ORIGINAL PAPER The placebo effect and homeopathy Marcus Z Teixeira*, Cristina H F F Guedes, Patrı ´cia V Barreto and Mı ´lton A Martins Department of Internal Medicine, School of Medicine, Universidade de Sao Paulo, Sao Paulo, Brazil Background: Like other forms of medicine, including Complementary and Alternative Medicine (CAM), homeopathy elicits expectations in patients. The physician–patient rela- tionship, personal and comprehensive treatment and lack of adverse effects are elements in creating positive expectations. Other elements may be associated with negative expectations. Methods: We conducted a systematic literature review on placebo and nocebo effects in acupuncture and homeopathy using Medline. Results: Findings on the psychophysiological and neuromediating mechanisms of the placebo–nocebo phenomenon are reviewed. Studies of these effects reveal how expecta- tions and unconscious conditioning can be measured by imaging and EEG methods. They result in significant, non-specific therapeutic effects, which may confuse the evaluation of the specific therapeutic effects treatment, hampering selection of the simillimum. Conclusions: Directions for future research on non-specific therapeutic effects of home- opathy to improve clinical practice and clinical research are discussed. Homeopathy (2010) 99, 119–129. Keywords: Placebo; Nocebo; Specific effects; Non-specific effects; Expectation; Conditioning; Imaging; qEEG; Homeopathy; Acupuncture Introduction Homeopathy is based on the principle of similitude, ad- ministering to the sick substances that cause similar symp- toms in healthy persons. In order to minimise the possible aggravations that such treatment could cause on the symp- toms of the original disease, Samuel Hahnemann proposed the pharmacotechnic method of dynamisation or potential- isation (serial dilution with succussion) to reduce the pri- mary effects of medication and develop its ‘latent dynamic’ power (Organon, paragraph 269). 1 However, for these very high dilutions, of infinitesimal pathogenetic power, to awaken the organism’s vital reaction, it is neces- sary to individualise each case of and medicine according to the totality symptoms (Organon, paragraphs 24–27, 162–165, 211–213). 1 To acquire a knowledge of the patient’s idiosyncratic characteristics to increase the probability of success in the choice of individualised medicine, the homeopathic physi- cian takes an individualising history (Organon, paragraphs 83–104) 1 asking the patient to describe in detail various classes of symptomatic manifestations (local, mental, gen- eral and physical). This process of individualisation is a gradual one and may require a prolonged observation pe- riod, with follow-up and different prescriptions, until the ideal medication (simillimum) is achieved. In this humanis- tic medical practice, the non-specific therapeutic effects of the doctor–patient relationship are likely to be increased by the patient’s expectations of the homeopathic method which meshes with the specific therapeutic effects of the medicines, making it difficult to evaluate the treatment by itself, both in routine clinical practice and in clinical research. Modern scientific research about the placebo–nocebo phenomenon emphasisies the need for a differentiation be- tween these therapeutic effects. The main objective of a ho- meopathic physician who seeks to stimulate the vital reaction of the organism by applying the principle of heal- ing similitude is to perfect the selection of the correctly individualised medicine (simillimum). This review discusses the psychoneurophysiological mechanisms that modulate the placebo–nocebo phenome- non 2,3 and its possible influence on effectiveness rates of *Correspondence: Marcus Zulian Teixeira, Hospital das Clı ´nicas da FMUSP, Servic ¸o de Clı´nica Me ´ dica Geral, Av. Dr. Ene ´ as de Car- valho Aguiar, 155, 4  andar, bloco 6-CEP: 05403-900, Sao Paulo, SP, Brazil. E-mail: marcus@homeozulian.med.br Received 13 July 2009; revised 15 January 2010; accepted 4 February 2010 Homeopathy (2010) 99, 119–129 Ó 2010 The Faculty of Homeopathy doi:10.1016/j.homp.2010.02.001, available online at http://www.sciencedirect.com