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CHAMOMILLA
HOMEOPATHIC DILUTION EFFECT
ON CENTRAL NERVOUS SYSTEM
An
Experimental Pharmacological Study
A. CRISTEA, S. TEODORESCU-NEGRES AND V. DARIE
Lab. Pharmacology,
Faculty of Pharmacy, Bucharest, Romania
1 - Introduction
2 - Methods
3 - Results
4 - Discussion
5 - References
The concept concerning the informational causality of
the drug effect (Cristea,1996) casts a new light on the importance of the
biological variability and of the individual reactivity for the drug effect and
pharmacotherapy. Therefore in the past years, we extended pharmacological
researches even over the extremes, represented by healthy individuals,
"sensitive" and "resistant" to a drug, selected from a
Gauss - distributed normal population. Because for centuries, assessment of
homeopathic drug effect was made on healthy humans "sensitive" to
this remedy, that is why we made the studies on individual reactivity, using
also a homeopathic remedy.
The
Chamomilla remedy was especially
selected by us for these studies. In allopathic therapy the Matricaria Chamomilla flowers are used
for the following pharmacodynamical actions: analgesic, antispastic
antiinflamatory, antihistaminic and antiseptical. In homeopathic therapy the
homeopathic drug Chamomilla is used
not only in unbearable colics and algia with different locations, accompanied
by an excitation of the central nervous system (CNS) which results in
agitation, irritability, fury, violence and aggression (including verbal), but
also in convulsions consecutive to a state of furious agitation.
We studied the effects of homeopathic remedy Chamomilla on CNS (Cristea et al., 1993), effects that are not used
in allopathic medicine. The blind screening methodology, well known in
allopathic pharmacology, was utilised for CNS action investigation. In our
experiment, we have proceeded according to the homeopathic principle of
individuals "sensitive" to certain remedy, principle which conditions
the efficiency of homeopathic therapy method. In order to select the
"sensitive" to Chamomilla
remedy - type, we used a simple
original procedure (Cristea,
1994; 1995).
2.1. TESTING SOLUTIONS
Low degree dilution, 5 C, and high degree dilution, 30
C, of homeopathic remedy Chamomilla
(Cham), were prepared, starting from mother-tincture of Cham, by successive
water dilution at a 1% rate and dynamisation (D), according to Hahnemann
homeopathic technique. It was processed comparatively to control groups
(non-treated and treated whith the solvent represented by the corresponding
dynamised (D) solution of 70 ° alcohol in distilled water).
The
treatment with Cham remedy was made per os, four times at a one day-period with
low degree dilutions and two times at three day-period with high degree
dilutions. The tests were made three hours after the latest administration. The
administration of reference drugs (amphetamine, diazepam, clonazepam, noraminophenasone)
was made per os, in a single dose and
the tests were made at a one hour-latence. Distilled water was used as solvent
for the reference drugs. The volumes administered per os were 0.1ml/10 grams
weight of mouse and 1 ml/100 g B.W.
2.2. ANIMALS
The chosen animal species were male albino mice and
male wistar rats with an average weight of 20 and 200 g respectively.
2.3. EXPERIMENTS
The blind screening methodology, well known in
allopathic pharmacology, was utilised for CNS actions investigation. Both
biological actions in healthy animal (n = 20, for each group) and therapeutical
effects in animals submitted to certain experimental morbide models
(homologated in allopathic pharmacology) (n = 10, for each group) were studied
for Chamomilla. The statistical
significance of the results (p < 0.05) were highlighted in the following
tests.
2.3.1. In
healthy animals, for the effect on the CNS tone:
-
actometric test using a photoelectric cells-actometer, for spontaneous
motility, was expressed in number of movements / minute, for each individual,
-
platform test using a circular platform, for evasion - investigation reflex,
was expressed in number of emergences / minute, for each individual,
-
wire test using a stretched wire, for redressement reflex,was expressed in
number of animals redressed / group,
-
rotational axe test using a classical rotational axe, for nimbleness, was
expressed in number of nimble animals / group,
-
group toxicity test, at crowd, without amphetamine, was expressed in number of
dead animals / group, at two hours.
2.3.2. Experimental
morbide models:
-
the actometric test, platform test, wire test and rotational ax test were used
for the tranquilizing effect,
-
chemical nociceptive stimul test using acetic acid 0,6%, 0.1 ml / 10 g B.W.,
i.p., for analgesic effect,
-
chemical - induced convulsions test using strychnine 0.8 mg / kg B.W., s.c.,
for anticonvulsivant effect,
-
chemical - induced narcose test using hexobarbital 80 mg / kg B.W, i.p., for
hypnotic effect.
