The placebo response may be influenced by genetic variations in brain signalling pathways say researchers who suggest ‘no-treatment controls’ be added to future clinical trials.

Writing in Trends in Molecular Medicine Kathyrn Hall and colleagues from Beth Israel Deaconess Medical Center in Boston said previous research had shown that the dopamine, opioid, endocannabinoid, and serotonin pathways helped mediate the placebo effect.

Evidence that genetic variations in these pathways can modify placebo effects raises the possibility of using genetic screening to identify placebo responders and thereby increase RCT efficacy and improve therapeutic care, they said.

This information could lead to better patient selection for clinical trials as well as identify how well a patient may respond to a drug according to their genotype.

“These are novel hypotheses that, to our knowledge, have not yet been discussed in the scientific literature,” Hall says.

“This broader conception that points to more personalized medicine calls for additional research.”

She suggests including a no-treatment control– in addition to placebo controls– in some future clinical trials.

“Our proposal to incorporate a formal placebo study into future clinical trials is innovative and could represent significant cost savings, leading to rapid access to knowledge of mechanisms involved in the placebo response across a wide variety of disease and drug regimens,” she said.

However, numerous regulatory, ethical, and clinical questions would need to be addressed before such innovations could be integrated into drug development and clinical care.