in all their completeness. . . How to regard them is the question — for they are so discontinuous with ordinary consciousness. Yet they may determine attitudes though they cannot furnish formulas, and open a region though they fail to give a map. At any rate, they forbid a premature closing of our accounts with reality

The function of the drug is to provide the stimulus: and any drug may serve, if it happens to suit the individual concerned. Ether had suited James; peyotl had made him sick — perhaps because he literally could not stomach it, perhaps because the circumstances in which he took it had been unfavourable.

But how does a drug, any drug, liberate the mind? Huxley believed the explanation must be sought in a theory advanced by Henri Bergson, and later elaborated by the Cambridge philosopher, Professor C. D. Broad. The original function of the brain, Broad thought, was basically not productive, but eliminative. It was designed 'to protect us from being overwhelmed and confused by the mass of largely useless and irrelevant knowledge, by shutting out most of what we should otherwise perceive or remember at any moment, and leaving only that very small and special selection which is likely to be practically useful'. This, Huxley decided, would explain what had happened to him, and to others who had had similar drug experiences. Ordinarily we get only a 'measly trickle' from the mind's vast resources. But a few individuals have a by-pass mechanism, enabling them to open the doors of perception; others construct one with the help of spiritual exercises; and others can utilise drugs.

On this hypothesis, the vision-inducing drug could be described as a password to open doors which, for most people, are ordinarily closed. There is no single password; each individual may have his own — or none. Only one drug in common use has rarely been employed for the purpose: alcohol. Alcohol and the hallucinogens, Humphrey Osmond has argued, are actually antithetical; alcohol

produces a downward transcendence, peyotl an upward one — the difference between levelling up and levelling down. Alcohol allows one to relate to others by being more sure of one's self. This, in small doses, is much better than not being able to relate at all, but it is a very precarious business, and selfishness may soon end in brawling and ill-temper. Peyotl acts not by emphasising one's own self but by expanding it into the selves of others, with a deepening empathy or in-feeling. The self is dissolved, and, in being dissolved, enriched . . .

Anthropological field workers, too, have reported that the shaman who takes a drink loses his powers of divination. It remains possible, therefore, that the pharmacological action of alcohol will eventually be shown to be qualitatively different from that of other drugs, so that the doors which it opens do not expand awareness but instead — as Malcolm Lowry suggested in Under the Volcano — facilitate the emergence of a second self, ordinarily kept hidden.

Even this, though, is uncertain. Alcohol may have the effects it does because in some as yet unexplained way our minds are programmed to react to it — as a shaman's is programmed to react to tobacco as a vision-inducer.

The most likely hypothesis is that although a measured quantity of a specific drug can, other things being equal, have statistically predictable effects within a culture, its effects can vary greatly with different cultures, as well as with different individuals, or with the same individual at different times — as Oliver Sacks' experiences treating patients with 'L Dopa', described in his Awakenings, so strikingly illustrated. The reactions to the drug, he found, appeared to be dictated not just by the personalities of the patients, but by fragmented elements of those personalities, too.

In ordinary circumstances, however, expectation is the most potent force in determining a drug's effects. When Dr Walter Pahnke tested a psylocybin mushroom derivative on theology students at Harvard, he found that the visions the students reported were indistinguishable from the visions they would have expected to get from a mystical experience. And from his study of the peyotl cult among the Huichol Indians of Mexico, Peter Furst concluded that beyond any sensations which could be attributed to the chemistry of the plant, 'there are powerful cultural factors at work that influence, if they do not actually determine, both con-    tent and interpretation of the drug experience'.

