The placebo phenomenon and the underlying mechanisms.

The clinical role of the placebo effect is a topic of increasing interest for the scientific community. Focus is shifting from the inert role of placebos in randomized controlled trials (RCTs) to potential effects in clinical applications, since the phenomenon is thought to be inherent in routine clinical practice, affecting therapy success rates. Mediation of the mind-brain-body relationship involves both psychosocial and neurobiological factors, the interaction of which comprises the placebo mechanisms. Psychosocial factors include environmentally induced expectations, reward expectations, and even conditioned responses to certain stimuli. Expectations also depend on previous experience of the patient with a similar procedure and can affect future responses. Moreover, the supportive bedside behavior of the clinician and the positive framing of information provided to the patient have proven to be of great importance, setting the foundations for reconsideration of standardized practices. Neurobiological mechanisms mediate these effects through neurotransmitter and neuromodulator pathways. The best understood mechanisms are those regulating non-opioid- and opioid-mediated analgesic responses that implicate specific brain regions of pain control and activation of endogenous opioids. Other responses concern, among others, hormonal control, motor performance, and antidepressant responses. Although mechanisms underlying placebo responses are not as yet completely elucidated, there is substantial evidence suggesting that placebo effects are indicative of healthy functioning of intact brain structures and occur through actual functional changes, and are not simply subjective symptom reports. These effects can be utilized in treatment optimization while maintaining an ethical and respectful manner toward the patient and the standardized disclosure procedures.