Placebo Effect
Placebo is a complex phenomenon in which the patient’s expectation of recovery affects their state of health

“How mental states shape physical health is more than the philosophical mind-body question. It’s a fundamental aspect of physiology that we must understand in order to push medicine forward. ” –
Prof. Asya Rolls, Ruth and Bruce Rappaport Faculty of Medicine

Positive expectations can vastly enhance our body’s immune system, but why? And how can this placebo effect be leveraged to optimize healing?

Unravelling the mysteries behind the Placebo Effect, researchers at the Rappaport Faculty of Medicine have shown how the brain’s ‘reward system’ transmits messages via the sympathetic nervous system that affect the efficiency of the immune system.

Publishing in the journal Nature Medicine, Profs. Asya Rolls and Shai Shen-Orr and doctoral student Tamar Ben-Shaanan, used new methods to show that triggering the reward system in the brain stimulates the immune system, causing it to operate more effectively and eliminate bacteria faster. In addition, the immune system memory was shown to become more robust against bacteria, with advance warning the next time.

“Placebo is a complex phenomenon in which the patient’s expectation of recovery affects his state of health,” explains Rolls. “Expectation of improvement and arousal of positive emotions are reflected in the activity of neurons in the brain. We decided to understand, at the molecular level, how areas of the brain associated with positive feelings affect the functioning of the immune system, which is basically the body’s main defense system. We have no doubt that this could lead to significant medical applications based on the effect of the brain on the body.”

“Our breakthrough was made possible thanks to two new technologies,” explains Prof. Shen-Orr. “One is DREADD technology, which enables precise activation of specific neurons, and the second is CyTOF technology, which enables high resolution characterization of hundreds of thousands of cells in the immune system. By coupling these two technologies, we were able to demonstrate a causal connection between the activation of specific neural circuits in the brain and the increased activity of cell populations in the immune system.

In the brain context, the researchers focused on the ventral tegmental area (VTA), a key component in the dopamine reward system. “This is the area of expectation for reward,” explains Rolls, “and it’s stimulated, for example, when someone offers us a bar of chocolate. We found that stimulation of this area activates the immune system’s anti-bacterial response, especially if it occurs before exposure to bacterial infection.

The researchers also mapped the sympathetic nervous system, the route through which messages pass from the brain to the immune system. This is responsible for immediate reaction in emergency situations and stress.



Prof. Asya Rolls

Prof. Shai Shen-Orr

Read the full article in Nature Medicine: