Effects of Ignatia amara in mouse behavioural models

Department of Pathology and Diagnostics, University of Verona (I), Italy.
Homeopathy: the journal of the Faculty of Homeopathy (Impact Factor: 0.76). 01/2012; 101(1):57-67. DOI: 10.1016/j.homp.2011.10.001
Source: PubMed


Ignatia amara (Ignatia), a remedy made from the Strychnos ignatii seeds, is used for anxiety-related symptoms, but consistent evidence of its activity in reproducible experimental models is lacking. An investigation was performed in order to assess on mice, by means of emotional response models, the activity of homeopathic Ignatia dilutions/dynamizations.
Groups of 8 mice of the CD1 albino strain were treated intraperitoneally for 9 days with 0.3ml of five centesimal (C) dilutions/dynamizations of Ignatia (4C, 5C, 7C, 9C and 30C). Control mice were treated with the same hydroalcoholic (0.3%) solution used to dilute the medicines. Diazepam (1mg/kg) was the positive reference drug. Validated test models for locomotion and emotional response, the Open-Field (OF) and the Light-Dark (LD) tests, were employed. Five replications of the same protocol were carried out, in a randomised way using coded drugs/controls.
In the OF the general locomotion of mice was slightly decreased by Ignatia 4C, but not by Ignatia 5C, 7C, 9C and 30C, indicating the absence of unspecific motor impairment or sedation by these dilutions/dynamizations. Ignatia and diazepam seemed to decrease the number of urine spots released in the OF during 10min, with borderline significance (P=0.083). In the LD the tested medicine showed anxiolytic-like activity (increase of time spent and distance travelled in the lit area), though to a lesser extent than diazepam. The highest and most significant difference with untreated controls (P<0.01) was observed with the 9C dilution/dynamization. Among the 5 replication experiments, the best drug effects were obtained where the baseline anxiety of mice was higher.
Homeopathic Ignatia dilutions/dynamizations (peak at 9C) modify some emotion-related symptoms in laboratory mice without affecting locomotion.

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    • "Moreover, others have shown that adverse effects of homeopathic drugs are exceedingly rare and these therapies are well tolerated. Direct evidence from placebo-controlled studies of Gelsemium sempervirens (Bellavite et al. 2011b; Magnani et al. 2010) and of Ignatia amara (Marzotto et al. 2012) showed that used dilutions have anxiolytic-like properties without weakening locomotion and without adverse or sedative effects. The Authors concluded their reply hoping that the difficult-to-solve technical issues of high dilutions, hormesis, and paradoxical reversal of the effects of drugs in future be addressed not through subjective opinions and jeering, but rather on the experiential ground, through patient and critical comparison of data and results (Bellavite,P., M.Marzotto, and A.Conforti. "
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    ABSTRACT: The group of P. Bellavite working at Verona university (Institute of Chemistry and Clinical Microscopy, then Department of Pathology and Diagnostics) has been involved in studies on leukocyte metabolism, inflammation, pharmacology of natural products for over twenty years. Part of its studies were dedicated to complementary medicine (phytotherapy, acupuncture, homeopathy, diet), as an Observatory of Complementary Medicine organized by Bellavite and other Verona University researchers was recognized by Institute of Chemistry and Clinical Microscopy since 1997. Starting from y. 2011, studies of the Verona group were the object of some critical opinions, as “letters” or “commentaries”, most of which from the same person, who was former collaborator of the same group until the end of y. 2010. As principal investigator in a series of studies conducted in collaboration with colleagues of Verona University I have the duty to clarify the questions raised. No experiment invalidating experimental findings was ever reported, while the effect of Gelsemium in neurological and behavioural models was reported by several independent laboratories. Even if the whole scientific interest of this provoked discussion could be scarce, its key points are reported here in the interest of completeness and precision of documentation. It should be noted that Bellavite and coworkers never critiqued the experimental work of others, and replied only to criticisms that were considered as inappropriate or affecting Verona university. The same person recently posted in RG website further personal opinions including redundant criticisms (to which we had previously carefully responded), personal attacks and even bizarre statements that by their very nature require no reply. If anyone would need further explanations she/he could contact directly the author ( Needless to say, the concept of "reproducibility" is not applicable to this synthesis of a literature debate.
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    • "The hypothesis stating that response to drugs in behavioural tests is strongly dependent on the baseline anxiety level of animals in each particular experiment and batch of mice is also supported by recent findings in our laboratory using Ignatia amara [16]. In any case, we are comforted by the observation that " Quite possibly small changes in the experimental procedure might account for the different results " [5], with which we -and no doubt many others working in the high-dilution pharmacology field -fully agree, and that denies the putative perfect reproducibility of experimental findings. "
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    ABSTRACT: As part of a rigorous investigation into the effects of Gelsemium sempervirens on laboratory mice, we performed two complete series of experiments and published three scientific papers. A recent commentary has, however, called into question the reproducibility and validity of these findings. In this article we discuss the major issues raised by this critique within the framework of methodological aspects and the interpretation of results of high-dilution and homeopathic research. The charge of non-reproducibility is shown to be unfounded, because a same homeopathic medicine displayed the same direction of effects in two well-validated models (light-dark and open-field), albeit with nonlinear patterns. The double-blind protocols and statistics by means of ANOVA were performed appropriately and the difference between dilutions of Gelsemium (5cH, 7cH, 9cH and 30cH with variations according to model) and placebo was statistically highly significant. Our investigations brought to light some problems related with the lack of activity of buspirone and diazepam (conventional anxiolytic drugs used as control) on some behavioural parameters, suggesting that Gelsemium may have broader action, and raising doubts as to the reliability of benzodiazepines as positive controls for homeopathic treatments. Concerning the plausibility of experiments in this field, disputed on the grounds of alleged lack of dose-response effect, we note that the latter is not at all uncommon, and can be accounted for by a host of possible reasons. In conclusion, our research line showed reproducible and consistent effects of Gelsemium in laboratory mice.
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    ABSTRACT: Riassunto Sono riportati i principali esperimenti svolti nel nostro laboratorio, mediante metodi rigorosi, attendibili e riproducibili, i cui risultati dimostrano che Istamina inibisce l'attivazione dei basofili umani e Gelsemium e Ignatia hanno effetti ansiolitici su modelli murini di comportamento. Tali sostanze agiscono in diluizioni/dinamizzazioni di tipo omeopatico, anche superiori alla costante di Avogadro-Loschmidt. Si presenta infine una ipotesi sintetica e generale dell'effetto omeopatico. Summary We report (Italian) the main experimental lines of our laboratory, where through rigorous and reliable methods we have shown that histamine inhibits the human basophil activation and Gelsemium and Ignatia regulate anxiety-like behaviours in laboratory mouse. These agents work also in dilutions/dynamizations which are beyond the Avogadro-Loschmidt constant. At the end we suggest a general hypothesis regarding the homeopathic effects.
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