International bioethic regulations of researches on
animal were complied with.
2.4. PROCEDURES FOR SELECTION OF "SENSITIVE"
TYPE
We found and developed a simple and safe methodology
for selecting the healthy type "sensible" to the action of an
allopathic or homeopatic drug (Cristea, 1994; 1995). This methodology consists
of the following:
-
establishing the physiological function appropriate for the pharmacological
investigation of the drug being studied;
-
determining the level of that physiological function in every individual from
the group suitable for the experimental or clinical study (at least 20
individuals and optimally 100 individuals);
-
tracing the Gauss bell-shaped curve, using the distribution frequency of the
values of the investigated physiological function in the group subject to
selection;
-
dividing the individuals into normal ones, the function being at level f =
average f±1 (about 67% of individuals)
and extreme ones with f > average f+1 and f < average f-1 (33% of the individuals);
-
selecting the healthy individuals "sensitive" to the drug under
study, either those with the function f > average f+1 or those with f
<average f-1 (16.5% of the
individuals);
-
classifying the "sensitive" healthy individuals by groups, for
purpose of the pharmaceutical research.
We tested the described methodology for the selection
of the "sensitive" healthy individuals, in both allopathic and
homeopathic pharmacology.
We have chosen the actometric test, in order to select
the "sensitive" type to Cham remedy, which test led us to divide the
animal collectivity, according to Gauss bell shaped distribution curve, in
animals with medium spontaneous motor activity ("normals") and in
animals with hypo- or hypermotility
("sensibles") (Figure 1).
Figure 1. Gauss bell-shaped curve, in actometric test for the
selection of the normal and the extreme types of CNS tone
Gauss'
normal distribution Theoretical Experimental
Individuals
between -1S.D. and +1S.D. 67% 65%
Individuals
between -2S.D. and +2S.D. 95% 96%
Statistical
analysis: N = 100; Mean = 16.684; Median = 17; Minimum
= 2; S.D. = 5.089; SEM = 0.522; Sum = 1585;
Variance
= 25.899
2.5. STATISTICS
The results were statistically processed by the
Student "t" and Wilcoxon tests for the values expressed in number of
obervations (%) at each individual and by Chi square test for values expressed
in number of indivuduals (%) being noticed in each group. The effects (%) were
calculated compared to a control group treated with the solvent.
From the point of view of bioethics, the number of
animals per group, was twenty for healthy animals (n = 20) and ten for animals
submitted to experimental disease models (n = 10).
The low degree dilution, 5 C, of Cham had an action in
the stimulatory sense, on "sensitive" healthy mice, with spontaneous
hypomotility, (n = 20), as it is shown in figure 2.
Figure 2. Stimulatory actions in healthy "sensitive" mice (with
hypomotility); n = 20 (for each test)
a)
Increase of motility (%); p < 0.01 (Student's t test)
b)
Modification of evasion-investigation reflex (%); p < 0.05 (Student's t
test)
c)
Increase of redressement reflex (%); p < 0.05 (Chi square test)
d)
Increase of nimbleness (%); p < 0.05 (Chi square test)
- increasing the motor activity by 58% (p<0.01) at
5 C (D) Cham; a dose of 10 mg/ kg B.W. per os of amphetamine (Amph) produced a
greater increase in spontaneous motility (154.06% ; p<0.001);
-increasing the evasion-investigation reflex by 24.18%
(p<0.01) at 5 C (D) Cham; to the contrary, a dose of 10 mg/kg weight per os
of Amph produced an important decrease of evasion- investigation reflex (
121.36%);
-increasing the redressement reflex by 30% at 5 C (D) Chamomilla; Amph increased redressement
reflex of 10%;
-increasing the nimbleness by 50% at 5 C (D) Chamomilla; Amph had no effect.
The low degree dilution also induced in
"sensitive" healthy mice with spontaneous hypomotility a state of
excitement on CNS, reported in the group toxicity test (n = 10) without Amph,
resulting in group lethality of 43.2% at 5 C (D) Cham, compared with 5 C (D)
alcohol; Amph induced a 100% lethality, compared with water as solvent, at 1
1/2 hours.
