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'Paradoxical pharmacology': therapeutic strategy used by the 'homeopathic pharmacology' for more than two centuries

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  • School of Medicine University of Sao Paulo
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'Paradoxical pharmacology': therapeutic strategy used by the 'homeopathic pharmacology' for more than two centuries

Abstract

Using the empirical or phenomenological research method by observing the effects of drugs in the human physiology, Samuel Hahnemann proposed the homeopathic treatment. He synthesized modern pharmacodynamic in the ‘primary action’ of the drugs and in the consequent and opposite ‘secondary action’ or ‘vital reaction’ of the organism. Noting that drugs with ‘contrary’ primary action to the symptoms of the diseases caused worsening of the symptoms after its withdrawal, as a result of secondary action of the organism, Hahnemann proposed using this vital reaction (secondary action) in a curative way, administering to sick individuals the drugs that caused ‘similar’ symptoms in healthy individuals (therapeutic use of the similitude principle). According to the clinical and experimental pharmacology, this secondary action (vital reaction) of the organism is observed in the ‘rebound effect’ or ‘paradoxical reaction’ of several classes of drugs, which is the scientific basis of the ‘homeopathic pharmacology’. In the last decade, exponents of modern pharmacology have suggested the therapeutic use of the paradoxical reaction (‘paradoxical pharmacology’), proposing the use of drugs that cause an exacerbation of the disease in the short term to treat these same diseases in the long-term. In this review, we compare the various aspects between the ‘homeopathic pharmacology’ and the ‘paradoxical pharmacology’, reinforcing the validity of homeopathic assumptions and expanding the knowledge to optimize both proposals.
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Original article
‘Paradoxical pharmacology’: therapeutic strategy
used by the ‘homeopathic pharmacology’ for more
than two centuries
Marcus Zulian Teixeira
School of Medicine, University of São Paulo, São Paulo, Brazil
ABSTRACT
Using the empirical or phenomenological research method by observing the effects of drugs in the
human physiology, Samuel Hahnemann proposed the homeopathic treatment. He synthesized
modern pharmacodynamic in the ‘primary action’ of the drugs and in the consequent and opposite
‘secondary action’ or ‘vital reaction’ of the organism. Noting that drugs with ‘contrary’ primary
action to the symptoms of the diseases caused worsening of the symptoms after its withdrawal, as
a result of secondary action of the organism, Hahnemann proposed using this vital reaction
(secondary action) in a curative way, administering to sick individuals the drugs that caused
‘similar’ symptoms in healthy individuals (therapeutic use of the similitude principle). According
to the clinical and experimental pharmacology, this secondary action (vital reaction) of the
organism is observed in the ‘rebound effect’ or ‘paradoxical reaction’ of several classes of drugs,
which is the scientific basis of the ‘homeopathic pharmacology’. In the last decade, exponents of
modern pharmacology have suggested the therapeutic use of the paradoxical reaction
(‘paradoxical pharmacology’), proposing the use of drugs that cause an exacerbation of the disease
in the short term to treat these same diseases in the long-term. In this review, we compare the
various aspects between the ‘homeopathic pharmacology’ and the ‘paradoxical pharmacology’,
reinforcing the validity of homeopathic assumptions and expanding the knowledge to optimize
both proposals.
Keywords: Homeopathy; Pharmacology; Pharmacodynamic Action of Homeopathic Remedy;
Secondary Effect; Rebound Effect; Paradoxical Reaction; Paradoxical Pharmacology.
Introduction
In the ancient Greece, Hippocrates recommended treatment of diseases by the principles of ‘contraries’
(contraria contrariis curentur) or ‘similar’ (similia similibus curentur), teaching that “whatever evil and from
where come, you might want to always treat or by contrary or by similar” (Liber de locis in homine). Based on
Corpus Hippocraticus, several exponents of the old medical schools spread these ways to treat [1].
The ‘principle of contraries’, which is applied to a large percentage of conventional modern therapeutic,
employs medicines with contrary (enantiopathic, antipathetic, opposite or palliative) action to the signs and
symptoms of the diseases, in order to minimize or neutralize their manifestations. On the other hand, the
‘principle of similars’ or ‘principle of similitude’, systematized by the homeopathic therapeutic, employs drugs
that possess the property of exhibiting signs and symptoms similar to those manifested by diseases, in order
to stimulate the organism to react against their own disturbances.
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The homeopathic method of treatment is based on four pillars: ‘principle of therapeutic similitude’, ‘proving of
medicinal substances on healthy individuals’, use of ‘serially diluted and shaken (dynamized) medicines’, and
prescription of ‘individualized medicines’. Although great importance was attributed to ‘dynamized medicines’
(infinitesimal or ultrahigh-diluted doses), which were introduced later in the homeopathic model to minimize
the possible ‘aggravation of the diseases’ in the application of the similitude principle, the first two pillars are
the proper foundation of the homeopathic epistemological model, remaining to ‘individualized medicine’ the
essential condition for awakening the therapeutic response.
In the last decade, exponents of modern clinical and experimental pharmacology have suggested a therapeutic
strategy similar to the one propagated by homeopathy for more than two centuries, called ‘paradoxical
pharmacology’, proposing the use of conventional drugs that cause an exacerbation of the disease in the short-
term to treat this same disease in the long-term.
In this review article, we propose identifying the conceptual and functional similarities between the
‘homeopathic pharmacology’ (therapeutic use of the similitude principle) and the ‘paradoxical pharmacology’
(therapeutic use of the paradoxical reaction), reinforcing the validity of homeopathic assumptions before the
modern scientific rationality and expanding the knowledge to optimize both proposals.
Similitude in homeopathy ‘Law of similars’
During the development of the homeopathic methodology, Samuel Hahnemann maintained an experimental
posture, using phenomenological research method to describing the effects of dozens of drugs in the human
health and correlating his observations with evidences from medical literature.
In the work that inaugurated the homeopathy (Essay on a new principle for ascertaining the curative power of
drugs, 1796) [2] and in the introduction of the Organon of medicine [3] he cited several reports of an opposite
‘secondary action of the organism’ after a ‘primary action of the drug’ described in your observations and in
hundreds of bibliographical references. These descriptions were illustrated with ‘examples of accidental
homeopathic cure’ reported by doctors of all times, supporting a scientific rationale for the principle of
homeopathic cure:
The seeds of the poison tree (Strychnos nux vomica) are very powerful; but the morbid symptoms it produces
are not yet accurately known. The most I know concerning them is derived from my own observation. The
primary action produce vertigo, anxiety, febrile rigour, and in their secondary action a certain immobility of
all parts, at least of the limbs, and a spasmodic stretching, according to the size of the dose. Hence they are
useful, not only, as is already known, in intermittent fever, but in cases of apoplexy. In their first direct action
the muscular fiber has a peculiar mobility imparted to it, the sensitive system is morbidly exalted to a species
of intoxication, accompanied by fearfulness and horror. Convulsions ensue. The irritability seems to exhaust it
itself during this continued action on the muscular fiber, first in the animal, then in the vital functions. On
passing into the indirect secondary action, there occurs a diminution of the irritability, first, in the vital
functions (general perspiration), then in the animal, and lastly in the natural functions. In the latter,
especially, this secondary action lasts several days. During the secondary action, there is a diminution of
sensibility. Whether in the primary direct action the tonicity of the muscles is diminished, to be
proportionately increased in the secondary action, cannot be accurately determined; this much, however, is
certain, that the contractility of the fiber is as much diminished in the secondary action, as it was increased in
the direct action”. (Essay on a new principle for ascertaining the curative power of drugs)
Arsenic, whose effects are so powerful upon the human economy that we cannot decide whether it is more
hurtful in the hands of the fool-hardy than it is salutary in those of the wise, - arsenic could never have
effected so many remarkable cures of cancer in the face, as witnessed by numerous physicians, among whom I
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will only cite Fallopius, Bernhardt, and Roennow, if this metallic oxide did not possess the homeopathic power
of producing, in healthy persons, very painful tubercles, which are cured with difficulty, as witnessed by
Amatus Lusitanus; very deep and malignant ulcerations, according to the testimony of Heinreich and Knape;
and cancerous ulcers, as testified by Heinze. The ancients would not have been unanimous in the praise which
they bestowed on the magnetic arsenical plaster of Angelus Sala against pestilential buboes and carbuncles, if
arsenic did not, according to the report of Degner and Pfann, give rise to inflammatory tumours which quickly
turn to gangrene, and to carbuncles or malignant pustules, as observed by Verzascha and Pfann. And whence
could arise that curative power which it exhibits in certain species of intermittent fevers (a virtue attested by
so many thousands of examples, but in the practical application of which, sufficient precaution has not yet
been observed, and which virtue was asserted centuries ago by Nicholas Myrepsus, and subsequently placed
beyond a doubt by the testimony of Slevogt, Molitor, Jacobi, J. C. Bernhardt, Jiingken, Fauve, Brera, Darwin,
May, Jackson, and Fowler) if it did not proceed from its peculiar faculty of excit ingfever, as almost every
observer of the evils resulting from this substance has remarked, particularly Amatus Lusitanus, Degner,
Buchholz, Heun, and Knape. We may confidently believe E. Alexander, when he tells us that arsenic is a
sovereign remedy in some cases of angina pectoris, since Tachenius, Guilbert, Preussius, Thilenius, and Pyl,
have seen it give rise to very strong oppression of the chest; Gresselius, to a dyspnea approaching even to
suffocation; and Majault, in particular, saw it produce sudden attacks of asthma excited by walking, attended
with great depression of the vital powers”. (Organon of medicine, “Examples of accidental homeopathic cure”)
With these several evidences, Hahnemann gathered ‘strong arguments’ that enabled him to induce a
