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Neurobiology of the placebo effect dates back to 1978, when Levine discovered that its analgesic action is reversed by naloxone. Since then, various studies have been performed to estimate the impact of placebo on brain metabolism and neurotransmission in analgesia, depression or the Parkinson's disease. A number of involved brain structures have been pinpointed, these including nucleus accumbens and the anterior cingulate cortex (ACC), while the role ofopioid regulation has been established as significant to the process. Currently, modern diagnostic appliances such as PET or fMRI are being used to determine the differences between placebo and drug effect on brain metabolism and, consequently, to identify factors responsible for therapeutic response and their potential correlation with a psychological impact. Environmental conditions, which may result in placebo efficacy increase of seven percent per decade during the last years, are also looked into. Although certain ethical and legal dilemmas appear considering the use of placebo, it is beyond any doubt that realising the influence of expectation and conditioning on the neurobiology of the placebo effect, as well as on the proper therapy, should enable better patient handling and treatment in the future.

Nociceptin/orphanin FQ (N/OFQ) is a neuropeptide discovered in the middle of the 1990. It possesses an amino acid sequence very similar to those of endogenous opioid peptides (particularly dynorphin A). However, N/OFQ lacks the N-terminal tyrosine necessary for activation of mu-, kappa- and delta- opioid receptors and therefore does not bind to opioid receptors but to its own nociceptin receptor (NOP). Opioid peptides also do not bind to the NOP receptor. In spite of structural similarities, the pharmacological profile of N/OFQ is different from and, in many cases, opposite to that of the opioids. Intracerebroventricular injection of N/OFQ induces hyperalgesia and decreases the analgesic actions of opioids, but induces analgesia when given intrathecally. N/OFQ blocks the rewarding effects of morphine, ethanol, and psychostimulants such as cocaine and amphetamine, but given alone it does not have rewarding effect. N/OFQ is metabolized to shorter fragments, such as N/OFQ(1-13), N/OFQ(1-11), N/OFQ(1-7) and N/OFQ(1-6). These fragments show biological activity. The effects of N/OFQ include regulation of the release of numerous neurotransmitters and hormones, as NOP receptors are located presynaptically in different brain structures. The aim of this review was to present current opinion on the role of N/OFQ in nociception, reward and drug dependence.