The high degree dilution, 30 C, also induced the
tranquilizing effect reported in the "sensitive" healthy mice with
hipermotility (n =20), by way of (Figure 3)
-decreasing the motility by 31.68% at 30 C (D) Cham
(p<0.01); a dose of 5 mg/ kg B.W. of diazepam (Diaz) per os produced a
decrease in spontaneous motility of 29.41% (p<0.01);
-decreasing the evasion-investigation reflex by 56.03%
at 30 C (D) Cham (p<0.01); the Diaz produced a decrease of
evasion-investigation reflex ( 61.92%);
-decreasing the redressment reflex by 20% at 30 CHD
Cham; Diaz produced a decrease of 20%;
-the nimbleness was not significantly modified at 30 C
(D); Diaz decreased by 10% the nimbleness.
Figure 3. Tranquilizing effect in healthy "sensitive"
mice with hypermotility
(n = 20, for each test)
a)
Decrease of motility (%); p < 0.01 (Studentís ìtî test)
b)
Decrease of evasion-investigation reflex (%); p < 0.01 (Student's t test)
c)
Decrease of redressement reflex (%); p < 0.05 (Chi square test)
d)
Decrease of nimbleness (%); p < 0.05 (Chi square test)
The high degree dilution, 30 C, induced the following
pharmacotherapeutical effects, in animals in which a disease syndrome has been
experimentally induced:
-anticonvulsivant action in mice (n = 10) has been
manifested by decreasing lethality by 30% at 30 C (D) Chamomilla; the clonazepam (Clonaz) 1 mg/kg B.W. decreased the
lethality by 50%:
-analgesic action in mice (n = 10) was distinguished
by decreasing the number of contorsions 33.8% at 30 C (D) Chamomilla (p<0.01); noraminophenasone (Noraminophen) 100 mg/kg
B.W., per os, induced a decrease of 51.1% in the number of contorsions
(p<0.001).
The
effects on hexobarbital-induced narcose were:
-antagonizing, while using low degree dilution, 5 C,
in "sensitive" healthy mice with hypomotility, (n = 10), as follows:
5 C (D) Cham decreased by 42.9% the percentage of narcosed mice, increased by
79.06% the latence of narcose (p<0.001) and decreased by 21.9% (p<0.05)
the period of narcose;
-potencying, while using high degree dilution, 30 C,
in "sensitive" healthy mice with hypermotility, (n = 10), as follows:
30 C (D) Cham decreased by 21.46% (p<0.01) the latence of narcose.
The
Diaz decreased by 39.51% (p<0.01) the latence of narcose and increased by
175.76% (p<0.01) the period of narcose.
No neuroleptic action was noticed in the catalepsy
test and postural test as well as in the palpebral ptosis test.
No miorelaxant action was recorded in the ipsilateral
flexion reflex test and postural test. The cornean and pineal reflexes were
also not been modified as well.
No opioid-like analgesic action was noticed in Hafner
test. For this reason, the analgesic action, statistically significant
performed in chemical nociceptive stimulation test, can only be of a minor
analgesic type and not of morphine-like type or can result from a known
peripheral antispastic action of Cham.
The
results including their statistical significance are summarized in Table 1.
TABLE 1: Summary of the Results
_______________________________________________________________________________________
Test Type
of Treatment n Effect
%±SEM P
motility
_______________________________________________________________________________________
Motility Hypo Cham
5 C 20 +58
± 1.55 <0.01 Student's
Amph 20 +154.06 ±1.18 <0.001
"
Hyper Cham
30 C 20 -31.68 ± 0.93 <0.01 "
Diaz 20 -29.41 ± 1.38 <0.01 "
_______________________________________________________________________________________
Evasion Hypo Cham
5 C 20 +
24.18 ±1.48 < 0.05 Student's
Investi- Amph 20 - 121.36 ± 2.43 <
0.01 "
gation Hyper Cham
30 C 20 - 56.03 ± 1.60 < 0.01 "
Reflex Diaz 20 - 61.92 ± 1.72 < 0.01 "
______________________________________________________________________________________
Analgesic
Hypo Cham 5 C 10 +33.8
± 1.79 < 0.01 "
Reflex Noraminophen 10 +
51.1 ± 1.52 < 0.001 "
______________________________________________________________________________________
Narcose Hypo Cham
5 C 10 +
79.06±0.24 < 0.001
"
with -21.90±
1.54 < 0.05
"
hexobar- Hyper Cham
30 C 10 -21.46± 0.06 < 0.01 "
bital +23;68
±4.55 <0.05 Wilcoxon
Latence/ Diaz 10 -39.51 ± 0.106 <0.01 Student's
Length +175.76
± 12.08 <0.01 Wilcoxon
_____________________________________________________________________________________
The results of these experimental pharmacological
researches indicate, for the homeopathic remedy Cham, a stimulatory action on
CNS, performed at low degree dilution, 5 C, in "sensitive" healthy
animal organism with hypomotility; it also validates the stimulating effects on
CNS described in the homeopathic pathogenesis of this remedy.