physiological mechanism to explain this ‘biphasic’ or ‘bidirectional’ action of drugs on the organism:
Every agent that acts upon the vitality, every medicine, deranges more or less the vital force, and causes a
certain alteration in the health of the individual for a longer or a shorter period. This is termed primary
action. […] To its action our vital force endeavors to oppose its own energy. This resistant action is a property,
is indeed an automatic action of our life-preserving power, which goes by the name of secondary action or
counter-action”. (Organon of medicine, paragraph 63)
He exemplifies this biphasic action (primary action of the drug followed by a secondary and opposite action of
the organism) in the non-pharmacological interventions and in the pharmacological effects of antipathic
treatments used at that time:
“[…] A hand bathed in hot water is at first much warmer than the other hand that has not been so treated
(primary action); but when it is withdrawn from the hot water and again thoroughly dried, it becomes in a
short time cold, and at length much colder than the other (secondary action). A person heated by violent
exercise (primary action) is afterwards affected with chilliness and shivering (secondary action). To one who
was yesterday heated by drinking much wine (primary action), today every breath of air feels too cold
(counteraction of the organism, secondary action). An arm that has been kept long in very cold water is at first
much paler and colder (primary action) than the other; but removed from the cold water and dried, it
subsequently becomes not only warmer than the other, but even hot, red and inflamed (secondary action,
reaction of the vital force). Excessive vivacity follows the use of strong coffee (primary action), but
sluggishness and drowsiness remain for a long time afterwards (reaction, secondary action), if this be not
always again removed for a short time by imbibing fresh supplies of coffee (palliative). After t he profound
stupefied sleep caused by opium (primary action), the following night will be all the more sleepless (reaction,
secondary action). After the constipation produced by opium (primary action), diarrhea ensues (secondary
action); and after purgation with medicines that irritate the bowels, constipation of several days’ duration
ensues (secondary action). And in like manner it always happens, after the primary action of a medicine that
produces in large doses a great change in the health of a healthy person, that its exact opposite, when, as has
been observed, there is actually such a thing, is produced in the secondary action by our vital force”. (Organon
of medicine, paragraph 65)
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Describing the sad results of the indiscriminate palliative (antipathic, enantiopathic) employment of
medicines (Organon of medicine, paragraphs 56-61), Hahnemann alerts to the risks of this undesirable
secondary action (vital reaction) of the organism that can produce “more serious disease or frequently even
danger to life and death itself”. This way, negating the efficacy of the conventional or palliative treatment
(principle of contraries), Hahnemann validates the homeopathic treatment (principle of similitude) through
the hypothetical syllogism or classical deductive logic “modus tollens” (‘mode that affirms through negation’ or
‘indirect proof’). Through various examples, he concludes that after such short antipathic amelioration,
aggravation follows in every case without exception” (Organon of medicine, paragraph 58), i.e., after a
primary action of palliative medicines occurs a secondary action of the organism, with worsening of
symptoms:
Important symptoms of persistent diseases have never yet been treated with such palliative, antagonistic
remedies, without the opposite state, a relapse - indeed, a palpable aggravation of the malady - occurring a
few hours afterwards. For a persistent tendency to sleepiness during the day the physician prescribed coffee,
whose primary action is to enliven; and when it had exhausted its action the day - somnolence increased; - for
frequent waking at night he gave in the evening, without heeding the other symptoms of the disease, opium,
which by virtue of its primary action produced the same night (stupefied, dull) sleep, but the subsequent
nights were still more sleepless than before; - to chronic diarrheas he opposed, without regarding the other
morbid signs, the same opium, whose primary action is to constipate the bowels, and after a transient
stoppage of the diarrhoea it subsequently became all the worse; - violent and frequently recurring pains of all
kinds he could suppress with opium for but a short time; they then always returned in greater, often
intolerable severity, or some much worse affection came in their stead. For nocturnal cough of long standing
the ordinary physician knew no better than to administer opium, whose primary action is to suppress every
irritation; the cough would then perhaps cease the first night, but during the subsequent nights it would be
still more severe, and if it were again and again suppressed by this palliative in increased doses, fever and
nocturnal perspiration were added to the disease; - weakness of the bladder, with consequent retention of
urine, was sought to be conquered by the antipathic work of cantharides to stimulate the urinary passages
whereby evacuation of the urine was certainly at first effected but thereafter the bladder becomes less capable
of stimulation and less able to contract, and paralysis of the bladder is imminent; - with large doses of
purgative drugs and laxative salts, which excite the bowels to frequent evacuation, it was sought to remove a
chronic tendency to constipation, but in the secondary action the bowels became still more confined; - the
ordinary physician seeks to remove chronic debility by the administration of wine, which, however, stimulates
only in its primary action, and hence the forces sink all the lower in the secondary its primary action, and
hence the forces sink all the lower in the secondary action; - by bitter substances and heating condiments he
tries to strengthen and warm the chronically weak and cold stomach, but in the secondary action of these
palliatives, which are stimulating in their primary action only, the stomach becomes yet more inactive; - long
standing deficiency of vital heat and chilly disposition ought surely to yield to prescriptions of warm baths,
but still more weak, cold, and chilly do the patients subsequently become; - severely burnt parts feel
instantaneous alleviation from the application of cold water, but the burning pain afterwards increases to an
incredible degree, and the inflammation spreads and rises to a still greater height; - by means of the
sternutatory remedies that provoke a secretion of mucus, coryza with stoppage of the nose of long standing is
sought to be removed, but it escapes observation that the disease is aggravated all the more by these
antagonistic remedies (in their secondary action), and the nose becomes still more stopped; - by electricity and
galvanism, with in their primary action greatly stimulate muscular action, chronically weak and almost
paralytic limbs were soon excited to more active movements, but the consequence (the secondary action) was
complete deadening of all muscular irritability and complete paralysis; - by venesections it was attempted to
remove chronic determination of blood to the head, but they were always followed by greater congestion; -
ordinary medical practitioners know nothing better with which to treat the paralytic torpor of the corporeal
and mental organs, conjoined with unconsciousness, which prevails in many kinds of typhus, than with large
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doses of valerian, because this is one of the most powerful medicinal agents for causing animation and
increasing the motor faculty; in their ignorance, however, they knew not that this action is only a primary
action, and that the organism, after that is passed, most certainly falls back, in the secondary (antagonistic)
action, into still greater stupor and immobility, that is to say, in to paralysis of the mental and corporeal
organs (and death); they did not see, that the very diseases they supplied most plentifully with valerian,
which is in such cases an oppositely acting, antipathic remedy, most infallibly terminated fatally. The old
school physician rejoices that he is able to reduce for several hours the velocity of the small rapid pulse in
cachectic patients with the very first dose of uncombined purple foxglove (which in its primary action makes
the pulse slower); its rapidity, however, soon returns; repeated, and now increased doses effect an ever
smaller diminution of its rapidity, and at length none at all - indeed - in the secondary action the pulse
becomes uncountable; sleep, appetite and strength depart, and a speedy death is invariably the result, or else
insanity ensues. How often, in one word, the disease is aggravated, or something even worse is affected by the
secondary action of such antagonistic (antipathic) remedies, the old school with its false theories does not
perceive, but experience teaches it in a terrible manner”. (Organon of medicine, paragraph 59)
Despite this secondary action of the organism be clearly observed after the primary action of the medicines in
moderate-large doses (Organon of medicine, paragraphs 65, 112), as an instinctive and automatic mechanism
of self-regulation of the internal environment (homeostasis), in homeopathic (small) doses, as result of weak
primary action of the medicine, is not perceived an “obvious antagonistic secondary action” (Organon of
medicine, paragraphs 66, 68, 112). In this situation, the organism “employs against it only so much reaction
(secondary action) as is necessary for the restoration of the normal condition”, and may be curative or not if
the therapeutic similitude principle is observed. In this case, it is worth mentioning that although little
significant (non “obvious”, “reacts only so much as is requisite”, “so much reaction as is necessary”, any more
considerable reaction than will suffice”, little effort is required”), the secondary action (vital reaction) of the
organism manifests itself and is perceived through their curative effects:
“[…] And in like manner it always happens, after the primary action of a medicine that produces in large
doses a great change in the health of a healthy person, that its exact opposite, when, as has been observed,
there is actually such a thing, is produced in the secondary action by our vital force”. (Organon of medicine,
paragraph 65)
In those older prescriptions of the often dangerous effects of medicines ingested in excessively large doses we
notice certain states that were produced, not at the commencement, but towards the termination of these sad
events, and which were of an exactly opposite nature to those that first appe ared. These symptoms, the very
reverse of the primary action (§ 63) or proper action of the medicines on the vital force are the reaction of the
vital force of the organism, its secondary action 62-67), of which, however, there is seldom or hardly ever
the least trace from experiments with moderate doses on healthy bodies, and from small doses none whatever.
