Simply put, memory of water (or of the homeopathic dilution medium such as a water alcohol mixture or lactose) is to be explained. The basis for this was created especially by the imprint theory sug-gested in 1967 by Barnard and Stephenson. The theory is based on the assumption that—despite increasing dilution—long polymer chains (chain-like chemical compounds), which come from the start-ing substance, form in a specific manner in the dissolution medium depending on the particular parent drug. (Barnard et al., 1967) Under the umbrella of imprint theory, other storage mechanisms have also been discussed that are based on other effects, such as certain ordered states of the dipoles of the water.

Likewise, water cluster formation (lump formation) has also been discussed. It is assumed that water molecules form larger subunits—so-called clusters—due to their hydrogen bonding, and these subu-nits may be responsible for storage of information. (Luu et al., 1980, 1981, 1982)

Also models have been suggested that combine the imprint theory with cluster formation. However, the extent to which water or water-alcohol mixtures form ordered structures at all, that are stable enough and exist for more than a split second, and thus may be responsible for the storage of ho-meopathic drug information, is again being increasingly discussed. (Jones et al., 1981)

In general, it can be said that so far, water research does not have a theoretical model that adequately describes all phenomena and properties of water. Consequently, many properties of water itself have not yet been sufficiently researched. Innovative work in the field of water research such as that of the group headed by Prof. Gerald H. Pollack may show new ways of finding out what types of previously unexplored stable structures exist in water. Pollack has shown that in contact with surfaces of various materials, water forms boundary layers that have differing physical properties. (Pollack, 2018)

With regard to homeopathy’s mechanism of action, there is repeated discussion of phenomena that are based on quantum effects or scientific ideas that were developed using quantum theory, a theory that goes beyond the conventional ideas of classical physics. For this purpose mathematical formal-isms (formula systems) were developed by the theoretical physicists Dr. Harald Atmanspacher and Prof. Dr. Hartmann Römer and the psychologist and homeopathy researcher Prof. Dr. Dr. Harald Wa-lach, but whose experimental implementation with regard to homeopathy is still a work in progress. (Atmanspacher et al., 2002)

In particular in the past few years there has been renewed in-depth discussion about whether, despite the many dilution steps for homeopathic high potencies, one can assume that there is actually a re-maining concentration of the starting material. It is claimed that studies using methods that have been developed in the context of nano-research have proven that above a certain dilution step a relatively constant concentration of the starting material in the form of nanoparticles (particles in the range of about 1 to 100 x 10-9 m) is established, which would support a material mechanism of action. In particular, the working groups headed by Prof. Jayesh Bellare (Bombay, India) and Prof. Iris Bell (USA) have presented experimental work on this. (Chikramane et al., 2010 2012; Bell et al., 2015a&b)

It is claimed that studies using methods that have been developed in the context of nano-research have proven that above a certain dilution step a relatively constant concentration of the starting mate-rial in the form of nanoparticles (particles in the range of about 1 to 100 x 10-9 m) is established, which would support a material mechanism of action. Thus, significantly higher concentrations may be present in homeopathic remedies than previously assumed. The French nuclear medicine specialist Dr. Jean-Louis Demangeat and the team of scientists headed by Prof. Vittorio Elia (Naples, Italy) have presented research work on experimental proof of nanostructures induced by succussion. (Demangeat, 2010, 2013 & 2015; Elia et al. 2014)

The research work by the Russian group of researchers headed by Prof. Alexander Konovalov and Dr. Irina Ryzhkina provides further signs of the existence of nanostructures in ultra-high dilutions. One interesting feature of this work is that the scientists generally work with dilutions, and they are not primarily concerned with researching the action mechanism of homeopathic active ingredients. (Konovalov et al., 2014)

The best known work currently on scientific evidence of the similarity principle stems from the two basic researchers Roeland van Wijk and Fred A. C. Wiegant. They examined the recovery process of cell cultures that were previously exposed to different cell toxins (arsenic and cadmium) or damaging heat. Primarily, the concentrations of stress proteins produced by cells as a response to damage were measured. Researchers were able to show that previously damaged cell systems recover faster when they are again confronted with the harmful substance in an attenuated form, either slightly re-heated or treated with dilute arsenic or cadmium. These experiments provide the first indications of how the similarity principle can be preclinically (on the cell model) investigated and physiologically (regarding the biological processes) understood. (van Wijk et al., 2006)

