Neurochemistry of Placebo Analgesia. Opioids, Cannabinoids and Cholecystokinin

Considerable progress has been made in our understanding of the neurochemistry of placebo effects and there is now compelling experimental evidence that different neuronal networks are responsible for different types of expectation-induced placebo effects. These include both opioid and nonopioid systems such as endocannabinoids and cholecystokinin (CCK). In general, what has emerged over the past few years is that the endogenous opioids and endocannabinoids are involved in placebo analgesia in different circumstances whereas CCK plays a key role in the opposite effect, namely, nocebo hyperalgesia. Therefore, the placebo-nocebo phenomenon can be envisioned as a continuum whereby different neurotransmitters are activated by different expectations, ranging from positive to negative. © 2013 Elsevier Inc. All rights reserved.