In the homoeopathic curative operation the living organism reacts from these only so much as is requisite to
raise the health again to the normal healthy state”. (Organon of medicine, paragraph 112)
An obvious antagonistic secondary action, however, is, as may readily be conceived, not to be noticed from the
action of quite minute homoeopathic doses of the deranging agents on the healthy body. A small dose of every
one of them certainly produces a primary action that is perceptible to a sufficiently attentive; but the living
organism employs against it only so much reaction (secondary action) as is necessary for the restoration of the
normal condition”. (Organon of medicine, paragraph 66)
In homoeopathic cures they show us that from the uncommonly small doses of medicine (§ 275-287) required
in this method of treatment, which are just sufficient, by the similarity of their symptoms, to overpower and
remove from the sensation of the life principle the similar natural disease there certainly remains, after the
destruction of the latter, at first a certain amount of medicinal disease alone in the organism, but, on account
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of the extraordinary minuteness of the dose, it is so transient, so slight, and disappears so rapidly of its own
accord, that the vital force has no need to employ, against this small artificial derangement of its health, any
more considerable reaction than will suffice to elevate its present state of health up to the healthy point - that
is, than will suffice to effect complete recovery, for which after the extinction of the previous morbid
derangement but little effort is required (§ 64, B)”. (Organon of medicine, paragraph 68)
Proposing to apply such ‘secondary action’ in a curative way (curative secondary action or effect), awakening a
‘vital reaction’ of the organism against its own disorders, Hahnemann suggested employing medicines that in
their ‘primary action’ produce symptoms similar to the ones of natural disease, thus widening the notion of
the ‘curative similitude’ (homeopathic method of treatment): every substance capable of provoking certain
symptoms in healthy individuals (due to the primary action of the drug), can be used to cure similar
symptoms in the sick (through the curative secondary action of the organism), according to the therapeutic
similitude principle. (Organon of medicine, paragraphs 24-28)
In summary, in the exemplification of the harmful effects of the use of moderate-large doses in accordance
with the antipathic treatment, Hahnemann reports that such secondary action (vital reaction) of the organism
(opposed in character to the primary action of the drug) is evidently observed (Organon of medicine,
paragraphs 58-61, 112). In the homeopathic treatment (minimal doses), Hahnemann reports that the curative
secondary action of the organism reacts to the primary action of the homeopathic doses only so much as is
requisite to raise the health again to the normal healthy state” (Organon of medicine, paragraphs 66, 68, 112).
As will be shown below, Hahnemann also employed the principle of therapeutic similitude with massive
(ponderable) doses of medicines, awakening a curative secondary action of the organism to conduct a complete
recovery. Thus, noting its manifestation in the most diverse situations, Hahnemann raises the principle of
therapeutic similitude (an opposite curative secondary action of the organism after the primary action of the
medicine) to the level of “natural law of cure” or “law of similars” (Organon of medicine, paragraphs 26-28, 50-
53), regardless of the doses, since the symptomatic individualization is respected:
The curative power of medicines, therefore, depends on their symptoms, similar to the disease but superior to
it in strength (§ 12-26), so that each individual case of disease is most surely, radically, rapidly and
permanently annihilated and removed only by a medicine capable of producing (in the human system) in the
most similar and complete manner the totality of its symptoms, which at the same time are stronger than the
disease”. (Organon of medicine, paragraph 27)
As this natural law of cure manifests itself in every pure experiment and every true observation in the world,
the fact is consequently established; it matters little what may be scientific explanation of how it takes place;
and I do not attach much importance to the attempts made to explain it. But the following view seems to
commend itself as the most probable one, as it is founded on premises derived from experience”. (Organon of
medicine, paragraph 28)
As mentioned previously, although Hahnemann used in the early stage of the homeopathic therapy
ponderable (massive) doses of drugs in accordance with the therapeutic principle of similitude, the
infinitesimal or ultrahigh-diluted doses have emerged in order to allow the organism to react to the primary
stimulus of the drugs without the possible toxicological disorders, observing later that they awakened and
healed different symptoms of the substantial doses, enlarging the therapeutic approach.
Similitude in modern pharmacology ‘Homeopathic pharmacology’
Building a bridge between the principle of similitude and the modern pharmacology (‘homeopathic
pharmacology’), one can find countless reports in pharmacological compendia and clinical and experimental
trials published in the scientific media describing the secondary reaction of the organism opposed to the
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primary action of the drug, which confirm Hahnemann’s theory. Such secondary action of the organism to
preserve organic homeostasis is known as ‘rebound effect’ by modern pharmacology [4-15].
According to Webster’s New World Medical Dictionary [16], ‘rebound effect’ means “the production of
increased negative symptoms when the effect of a drug has passed or the patient no longer responds to the
drug; if a drug produces a rebound effect, the condition it was used to treat may come back even stronger
when the drug is discontinued or loses effectiveness”. Also named by the term ‘paradoxical reaction’ of the
organism, one of the ironies of this phenomenon is that it makes the patients experience the very same effects
they had hoped to make disappear by using palliative drugs, thus deconstructing the main pillar of modern
pharmacological therapy, i.e., the treatment by principle of contraries. Although its exact mechanism remains
unclear, the main hypothesis to explain the rebound (paradoxical) effect is that it might be caused by
increased responsiveness (up-regulation) of the receptors of the involved drug.
In general terms, rebound effect is the result of the attempts of the organism to bring itself back into balance
(homeostasis) after a drug is taken in order to neutralize the disease symptoms. Described in 1860 by
Sorbonne professor Claude Bernard as “fixité du milieu intérieur”, the term ‘homeostasis’ was minted in 1929
by Harvard physiologist Walter Bradford Cannon to name the tendency or ability of living beings to keep
their internal environment constant through self-adjustment of their physiological processes. Such
physiological processes or homeostatic mechanisms are present at all levels of the biological organization from
the simplest of cells to the most complex mental and emotional functions.
Illustrating these assertions, drugs classically used in the treatment of angina pectoris -blockers, calcium
channel blockers, nitrates, and others) with beneficial effects in their primary effect (anti-angina), might
awaken a paradoxical increase of the frequency and intensity of chest pain after discontinuation or irregular
use of doses, which sometimes does not respond to any therapeutic means. Drugs used for the control of
arterial hypertension -2 agonists, β-blockers, ACE inhibitors, MAO inhibitors, nitrates, sodium
nitroprusside, hydralazine, and others) might produce rebound arterial hypertension as a paradoxical
reaction of the organism to the primary stimulus; antiarrhythmic drugs (adenosine, amiodarone, β-blockers,
calcium channel blockers, disopyramide, flecainide, lidocaine, mexiletine, moricizine, procainamide, quinidine,
digital, and others) may awaken a rebound exacerbation of basal ventricular arrhythmias, when the
treatment is interrupted. Hypolipidemic drugs (clofibrate, colestipol, colestiramine, nicotinic acid, fluvastatin,
lovastatin, pravastatin, and others), used in its primary action to treat hyperlipidemia, promote increased
rebound of lipid after their interruption. Antithrombotic drugs (argatroban, heparin, salicylates, warfarin,
clopidogrel, and others), employed due to their primary effect in the prophylaxis of thrombosis, can promote
thrombotic complications as paradoxical reaction of the organism.
In the use of psychiatric drugs such as anxiolytics (barbiturates, benzodiazepines, carbamates, and others),
sedative-hypnotics (barbiturates, benzodiazepines, morphine, promethazine, zopiclone, and others), stimulants
of the central nervous system (amphetamines, caffeine, cocaine, mazindol, methylphenidate, and others),
antidepressants (tricyclic, MAO inhibitors, selective serotonin reuptake inhibitors, and others) or
antipsychotics (clozapine, phenothiazines, haloperidol, pimozide, and others) it can be observed a paradoxical
reaction of the organism, which seeking to keep organic homeostasis, promote the appearance of symptoms
contrary to the ones expected from their primary therapeutic use, consequently worsening the initial clinical
picture. Drugs with anti-inflammatory primary action (corticosteroids, ibuprofen, indometacin, paracetamol,
salicylates, and others) might trigger paradoxical reactions of the organism that increase inflammation
together with the serum concentration of its mediators. Drugs with analgesic primary action (caffeine,
calcium channels blockers, clonidine, ergotamine, methysergide, opiates, salicylates, and others) can exhibit
significant hyperalgesia as a rebound effect. Diuretics (furosemide, torasemide, triamterene, and others)
enantiopathically used to diminish the volume of plasma (edema, arterial hypertension, congestive heart
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failure, and others) may cause rebound retention of sodium and potassium thus increasing the basal volume
of plasma.
Drugs primarily used as anti-dyspeptic (antacids, H2 antagonists, misoprostol, sucralfate, protons pump
inhibitors, and others) in the treatment of gastritis and gastro-duodenal ulcers might promote, after the
primary decrease of acidity, rebound increase of the production of hydrochloric acid by the stomach eventually
causing perforation of chronic gastro-duodenal ulcers. Bronchodilators (adrenergic drugs, sodium
chromoglycate, epinephrine, ipratropium, nedocromil, formoterol, salmeterol, and others) used in the
treatment of bronchial asthma can worsen bronchial constriction as paradoxical response of the organism to
the interruption or discontinuation of treatment. Antiresorptive drugs (bisphosphonates, denosumab, and
others), given to treat osteoporosis, can cause paradoxical atypical fractures after their biological effect (half-
life), as a result of rebound increased of the osteoclastic activity. Immunomodulatory drugs (natalizumab,
fingolimod, and others) used in the treatment of multiple sclerosis, can cause immune reconstitution
inflammatory syndrome (IRIS) with rebound worsening of disease, after treatment withdrawal, among others
[4-15].
Despite such phenomena appearing in a minority of individuals in view of their idiosyncratic nature,
contemporary scientific evidences point to the occurrence of severe and fatal iatrogenic events as a function of
the rebound effect or paradoxical reaction of the organism following the discontinuance of many classes of
modern enantiopathic drugs [6]. As a result of primary anticoagulant action, all types of non-steroidal anti-
inflammatory drugs awaken thrombogenic paradoxical reactions after discontinuation, leading to a significant
increase to the incidence of thrombosis and causing acute myocardial infarction (AMI) and encephalic
vascular accidents (EVA) [7,17,18].
Analogously, long-acting β-agonist bronchodilators after their primary bronchodilator action can cause
significant irreversible and fatal paradoxical bronchospasm [8,19,20]. Antidepressant agents, inhibiting the
recapture of serotonin (SSRIs), promote a rebound exacerbation of suicidality after an initial improvement of
this same symptom [9,21,22]. After a primary increase of their pleiotropic effects (vascular protective), statins
cause paradoxical and fatal vascular events (AMI, EVA) [10,23,24]. Proton-pump inhibitors (PPIs) cause
rebound hypergastrinemia and acid hypersecretion after an initial decrease of acidity, thus exacerbating
gastritis and ulcers, gastric cancer and carcinoid tumor [11,25,26]. In addition to severe paradoxical atypical
fractures after denosumab withdrawal [13,27] and severe relapses of multiple sclerosis after natalizumab
withdrawal [14,28,29], recent studies warn of fatal risks inherent to the rebound effect of others drugs of
modern biological therapy [30,31].
According to this evidence of the modern pharmacology, rebound effect or paradoxical reaction of the organism
has an intensity higher than the one of the symptoms originally suppressed: in controlled studies, in relation
to the placebo, a risk of ischemic accidents was 3.4 times larger after salicylates withdrawal, 1.52 times larger
after non-steroidal anti-inflammatory drugs withdrawal, 1.67 times larger after rofecoxib withdrawal, and
1.69 times larger after statins withdrawal; a risk of suicidal behaviours 6 times larger after SSRI
antidepressants withdrawal, and a risk of fatal paradoxical bronchospasm 4 times larger after long-acting
beta agonists withdrawal.
With similar estimates to the rebound effect of other drugs, long-acting beta agonists cause approximately 1
rebound bronchospasm followed by death every 1,000 patients-year-use, corresponding to 4,000-5,000
deaths/year in 2004 in the USA alone (40,000-50,000 worldwide) [8,32]. SSRI antidepressants cause
approximately 5 rebound suicidality events every 1,000 teenagers patients-year-use, corresponding to 16,500
suicidal behavior or thoughts in 2007 only in USA [9]. Salicylates cause approximately 4 rebound acute
myocardial infarction every 1,000 patients-year-use [33,34]. Studies described the increased incidence of
gastric carcinoids in last decades (400% in men and 900% in women) in view of the growing consumption of
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the PPIs [11]. Bisphosphonates cause 1-3 severe paradoxical atypical fractures every 1,000 patients-year-use
[13]. Natalizumab awakens rebound worsening of multiple sclerosis around 10% of patients who discontinued
treatment [14].
The rebound effect appears some time (hours to weeks) after the decrease or discontinuation of the treatment
(‘withdrawal syndrome’) according to the pharmacokinetic properties of the involved drug and the
idiosyncratic peculiarities of the individuals: average of 10 days for salicylates, 14 days for the non-steroidal
anti-inflammatory drugs, 9 days for the rofecoxib, 7 days for the SSRI antidepressants, 7 days for the statins,
and 7-14 days for the PPIs. The duration of the rebound effect is also variable: remaining for 30 days with
rofecoxib, 21 days with SSRI antidepressants, and 30 days with PPIs. The duration of the treatment did not
show association with the risk of awakening the paradoxical events.
Despite the fact that the drug withdrawal (‘half-life’ time) is a prerequisite for the manifestation of the
paradoxical reaction of the organism or rebound effect, because the primary effect of the drug lasts as long as
the receptors are stimulated, studies show that the rebound effect can occur even during drug use, occurrence
which can be explained by the phenomenon of ‘tolerance’ (adaptation of the organism to the drug with the loss
of pharmacological effect). On the other hand, the slow and gradual decrease of the doses, avoiding an abrupt
discontinuation, is a procedure to minimize the manifestation of the rebound effect.
As evidenced by clinical and experimental pharmacology [4-15], the common properties of the rebound effect
or paradoxical reaction of the organism are the same as the ones of the homeopathic secondary action
described by Hahnemann (Organon of medicine, paragraphs 59, 64, 69): (i) it appears only in susceptible
individuals, who present in their constitution symptoms similar to the pathogenetic effects of the drug; (ii) it
does not depend on the drug, repetition (magnitude) of doses or type of symptoms (disease); (iii) it appears
after the primary action of the drug (discontinuation or decrease of the doses), as an automatic manifestation
of the organism; (iv) it induces an organic state (symptoms) opposite and greater in intensity and/or frequency
than the primary action of the drug; (v) the magnitude of its effect is proportional to the intensity of the
primary action of the drug.
Use of modern drugs according to the principle of similitude ‘New homeopathic medicines’
In order to learn the healing properties of drugs to allow for the application of the principle of therapeutic
similitude, homeopathy employs the ‘proving of medicinal substances on healthy individuals’ or ‘homeopathic
pathogenetic trials (HPTs) as its model of pharmacological clinical research. HPTs can be compared to the
modern ‘phase I studies’ which takes into account all types of primary or direct actions, the so -called
pathogenetic effects or symptoms (mental, general or physical), awakened by drugs on the state of human
health. These very same pathogenetic effects are called by modern pharmacology as therapeutic, adverse or
side effects of the drugs.
Although Hahnemann laid down the ideal stipulations to carry out HPTs (Organon of medicine, paragraphs
105-145), the Homeopathic Materia Medica (compendium which brings together the primary or pathogenetic
effects of substances) is actually composed by a compilation of the signs and symptoms recorded along the
testing of thousands of drugs in both healthy and ill individuals, in ponderable (substances in raw state) and
diluted (dynamized medicines) doses. In this way, it comprises the pictures of artificial states of the disease
needed to apply the homeopathic therapeutic method.
To substantiate the validity of pathogenetic trials with ponderable doses and/or on ill individuals,
Hahnemann observed that the effects of experiments described by previous authors carried out with “large
doses of medicinal substances” on healthy (poisonings) and ill (therapeutic overdoses) individuals were very
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similar to his observations while testing the very same substances on himself and other healthy individuals
(Organon of medicine, paragraphs 110-112).
I saw, moreover, that the morbid lesions which previous authors had observed to result from medicinal
substances when taken into the stomach of healthy persons, either in large doses given by mistake or in order
to produce death in themselves or others, or under other circumstances, accorded very much with my own
observations when experimenting with the same substances on myself and other healthy individuals. These
authors give details of what occurred as histories of poisoning and as proofs of the pernicious effects of these
powerful substances, chiefly in order to warn others from their use; partly also for the sake of exalting their
own skill, when, under the use of the remedies they employed to combat these dangerous accidents, health
gradually returned; but partly also, when the persons so affected died under their treatment, in order to seek
their own justification in the dangerous character of these substances, which they then termed poisons. None
of these observers ever dreamed that the symptoms they recorded merely as proofs of the noxious and
poisonous character of these substances were sure revelations of the power of these drugs to extinguish
curatively similar symptoms occurring in natural disease, that these their pathogenetic phenomena were
intimations of their homoeopathic curative action, and that the only possible way to ascertain their medicinal
powers is to observe those changes of health medicines are capable of producing in the healthy organism; for
the pure, peculiar powers of medicines available for the cure of disease are to be learned neither by any
ingenious a priori speculations, nor by the smell, taste or appearance of the drugs, nor by their chemical
analysis, nor yet by the employment of several of them at one time in a mixture (prescription) in diseases; it
was never suspected that these histories of medicinal diseases would one day furnish the first rudiments of
the true, pure materia medica, which from the earliest times until now has consisted solely of false
conjectures and fictions of the imagination - that is to say, did not exist at all.” (Organon of medicine,
paragraph 110)
The agreement of my observations on the pure effects of medicines with these older ones - although they were
recorded without reference to any therapeutic object, - and the very concordance of these accounts with others
of the same kind by different authors must easily convince us that medicinal substances act in the morbid
changes they produce in the healthy human body according to fixed, eternal laws of nature, and by virtue of
these are enabled to produce certain, reliable disease symptoms each according to its own peculiar character”.
(Organon of medicine, paragraph 111)
In this regard, it is worth observing that the historical revisions carried out by Robert Ellis Dudgeon [35] and
Richard Hughes [36] show that most of the symptoms listed in the works of homeopathic materia medica
written by Hahnemann (Fragmenta de Viribus Medicamentorum Positivis, Materia Medica Pura and The
Chronic Diseases) arise from the use of medicines in ponderable (moderate-large) doses and on ill individuals.
According to Hughes [36], in 1805, Hahnemann published the pathogenetic studies of 27 remedies in
Fragmenta de Viribus Medicamentorum Positivis [37], which thus represents the first homeopathic materia
medica that he used in his clinical practice. The sources of the pathogenetic symptoms listed were his own
observations (of poisonings, therapeutic overdoses, self-experimentation and tests on other healthy
individuals) as well as the ones ‘by others’ and reported in the literature. In this context, ‘observations by
others’ (namely, reports of poisonings in healthy individuals and therapeutic overdoses in the ill) represent a
large fraction of most pathogenetic studies published in the six volumes of Materia Medica Pura [38], in which
only 13 of the 61 remedies do not present such kind of data. Still in Köthen, Hahnemann published between
1828-1830 the 4 volumes of the first edition of The Chronic Diseases [39], which introduced 17 new and 5
extended pathogenetic studies of remedies already published in Materia Medica Pura. With the only exception
of Kalium carbonicum and Natrum muriaticum - which were tested in potentiated doses (30cH) and in (2 and
3, respectively) healthy individuals - the remainder of medicines were tested in diversified potencies (e.g.
‘small portions of a grain’, 2nd and 3rd trituration, 6th and 30th potency) and on individuals suffering from
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chronic diseases. The second edition of The Chronic Diseases, published between 1830-1835, added 25
pathogenetic studies (13 new and 12 already published in Materia Medica Pura and extended) to the 22 listed
in the first edition. In both editions, the pathogenetic manifestations listed are adverse and side effects of
drugs prescribed to patients suffering from chronic diseases. Referring to the written “Examination of the
sources of the common materia medica”, cited as preamble to the second volume of the Materia Medica Pura,
Hughes stated explicitly: “Hahnemann’s own additions to the second issue of his work must be of th e same
character as his contributions to the first, i.e., they must be collateral effects of the drugs observed on the
patients to whom he gave them” [36].
Analogously, homeopathic treatment was also accomplished with ponderable (moderate-large) doses on the
grounds of the pathogenetic manifestations observed after the intake of ponderable doses by healthy
(poisonings) and ill (therapeutic overdoses) individuals. In work that inaugurates the homeopathy [2],
Hahnemann mentions the use of drugs of his time in the homeopathic treatment of numerous diseases and
epidemics (uterine colic with Matricaria chamomilla; autumnal dysentery with Arnica montana; painful
indurations of the lymph nodes with Conium maculatum; paralytic and spasmodic affections with Solanum
dulcamara; chronic hemorrhages, mania and seizures with Hyosciamus niger; tremors, fasciculations, cramps
and intermittent fevers with Ignatia amara; amaurosis, cataracts and opacities of the cornea with Anemona
pratensis, etc.), applying them according to the principle of similitude (‘adverse/side effects mentioned in
literature) and substantial doses. In The Lesser Writings [40], Hahnemann describes similar applications in
other epidemic diseases (remittent and scarlet fevers, typhus, cholera, etc). In 1799, during an epidemic of
scarlet fever [41] Hahnemann used for the first time diluted and agitated doses in order to decrease the
pathogenetic power of doses and thus avoid aggravation [42]. In 1814, during the treatment of typhus or
hospital fever [43], Hahnemann outlined the pharmacotechnique of potentization (serial dilutions and strong
agitation). The “theory of potentization” strictly speaking only appeared in 1827 [44], when Hahnemann
incorporated the processes of trituration and succussion in order to develop and exalt the “dynamic medicinal
powers of natural substances”.
In addition to the examples of classical homeopathic medicines that were derived in the past from
conventional drugs (Ammonium, Arsenic, Borax, Camphora, Chamomilla, Digitalis, Hydrastis, Mercurius,
Nux vomica, Opium, Sulphur, Valeriana, among others), some modern studies have used conventional drugs
in accordance with the curative rebound effect: contraceptive drugs used as inducers of rebound ovulation and
consequent pregnancy [45]; central nervous system stimulants used with beneficial effect on attention deficit
hyperactivity disorder (ADHD) [46]; among others.
Retracing classic homeopathy steps to conclude this research [47-52], we systematized the use of modern
conventional drugs according to the principle of therapeutic similitude. This proposal suggests stimulating the
curative rebound effect (paradoxical reaction) by employing conventional drugs that caused similar symptoms
(primary actions or pathogenetic effects) in healthy or ill individuals.
To make this proposal operative a Homeopathic Materia Medica of Modern Drugs grouping together all
primary (therapeutic, adverse and side) effects of drugs (described in The United States Pharmacopeia
Dispensing Information [53]) according to the traditional chapter scheme of the homeopathic
materia medica was needed. To facilitate the effective selection of an individualized medicine, which is the
basic premise for successful homeopathic treatment, the second stage involved the elabo ration of a
Homeopathic Repertory of Modern Drugs, where symptoms (primary or direct effects) and their corresponding
remedies are arranged as in the classical homeopathic repertories [49].
This research project is entitled New Homeopathic Medicines: use of modern drugs according to the principle
of similitude” and can be found in free online version at http://www.newhomeopathicmedicines.com.
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Paradoxical pharmacology
Therapeutic approach suggested by Richard A. Bond in 2001 [54,55], the ‘paradoxical pharmacology’ proposes
a strategy to treat chronic diseases using the paradoxical drug reactions, where the therapeutic effect is
derived from compensatory response, rather than the primary or direct drug effect. These paradoxical or
bidirectional drug reactions produce an outcome that is opposite to the outcome that would be expected from
the drug’s known effects. Such bidirectional reactions arise in a wide variety of drug classes, to a greater or
lesser frequency, in the same or different individuals and not related to the doses used. Although
incompletely understood, the clinical paradoxical effect occurs when conflicts arise at different levels in self -
regulating biological systems, as complexity increases from subcellular components (channels, enzymes,
receptors, transporters, organelles, etc.) to cells, tissues, organs, and the whole individual [56-60].
As a possible general hypothesis to explain the functioning of the paradoxical pharmacology is the “difference
between the chronic versus the acute effect of drugs”. Reiterating that the acute and chronic responses to
drugs often differ substantially and, indeed, are often opposite in nature, Bond [54] warns that most
contraindications for drugs are predicted on the basis of the false assumption that the chronic effect will be
simply a more prolonged version of the acute effect, in view of the fact that experiments that analyze chronic
effects are not performed, in part, because we cannot see how to get by the initial contraindications. Certain
drugs also lose effectiveness with time (tolerance, tachyphylaxis or desensitization) as is the case of the
analgesic effects of opioids that wane with repeated administration for weeks or months.
Occurring at any physiological system, with various drug classes and without changing doses, the
mechanisms of such paradoxical and bidirectional effects include different actions at the same receptor, owing
to changes with time and downstream effects (e.g., β-blockers with intrinsic sympathomimetic activity);
stereochemical effects (e.g., salbutamol); multiple receptor targets with or without associated temporal effects
(e.g., procainamide); antibody-mediated reactions (e.g., heparin-induced thromboembolism); pharmacokinetic
competing compartment effects (e.g., bicarbonate); disruption and non-linear effects in oscillating systems
(e.g., dopaminergic agents), systemic overcompensation (e.g., antiretroviral therapy and immune
reconstitution inflammatory syndrome), and other higher-level feedback mechanisms (e.g., digoxin) and
feedback response loops at multiple levels (e.g., isotretinoin-associated acne fulminans), among others [60].
Some examples of paradoxical and bidirectional drug effects are illustrated in different pharmaceutical or
systems classes: immunomodulators (e.g., systemic glucocorticosteroids, TNFα antagonists), antineoplastic
agents and carcinogens (e.g., chemotherapy, radiotherapy, arsenic), antidysrhythmic drugs (e.g.,
procainamide, isoprenaline), antihypertensive drugs (e.g., methyldopa, clonidine, guanabenz, moxonidine,
thiazides), vasodilators (e.g., nitrates), drugs for congestive heart failure (e.g., β-blockers, ACE inhibitors,
angiotensin II receptor antagonists, hydralazine), lipid-modifying drugs (e.g., fibrates, ezetimibe), inotropes
and chronotropes (e.g., isoprenaline, epinephrine, β-blockers and calcium channel blockers), vasoconstrictors
(e.g., ergot alkaloids, vasopressin), anaesthetics (e.g., sevoflurane, ketamine, propofol), antiepileptic drugs
(e.g., benzodiazepines, barbiturates, hydantoins), hypnosedatives (e.g., anticholinergics, antihistamines,
antispasmodics, barbiturates, benzodiazepines, bromides, chloral hydrate, ethanol, opioids), psychotropic
drugs (e.g., antidepressants, antipsychotics), peripheral nervous system drugs (e.g., acetylcholinesterase
inhibitors, capsaicin), antidyskinetic drugs (e.g., dopaminergic agents), acid-base agents (e.g., sodium lactate,
bicarbonate), bone metabolism agents (e.g., parathyroid hormone, bisphosphonates), electrolytes (e.g.,
hypertonic saline, magnaesium hydroxide), glycaemic agents (e.g., insulin, antiglycaemics), steroid hormones
(e.g., dexamethasone suppression), thyroid agents (e.g., iodine, lithium), antihyperuricaemics (e.g., xanthine
oxidase inhibitors, urate oxidases), gastrointestinal agents (e.g., opioids, cholecystokinin or ceruletide),
haematological agents (e.g., erythropoietin, vitamin K antagonists, platelet adenosine diphosphate receptor
antagonists), respiratory agents (e.g., short- and long-acting β2-agonists, oxygen), skin agents (e.g., high-
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intensity long-wave ultraviolet light and 8-methoxypsoralen, histamine1-receptor antagonists), among others
[60].
In terms of ‘doses’, Smith et al [60], claim that “clinical bidirectional and paradoxical effects are not
necessarily of explicit dose responsiveness”, and “do not necessarily occur at doses different from those
producing anticipated effects”: “they may occur at entirely appropriate doses or regardless of dose, in intended
or unintended target systems”, and “they may arise in the same patient at the same doses in different
circumstances (known or unknown physiological or pathological states in time)”. In view of these aspects (no
relationship with doses), the authors ruled out the mechanism of hormesis (biphasic dose-response curve,
with beneficial or stimulatory effects at low doses and adverse or inhibitory effects at high doses) [61] as an
explanation for the phenomenon.
As in various physiological systems, in which an external primary stress can result in a secondary
compensatory benefit, a ‘pharmacologic stress’ can be used therapeutically to gain long -term benefit:
“exacerbating a disease (acute or short-term effect) can make use of the body’s compensatory and redundant
mechanisms to achieve a beneficial long-term response (chronic effect)”. Like other authors [56], Bond warns
that dosing will be a serious concern in this strategy, proposing as a general rule “start at a very low dose and
increase the dose over a period of weeks” [54].
