Apomorphine Versus Addiction

Chapter Two

“Experience is the name we give our mistakes”
— Oscar Wilde

By early 1918 Dent, now medically qualified, took his first proper job – a five- year stint as resident house doctor at St. Pancras workhouse. St Pancras is now a small hospital but Victorian workhouses were typically designed to deter malingerers and bore an uninviting visage. It had eight, cramped and stuffy fifty bed wards catering for the chronically sick and elderly with an additional four wards for the mentally ill. Every conceivable infirmity was in evidence but when, due to WW1, there came the added influx of de-mobbed amputees, and shell-shocked veterans, St Pancras with a skeleton and inexperienced staff, struggled to cope.

St Pancras Hospital today

St Pancras Hospital today

This was a tough medical baptism but got tougher when London was hit with a deadly wave of Spanish flu. St. Pancras simply couldn’t bury its dead fast enough. Overnight there were over two hundred cases but only six vaccines! Dent used these up on the pneumonic cases and, to avoid suspicion of favouritism, injected the remainder with sterile water with apparent equal benefit! Eventually Dent was so exhausted that he himself collapsed and had to be stretchered off the job. Mercifully, things soon calmed down but by Spring 1919 another wave of the deadly virus finished off those with an already weakened immunity.

Routine at St Pancras usually meant a birth a day, regular suicide attempts and a variety of complex and disturbing self-inflicted wounds. One woman burnt her entire body with a candle and died of “septic shock”, but apparently without pain. On another day a man was delivered from Kings Cross station with a terrible fracture to his remaining leg that was probably a boon to begging. The staff set it in splints but in the morning the splints were off and the thigh bent double. Dent suspected a nightmare and reset the leg but again by morning the man cradled his foot by his ear. This time the leg was set in plaster with exactly the same result. Then, quite by coincidence, a visiting member of staff recognised the patient from a hospital in York where much the same sequence of events had occurred. Challenged by this precedent St Pancras had to do better than York so St. Pancras’s three doctors helped by nurses took it in turns. They set the leg in wood, in plaster, in bed, in the mental ward and finally in the padded room. Eventually, nine months later, the leg was straight and healed. Blaspheming, furiously, the patient was finally returned by train to York. They never saw him again.

It was at St Pancras that Dent first used Apo’ on the inebriated. Every Saturday night they would be rounded up from the nearby KIDgutters and brought to the workhouse. It was Dent’s job to handle admissions, which, for the comatose, usually meant the stomach pump. This was an unpleasant job for they were often extremely dirty, infested with lice and belligerent. Dent decided to use the emetic property of Apo’ as he could administer it quickly and at arm’s length. It was a good idea. The job took much less time and the intake were rendered compliant by the other less-known side effect of Apo’; a deep sleep. It is a curious feature of the confused reputation of Apo’ that the emphasis is always placed on its emetic property when, in respect of recovery from addiction, its other side effect – the somnambular dimension – is probably more useful, particularly when dealing with anxiety and withdrawal.

Another British doctor, Basil Merriman, corresponded in 1962 that Apo’ had a “central depressing action” that had benefit for those fighting metabolic changes due to alcoholism and as a stabiliser for those suffering from “craving” adding;

            “…..the sedative properties of Apomorphine should be far more widely known than they  are…..”

It seems, over fifty years later, that we still do not know to what extent this dimension of Apo’ a full agonist could be a factor in any therapeutic effect for those recovering from addiction and particularly for those attempting recovery at the “compulsive” end of the addiction spectrum or if Apo’ has the property of a partial agonist when delivered in small doses?

In the early 1920s, amid the anonymous and destitute, Dent identified that the first barrier to treatment of addiction was the orthodoxy that didn’t even recognise the need. The following quote appeared in Dent’s second book “The Human Machine” (an original analysis of how a range of behaviours affect the human organism.)

I know of no medical text book that includes advice on the treatment of acute misery or grief, no drugs are prescribed for broken hearts, and Dutch courage is all that is advised for terror.”

photo-5-Recovered
It was dawning on Dent just how ill-equipped his medical training had left him to meet the challenges of intoxication and addiction. Dent was therefore initially motivated by feelings of inadequacy in the face of a large and growing problem.

Lamentably, most history on Dent tends to mention who he treated rather than how he treated and, accordingly, you could be forgiven for believing that he only moved in a narrow social group of “names” or social climbers and that he was close to some sort of narrow coterie of the medical establishment. This would be a mistake. Dent, first and foremost, was an outsider armed with little more than the courage of his convictions yet, like the condition he fought, he recognised no boundaries:

Every form of alcoholism exists. There is every degree of susceptibility in the drinker from almost absolute intolerance to the ability to cope with three or four bottles of whisky daily. Drinkers may also vary in weight, age, mental stability, heredity and their circumstances, which include wealth, worries and work.”

