European Headache Federation recommendations for placebo and nocebo terminology.

BACKGROUND AND AIM: Despite recent publications, practitioners remain unfamiliar with the current terminology related to the placebo and nocebo phenomena observed in clinical trials and practice, nor with the factors that modulate them. To cover the gap, the European Headache Federation appointed a panel of experts to clarify the terms associated with the use of placebo in clinical trials. METHODS: The working group identified relevant questions and agreed upon recommendations. Because no data were required to answer the questions, the GRADE approach was not applicable, and thus only expert opinion was provided according to an amended Delphi method. The initial 12 topics for discussion were revised in the opinion of the majority of the panelists, and after a total of 6 rounds of negotiations, the final agreement is presented. RESULTS/RECOMMENDATIONS: Two primary and mechanism-based recommendations are provided for the results of clinical trials: [1] to distinguish the placebo or nocebo response from the placebo or nocebo effect; and [2] for any favorable outcome observed after placebo administration, the term "placebo response" should be used, and for any unfavorable outcome recorded after placebo administration, the term "nocebo response" should be used (12 out of 17 panelists agreed, 70.6% agreement). The placebo or nocebo responses are attributed to a set of factors including those that are related to the medical condition (e.g. natural history, random comorbidities, etc.), along with idiosyncratic ones, in which the placebo or nocebo effects are attributed to idiosyncratic, or nonspecific mechanisms, exclusively (e.g. expectation, conditioning, observational learning etc.). To help investigators and practitioners, the panel summarized a list of environmental factors and idiosyncratic dynamics modulating placebo and nocebo effects. Some of them are modifiable, and investigators or physicians need to know about them in order to modify these factors appropriately to improve treatment. One secondary recommendation addresses the use of the terms "placebo" and "nocebo" ("placebos" and "nocebos" in plural), which refer to the triggers of the placebo/nocebo effects or responses, respectively, and which are inert agents or interventions that should not be confused with the placebo/nocebo responses or effects themselves (all panelists agreed, 100% agreement). CONCLUSION: The working group recommends distinguishing the term response from effect to describe health changes from before to after placebo application and to distinguish the terms placebo(s) or nocebo(s) from the health consequences that they cause (placebo/nocebo responses or effects).

The Meaning Response, "Placebo," and Methods.

In 2002, Dan Moerman outlined three candidate explanations for the "placebo response": the "conditioned stimulus-response," Irving Kirsch's "response-expectancy" explanation, and the "meaning response." The meaning response, Moerman argued, was the only one of the three candidate explanations that could cover all the data, gained from decades of RCTs and centuries of historical record. Moerman went so far as to propose replacing the term "placebo effect/response" with the term "meaning response," because people are not responding to placebos, since there is nothing to respond to; people are responding to meanings. There is evidence of medically significant meaning responses where there is no evidence for conditioning. Similarly, there is evidence for such responses where those subject to them lack the knowledge-epistemic capital-required to form the beliefs which might constitute an expectation. Something else, neither conditioning nor propositional attitudes, explained placebo responses, and Moerman proposed the meaning response. While the authors consider the meaning response to avoid the pitfalls of conditioning and response-expectancy, it has been subject to criticism. The criticisms have focused on what is seen as the explanation falling foul of the naturalistic demand and not fitting with prevalent predilections in the philosophy of mind and cognitive science. This article seeks to allay these worries and proposes the inclusion of ethnomethodological fieldwork in future research.

The argument for single-purpose robots.

The argument by Lake et al. to create more human-like robots is, first, implausible and, second, undesirable. It seems implausible to me that a robot might have friends, fall in love, read Foucault, prefer Scotch to Bourbon, and so on. It seems undesirable because we already have 7 billion people on earth and don't really need more.

Against the "placebo effect": a personal point of view.

The author reviews 10 of his favorite studies which are said to be about the "placebo effect," but which, instead, show the significance of meaning in a medical context. "Placebos," he argues, are inert substances which can't do anything. Yet it's clear that after the administration of such drugs, things do happen. The one (and maybe only) clear thing here is that whatever happens is not due to the placebo (that is what "inert" means). But placebos can be of various colors and forms which can convey compelling meaning to patients. They often represent medical treatment in compelling ways; they can be metonymic representations of the entire medical experience (a metonym is a representation where a part of something comes to represent it all, as in "counting noses," where the nose represents the whole person, or a "White House statement" where the White House represents the Executive Branch of the US Government; here, the pill represents the whole medical experience). More precisely, they can be metonymic simulacra (a simulacrum is a sort of artificial object, like a statue rather than a man, or a placebo rather than an aspirin). Such objects are well known for their powerful abilities to contain and convey meaning; for example, a European cathedral ordinarily is constructed of thousands of metonymic simulacra, from the rose window to the altar. In this context, a placebo can repeatedly remind the patient of the medical encounter, its shadings and comforts. Placebos can convey the physicians innermost feelings about medication and treatment; and the clinician can by her simple presence enhance the effectiveness of a medical procedure (and a clinician is hardly a placebo, hardly inert). Inert placebos can help us see the human dimensions of medical treatment; but calling these things "placebo effects" dramatically distorts our understanding of such treatments, by focusing on the inert, and avoiding the meaningful. Think "meaning response," not "placebo effect."