Some examples of prescription of drugs that cause similar effects to those which are to be treated are cited in
the literature in which paradoxical and bidirectional responses may be harnessed for benefit. Congestive
heart failure (CHF) is a disease of impaired cardiac contractility usually as a result of ischemic damage to the
heart muscle, and the acute use of β-adrenoceptor agonists, increasing cardiac contractility, improved
hemodynamic and decreased symptoms of CHF.
However, their chronic use resulted in an increase in mortality. On the contrary, while the short-term use of
β-adrenoceptor antagonists (β-blockers: carvedilol, metoprolol) exacerbate the CHF (worsening of disease), the
long-term use results in an increase in cardiac contractility and a decrease in mortality [54,59,60,62]. The
same is observed with calcium channel blockers [63].
Analogously, β2-adrenoceptor agonists are the most potent bronchodilators and play a major role in every
stage of asthma management; however, as previously mentioned, their chronic use is associated with
irreversible and fatal paradoxical bronchospasm (asthma-related deaths). On the other hand, while the short-
term use of β-adrenoceptor antagonists -blockers) produces bronchoconstriction and worsening asthma, the
long-term use produces bronchodilation and a positive outcome in asthmatics [54,59,64,65].
Additional examples include the use of methylphenidate (central nervous system stimulant) in the treatment
of hyperactivity disorders, and the use of serotonin 5-HT1A receptor agonist (mediator of hyperalgesia) to
produce analgesia [59]. Thiazides have long provided paradoxical antidiuretic benefit in the treatment of
diabetes insipidus, reducing polyuria and increasing urine osmolality [66].
Arsenic trioxide (As2O3), a major carcinogenic agent that is employed by homeopathy for more than two
centuries to treat various types of cancer (as initially described), have been used paradoxically as a promising
anticancer agent (e.g., in acute promyelocytic leukemia) [67,68], among others [60].
Non-pharmacological examples of short-term detrimental behaviors (exercising, dieting, saving money,
disciplining education, among others) for a long-term benefit are also described: exemplifying, exercises that
expose the heart to brief episodes of ischemia protect the myocardium from cell death produced by subsequent
prolonged ischemic episodes [54,59].
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Discussion
Despite the different terminologies consequent to scientific knowledge of different times, descriptions and
properties of ‘secondary action’ or ‘vital reaction’ of the homeopathic model present similar aspects to the
‘rebound effect’ or ‘paradoxical reaction’ of modern pharmacology, indicating they are the same phenomena.
Both phenomena are manifestations of the secondary effects and opposite of the organism to the primary
effects of the drugs, indicating a homeostatic response of the organism to return to initial balance modified by
the inducing agent. Demonstrating its universal character, the rebound effect (paradoxical reaction) can occur
with all classes of drugs with contrary (enantiopathic) action to the symptoms of diseases and in different
individuals, although it manifests itself in a minority of individuals in view of its idiosyncratic character.
By definition, the manifestation of the rebound effect always reaches an intensity and/or frequency greater
than the disturbance initially suppressed by the drug, causing a worsening of the natural disease. Described
in detail in studies about the rebound effect, the ‘magnitude’ of this paradoxical phenomenon can cause
serious and fatal iatrogenic diseases on users of various classes of modern drugs . In view of this magnitude,
the curative use of the rebound effect (paradoxical reaction) has great therapeutic potential.
Despite not being valued in recent studies of ‘paradoxical pharmacology’, it is worth mentioning that this
secondary action of the organism occurs in the absence of primary action of the drug. In studies on the
rebound effect, this property is restricted to ‘half life’ time of each drug, which varies around 7-14 days after
discontinuation of drugs with short-medium half-life; in drugs of deposit (bisphosphonates, for example) this
time is longer. However, other aspects of extreme importance must also be observed: even during treatment,
some studies show the manifestation of the rebound effect, which can be justified by the gradual decrease of
dosage or temporary discontinuation (therapeutic failure). According to individual idiosyncrasy, small changes
in drug serum concentration can trigger the paradoxical phenomenon. Still on this property, the phenomenon
of ‘tolerance’ (tachyphylaxis or desensitization) should also be valued: as previously mentioned, even during
the treatment the adaptation of the organism to the drug can occur with the loss of primary pharmacological
action, allowing the manifestation of secondary or paradoxical reaction of the organism.
As described in paradoxical pharmacology [60], the awakening of paradoxical reaction of the organism is
independent of the doses of the drugs, property also observed in the homeopathic model and in the studies on
the rebound effect (unlike the hormetic mechanisms) [61,69-74]. However, if drugs that cause similar effects
to those which are to be treated are prescribed, their strong doses can cause worsening of natural diseases,
with disastrous consequences. As well as the homeopathic model uses ultrahigh-diluted doses of medicines to
arouse the curative secondary action of the organism safely (avoiding the ‘homeopathic aggravations’), Bond
[54] proposes as a general rule “start at a very low dose and increase the dose over a period of weeks”.
Unlike strong doses that awaken a curative paradoxical reaction in a lot of individuals (with the damages of
the side effects and the initial aggravation of the diseases), ultrahigh-diluted or very low doses (although they
are safe for your smaller pathogenetic power) arouse the curative secondary action only in individuals with
idiosyncratic characteristics of the drug (importance of the ‘individualized medicine’ in accordance with the
totality of characteristic symptoms). These are aspects that should be taken into consideration in the choice of
the drug and the dose.
On the other hand, studying and describing the various physiological mechanisms involved in the
manifestation of the rebound effect or paradoxical reaction of the organism, the ‘paradoxical pharmacology’
brings important subsidies to elucidate the modus operandi of the homeopathic vital reaction, general term
used to describe the opposite and secondary action of the organism (after cease the primary action of the drug)
in order to maintain the internal homeostasis (“life-preserving power”, according to Hahnemann).
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Conclusion
A great number of iatrogenic diseases could be avoided if the health professionals were elucidated about the
homeostatic maintenance controlled through the rebound effect or paradoxical reaction of the organism,
preventing the worsening of clinical functions with the slow and gradual discontinuation of the drugs used
according to the principle of the contraries [12,15]. Although they are not included in the conventional adverse
events for drugs, “drug discontinuation effects are part of the pharmacology of a drug” [65], and should be
routinely incorporated into the teaching of modern pharmacology.
Describing the sad results of the indiscriminate antipathic or palliative employment of drugs (Organon of
medicine, paragraphs 59-61), Hahnemann alerts to the possible risks produced by secondary action (rebound
effect) of the organism, validating the principle of similitude through the deductive logic “modus tollens” or
“indirect proof”:
If these ill-effects are produced, as may very naturally be expected from the antipathic employment of
medicines, the ordinary physician imagines he can get over the difficulty by giving, at each renewed
aggravation, a stronger dose of the remedy, whereby an equally transient suppression is effected; and as there
then is a still greater necessity for giving ever - increasing quantities of the palliative there ensues either
another more serious disease or frequently even danger to life and death itself, but never a cure of a disease of
considerable or of long standing”. (Organon of medicine, paragraph 60)
Since 1997, we have grounded scientifically the ‘old’, ‘classic’ or ‘traditional’ similia principle, that was
founded by Hahnemann on ‘symptom similarity’ (Organon, paragraphs 22-70), confirming the principle of
similitude as ‘natural law’ through the continuous study of modern reports of increased iatrogenic events after
withdrawal of enantiopathic drugs and demonstrating the importance of the rebound (paradoxical) symptoms
in promoting deep alterations in the organic balance, although it was deemed ‘unviable’ and ‘non-
scientific’ by other authors at the time:
“The old principle of similarity was formulated as a general ‘law’ on the basis of empirical evidence and
analogical reasoning, but this kind of formulation does not allow any progress in the search for the possible
mechanism of the alleged therapeutic effects. […] The last question is whether these concepts can be extended
to the ‘classic’ similia principle that was founded on ‘symptom similarity’. This is the most controversial point
because the analysis of symptoms does not appear to be as ‘scientific’ as the objective measurement of some
physiological or biochemical parameter. The use of symptoms as the basis for the choice of remedy appears to
be in contradiction with modern scientific medicine, which demands explanations at the biochemical and
molecular level”. [74]
Using these rebound symptoms in a curative way, the homeopathic (paradoxical) pharmacology stimulates
the body to react against their own diseases.
As well as suggested by the spreaders of the principle of therapeutic similitude for more than two centuries
[48], Bond and Giles encourage the scientists and researchers to examine the paradoxical phenomenon
systematically, changing the dogma of current treatment and incorporating new approaches to the modern
therapeutic arsenal:
The identification of the phenomena of temporal differences in the effects of both agonists and antagonists in
numerous drug classes has, at first observation, seemed extremely paradoxical. However, as scientists, our
natural inclination is to ask the question ‘why?’. Over the coming years the mechanistic basis for such
behavior will undoubtedly be revealed, and the paradox will be no more. […] Nevertheless for those of us who
have felt compelled to challenge dogma of current treatment paradigms because we observed paradoxical
behavior, the path has been long and challenging. Seemingly ‘simple’ explanations of mechanism of action of a
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particular drug class become turned on their head, and obtaining funding, and acceptance of paradigm-
shifting ideas by peers, takes many years”.[59]
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Licensed to GIRI
Support: authors declare that this study received no funding
Conflict of interest: authors declare there is no conflict of interest
Received: April 11th, 2014; Revised: November 26th , 2014; Published: December 20th, 2014.
Correspondence author: Marcus Zulian Teixeira, mzulian@usp.br, www.fm.usp.br/homeopatia, www.homeozulian.med.br.
