Treatment without an active molecule can still relieve some patients. But by what physiological mechanisms?
At the Institut Curie, a Parisian cancer centre, the question arose of opening a homeopathy consultation. Not to treat patients, but to help them better cope with the side effects of chemotherapy: “We finally did not make this choice, because there is no scientific evidence to justify it,” says Carole Bouleuc, head of the supportive care department. On the other hand, this doctor never discourages patients who use it: “If the placebo effect associated with this practice can reduce nausea, fatigue or anxiety without interfering with care, it is not a problem,” she says.

Contrary to a widespread idea, the famous “placebo effect” – the only one that serious studies recognize as homeopathy – is not synonymous with no effects. Far from it, even. Of course, technically, a placebo is a tablet devoid of any active ingredient. Nothing more than agglomerated sugar or flour. But doctors have known since ancient times that simply prescribing a patient with a treatment, even if in fact completely inert, can already help to improve his condition.

Moreover, to evaluate the efficacy of new molecules, manufacturers must compare them to placebos, without patients knowing whether they are taking the real or the fake remedy: it is thus a question of ensuring the proper efficacy of the tested product, a sine qua non condition for obtaining reimbursement by the community.

But if the placebo has gained its reputation in pharmaceutical research, it remains discredited in medicine – which doctor would admit today to treat his patients in this way? “A sugar tablet will never reduce the size of a tumor, nor will it help the body get rid of a virus, but it can play an important role in some symptoms,” says Dr Jean-Pierre Thierry, medical advisor of France assos santé.

Chronic pain, migraines, depression, anxiety, post-traumatic stress, insomnia, allergies, gastrointestinal disorders and even Parkinson’s disease: for all these pathologies, studies have shown the usefulness of these fake drugs.

Even in surgery!
Even more surprisingly, the placebo effect even plays a role in surgery. Clinical trials have been conducted to evaluate the real effectiveness of certain operations, particularly those where the result remains quite subjective (in pain related to osteoarthritis of the knee, for example). In these trials, patients underwent “false” procedures: taken to the OR, put to sleep, incised and sewn up, they did not benefit from the surgical procedure itself. And yet, most experienced a similar reduction in symptoms to that observed in patients who had actually undergone surgery.

How can these reactions be explained? Often mistaken for a mere psychological effect, the placebo effect has physiological foundations: “The administration of a fake drug triggers reactions in the brain, with the production of neurotransmitters such as endorphins, dopamine or canabinoids,” says Frédéric Lagarce, Dean of the Faculty of Pharmacy in Angers. But by what process? It remains quite mysterious. Most experts see it primarily as a consequence of the rituals surrounding care: “It is the biological response to feeling cared for by a doctor,” says Ted Kaptchuk, a professor at Harvard University (USA).

Not all patients are receptive to it
This researcher has given himself a mission: to give the placebo a place finally recognized in medical practice. “This could provide a simple solution for some patients, without side effects,” he pleads. But to convince doctors, many questions remain to be resolved. To better understand the underlying biological mechanisms, for example. Or to be able to identify “answering” patients, those for whom the placebo effect works.

Because we are not all equal in this matter. In Prof. Kaptchuk’s team, a molecular biologist has uncovered a genetic variation that would make people more or less receptive, through the complex brain mechanisms involved in pain and inflammation. “Such a discovery needs to be confirmed by other work,” the American doctor nuanced.

A study published in Nature Communications last September revealed other characteristics common to patients most sensitive to placebo. Both anatomical characteristics, such as a thicker sensorimotor cortex, and psychological characteristics – with greater attention to the signals emitted by their bodies. “By crossing these different elements in patients with chronic pain, we were able to identify upstream those who then responded best to a fake drug,” says one of the authors of this publication, Professor Vania Apkarian of the University of Chicago.

No need to lie?
But the key question remains: can we get an effect while telling the patient that he is taking a fake drug? Until now, it was accepted that this was impossible. This represented a major obstacle to the use of placebo, due to the obligation of transparency towards patients imposed by medical ethics. Professor Kaptchuk has therefore decided to provide a scientific answer to this question. “At first, all my colleagues laughed in my face,” he recalls. However, he has conducted four studies in fatigue related to cancer, migraine, functional colitis and chronic back pain, each time telling patients that he was giving them tablets without active ingredients: “Depending on the pathology, the symptoms have indeed decreased by 15 to 30%,” he says with a smile.

These results are quite disturbing for homeopaths. Because if there is no longer even the need to make patients believe that their granules are drugs for the placebo effect to work, it is all their practice that loses its justification…

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