Drugs and drink

Scientists, then, have at last begun to ask relevant questions about drugs, and are beginning to get some answers. But the answers have been largely ignored, or rejected, because they do not fit in with society's preconceptions about drugs. One of the commonest assumptions, for example, is that alcohol has in some measure been tamed, and consequently can safely be put in a different category from other drugs. But a research project undertaken by Dr Harris Isbell and his associates at Lexington has revealed that almost all the reactions of subjects who were given barbiturates in the experiment, from mild tipsiness to delirium tremens, duplicated those of alcohol — so closely, Brecher thought, that 'the barbiturates might be labelled a "solid alcohol" and alcohol classed as a "liquid barbiturate": The differences between them were chiefly the consequence of the barbiturates being available in more concentrated form. Otherwise, the evidence suggested, there was no logical reason why the barbiturates and alcohol should not be placed on the same legal footing. Yet in practice, as Brecher put it,

society takes a very different stance with respect to the twin drugs. Alcohol is treated as a non-drug; it is on sale in multidose bottles at 40,000 liquor stores and in countless other outlets as well; it is freely sold to those 'of age' in saloons, taverns, cocktail lounges, nightclubs, roadhouses, and even ordinary family restaurants; and more than $250 m a year is spent on advertising alcohol. The barbiturates, by contrast, are legally saleable only on prescription in pharmacies; other sales are severely punishable criminal offences. It is a curious fact, indeed, that Americans today are bombarded with advertising urging them to buy a liquid that, if secured without a prescription in tablet or capsule form, could lead to imprisonment for both seller and buyer.

In clinical terms, Isbell's experiments have also showed that the effects of alcohol and the barbiturates on health are more serious than those of the opiates. If its social side effects are taken into consideration, alcoholism emerges as by far the most serious of the Western World's drug problems. According to an estimate published early in 1972 by the National Institute on Alcohol Abuse and Alcoholism in America, nearly ten per cent of the nation's drinkers at that time were alcoholics, doing incalculable damage to their health, wrecking their families' lives, costing $15 billion annually in damage to property, loss of working time, and welfare payments, and causing havoc on the roads. In the same year, Lord Rosenheim, Chairman of the Medical Council on Alcoholism in Britain, warned that the number of alcoholics was much higher than doctors realised — there were 350,000 in Britain, he estimated, but there might be as many as half a million — and that alcohol caused far more actual illness, as well as misery, than all the other drugs such as cannabis, heroin and LSD put together.

In both countries, too, the number of alcoholics has been rising — so rapidly, in Britain an international conference on the subject in London was told in 1973, that they would top the million mark by 1980. Many other countries in different parts of the world have reported the same trend. Zambia, Kenneth Kaunda complained that winter, was becoming a nation of drunkards; and he threatened to resign if they did not learn to control their excessive drinking habits. Yet the World Health Organisation, faced with such reports from all over the world, could do little more than file them. 'So far as I am concerned', Dr Dale Cameron, head of WHO's Drug Dependency Unit, said in 1971, 'alcohol is probably the king of the mountain,' but so far as the U.N. was concerned, the king could do no wrong, because by tacit consent alcohol had not been included in drug conventions. In logic, or sense, such an omission was impossible to justify — as the Shafer Committee recognised. American laws, its report noted, had made alcohol the preferred social drug, but 'that historical fact should not prevent further evaluation of this preference'. On the Committee's own evaluation, alcohol dependence was 'without question the most serious drug problem in this country today'.

This is not, of course, to suggest that a campaign to wean people away from alcohol could blithely stress the relative safety of, say, cannabis as an alternative. Indeed the latest reports on cannabis, published by the U.S. Senate Subcommittee on Internal Security, strongly suggest that the drug carries greater dangers, mental and physical, than has earlier been recognised. This discovery appears to be partly due to more, and more sophisticated, research projects; partly to the recent development of stronger, more dangerous forms of the drug; partly to some as yet unexplained psychological reaction among users (perhaps more people are taking it not for a 'lift', but as a narcotic).

The evidence provides a salutary reminder that any drug, and all drugs, can have adverse effects. To judge from the introduction to the published volume of evidence, by Senator James Eastland, though, the lesson that banning a drug is the certain way massively to increase the sales of it has not been learned. He is aware that ten times as much cannabis gets into the country as is seized Ca fairly conservative estimate). He is also aware that in the past five years seizures of marihuana have increased tenfold, and of hashish, twenty-five-fold. But it still has not got through to him why. Dr Henry Smith Williams's 1938 prophecy has come true; prohibition of cannabis has brought a five billion dollar racket in its train.