While placebos have been central in clinical trials for many years, and exploited by quacks for centuries, their full potential has not yet been tapped. Anjuli Sharma explores the curiosities of the placebo effect, and our growing understanding of the conscious and unconscious physical processes they trigger.
During my years of studying pharmacology at university, I became accustomed to hearing about the strange stories associated with scientific discovery and research. One module in particular, on pain and the nervous system, was littered with countless snippets from the wider world of research.
I remember sitting in a small, crowded lecture theatre, scribbling notes on the mysteries of pain, learning the ways in which researchers were attempting to untangle chronic pain to treat patients. For me these stories offered a fascinating human dimension to lectures that were otherwise crammed with complex drug names and mechanisms.
Perhaps the most intriguing story that captured my attention was of a phenomenon that has been around for centuries: the placebo effect.
Placebos are commonly seen in the context of clinical trials – a type of trial that compares how effective and safe a new drug treatment is. The term ‘placebo’ is derived from the Latin for ‘to please’. It’s a treatment that contains no active ingredient, and sometimes comes in the form of a sugar pill.
The placebo effect is when some people have a response to taking a placebo: for example, their symptoms improve. In traditional clinical trials, half the participants receive an experimental drug and the other half receive a placebo. To prevent bias in the results, many of these trials are ‘double blind’ – where neither the participants nor the researchers conducting the study know who has received which treatment until the end of the treatment period.
For clinicians, the placebo effect presents a hurdle: to prove that a medicine is effective, pharmaceutical companies must demonstrate that their drug produces the desired effects, and that these effects are significantly greater than those in the placebo control group. But how did placebos become such an important part of the clinical trials process?
Psychology and pain on the battlefield
The story of placebos started in the midst of World War II in Italy. The enemy was closing in and soldiers were being seriously injured. Anaesthesiologist Henry Beecher, stationed at the medical tent, noticed something strange. While many of the soldiers he was about to give morphine to had very severe injuries, the pain that they appeared to be experiencing did not seem proportional to the extent of their injuries.
Beecher observed that alternative factors, aside from drugs, were influencing the way that pain was experienced. He realised that soldiers’ expectations, emotions and the context of the injury were acting as modulators of pain: soldiers who knew that their injury would allow a return to safety and escape the front line appeared to experience less pain.
Back in the US, Beecher became an advocate for the placebo-controlled clinical trials that continue to shape modern healthcare and the practice of drug development.
Charlatans and chicken guts
Despite it being a key component in the modern-day gold-standard clinical trials, doctors, researchers and patients continue to debate the ethics of the placebo effect and whether it is acceptable to deceive patients about their treatment. These moral quandaries are perhaps unsurprising when we consider the placebo effect’s murky past – charlatans and quacks have no doubt hijacked its effects to exploit vulnerable people seeking treatment. One extreme example of such medical fraud came in the form of “psychic surgery”.
During “psychic surgery” the surgeon would place their hands onto the skin of a conscious patient and, with no anaesthesia or medical instruments, would appear to pull out diseased tissue and organs from the patient’s body. Accounts of such surgery first appeared in the Philippines in the 1940s, and it began to gather an international following during the 1960s. In the US it was publicised via FATE, a magazine devoted to paranormal phenomena.
Touted as a miracle cure for chronically ill patients, at its peak the practice attracted several thousand “health tourists” to the Philippines, with many sharing stories of miraculous recovery alongside videos demonstrating the unusual surgery.
But by the 1970s any medical credibility that the practice had had was waning. Doctors, journalists and professional magicians exposed the ‘surgery’ as nothing more than sleight-of-hand tricks using grisly chicken guts that were exhibited to patients as proof of successful removal of disease. Many patients returned home feeling either no difference or a decline in their physical symptoms.
As a result, the American Medical Association began to discourage patients from seeking the treatment, deeming the entire practice as a fraud that sought to exploit the unwell.
Nevertheless, there is something intriguing to witness in the spectacle of psychic surgery. For the people who claimed to be healed or felt some benefit after the ‘surgery’, their suffering was alleviated – in these cases, doctors attributed recovery to the placebo effect, with the behaviours of the healers, the rituals and patient expectations leading to a positive response.
These fraudulent cases, and even double-blind drug trials, involve a degree of deception. But does this have to be the case? Is it possible for placebos to be used in an open and honest way?
Recent research has indicated that open-label placebo trials, where patients know that they are receiving a placebo, can still produce a positive effect. One of the early trials using “placebos without deception” was conducted by a team at Harvard led by Ted Kaptchuk. The study was for patients with irritable bowel syndrome (IBS). Patients were randomly placed into one of two groups: a placebo group who were told to take a placebo pill twice daily, and a no-treatment group.
Before the trial, patients were told that “placebo pills, something like sugar pills, have been shown in rigorous clinical testing to produce significant mind-body self-healing processes”. The results were astonishing: 59 per cent of patients who knew they were taking the placebo reported an improvement in symptoms compared with 35 per cent in the no-treatment group.
Participant Linda Buonanno, who received the placebo, felt an almost complete relief from her symptoms: “I felt fantastic. I knew they were just sugar pills, but I was able to go out dancing and see my friends again.”
Since this study, reviews and further analyses have shown open-label placebo trials to be a promising new avenue of research, though much work is still needed with respect to the condition studied and the trial design.
The future of the placebo
Although a placebo is a fake pill, it can trigger very real chemical pathways in the body that can be measured. Research into the biological basis of the placebo effect shows that many different conscious and unconscious processes could be involved, from Pavlovian classical conditioning to our expectations of a drug or treatment.
As more studies are carried out, could there be a way for these processes and the placebo effect to be harnessed for use in routine medical care? Neuroscientist and self-professed “placebologist” Luana Colloca certainly thinks so. She suggests that one potential application of an “honest placebo” could be a prescription of a blister pack of painkillers containing a combination of both active drugs and placebo pills – although the patient is aware that some may be placebo, they do not know which.
As well as being a more open approach to the use of placebos, this system could have other benefits, including reducing side effects associated with medication, drug dependency and costs.
But while scientists continue to investigate the mechanisms and debate the ethical conundrums surrounding this research, it has become clear that placebos have a much bigger role to play in the story of pain and healing than the simple inactive pills they were once considered to be.
About the contributors
Anjuli is a graduate trainee at Wellcome. Prior to joining Wellcome, she studied Pharmacology and Physiology at King’s College London.
Steven is a photographer at Wellcome. His photography takes inspiration from the museum’s rich and varied collections. He enjoys collaborating on creative projects and taking them to imaginative places.