[7,8] Neurobiological mechanisms Research into the neurobiology of responsiveness http://www.selleckchem.com/products/Imatinib-Mesylate.html to placebo has addressed placebo analgesia; accordingly, the neurobiology of placebo effects is commonly considered in terms of opioid and non-opioid mechanisms.[9,10] Several studies have demonstrated that placebo effects can be completely or partially reversed by the opioid antagonist naloxone, supporting the involvement of endogenous opioids in some analgesic effects of placebo.[11?C14] Furthermore, analgesic effects of placebo are likely to be inhibited by the peptide cholecystokinin (CCK) for they are potentiated when a CCK antagonist is administered. Considered together, these studies demonstrate that some mechanisms of placebo operate by altering the activity of both CCK and endogenous opioids.

[12,15,16] PLACEBO IN CLINICAL TRIALS The placebo, a pharmaceutically inert substance (typically a sugar pill), is the clinical researcher’s analogue to the scientist’s control experiment. To prove a new treatment effective above and beyond the psychological results of a simple belief in the ability of the drug to cure, a researcher compares the results of the experimental treatment for an illness with those obtained from the placebo. The placebo-controlled trial ??is widely regarded as the gold standard for testing the efficacy of new treatments.??[17] Interest in placebo effects began only with the widespread adoption of the placebo-controlled clinical trials after World War II. The randomized clinical trial was a major methodological breakthrough in medicine and the best evidence for new treatment came from randomized placebo-controlled (RCT) double-blind studies.

It was noticed that patients improved, sometimes dramatically, in placebo control arms. Henry Beecher popularized this observation in his famous proto-meta-analysis which claimed that about 35% of the patients responded positively to placebo treatment.[18,19] ETHICS OF PLACEBO-CONTROLLED TRIALS The use of a placebo in clinical research continues to be a topic of debate in the medical community in recent times. Some argue that the use of placebos is often unethical because alternative study designs would produce similar results with less risk to individual research participants. Others argue that the use of placebos is essential to protect the society from the harm that could result from the widespread use of ineffective medical treatments.

Critics of placebo-controlled trial or trials that include an untreated control group cite Article 11.3 of the Declaration of Helsinki: ??In any medical study, every patient including those of control group, if any should be assured of the best proven diagnostic and therapeutic methods and no patient should suffer from AV-951 unnecessary pain.??[20] In randomized clinical trials, for kinase inhibitor Erlotinib conditions having no effective treatment, the control regimen with which the new treatment is compared, is warranted to establish the evidence.