And in respect of its pathology:

             “The immediate effect of alcohol in excess is drunkenness, but alcohol poisons the whole organism and produces lasting changes especially in the stomach, liver and nervous system.”

By merely scratching the surface of Dent’s history through his writings and the observations of others it is clear that “equality”, another Quaker testimony, was a constant watchword. Heroin dependency in the first half of the 1900s was certainly a preserve of the middle and professional classes but alcohol dependency was not. While at the workhouse Dent, interested in neonatal withdrawal symptoms, conducted a post-mortem on a one year old child to find a “hob-nailed liver” probably as a result of its mother’s drinking during pregnancy but perhaps also because alcohol would have been used to keep the baby quiet. The complexities of addiction, its multi-factorial causes and effects were going to occupy Dent for the rest of his life and, as his writings testify, he was never territorial about what he learnt. His empiricism backed by utilitarian ideals was matched by a constant willingness to share and encourage others with his stewardship of a pioneering discipline. Apo’ modus Dent has been thinly described as “defined by social context” (Virginia Berridge)  but this view fails to reflect that from Dent’s early perspective there was no context, moral, social, medical or otherwise.  Quite simply the problem of addiction and its causes was barely recognised and any notion of successful treatment a pipe dream. He wrote;

“When confronted by a case of misery or anxiety it is useless to give nothing but sympathy. As doctors we are expected to do more than that.”

Against this hapless atmosphere and the tendency amongst other doctors to recommend whisky or beer for alcoholism Dent recalled the inebriated at St Pancras remembering how those injected with Apo’ had appeared different on Sunday morning when compared to those previously dealt with by stomach pump. They seemed calmer, more assured and thankfully for the staff, more co-operative. Why was this? What was going on and how could he provide the answers that science could not???

Dent mulled over the idea of developing a systematic treatment using Apo’ as the basis for a scientific paper. This was not going to be easy. There was resistance within his hidebound profession and throughout society as “drunkenness” was stigmatised with thoughts of punishment placed well before any notions of treatment. Even at the end of his career Dent still objected to the blatant way theatre and television portrayed the “drunk” as a figure of fun. Dent’s early talk of addiction being a “disease” which, if reduced, could benefit society was regarded in the 1920s with widespread incredulity and suspicion. The institutions of Church, Law and Medicine were, by and large, still driven by Victorian and punitive sensibilities and Dent, now married with a young family, knew that any plan of developing a treatment for addiction amid the chaotic confines of St Pancras would be impossible. One day he was forced to knock unconscious a syphilitic patient who was trying to bite him and on another he delivered a headless baby. The minister arrived hot foot from the nearby church expressing annoyance that he was too late to administer the last rites.

 “Why didn’t you keep it alive? God in his infinite mercy could’ve saved its soul.”

This was too much for Dent:

“Well, when dishing out souls, why did your ‘infinitely merciful’ God run out of heads?”

Dent set up in general practice in West London and proceeded to outline a protocol for Apo’ as a way of tackling alcohol dependency. The need within the medical profession was acute as typified by a conversation Dent overheard between two doctors discussing their approach;

Doctor “A”; Do you know who Doctor “C” sends his drunks to?”

Doctor “B”; “Oh he sends them to Doctor “D.”

Doctor A; Oh really! And who does “D” send them to?”

Dent supposed that the patient was long dead before he ever got to “Dr Z” but just as bad in Dent’s opinion was the prevalence of prescribing alcohol or another drug that masked or exacerbated any underlying cause. Dent believed that medical science could and should be able to do better.

“We must, however, be on guard against the habit of prescribing alcohol or sleeping draughts, both of which, are likely to become increasingly necessary to the patient.” 

Despite the overwhelming need for fresh ideas Dent was required to be more organised than his character allowed. He was a polymath with an insatiable appetite for knowledge and though he had used Apo’ on numerous occasions at St Pancras his individualistic methods lacked the detailed analysis necessary for such an undertaking. His first paper to the British Medical Association was rejected with a curt letter suggesting he try again in six years time. Six years! This was devastating for Dent who had agonised about what the safe dose of Apo’ could be, admitting on occasion to giving up to forty times what was recommended! Falling so emphatically at the first fence had left Dent vulnerable, doctors needed to have their methods recognised before any degree of legal protection could exist. What if Apo’ made people ill, or worse? Dent was on his own, floundering, and cast there by his own enthusiasm. Luckily at that moment he managed to cross paths with an acquaintance.

Dent!” came the cry, “What on earth is wrong? You look terrible.”

Weakly Dent explained about the failed paper, his rejection and the deep frustration at having to wait six whole years before resubmission.