The
comparison with amphetamine, considered as a reference substance, suggests that
the stimulating effect on CNS by the homeopathic remedy Cham is not an
amphetamine-like effect. The stimulatory action on CNS is usually related to
the polinic derivates located in the aerial part of the plant and quoted for
anticonvulsivant effect (Guermonprez et
al., 1989).
The
results also show some inhibitory effects, namely inhibition of the CNS
(tranquilizing, analgesic, anticonvulsivant), significantly performed at high
degree dilutions, 30 C, either in "sensitive" healthy animal organism
with hyperexcitability and hypermotility or in animal organism submitted to
experimental morbid syndrome such as pains and convulsions.
Our
experimental pharmacological researches complete the researches performed by
Guillemain (1983). The cited author reported that, at 3 C and 4 C dilutions,
the Cham remedy significantly diminishes the number of fights in rats after
exposure to electric shocks. Moreover, using 3 C and 4 C Cham or 5 C Coffea treatment, the author recorded
decreased coffein-induced motor hyperactivity in male rats.
These pharmacotherapeutical effects prove
experimentally the validity of the homeopathic therapeutical principle of
similitude ("Similia similibus
curentur").
Concerning
the value of this therapeutic principle, we discussed in another paper
(Cristea, 1996), both informationally and cybernetically, the four
physiological adjustement modalities, i.e. iso-, homeo-, allo- and
enantio-regulation, in the biocybernetical mechanisms i.e. feed-back and
feed-before (feed-forward).
It
is in worth saying, that the effects observed in our experiments have had,
without exception, a highly statistical significance (p<0.01) in
"sensitive" extreme individuals and were statistically non
significant (p>0.05) in "resistent" extreme individuals. Thus, we
successfully demonstrated the quieting effect of the homeopathic remedy Cham,
at high-degree dilution 30 C, in "sensitive" healthy mice, with
spontaneous motor restfulness. We were also able to reproduce the experimental
pathogenesis of the remedy Cham, in low-degree dilution of 5 C, refering to
restfulness in "sensitive" healthy individuals, selected for their
spontaneous motor hypoactivity. These results prove the objective value of experiments in healthy individual, though
"sensitive" to certain remedy, promoted by Hahnemann.
In
our opinion, the "sensitive" and "resistent" extreme
individuals, within a population with normal Gauss-like biological variability,
represent psycho-neuro-endocrine typologies which should be the object of future
biological and pharmacological studies.
This
assessment is based on our allopathic pharmacological studies on
"sensitive" individuals (Cristea 1993, Cristea, 1994). Using our
method in the allopathic pharmacology studies on the relationship between the
"alarm" adrenergic system and the "modulator" endogenous
opioid system, we were able to select the adrenergic type individuals (A)
(described by Rosenman, 1970) and the opioid type individuals (O) (described by
Cristea A., 1993), both experimentally and clinically. The experimental
pharmacology research made on type A and type O individuals proved that type A
individuals are "sensitive" to Clonidine (Clon) while type O
individuals are "sensitive" to naloxone (Nalx). Also we emphasized on
the dose-effect curves, the double-way effect of Clon and Nalx, on stress
analgesia, with distinct inflexion points, for the normal and the two extremes
individuals of type A and type O (Cristea et
al., 1995). Ignoring or analysing the biological variability represents a real
problem evolving from european pharmacological debates (Black, 1995).
In
conclusion, we consider that the results of these studies justify the
opportunity of future researches concerning the intimate mechanism of the
exciting action on CNS, of homeopathic drug Chamomilla, an action which
explains the quieting effect, in accordance with the therapeutical principle of
similitude.
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ignore, reduce or analyse?, 1st European
Congress of Pharmacology, Milan, Italy.
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Cristea, A. (1994) Mechanisms of stress
analgesia in opioid and adrenergic types of behaviour, VIIth Congress of ECNP,
Jerusalem, Israel; Europ.
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evidentierea tipului de individ sanatos, "sensibil" la un medicament
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Cristea, A., Negres, S., Joean, D.
(1995) The double-way effects of naloxon and clonidine, on experimental stress
analgesia, Rom. J. Physiology 1-4, 137-143.
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pharmacology, X Intern. Congress of
Cybernetics and Systems, Bucharest, Romania.
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and Enantio-regulation of the biocybernetic systems, X Intern. Congress of
Cybernetics and Systems , Bucharest, Romania.
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M.(1989) Matière Médicale Homéopathique, Boiron Publisher; Lyon, pp. 188-193.
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