Physical experimental methods

In recent decades, numerous experiments have been conducted to decode homeopathy’s physical mechanism of action. High-potency medicines were compared with placebo mainly using standard spectroscopic methods, to draw conclusions about physical differences. Significant results that were obtained with Raman and NMR spectroscopy (methods that examine the molecular structure with stimulation using laser light or magnetism), were successfully reproduced. A detailed overview of the different experimental examinations in physics is provided in Witt’s metastudy (Witt, 2006) and the recently published review of the state of basic research in physics (Klein et al., 2018; Tournier et al., 2019). The qualitative evaluation of this review included 203 physical experiments whose documenta-tion quality was rated as good to very good in prior publications by the respective reviewers. 73% of these 203 experiments report on differences between homeopathic preparations and controls, and according to the authors of the review, a further substantial increase in the experimental quality stand-ards is required in future reproductions for many of the experiments in order to indicate reliable proof.

Research on living organisms

Likewise, statistically significant results with regard to the effect of high potency remedies were ob-tained with test systems that work with plant, animal and cell systems. In this case, the focus is less on how the drug works and more on whether it is possible to prove significant effects. The research teams led by Dr. Peter Christian Endler and PD Dr. Stephan Baumgartner have presented especially promising results.

Endler’s research primarily focuses on tadpoles, which are randomized (assigned randomly) to differ-ent groups and then treated differently in a blinded approach (the investigator does not know which group is receiving the drug and which the placebo). This amphibian model is based on the influence of the development of the tadpole into a frog by treatment with the thyroid hormone thyroxine, which accelerates the rate of transformation. Endler has conducted numerous trials, including trials with potentized thyroxine compared to placebo to impact the speed of metamorphosis (transformation). In another series of tests all the tadpoles were pretreated first with slightly diluted thyroxine and subse-quently further treated with either placebo or potentized thyroxine. The aim of the research was to determine whether the administration of homeopathically prepared thyroxine cancels the accelerated transformation through material thyroxine. Endler et al. were able to show that the tadpoles treated with a homeopathic high potency actually developed more slowly than those treated with placebo. (Zausner et al., 2002; Endler et al., 2003; Graunke, 2007; Welles et al., 2007; Lingg et al., 2008)

The research group led by the physicist Baumgartner also expended great efforts on experimental research. Their focus is on ultra-high dilutions: on the one hand in physical studies, on the other, their effects on in-vivo test systems. Very plausible results that support the impact of highly potentized homeopathic preparations were obtained with a test system consisting of duckweed cultures, a standard system in ecotoxicology (research on environmental toxins). Since then, several experiments have been carried out with this test system, such as the measurement of the influence of potentized plant hormones (gibberellins) on the growth of duckweed. (Scherr et al., 2009; Jäger et al., 2010) Likewise, an attempt was made to treat deficient duckweed (calcium, iron or magnesium deficiency) with potentized remedies. In the case of calcium deficiency clear effects of homeopathic potencies on plant growth are observed. Meaningful results were also obtained with duckweed in an intoxica-tion/detoxification model. Healthy organisms are initially poisoned with a toxic substance here and thus put in an artificial disease state. They are then treated with high homeopathic dilutions of the same or a similar substance on a randomized, blinded, and placebo-controlled basis. Next, there is a statistical evaluation as to whether the samples treated with homeopathic medicines subsequently show different growth characteristics from those treated with placebo. Promising experiments with this approach have already been performed on duckweed poisoned with arsenic. (Jäger et al., 2011) With the support of Hevert-Arzneimittel, this experimental approach has now also been tested on duckweed poisoned with mercuric chloride with the aim of also applying this model to more complex research topics. (Jäger et al., 2019) The review by Ücker et al., 2018, provides a newer overview of all plant experiments within homeopathy research.

