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  Sinemet, Sinemet, Sinemet plus!

  We have a penchant for all things yellow

  Our favourite colour, it’s oh so mellow!

  When one of us is sick or disturbed

  We just give him little yellow pills

  And in 20 seconds, he’s feeling better.

  I now wanted to understand more about substance abuse – a topic that I had read little about since extracurricular reading during medical school. I started to plough through the reams of academic theorising and barely comprehensible psychobabble that had been published in medical journals. The experimental work of Berridge and Robinson, the imaging studies of Nora Volkow in cocaine addicts and Koob and Le Moal’s theory of hedonistic homeostatic dysregulation were instructive but it was the unsentimental fieldwork of the arch self-experimenter, William Burroughs, that best helped me to understand DOPA abuse. I re-read Junkie and Naked Lunch and this time I paid particular attention to Burroughs’ descriptions of the ‘algebra of need’ and the machinery of control. In a spirit of scientific enquiry, Burroughs had offered his neurones up as a culture medium for the junk virus. Unsentimental and factual, he wrote as if his thoughts had the quality of self-evidence:

  Because there are many forms of addiction I think they will all obey basic laws. The drug addict will do anything to satisfy total need … A rabid dog cannot choose but bite. The addict of any sort has sacrificed all control, and is as dependent as an unborn child.

  – Naked Lunch

  Burroughs often spoke of his self-hatred of the addict lifestyle. He considered junk to be an analgesic that killed the pain and pleasure implicit in awareness. He quoted the British neurophysiologist Sir Charles Sherrington as stating that pain is the psychic adjunct to an imperative protective reflex. Heroin destabilised the vegetative nervous system and cut off all feeling, diminishing the addict to a passive plant-like existence. Burroughs believed addiction was neither a moral failing nor a psychiatric disorder. ‘It’s as psychological as malaria’ he wrote.

  Life telescoped down to ‘fixes’, anticipation of the next hit and the paraphernalia of addiction. As the junk parasite infested the body all other interests and activities lost their importance. The junky needed to score to get out of bed in the morning, to shave and eat breakfast. Junk was in some way alive and the junky was a saprophyte:

  The addict runs on junk time. His body is the clock, and junk runs through it like an hourglass. Time has meaning for him only with reference to his need.

  – Naked Lunch

  Burroughs never idealised or promoted the junkie lifestyle. He was not an advocate of drug use but regarded drug addiction as a medical rather than criminal issue. Nevertheless, many heroin addicts dying in highrise squats now regarded Naked Lunch as their Bible. For them he had become the bard of the decaying city.

  In Burroughs opinion junk blanked out torment, eased the passage of painful time and had the potential to protect a vulnerable individual from schizophrenia and alcoholism. Regular usage of narcotics created an irresistible, pleasureless desire at the expense of everything else. Junkies were members of a disreputable and immediately recognisable club but only accepted they were different from the herd when they ran out of dope. They were bores who went through the motions, heroin was profane.

  In the Introduction of the original Junk manuscript I found passages that differentiated the requirement for prescribed medicines from the desire for recreational drugs:

  The junkie needs junk like the diabetic needs insulin. Junk creates a deficiency so that the body cannot function without more junk at regular intervals. It seems that junk takes over the function of certain body chemicals during addiction. Withdrawal of junk creates a deficiency condition, which continues until the body gets back in production on the chemicals that were replaced by junk. When I say ‘habit forming drug’ I mean a drug that alters the endocrine balance of the body in such a way that the body requires that drug in order to function. So far as I know, junk is the only habit-forming drug according to this definition.

  In ‘Letter of a Master Addict’ he distinguished the junkie from the insulin-dependent diabetic:

  The diabetic will die without insulin, but he is not addicted to insulin. His need for insulin was not brought about by the use of insulin. He needs insulin to maintain a normal metabolism. The addict needs morphine to maintain a morphine metabolism, and so avoid the excruciatingly painful return to a normal metabolism.

  Narcotic addiction was a drug-induced metabolic disturbance, a form of chronic poisoning that created a craving as intense as thirst and for which the only antidote was more junk.

  Although the Parkinson dysregulators had been prescribed L-DOPA as a life-enhancing medicine, similar mechanisms seemed to be at work. Their medicine no longer made them feel better or well but was still badly needed. Burroughs emphasised that ‘Junk is not a Kick’. L-DOPA had led to disinhibition, impaired decision-making and an escalation of medication use. Cutting the L-DOPA dose by half and restricting apomorphine had reduced the risky behaviour of the first patient but deprived him of his zip. He was more ‘manageable’ and more acceptable to his wife but he now complained that he felt flat and had lost all joie de vivre. Several months after his dependence had been brought under control he wrote me a letter:

  I have stopped cross-dressing since I reduced my daily dose of dopa and find this to be much more socially acceptable. But privately I must admit that I rather miss my skirts as I used to get a blast of ‘feel good factor’ when I put them on, that overrode any aches and pains I may have had at that time.