Cathedrals, symphony orchestras, and iPhones: the cultural basis of modern technology.

The distinctions drawn by Vaesen are plausible when we are comparing chimpanzees and human beings somewhere between the middle Paleolithic and the Neolithic. But since then new kinds of organization have vastly outstripped these neurological differences to account for the enormous advancement of human technology - from cuneiform to the iPhone - leaving our remarkable evolutionary cousins far behind.

Ethnopharmacological field studies: a critical assessment of their conceptual basis and methods.

Ethnopharmacology as a well-defined field has a relatively short history, but for centuries researchers have been interested in the observation, description, and experimental investigation of indigenous drugs and their biological activities. Today, such articles are published in a variety of journals among which the Journal of Ethnopharmacology has a prominent position as well as in book monographs. As any other area of scientific endeavour, this field requires a critical and engaged discussion about the conceptual basis, the relevant methods and the overall standards necessary for excellence. Here we review recent ethnopharmacological field studies in order to highlight achievements and future needs for improving the quality of such studies. The basis for this review is 40 field studies published in the years 2007 and 2008 in the Journal of Ethnopharmacology. Researchers need to have a clear vision for what and how they want to achieve a conceptually and methodologically sound approach and as in all disciplines adherence to internationally recognized methodological standards is essential. Here we review not only the basic conceptual requirements but also the minimal methodological (i.e. botanical, anthropological/historical,ethnomedical) standards and ways how to quantify ethnopharmacological information. Future uses of such information both in the context of experimental research and in applied projects highlight the multiple roles of such data generated in ethnopharmacological field studies. This review cannot be a book of recipes on how to conduct such research but highlights minimal conceptual and methodological requirements for use in future projects.

Agreement and meaning: rethinking consensus analysis.

This study provides a critical perspective on "informant agreement (consensus) analysis" as it is used in ethnobotany and ethnopharmacology. It recasts the concept at a higher cultural level, and it describes the cultural agreement about reported medicinal plant use for the native peoples of North America. It examines some plant use categories around which there is significant cross cultural agreement, and some categories which lack such agreement. The study then proposes a theoretical approach to understanding the efficacy of plants lacking significant consensus in their usage. The study considers the implications of this second form of efficacy defined here as the "meaning response", but often referred to as the "placebo effect".

"Symbols and selectivity" revisited.

The author recalls how he came to do one of the first statistical analyses of native American medicinal plants, published in volume 1 of Journal of Ethnopharmacology. The background of that paper, "Symbols and Selectivity," involved a great deal of serendipity.

Native Americans' choice of species for medicinal use is dependent on plant family: confirmation with meta-significance analysis.

We test the hypothesis that the choice by traditional people of species of plants for medicinal use does or does not depend on the families to which those species belong. Our geographic context is continental North America north of the Rio Grande River. Our plant context is flowering plants. Our ethnological context is Native American traditions. Our null hypothesis is that the probability of any species being medicinal is the fraction of all species that are medicinal, no matter the family to which that species may belong. Classical statistical techniques and the experience of ethnobiologists had already made it clear that among very large plant families, most have either very many or very few medicinal species. Here we use intense computation to simulate thousands of data sets to create predictions to compare with the observed data for medium and small families. Our results clearly show that a surprising number of medium and small families also have very many or very few medicinal species. Recent molecular, fossil and cytological studies have confirmed the evolutionary naturalness of most plant families. This suggests that species in the same family may have inherited from common ancestors similar ecological adaptations, such as ways to protect themselves from herbivores, pathogens or decomposers. Some of these adaptations affect the physiology of the attacking organisms, suggesting an explanation for the clear preferences of Native American traditions to choose medicinal species from some families much more than from others, regardless of the size of those families.

The meaning response and the ethics of avoiding placebos.

Because the "placebo effect" seems to result from "deception," it is often disparaged and despised. Rethinking this and realizing that these benefits flow largely from the meaning of medical encounters (and are far better understood as "meaning responses"); realizing that there need be no deception to elicit them and that they are often very desirable, engaging fundamental human biological pathways, puts the ethical dilemma in a new light. It seems unethical to avoid--to evade--coming to a full understanding of how meaning can so profoundly improve human well-being.

Deconstructing the placebo effect and finding the meaning response.

We provide a new perspective with which to understand what for a half century has been known as the "placebo effect." We argue that, as currently used, the concept includes much that has nothing to do with placebos, confusing the most interesting and important aspects of the phenomenon. We propose a new way to understand those aspects of medical care, plus a broad range of additional human experiences, by focusing on the idea of "meaning," to which people, when they are sick, often respond. We review several of the many areas in medicine in which meaning affects illness or healing and introduce the idea of the "meaning response." We suggest that use of this formulation, rather than the fixation on inert placebos, will probably lead to far greater insight into how treatment works and perhaps to real improvements in human well-being.