How to cite this article: Teixeira MZ. ‘Paradoxical pharmacology’: therapeutic strategy used by the ‘homeopathic
pharmacology’ for more than two centuries. Int J High Dilution Res [online]. 2014 [cited YYYY Month dd]; 13(49): 207-
226. Available from: http://www.feg.unesp.br/~ojs/index.php/ijhdr/article/view/714/740
... In other words, using drugs which cause adverse events similar to the manifestations of disease to treat them homeopathically. This means employing the rebound effect (paradoxical reaction) with curative intention [37][38][39][40][41][42][43][44][45][46]; results are promising and indications countless. An example is provided by the use of potentized estrogen for treatment of endometriosis-related pelvic pain [44][45][46]. ...
... Reference sources were studies and reviews on the rebound effect we published since 1998 [7][8][9][10][11][12][13][14][15][16][17][18][19][20][37][38][39][40][41][42][43][44][45][46]. The data were updated through a search of recent studies included in database PubMed using keywords 'rebound', 'withdrawal', 'paradoxical', 'acetylsalicylic acid', 'anti-inflammatory', 'bronchodilator', 'antidepressant', 'statin', 'proton pump inhibitor', 'bisphosphonate', 'biological therapy' and 'immunomodulatory drug'. ...
... The data were updated through a search of recent studies included in database PubMed using keywords 'rebound', 'withdrawal', 'paradoxical', 'acetylsalicylic acid', 'anti-inflammatory', 'bronchodilator', 'antidepressant', 'statin', 'proton pump inhibitor', 'bisphosphonate', 'biological therapy' and 'immunomodulatory drug'. We also describe suggestions for use of modern drugs according to the therapeutic similitude principle [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46]. This is, by applying the rebound effect (paradoxical reaction) with curative intention; examples from present-day clinical practice are provided. ...
Article
Full-text available
Introduction: Homeopathy employs the so-called ‘principle of similars’ as therapeutic method, which consists in administering medicines that cause certain symptoms in healthy individuals to treat similar symptoms in sick individuals (similia similibus curantur)to arouse a secondary and healing reaction by the body against its own disorders. This secondary (vital, homeostatic or paradoxical) reaction of the body is based on the ‘rebound effect’ of modern drugs, a type of adverse event that occurs following discontinuation of several classes of drugs prescribed according to the ‘principle of contraries’ (contraria contrariis curantur). Aim: The present review sought to scientifically substantiate the homeopathic healing principle vis-à-vis experimental and clinical pharmacology through a systematic study of the rebound effect of modern drugs or paradoxical reaction of the body. Methods: Employing as reference the studies and revisions on the subject that we have published since 1998, we updated the data adding recent studies cited in database PubMed. Results: The rebound effect occurs after discontinuation of several classes of drugs with contrary action to the symptoms of diseases, exacerbating them to levels above the ones present before treatment. Regardless of disease, drug, dose and duration of treatment, the rebound phenomenon manifests in a small proportion of susceptible individuals. Following the homeopathic premises, modern drugs might also be used according to the principle of therapeutic similitude, thus employing the rebound effect (paradoxical reaction) in a curative manner. Conclusions: Evidenced in hundreds of studies that attest to the similarity of concepts and manifestations, the rebound effect of modern drugs scientifically substantiates the principle of homeopathic cure. Although the rebound phenomenon is an adverse event studied by modern pharmacology, it is not known by healthcare professionals, thus depriving doctors of knowledge indispensable for a safe management of drugs.
... Ampliando esse corpo de evidências, expoentes da farmacologia moderna vêm sugerindo, na última década, uma estratégia terapêutica intitulada 'farmacologia paradoxal', semelhante à propagada pelo modelo homeopático há mais de 2 séculos, propondo o emprego de drogas convencionais que causam uma exacerbação da doença em curto prazo para tratar FUNDAMENTAÇÃO CIENTÍFICA DO PRINCÍPIO DE CURA HOMEOPÁTICO NA FARMACOLOGIA MODERNA esta mesma doença em longo prazo [24][25][26][27][28][29][30][31][32][33][34][35][36]. De forma análoga, desde o início de nossos estudos [7][8][9], vimos propondo empregar os fármacos modernos segundo o princípio da similitude terapêutica, sugerindo utilizar as drogas que causam eventos adversos similares às manifestações das doenças para tratá-las homeopaticamente, utilizando o efeito rebote (reação paradoxal) de forma curativa [37][38][39][40][41][42][43], com resultados animadores e inúmeras indicações [44][45][46]. Ilustramos essa tese com a aplicação de estrogênio dinamizado para o tratamento da dor pélvica associada à endometriose (vide artigo específico neste mesmo dossiê). ...
... Empregando como fonte de referência os estudos e revisões sobre o efeito rebote que vimos publicando desde 1998 [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][34][35][36][37][38][39][40][41][42][43], atualizamos os dados com trabalhos recentes citados na base de dados PubMed através de pesquisa com as palavras-chave 'rebound', 'withdrawal', 'paradoxical', 'acetylsalicylic acid', 'anti--inflammatory', 'bronchodilator', 'antidepressant', 'statin', 'proton pump inhibitor', 'bisphosphonate', 'biological therapy' e 'immunomodulatory drug'. Descrevemos também as propostas que sugerem o uso dos fármacos modernos segundo o princípio da similitude terapêutica [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46], empregando o efeito rebote (reação paradoxal) de forma curativa, com exemplos na prática clínica atual. ...
... Empregando como fonte de referência os estudos e revisões sobre o efeito rebote que vimos publicando desde 1998 [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][34][35][36][37][38][39][40][41][42][43], atualizamos os dados com trabalhos recentes citados na base de dados PubMed através de pesquisa com as palavras-chave 'rebound', 'withdrawal', 'paradoxical', 'acetylsalicylic acid', 'anti--inflammatory', 'bronchodilator', 'antidepressant', 'statin', 'proton pump inhibitor', 'bisphosphonate', 'biological therapy' e 'immunomodulatory drug'. Descrevemos também as propostas que sugerem o uso dos fármacos modernos segundo o princípio da similitude terapêutica [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46], empregando o efeito rebote (reação paradoxal) de forma curativa, com exemplos na prática clínica atual. ...
Article
Full-text available
Resumo Introdução: O modelo homeopático de tratamento utiliza o ‘princípio dos semelhantes’ como método terapêutico, administrando medicamentos que causam determinados sintomas em indivíduos sadios para tratar sintomas semelhantes em indivíduos doentes (similia similibus curantur), com o intuito de despertar uma reação secundária e curativa do organismo contra os seus próprios distúrbios. Essa reação secundária (vital, homeostática ou paradoxal) do organismo está embasada no ‘efeito rebote’ dos fármacos modernos, evento adverso observado após a descontinuação de diversas classes de drogas que utilizam o ‘princípio dos contrários’ (contraria contrariis curantur) como método terapêutico. Objetivo: Esta revisão visa fundamentar cientificamente o princípio de cura homeopático perante a farmacologia clínica e experimental, através do estudo sistemático do efeito rebote dos fármacos modernos ou reação paradoxal do organismo. Métodos: Empregando como fonte de referência os estudos e revisões sobre o tema que vimos publicando desde 1998, atualizamos os dados acrescentando pesquisas recentes citadas na base de dados PubMed. Resultados: O efeito rebote ocorre após a descontinuação de inúmeras classes de fármacos com ação terapêutica contrária aos sintomas das doenças, exacerbando-os a níveis superiores aos anteriores do tratamento. Independente da doença, da droga, da dose e da duração do tratamento, o fenômeno rebote se manifesta numa pequena proporção de indivíduos suscetíveis. Seguindo as premissas homeopáticas, os fármacos modernos também podem ser utilizados segundo o princípio da similitude terapêutica, empregando o efeito rebote (reação paradoxal) de forma curativa Conclusões: Evidenciado em centenas de estudos que atestam a similaridade de conceitos e manifestações, o efeito rebote dos fármacos modernos fundamenta cientificamente o princípio de cura homeopático. Embora o fenômeno rebote seja um evento adverso estudado pela farmacologia moderna, ele não é conhecido pelos profissionais da saúde, privando a classe médica de um saber indispensável ao manejo seguro dos fármacos. Abstract Introduction: Homeopathy employs the so-called ‘principle of similars’ as therapeutic method, which consists in administering medicines that cause certain symptoms in healthy individuals to treat similar symptoms in sick individuals (similia similibus curantur)to arouse a secondary and healing reaction by the body against its own disorders. This secondary (vital, homeostatic or paradoxical) reaction of the body is based on the ‘rebound effect’ of modern drugs, a type of adverse event that occurs following discontinuation of several classes of drugs prescribed according to the ‘principle of contraries’ (contraria contrariis curantur). Aim: The present review sought to scientifically substantiate the homeopathic healing principle vis-à-vis experimental and clinical pharmacology through a systematic study of the rebound effect of modern drugs or paradoxical reaction of the body. Methods: Employing as reference the studies and revisions on the subject that we have published since 1998, we updated the data adding recent studies cited in database PubMed. Results: The rebound effect occurs after discontinuation of several classes of drugs with contrary action to the symptoms of diseases, exacerbating them to levels above the ones present before treatment. Regardless of disease, drug, dose and duration of treatment, the rebound phenomenon manifests in a small proportion of susceptible individuals. Following the homeopathic premises, modern drugs might also be used according to the principle of therapeutic similitude, thus employing the rebound effect (paradoxical reaction) in a curative manner. Conclusions: Evidenced in hundreds of studies that attest to the similarity of concepts and manifestations, the rebound effect of modern drugs scientifically substantiates the principle of homeopathic cure. Although the rebound phenomenon is an adverse event studied by modern pharmacology, it is not known by healthcare professionals, thus depriving doctors of knowledge indispensable for a safe management of drugs.
