Repeatability of experiments is an important criterion of modern research and a major challenge for homeopathic basic research. There is no recent overview about basic research studies in high homeopathic potencies that have been subjected to laboratory-internal, multicenter or independent repetition trials. We considered biochemical, immunological, botanical, cell biological and zoological studies on high potencies, i.e. beyond a dilution of 10(-23). Main sources of information were reviews, personal contact with members of the homeopathic basic research community, and the MEDLINE and HOMBREX databases. Studies were extracted from the publications and grouped into models. Studies were further sorted according to repetition type (laboratory-internal, multicenter, or independent) and results achieved. A total of 107 studies were found. Of these, 30 were initial studies. In the attempt to reproduce one of these initial studies, 53 follow-up studies yielded comparable effects (35 laboratory-internal, 8 multicenter, 10 independent repetitions), eight studies showed a consistent, yet different result from the initial study (2 laboratory-internal, 2 multicenter, 4 independent repetitions), and 16 studies yielded no effects (5 laboratory-internal, 2 multicenter, 9 independent repetitions). When all repetitive studies are considered, 69% reported effects comparable to that of the initial study, 10% different effects, and 21% no effects. Independently performed repetition studies reported 44% comparable effects, 17% different effects, and 39% no effects. We identified 24 experimental models in basic research on high homeopathic potencies, which were repeatedly investigated. 22 models were reproduced with comparable results, 6 models with different results, and repetition showed no results for 15 models. Independent reproductions with either comparable or different results were found for seven models. We encourage further repetition trials of published studies, in order to learn more about the model systems used and in order to test their repeatability.

The effects ofArnica montana6cH on the individual modulation of acute inflammation kinetics in rats were evaluated. Adult male Wistar rats were inoculated with 1% carrageenan into the footpad and treated withArnica montana6cH, dexamethasone (4.0 mg/kg; positive control) or 5% hydroalcoholic solution (negative control),per os, each 15 minutes, between 30 and 180 minutes after the irritant inoculation. Histopathological and immunohistochemistry procedures were done in order to get a panel of inflammatory positive cells for CD3 (T lymphocytes), CD45RA (B lymphocytes), CD18 (beta 2 integrin), CD163 (ED2 protein), CD54 (ICAM‐1), and MAC 387 (monocytes and macrophages). The statistical treatment of data included aposterioriclassification of animals from each group (N= 20) in two subgroups presenting spontaneousprecociousorlateoedema. Animals that presented precocious oedema were less responsible toArnica montana6cH in relation to hemodynamic changes. Instead, rats that exhibitedlateoedema presented less intense oedema (P= .01), lower percentage of mast cell degranulation (P= .0001), and increase in lymphatic vessels diameter (P= .05). The data suggest an individually qualitative adjustment of inflammatory vascular events byArnica montana6cH.

The last comprehensive review of experimental research on effects of homeopathic treatments on plants was published in 1984, and lacked formal predefined criteria to assess study quality. Since then several new studies with more advanced methods have been published.To compile a review of the literature on basic research in homeopathy with healthy plants with particular reference to studies investigating specific effects of homeopathic remedies.The literature search included English, French, German, Italian, Portuguese and Spanish publications from 1920 to April 2009, using predefined selection criteria. We included experiments with healthy whole plants, seeds, plant parts and cells. The outcomes had to be measured by established procedures and statistically evaluated. We developed a Manuscript Information Score (MIS) and included only publications which provided enough information for proper interpretation (MIS>or=5). A formalised Study Methods Evaluation Procedure (SMEP) was used to evaluate these studies, and the subgroup of studies with adequate controls to identify specific effects.A total of 86 studies in 79 publications was identified, 43 studies included statistics, 29 had MIS>or=5, and 15 studies investigated the specificity of homeopathic preparations. Specific effects of decimal, centesimal and fifty millesimal potencies were found including dilution levels far beyond the Avogadro number. In consecutive series of potencies only some of the tested potencies showed effects. There were many individual studies with diverse methods and very few reproduction trials.Healthy plant models seem an useful approach to investigate basic research questions about the specificity of homeopathic preparations. More investigations with more advanced methods are recommended, especially in the sectors of potentisation techniques, effective potency levels and conditions for reproducibility. Systematic negative control experiments should become a routine procedure to control the stability of the experimental systems.