 “Oh, bloody hell Dent, forget them, they wouldn’t be interested. You should take your ideas to Dr Kelynack, he runs the Society for the Study of Inebriety, he’s your man.”

It was an extraordinary measure of just how isolated Dent was that, despite his interest in addiction, which by now had spanned twelve years, he had never even heard of this society that, like him, was also based in London.

The next morning Dent sat nervously in Kelynack’s waiting room until it was his turn. Once inside the great man’s consulting chamber Dent briefly explained his problem and the fate of his maligned paper. Kelynack rang a loud bell and his receptionist appeared.

“Tell all those in the waiting room that I’ve been taken ill and am seeing my doctor. Make new appointments.”

Then, turning to Dent;

 “Please, read me your paper, the rest of the morning is yours!”

This was the first encouragement that Dent had ever received for his project. He had already read his paper to a small medical group that was almost entirely asleep by the end. Kelynack however, was enthusiastic and each man immediately recognised in the other a shared purpose. Kelynack invited the reinvigorated Dent to contribute to a lecture the following week. Kelynack was the editor of the Society’s journal but was nearing the end of his tenure.  The Society for the Study of Inebriety would soon change its title to The Society for the Study of Addiction (SSA) and needed new blood. Dent succeeded Kelynack as editor in 1941.

That first lecture was an eye-opener for Dent mainly because he had to endure another doctor who….

CARTOON 4

had the audacity to talk of paraldehyde-addiction and he had made every single one of them. He turned alcoholics into paraldehyde addicts, which he thought was preferable. The stuff was cheap and had a similar action to alcohol but was so offensive in its taste and smell that they couldn’t take much. This is a fallacy because, for the addict, no horrible taste or smell will prevent its victim from taking a drug once he is addicted to it. I have found it is a harder addiction to treat than even to pethedrine or heroin”

This doctor ran a residential home in the Midlands for the purpose of “treatment” which Dent found intolerable for the reasons outlined. They became bitter rivals at the Society but Dent had no qualms about upsetting someone who was behaving “unethically” due to his having a commercial operation to protect. Specifically, Dent felt uncomfortable with the entire concept of the residential rehab industry because he believed it ultimately made things worse for the patient who would be better off facing up to rather than shielded from the realities of his situation, often in the luxurious and frequently expensive confines of a rest home. But the real focus of Dent’s dis-aproval  was the prevalence among doctors to advocate one form of addiction over another. When comparing the relative merits of all pharmacological approaches, Apo’ scores highly because, to date, not one single case of WILFREDphysiological dependence to it has been recorded. Moreover,  oral administration of the drug is safe because, due to its emetic property, it is impossible to accidentally overdose. Unfortunately, medicine and research into drug addiction therapies has been reluctant to try and understand why Apo’ was effective at overcoming withdrawal, combatting craving and providing a gateway to an abstinence model. And it was to abstinence, surely the ideal of all addiction therapies, that Dent felt compelled to provide. Over the intervening years this ideal has given way to many protracted treatments that involve dependency on prescription and, in the case of certain maintenance treatments, addictions that are many times harder to shift than the original. In light of this it is perhaps worth noting what Dent said about his main thesis:

…..the human organism has to maintain a balance in a changing, uncomfortable world. If it is petted, if it is unduly sympathised with, it becomes less and less able to face the world. It can become addicted to anything that anaesthetises it against discomfort or unduly softens its surroundings. Too much care, too much sympathy, or mistaken help, is never the best treatment in the long run. If a person can have his mechanism sufficiently repaired for it to face his circumstances and then be encouraged to struggle with his difficulties, it is quite possible that he will overcome them and enjoy the struggle as well as the victory.” 

Reading these words it is clear that Dent was an inspiring character. He didn’t talk much but when he did,  people listened. His understanding about addiction and what preceded it was already profound, but what drove him to use Apo’ was primarily its safety and secondly, because it permitted the patient to immediately stand at very heart of his own recovery or re-discovery. Dent believed it his professional responsibility to seek a mechanism which equipped patients to throw off difficulties rather than bear them under the fog and dead weight of pharmacology. Apo’ was a short neuropharmacological solution with an individually empowering dimension. Irrespective of its merits or failings  the abject failure since the 1950s of science and medicine to provide sustainable abstinence strategies for the disease of addiction has to be a cause of regret, but in almost every area of medicine we are now subject to a culture of dependence and a “pill a day” society, which springs from a failure to emphasise the capacity in every individual to overcome, and for the organism to restore itself to the default position. The tragic consequences of this combined failure, both for society and countless individuals, is impossible to quantify, but, only recently, even the spineless David Cameron has been forced to express misgivings at the readiness among doctors to routinely and unnecessarily prescribe antibiotics. This belated reaction to the culture of pharmaceutical maintenance lobbied for continually and supported by weak government has finally begun to register. As the Italian proverb declares; ‘If you hang about with cripples, you learn to limp” seems to be a fair reflection of where our legislators and overweening culture has brought us and something that has to be resisted at every level. It may be compassionate to support maintenance therapies if that is the best alternative but not if they lead to greater harm.

