Placebomics: Where placebo and genetics meet

The article by Wang et al. (see above) further explores the concept of the placebome and puts it into relation to similar gene networks thought to be active in drug action (drug modules) and in disease aetiologies and responses to treatment (disease modules). Within this framework, the researchers hope to further decipher the physiological basis of placebo and to find the raisons for differences of the strength of placebo in diseases where this effect is high (such as  alcoholism, anxiety, asthma, Crohn’s disease, depression, diabetic neuropathies, duodenal ulcer, epilepsy, eating disorders, fibromyalgia, irritable bowel syndrome, Parkinson disease, migraine disorders, osteoarthritis, chronic pancreatitis, restless leg syndrome, schizophrenia, and ulcerative colitis) versus diseases where this effect is low or absent (such as bacterial infection, infertility, viremia, pneumothorax, uremia, hepatocellular carcinoma and renal cell carcinoma. There have been about 15 candidate genes identified which may be implicated at the origin of the placebo effect; further research will more clearly reveal their role, the involvement of particular mutations, and eventually allow to identify individuals, based on genetic tests, who are naturally carrying a strong placebo effect predispostion (giving rise to the field of placebomics).

Possibility of “Placebo-Drug Interactions” and “No-Treatment Arms” in Clinical Trials

Knowing that neurotransmitter pathways are involved in placebo responses now raises a new consideration for both patient care and clinical research. Since seemingly neurotransmitter pathways are modified by genetics and are pathways that both drugs and the placebo act on,  drugs could change a placebo response and a placebo response could modify a drug response. This potential overlap between placebo, drug treatment and disease adds to the complexity of the placebome and underscores the importance of understanding how it fits into larger more complex networks.

The possibility that there could be a placebo-drug interaction as a result of genetic variation in placebo pathway genes suggests that one needs to refine and recalibrate the assumptions of placebo controls in randomized clinical trials. An important next step in describing the placebome would be to include a no-treatment control in placebo-controlled randomized clinical trials. This approach might be cost effective and allow for a broad view of placebo response genes and other molecules across varying conditions and treatments.

It may no longer be sufficient for pharmaceutical research to include in randomized clinical trials a “placebo arm,” which is designed to control for the non-specific, non-pharmacological effects that are part of the administration and receipt of clinical treatment. In order to properly study the placebo response,  a frank “no -treatment” control may have to be incorporated into well designed future clinical trials. This may help to provide the right treatment in the right place at the right time, not only for the responding patient, but also for the “placebo patient”.

Note that Thasso Post had in the past articles on placebo entitled *Outssmarting the placebo effect” (here) and “Pain: Placebo’s sweet hot spot in the brain identified” (here).

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