This is a systematic review of the animal models used in studies of high dilutions. The objectives are to analyze methodological quality of papers and reported results, and to highlight key conceptual aspects of high dilution to suggest clues concerning putative mechanisms of action. Papers for inclusion were identified systematically, from the Pubmed-Medline database, using 'Homeopathy' and 'Animal' as keywords. Only original full papers in English published between January 1999 and June 2009 were included, reviews, scientific reports, thesis, older papers, papers extracted from Medline using similar keywords, papers about mixed commercial formulas and books were also considered for discussion only. 31 papers describing 33 experiments were identified for the main analysis and a total of 89 items cited. Systematic analysis of the selected papers yielded evidence of some important intrinsic features of high dilution studies performed in animal models: a) methodological quality was generally adequate, some aspects could be improved; b) convergence between results and materia medica is seen in some studies, pointing toward to the possibility of systematic study of the Similia principle c) both isopathic and Similia models seem useful to understand some complex biological phenomena, such as parasite-host interactions; d) the effects of high dilutions seem to stimulate restoration of a 'stable state', as seen in several experimental models from both descriptive and mathematical points of view.

This paper focuses exclusively on experimental models with ultra high dilutions (i.e. beyond 10(-23)) that have been submitted to replication scrutiny. It updates previous surveys, considers suggestions made by the research community and compares the state of replication in 1994 with that in 2015. Following literature research, biochemical, immunological, botanical, cell biological and zoological studies on ultra high dilutions (potencies) were included. Reports were grouped into initial studies, laboratory-internal, multicentre and external replications. Repetition could yield either comparable, or zero, or opposite results. The null-hypothesis was that test and control groups would not be distinguishable (zero effect). A total of 126 studies were found. From these, 28 were initial studies. When all 98 replicative studies were considered, 70.4% (i.e. 69) reported a result comparable to that of the initial study, 20.4% (20) zero effect and 9.2% (9) an opposite result. Both for the studies until 1994 and the studies 1995-2015 the null-hypothesis (dominance of zero results) should be rejected. Furthermore, the odds of finding a comparable result are generally higher than of finding an opposite result. Although this is true for all three types of replication studies, the fraction of comparable studies diminishes from laboratory-internal (total 82.9%) to multicentre (total 75%) to external (total 48.3%), while the fraction of opposite results was 4.9%, 10.7% and 13.8%. Furthermore, it became obvious that the probability of an external replication producing comparable results is bigger for models that had already been further scrutinized by the initial researchers. We found 28 experimental models which underwent replication. In total, 24 models were replicated with comparable results, 12 models with zero effect, and 6 models with opposite results. Five models were externally reproduced with comparable results. We encourage further replications of studies in order to learn more about the model systems used.

Atropa belladonna and Echinacea angustifolia have been used in homeopathy as modulators of inflammatory processes, in simple potency or 'accord of potencies', as recommended by homotoxicology. We evaluated their effects on leukocyte migration and macrophage activity induced by experimental peritonitis in vivo. Mice were injected (i.p.) with LPS (1.0mg/kg) and treated (0.3ml/10g/day, s.c.) with different commercial forms of these medicines. Echinacea angustifolia D4--a simple potency preparation--and Belladonna Homaccord, Belladonna Injeel, Belladonna Injeel Forte, Echinacea Injeel and Echinacea Injeel Forte--all in 'accord of potencies'--were tested. The association of A. belladonna and E. angustifolia in 'accord of potencies' produced an increase of polymorphonuclear cell migration (Kruskal-Wallis, P = 0.03) and a decrease of mononuclear cell percentages (Kruskal-Wallis, P < or = 0.04), when compared with control, mainly in preparations containing low potencies. The proportion of degenerate leukocytes was lower in the treated groups, compared to a control group (P < or = 0.05). The treated groups showed increased phagocytosis (P < or = 0.05), mainly in preparations containing high potencies. Our results suggest that A. belladonna and E. angustifolia, when prepared in 'accord of potencies', modulate peritoneal inflammatory reaction and have a cytoprotective action on leukocytes.