A friend of many years sought my help in 2019 for what seemed, judging by the symptoms, to be uncomplicated heartburn. He worked in hospitality and he worked hard with plenty of stress as he was self-employed and an employer. Initially over-the-counter omeprazole and Gaviscon managed the symptoms but they returned aggressively at which point I insisted he visit his GP as weight-loss was also becoming apparent. The GP immediately referred him to hospital where a progressed lesion in his oesophagus just above the pyloric sphincter was identified. A biopsy was taken and sadly, based on pathology, he was diagnosed with oesophageal cancer Stage 4 and sent for treatment. For the next 12 months which included many months of the Covid19 pandemic he was either in, or going into, hospital. He had ten courses of radiotherapy as surgery was out of the question. He lost his hair and most of his body weight. He had chemotherapy as part of a clinical trial on which he sought my advice. Reading his notes and watching him deteriorate I told him he had nothing to lose and anyway the clinical trial was far from radical just a variation on timing of treatment.
I visited when I could and got angry when, during a brief opening-up between the first and second Covid lockdowns, I found him working in his restaurant. His immune suppression was enough to assure certain death should he contract Covid19. He felt great he told me and put it down to Traditional Chinese Medicine (TCM) and his newly found religion; he was placing his faith in Jesus. This I found somewhat worrying. Over the first year of his illness he had changed. Gone was his over-powering work-ethic, gone was the aggressive determination. He was calm, confident and assured. He also truly believed in the power of TCM to cure him and in the evangelical Christian message that he would be healed.
I was conflicted. I normally would have been assertively dismissive of either as effective treatment but in his case I desisted given the sheer hopeless of his situation. When first diagnosed he asked me about treatment success. The survival rate for Stage 4 cancer at 5 years didn’t exist I could only find a survival rate for 1 year and it was a lousy 20%. When I reluctantly shared these figures he was silent and left to tell his close family which was, he told me later, the hardest thing he ever had to do.
I have over the years poked fun at all forms of alternative medicine. In particular I despise homeopathy as bumkum and a money making racket. Herbal medicine, outside the orthodox sphere, is not much better and the bizarre lengths alternative practitioners go to dupe the vulnerable never ceases to enrage me and this includes fringe Christian sects. I have made myself unpopular with many pharmacy colleagues who promote this nonsense but I do not hesitate as I believe it unethical.
What I do accept is the power of placebo. This has been well established since the 1940s in well-designed studies particular in the management of acute pain. Thomas Jefferson, the third president of the USA, wrote about placebo in the early 1800s suggesting that use of “Bread Pills” and “Coloured Water” are a much better option to the high doses of mercury and opium being prescribed by physicians of the time. When challenged about the ethics of this he suggested it was a justified “Pious Fraud”.
David Robson in his book The Expectation Effect outlines recent research that identifies a biological basis for the placebo effect, an effect that goes beyond the psychological effect. The brain is essential a prediction machine and the thinking process produces an expected outcome which results in not just wishful thinking but a real biological effect. The body is primed to produce needed endogenous molecules that can reduces symptoms and induce healing. Endorphins and enkephalins, endogenous opiates, have long been known and mental conditioning ensures their released in sufficient quantities to reduce the intensity of pain. Conditioning is dependent on emotions and expectations; soldiers taken off the battle-field feel secure and relieved, a patient treated by a caring competent nurse in a hospital setting likewise. In pain the placebo effect can be as high as 90%. Bizarrely the use of naloxone, an opioid receptor blocker, has been shown to reduce the placebo effect confirming that the placebo effect for pain is mediated via endogenous opioids.
But not just pain, other conditions can be impacted by the expectation effect and conditioning. Dopamine is released in Parkinson Disease when using placebo tablets and in sufficient quantities to reduce motor-symptoms of the disease. Anti-inflammatory agents are released in allergic conditions and endogenous vasodilators in angina. The expectation response can be increased by a range of conditioning factors; use of a dummy medicine, the form of the medicine (injection is best), size of the pill, its colour, pervious experience of a drug. Marketing is also a powerful conditioner and explains why branded medicines are often considered more effective than generics. Marketing may also explain why the placebo effect is becoming more powerful over time as more people are exposed to direct-to-consumer advertisements from the pharmaceutical industry.
And off course the opposite is true. Warning about side-effects increases the likelihood that a medicine will be associated with an adverse effect – the nocebo effect. Again this is more than suggestion; negative thinking releases endogenous chemicals. In one study negative expectations were shown to trigger the release of cholecystokinin (CCK) which boosts the transmission of pain signals.
In mid-2022 my friend started to put on weight, got his hair back and in August of that year was given the all clear. The Stage 4 cancer had gone. He and his family were ecstatic and his commitment to TCM and Jesus only increased. His GP was amazed saying he and the oncology team had never seen anything like this but they know it can happen. Perhaps conventional chemotherapy in this case just worked better than expected. A GP friend to whom I told this story was of the opinion that he should sue the hospital for an incorrect diagnosis that led to unnecessary treatment. Perhaps he was not at Stage 4. Will it return? Miracles it seems do happen but can be explained and whatever the explanation in this case was there a role for a placebo effect?
Placebo and nocebo research is a fascinating and emerging area of medical science. The key is to see how this natural principle can be properly harnessed within orthodox medicine rather than leaving it to the quakes and snake oil sellers.
I am a pharmacist in Belfast.