  Burroughs described similar feelings of hollowness and ennui when he was off junk:

  Then you hit a sag. It is an effort to dress, get out of a chair, pick up a fork. You don’t want to do anything or go anywhere. The junk craving is gone but there isn’t anything else.

  – Junkie

  After I had managed to successfully withdraw another of the addicted patients from damagingly high doses of L-DOPA, his wife took me to one side and thanked me for returning her husband to her after two years of hell. His secretiveness, capricious moods and Jekyll and Hyde behaviour had vanished and he had returned to being the loving compassionate man she had married. She was eternally grateful for what I had done, but her husband complained to me in confidence that a dense fog had descended on his life and he had lost his ‘buzz’.

  Although much of Burroughs’ ‘word hoard’ had been written in a narcotic and marijuana haze, he emphasised that junk stifled the creative urge. Apomorphine had been the turning point between life and death and without its help he would never have been able to put together the fugues from which Naked Lunch emerged. Freed from opioids his drive returned and with the disinfected eyes of the revived writer he could clearly visualise the Inferno.

  A well-known novelist with Parkinson’s disease who I had been treating for several years told me that his literary productivity was greatly enhanced by the use of apomorphine injections and he refused to cut back despite the fact that his arms were covered in puncture marks and bruises and his continuous writing was destroying his relationship with his wife. When I asked him why he was using apomorphine at times when he was already mobile, he took a picture of his rose garden out of his pocket and turned to me, ‘Beautiful, isn’t it, doctor? But after I have taken an injection it becomes exquisite.’

  A few months after his apomorphine treatment in London, Burroughs wrote:

  Tanger extends in several directions. You keep finding places you never saw before … Objects, sensations hit with the impact of hallucination. I now see with the child’s eyes, the Lazarus eyes of return from the gray limbo of junk. But what I see is there. Others see it too.

  – Interzone

  Burroughs’ literary resurrection had probably resulted from his withdrawal from the narcotic fog but after listening to my writer patient I began to wonder whether apomorphine itself might have been a contributory factor that allowed him to put the final touches to Naked Lunch
.

  Dr Dent put great store on the fact that apomorphine needed to be injected at regular 1–2 hour intervals around the clock for 7–10 days in order to be effective. He also stressed in his lectures that not a single one of his patients treated for anxiety rather than for alcoholism had ever become addicted to apomorphine.

  The importance of following Dent’s treatment protocol was further emphasised by Burroughs after his doctor’s death:

  It is essential to the success of the treatment to give a sufficient quantity of apomorphine over a sufficient period of time … With sublingual administration it is quite easy to control or eliminate nausea and the entire treatment can be carried out successfully without a single instance of vomiting. The concentration of apomorphine in the system must reach a certain level for the treatment to be successful. I have known doctors in America who gave two injections of apomorphine per day. This is quite worthless.

  – New Statesman, 1966

  The first patient I had seen with dopamine dysregulation had abused apomorphine by repeatedly injecting the drug whenever he began to feel he was switching off. We also saw several other patients who were overusing their ‘rescue’ shots. On the other hand the more severely disabled individuals who were being treated with the apomorphine pump rarely increased their dose and some voluntarily reduced it. I reasoned that repeated intermittent administration could subvert the dopamine system and lead to an increased wanting for apomorphine whereas delivery of the drug by infusion tonically stimulated the dopamine receptors and corrected the metabolic imbalance.

  Neither Doctor Dent nor Burroughs were aware that apomorphine stimulated dopamine receptors. The important dopamine innervation of the limbic edge of the brain now known to be important for motivation and reward would not be discovered for another twenty years and the mapping of dopamine receptor reductions in drug addicts was a very recent finding. Dent’s method was a rough approximation of the continuous stimulation of the dopamine receptors we had achieved with our apomorphine pumps.

  As time passed, our radical suggestion of DOPA addiction in Parkinson’s disease gained support, especially from experimental psychologists. Effective control of the motor symptoms in Parkinson’s disease with L-DOPA or apomorphine could inadvertently lead to unwanted overdose effects on the relatively undamaged limbic and prefrontal dopamine pathways of the parkinsonian brain, culminating in undesirable cognitive and emotional changes.

  The patients’ narratives continued to spawn my research projects and led to fruitful collaborations with cognitive neuroscientists. Positron emission tomographic (PET) studies showed that L-DOPA had the capacity to induce procurement of more medication, irrespective of whether the effect of the drug was perceived to be pleasurable. The reward pathways had been sensitised resulting in an increased outpouring of dopamine. This in turn led to a heightened desire and an obligate requirement for more medication.

  The seamstress told me that as long as she continued to organise her button collection she was able to prevent her DOPA ‘switch offs’. Any attempt by her husband to stop her from punding was angrily resisted. The possibility that rewarding activities might offer new avenues of treatment for the ‘on-off phenomenon’ was completely unexplored. I took her anecdote as encouragement for future research.