The results published in 2009 by Bellavite also support the impact of homeopathic high potencies. This involved an experiment in which the activity of the mice was tested. Mice that were treated with gelsemium, showed significantly more active behavior towards placebo-treated mice. (Bellavite et al., 2009)

A general problem of clinical homeopathy research is that positive study results are regularly disqualified because the study quality would not meet accepted standards; with negative results, however, the efficacy of the entire treatment direction is called into question in general, although “homeopathy” is not a uniform method of treatment. In "traditional" or "classical homeopathy,” in which the accurate history (medical history and symptoms) of the patient is an essential part of treatment, the medicines are, for example, individually selected: Consequently, the examination of the method according to current standards of clinical research becomes a challenge, since a particular disease is not treated in a large patient group with the same medicine. In addition, there are many other homeopathic treatment methods, such as complex homeopathy, which are more accessible to the standards of clinical re-search. Correspondingly, the current study situation is just as complex.

In overview articles, referred to as reviews, on the status of clinical homeopathy research, the ques-tion being discussed in the past was mostly based on whether homeopathic remedies work at all, regardless of the type of drug, the treatment method or the particular indication (disease). Thus, a wide variety of clinical studies with homeopathic remedies were considered together, without making any distinctions. Just as controversial are the major reviews that were done on homeopathy and were widely published.

For example, K. Linde et al. published a meta-analysis in 1997, in which 89 placebo-controlled studies (testing a medicine compared to placebo) were evaluated in the internationally known medical journal “The Lancet.” The result of the meta-analysis was that homeopathy was statistically proven superior to placebo. (Linde et al., 1997) R. Mathie, who analyzed 93 studies in 2003, and M. Dean (2004), who included 205 homeopathy studies in his analysis had likewise positive results establishing the effica-cy of homeopathy.

A furor was caused by the 2005 overview study by Shang et al., also published in the “The Lancet,” that compared 110 placebo-controlled homeopathy studies with 110 comparable studies of conven-tional treatment. (Shang et al., 2005) Even if ultimately only 8 homeopathy studies and 6 conventional treatment studies were considered good enough to be evaluated by the authors, the negative result of the analysis for homeopathy was pronounced the “end of homeopathy” in the media, because, ac-cording to them, the lack of efficacy for homeopathy had finally been scientifically proven. The methodology of Shang et al. and the approach of the study was then heavily criticized by many sources. There is further heated debate about which methods from evidence-based medicine can be used for homeopathy and the extent to which these do justice to homeopathy.

Now the trend in assessing clinical studies is to no longer test “homeopathy“ as a whole, but rather to perform smaller meta-analyses on specific indications, as makes sense, because this will provide clearer results. And there are some positive meta-analyses on the efficacy of homeopathy for specif-ic medical conditions. For example, the meta-analysis by Taylor et al. from 2000 and that by Lüdtke and Wiesenauer from 1997 support the efficacy of homeopathic treatments for hay fever. In addition to these meta-analyses there are several other positive analyses, such as for the homeopathic treat-ment of fibromyalgia (Boehm et al., 2014) or life-threatening diarrhea in children (Jacobs et al., 2003).

Robert T. Mathie and his co-authors pursue another method for defining the issue of meta-analyses. In recent years, he has published several review works that include only studies that are based on a specific homeopathic treatment approach (individualized or non-individualized prescription) or a spe-cific study design (placebo-controlled or controlled by another comparison medication). (Mathie et al. 2014, 2017 & 2018) When assessing the individual studies, Mathie et al. base their meta-analyses on guidelines of the Cochrane Collaboration so that the results can be described as reliable in terms of evidence-based medicine. In these meta-analyses, it was apparent that most of the studies show pos-itive results in favor of homeopathic treatment, but the number of high-quality studies is still too low to enable a definitive conclusion.

Building on the knowledge that the individualized treatment especially in the field of classical home-opathy can only be reproduced with difficulty using the usual standards of evidence-based medicine, attempts are increasingly being made to demonstrate the efficacy of homeopathy using health ser-vices research methods. The long-term treatment success of homeopathically treated patients is in-vestigated in what are referred to as outcome studies. The largest outcome study that included about 4,000 patients was published in 2005 by Witt et al. (Witt et al. 2005) Generally such studies demon-strate that the health of patients can be significantly improved with homeopathic treatments, and of-ten in the case of chronic diseases the use of conventional drugs can be reduced or even completely avoided. Critics of homeopathy however attribute these successes exclusively to placebo effects.