Placebos have been shown to relieve pain — a phenomenon known as placebo analgesia. A new study by Petrovic and colleagues has found that placebos can also affect emotion, alleviating the impact of unpleasant experiences.

Placebo analgesia and reward processing have similar characteristics: both involve anticipation of a positive outcome and are highly dependent on expectation. The authors conjectured that as emotion is closely associated with reward, it might also be affected by placebos. To test this, they used the so-called 'expectation manipulation' paradigm, in which a treatment expectation was induced in participants one day before the test day, using drugs that have well-established specific effects on emotion (that is, anxiolytic drugs and their blockers).

On day 1, participants were asked to rate the unpleasantness of neutral and disturbing pictures that were shown to them with or without the administration of an anxiolytic drug and its blocker. They were told in advance about the possible effect of the drug and its blockers on their perception of unpleasantness. As expected, the anxiolytic drug reduced the participants' perceived unpleasantness of the disturbing pictures, an effect that was reversed by administration of the drug's blocker.

On day 2, participants were told that the same treatments would be applied while their brains were scanned with functional MRI (fMRI). However, they were, in fact, treated with saline instead. The unpleasantness ratings of the disturbing pictures under the placebo condition (in which participants thought they had received the anxiolytic drug) were reduced by 29% compared with ratings under the control condition (in which participants thought they had received the drug followed by its blocker).

Interestingly, like placebo analgesia, the rostral anterior cingulate cortex (rACC) and the lateral orbitofrontal cortex (lObfc) — regions of the brain that are important in reward expectation — were activated by the emotional placebo. The increase in the activity of the rACC, but not that of the lObfc, correlated with the decrease in unpleasantness ratings of the pictures after the placebo treatment. In other words, the participants who reported the largest placebo response also showed the most extensive rACC activation.

These findings indicate that placebo analgesia — or the placebo effect in general — might be a special form of reward processing. This could shed new light on the evolutionary advantages of this powerful and fascinating phenomenon.