The biochemical bases for reward. Implications for the placebo effect.

The authors propose that the placebo effect is mediated by reward-related mechanisms. Recent evidence suggests that it is the expectation of reward (in this case, the expectation of clinical benefit) that triggers the placebo response. In Parkinson's disease, the placebo effect is mediated by the release of dopamine in the striatum. The authors argue that placebo-induced dopamine release in limbic structures, particularly in the nucleus accumbens, could also be a major biochemical substrate for the placebo effect encountered in other medical disorders. Other neuroactive substances involved in the reward circuitry (e.g., opioids) are also likely to contribute to the placebo response, and such contribution may be disorder specific (e.g., opioid release in placebo analgesia; serotonin regulation in response to placebo antidepressants). In addition, placebos may have a role in substitution programs for the treatment of drug addiction.