  Tim Lawrence, a young film stuntman with Parkinson’s disease, had related on a BBC Horizon programme how he had inadvertently discovered that the Class A drug ‘Ecstasy’ (MDMA) had helped him to override his severe motor blocks. The TV footage showed him shedding his parkinsonian straitjacket and performing incredible dance floor backflips, swallow dives and somersaults. It seemed likely that Ecstasy was releasing large quantities of serotonin and this was having the effect of making his movements smoother and more fluid but I also wondered if the drug might be acting as a salient incentive for his dopamine reward system.

  The chances of getting experiments involving ‘Ecstasy’ through the ethics committee and University College’s Research and Development Department were small, so I settled on a test in which the patient volunteers would receive small financial gratuities for achieving card-sorting targets. The results revealed that patient volunteers with dopamine dysregulation and punding were more responsive to pecuniary inducement than matched patients with Parkinson’s disease who had no addictive behaviour. One rewarded patient more than doubled his speed of sorting and switched spontaneously from ‘off’ to ‘on’ without the need for L-DOPA.

  I had a hunch that this exaggerated feedback system for predicted rewards might stem from a more generalised effect of dopaminergic drugs like cocaine and amphetamine on the brain’s motivational apparatus. The improvements seen with placebo medication in drug trials also probably occurred as a direct consequence of an increased surge of dopamine activity in the brain. The recognised healing powers of dance, exercise and music might also result from a fulfilling short-lived release of catecholamines.

  After his successful withdrawal from junk, Burroughs had written to Dr Dent saying that he would be keen to collaborate on a book about narcotic addiction. His self-experimentation had provided me with insights into the cause of dependency and its treatment, and pointed the way towards a thesis. Not long after the publication of Naked Lunch in 1961, Burroughs was asked to deliver a paper at the 69th Annual Convention of the American Psychological Association in Manhattan on the differences between narcotics and psychedelic drugs. In his well-received talk he emphasised that exposure to drugs was always the first step on the road to addiction.

  Burroughs knew all about the dissociation of liking from wanting, long before Berridge and Robinson’s incentive salience theory was published in 1998. He also knew that junk laid down refractory narcotic memories by re-igniting processes involved in the normal ontogeny of reward circuits, and that effective treatment (permanent withdrawal) would require neuronal re-maturation.

  He believed that all humans were hard-wired to be insatiable wanting machines. Sugar, laxatives and even shoplifting had the potential to become external objects of false satisfaction. Provided a novelty factor was introduced almost anything could be turned into a consumable. Corporations increased their stranglehold on the masses by alluring advertising. Junk was the ultimate merchandise and, in his paranoid but prescient world, a part of the global conspiracy.

  To say it country simple, most folks enjoy junk. Having once experienced this pleasure, the human organism will tend to repeat it and repeat it and repeat it. The addict’s illness is junk. Knock on any door. Whatever answers the door give it four and a half grain shots of God’s Own Medicine every day for six months and the so called ‘addict personality’ is there.

  – New Statesman, 1966

  In further experiments carried out with the brain imagers at the Hammersmith Hospital, we were able to show that advertising (showing images of anti-Parkinson pills, food or sexually explicit pictures) reinforced dysregulation in the DOPA addicts and suggested that behavioural addictions like binge-eating and compulsive sexual disorder seen in some of the dopamine addicts could potentially increase drug wanting.

  We next investigated the underlying cause for the ‘overuse’ of medication in the dysregulators. The beads task is a neuropsychological test that probes how much information an individual gathers before they make a decision. Research carried out with this test showed that both DOPA addicts and illicit drug users responded far more rapidly and made more irrational choices than matched control groups, despite having intact working memories. This increased tendency to jump to conclusions without considering the consequences linked the Parkinson overusers to substance dependence and provided me with further evidence that the wanting of more and more L-DOPA was started and maintained by a destructive dopaminergic impulsivity rather than a loosening of the ‘angels of restraint’ in the inhibitory pre-frontal cortex.

  Burroughs also anticipated the psychopharmacological phenomenon of reinstatement whereby a morphine addict, abstinent from drugs for ten years, could become re-addicte
d after a single new exposure, whereas a newcomer to junk took at least six months to get hooked (‘once a junky always a junky’). He also understood that the ‘wanting system’ became more active the less likely it was that an individual could obtain ‘a hit’.

  I openly recognised that Burroughs’ raw data had informed the design of some of my experiments. It was all a matter of listening carefully to his wondrous flights of scientific fantasy. All he had ever wanted was to be part of the scientific debate but he had been excluded by a fellowship of personal interest. He had walked the talk but had been ignored.

  By 2005 and before we had finished writing up all our research, dopamine had become a celebrity neurotransmitter, the ‘sex drugs and rock and roll’ hormone used by journalists along with brain imaging to give their clickable ‘public awareness’ news stories a scientific gloss. Anything that was desired and therefore potentially harmful was reported in the press as due to a rush of dopamine in the reward centres. Despite his mass of self-contradiction, Burroughs may well have had something important to say about this plethora of unscientific sloppy reportage and undue emphasis on sensationalist quantity over quality.