By the late 1930s Dent, encouraged by his involvement with Kelynack and others at SSA, set about revising his paper and treatment with Apo’. However, Dent’s early mistake (and one he never recovered from) was to attribute the vomiting side effect of Apo’ as the main factor in its efficacy.  By pairing alcohol with Apo’ he inferred that a conditioned taste aversion or a conditioned reflex similar to Ivan Pavlov’s behavioural studies would ensue. The patient would receive Apo’ followed immediately by alcohol and then, because of the side effect of Apo’, be sick. This gruelling regime would continue every few hours for two or three days by which time Pavlovian theory suggested that the patient would associate alcohol with being sick and no longer want it. Abstinence was therefore ‘achieved as a conditioned response to a vile experience’ which was met with approval in some circles that saw “drunkeness” as a moral failure and deserving of punishment. This was never Dent’s intention but to have a label like “aversion” as a hook to hang his treatment on was in some ways a good idea. It could be explained in terms of the “Pavlovian” behavioural studies and theories of conditioning that were vogue at the time but it was a bad idea because, on its own, “aversion” simply does not work. Dent soon recognised this but initially attributed the success to the vomiting reflex. Dent explained that if he had wanted to use aversion as the sole basis for treatment that Apo’ was nowhere near the best as violent bouts of vomiting induced by  emetine was far more effective. Emetine was used a lot in American prisons where, against their will, inmates were forced to swallow their regurgitated mixture of alcohol and emetine over and over again. This provided a truly unforgettable association of sickness and horror but, as an effective treatment for overcoming the compulsion of addiction, emetine is entirely useless.

Dent aged about forty. Photo: courtesy of A. Buchanan.

Dent aged about forty. Photo: courtesy of A. Buchanan.

Today “aversion” is a dirty word. It evokes scenes of punishment and treatments against a patient’s will. Aversion though has never been properly understood in terms of neural activity. It is the flipside to reward because survival depends on our ability to identify both rewarding and aversive stimuli. Recent studies have begun to look at how different sub populations of dopamine neurons react to aversive stimuli (Matsumoto & Hikosaka 2009) with some surprising results that could have implications for how we may interpret the underlying mechanism for addiction and its treatment. Kent C. Berridge in 1998 recognised how aversive dopaminergic stimulation was difficult to interpret in terms of its positive effect because of the difficulty of devising a test that could be both aversive and voluntarily submitted to. In its embryonic form Apo’ modus Dent was one such treatment because his patients were co-operative, voluntarily presented themselves for treatment, and were fully conversant with every aspect of his method. Dent in fact discouraged those who wanted treatment for anything other than entirely selfish reasons and the man who said; “I’d like to try it as a birthday present for my wife”was respectfully asked to reconsider. Berridge also pointed out that any voluntary aversive treatment must have a rewarding dimension upon conclusion that might equate with that surge of relief felt after finally facing and overcoming an unpleasant task or duty.  This is undoubtedly true but the unanswered question in respect of Apo’ is the hypothetical connection between both aversion and cognitive repair via a drug with the power to reboot or repair the neural pathways compromised by addiction itself. It is an interesting area and remains a largely unexplored dimension of this treatment. Typically, for example, convalescence after opiate withdrawal takes several months but Dent’s patients were consistently able to return to work within a week!

Dopamine mediates between motivation, memory and learning. What if Apo’, the dopamine agonist, with affinity for each of the dopamine receptors registers a significantly aversive but voluntary experience in terms of its beneficial salienc allowing the brain to imprint subsequent rewarding patterns of behaviour as critical to survival? Where would such an approach fit into the accounts by addicts who talk convincingly in terms of the no gain without pain” strategy towards recovery?

At this point it should be pointed out that this is not a recommendation for “aversion” with Apo’ but an academic curiosity about an aspect of this treatment which could never have been properly understood at the time but certainly worth revisiting by biological psychologists in terms of what has been understood since.

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One Response

  1. Jonathan Naess says:

    The fact that I understand 400 people died last year from methadone abuse (ONS) without the choice of an abstinence programme with Apomorphine or a suitable dopamine alternative, seems a tragedy. As a mental health service user I am painfully aware of the vested interests of the psychiatric system and drug companies. And as you quote… “What we think we know stops us from learning”
    I think your work in reviving understanding of Dent’s pioneering efforts and the broader reception of apomorphine are outstanding. Best wishes

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