... Ampliando esse corpo de evidências, expoentes da farmacologia moderna vêm sugerindo, na última década, uma estratégia terapêutica intitulada 'farmacologia paradoxal', semelhante à propagada pelo modelo homeopático há mais de 2 séculos, propondo o emprego de drogas convencionais que causam uma exacerbação da doença em curto prazo para tratar esta mesma doença em longo prazo [24][25][26][27][28][29][30][31][32][33][34][35][36]. De forma análoga, desde o início de nossos estudos [7][8][9], vimos propondo empregar os fármacos modernos segundo o princípio da similitude terapêutica, sugerindo utilizar as drogas que causam eventos adversos similares às manifestações das doenças para tratá-las homeopaticamente, utilizando o efeito rebote (reação paradoxal) de forma curativa [37][38][39][40][41][42][43], com resultados animadores e inúmeras indicações [44][45][46]. Ilustramos essa tese com a aplicação de estrogênio dinamizado para o tratamento da dor pélvica associada à endometriose (vide artigo específico neste mesmo dossiê). ...
... Empregando como fonte de referência os estudos e revisões sobre o efeito rebote que vimos publicando desde 1998 [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][34][35][36][37][38][39][40][41][42][43], atualizamos os dados com trabalhos recentes citados na base de dados PubMed através de pesquisa com as palavras-chave 'rebound', 'withdrawal', 'paradoxical', 'acetylsalicylic acid', 'anti-inflammatory', 'bronchodilator', 'antidepressant', 'statin', 'proton pump inhibitor', 'bisphosphonate', 'biological therapy' e 'immunomodulatory drug'. Descrevemos também as propostas que sugerem o uso dos fármacos modernos segundo o princípio da similitude terapêutica [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46], empregando o efeito rebote (reação paradoxal) de forma curativa, com exemplos na prática clínica atual. ...
... Empregando como fonte de referência os estudos e revisões sobre o efeito rebote que vimos publicando desde 1998 [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][34][35][36][37][38][39][40][41][42][43], atualizamos os dados com trabalhos recentes citados na base de dados PubMed através de pesquisa com as palavras-chave 'rebound', 'withdrawal', 'paradoxical', 'acetylsalicylic acid', 'anti-inflammatory', 'bronchodilator', 'antidepressant', 'statin', 'proton pump inhibitor', 'bisphosphonate', 'biological therapy' e 'immunomodulatory drug'. Descrevemos também as propostas que sugerem o uso dos fármacos modernos segundo o princípio da similitude terapêutica [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46], empregando o efeito rebote (reação paradoxal) de forma curativa, com exemplos na prática clínica atual. ...
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Resumo Introdução: O modelo homeopático de tratamento utiliza o ‘princípio dos semelhantes’ como método terapêutico, administrando medicamentos que causam determinados sintomas em indivíduos sadios para tratar sintomas semelhantes em indivíduos doentes (similia similibus curantur), com o intuito de despertar uma reação secundária e curativa do organismo contra os seus próprios distúrbios. Essa reação secundária (vital, homeostática ou paradoxal) do organismo está embasada no ‘efeito rebote’ dos fármacos modernos, evento adverso observado após a descontinuação de diversas classes de drogas que utilizam o ‘princípio dos contrários’ (contraria contrariis curantur) como método terapêutico. Objetivo: Esta revisão visa fundamentar cientificamente o princípio de cura homeopático perante a farmacologia clínica e experimental, através do estudo sistemático do efeito rebote dos fármacos modernos ou reação paradoxal do organismo. Métodos: Empregando como fonte de referência os estudos e revisões sobre o tema que vimos publicando desde 1998, atualizamos os dados acrescentando pesquisas recentes citadas na base de dados PubMed. Resultados: O efeito rebote ocorre após a descontinuação de inúmeras classes de fármacos com ação terapêutica contrária aos sintomas das doenças, exacerbando-os a níveis superiores aos anteriores do tratamento. Independente da doença, da droga, da dose e da duração do tratamento, o fenômeno rebote se manifesta numa pequena proporção de indivíduos suscetíveis. Seguindo as premissas homeopáticas, os fármacos modernos também podem ser utilizados segundo o princípio da similitude terapêutica, empregando o efeito rebote (reação paradoxal) de forma curativa Conclusões: Evidenciado em centenas de estudos que atestam a similaridade de conceitos e manifestações, o efeito rebote dos fármacos modernos fundamenta cientificamente o princípio de cura homeopático. Embora o fenômeno rebote seja um evento adverso estudado pela farmacologia moderna, ele não é conhecido pelos profissionais da saúde, privando a classe médica de um saber indispensável ao manejo seguro dos fármacos. Abstract Introduction: Homeopathy employs the so-called ‘principle of similars’ as therapeutic method, which consists in administering medicines that cause certain symptoms in healthy individuals to treat similar symptoms in sick individuals (similia similibus curantur)to arouse a secondary and healing reaction by the body against its own disorders. This secondary (vital, homeostatic or paradoxical) reaction of the body is based on the ‘rebound effect’ of modern drugs, a type of adverse event that occurs following discontinuation of several classes of drugs prescribed according to the ‘principle of contraries’ (contraria contrariis curantur). Aim: The present review sought to scientifically substantiate the homeopathic healing principle vis-à-vis experimental and clinical pharmacology through a systematic study of the rebound effect of modern drugs or paradoxical reaction of the body. Methods: Employing as reference the studies and revisions on the subject that we have published since 1998, we updated the data adding recent studies cited in database PubMed. Results: The rebound effect occurs after discontinuation of several classes of drugs with contrary action to the symptoms of diseases, exacerbating them to levels above the ones present before treatment. Regardless of disease, drug, dose and duration of treatment, the rebound phenomenon manifests in a small proportion of susceptible individuals. Following the homeopathic premises, modern drugs might also be used according to the principle of therapeutic similitude, thus employing the rebound effect (paradoxical reaction) in a curative manner. Conclusions: Evidenced in hundreds of studies that attest to the similarity of concepts and manifestations, the rebound effect of modern drugs scientifically substantiates the principle of homeopathic cure. Although the rebound phenomenon is an adverse event studied by modern pharmacology, it is not known by healthcare professionals, thus depriving doctors of knowledge indispensable for a safe management of drugs. //
... Primary action (therapeutic effect) of modern drugs followed by secondary action and opposite (rebound effect or paradoxical reaction) of the body. suggesting the homeopathic use of modern drugs employing the rebound effect in a therapeutic way, [16][17][18][19][20][21][22] proposing to prescribe drugs, in dynamized doses, which present a similar set of signs and symptoms in their primary action to the manifestations of sick individuals. ...
... Such new homeopathic medicines cover signs and symptoms absent in the classical homeopathic pathogenetic trials and will allow treating countless modern disorders, diseases, and syndromes with homeopathy. [16][17][18][19][20][21][22] ...
... Since 2003, we advocate the use of the rebound effect of modern drugs with curative intent [8][9][10][11][12][13] . For this purpose, patients are given drugs in ultra-diluted doses, which caused a similar set of adverse events aiming at stimulating the homeostatic reaction of the body against its own disorders. ...
... The proposal entitled "New Homeopathic Medicines: use of modern drugs according to the principle of similitude" [8][9][10][11][12][13] was described and systematized in a database composed of three distinct works: ...
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Homeopathy employs the so-called ‘principle of similars’ as therapeutic method - which consists in administering medicines that cause certain primary symptoms in healthy individuals to treat similar symptoms in sick individuals (similia similibus curantur) – in order to induce a secondary and healing reaction of the body against its own disorders. This secondary (vital, homeostatic or paradoxical) reaction of the body is based on the ‘rebound effect’ of modern drugs, a type of adverse event that occurs following discontinuation of several classes of drugs prescribed according to the ‘principle of contraries’ (contraria contrariis curantur). Since 1998, we have been bridging the gap between homeopathic and conventional pharmacology through the systematic study of the rebound effect of modern drugs, scientifically confirming the homeopathic postulate (primary action of the drug followed by secondary and opposite reaction of the organism) and the homeopathic healing principle. Following the homeopathic premises, conventional drugs can be employed according to the therapeutic similitude principle provided they cause primary symptoms (therapeutic, adverse and collateral effects) similar to the symptomatic manifestations of sick individuals. Since 2003, we are proposing the use of the rebound effect of modern drugs in a curative manner, administering to patients, in ultra-diluted doses, the drugs that cause a set of similar adverse events. Entitled “New Homeopathic Medicines: use of modern drugs according to the principle of similitude”, this proposal are been made available in a database composed of three free-access bilingual digital books.
... Assuming that the principle of therapeutic similitude is a "natural law of cure," since 2003, we have been suggesting the homeopathic use of modern drugs employing the rebound effect in a therapeutic way [15][16][17][18][19] , proposing to administer, in ultra-diluted doses, drugs that present, in their primary action, a set of signs and symptoms similar to the manifestations of sick individuals. ...
Article
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When Samuel Hahnemann systematized homeopathy and the effects of drugs on the state of human health, he described the primary action of drugs and the following secondary and opposite reaction of the body. Seeking to apply this secondary action or vital reaction of the body as therapeutic method, he postulated the “principle of cure by similars”, i.e. the prescription to ill individuals of drugs that cause similar symptoms in the healthy (similia similibus curentur). In modern pharmacology, this secondary action (vital reaction) of the body is known as rebound effect or paradoxical reaction. It has been observed after discontinuation of several classes of palliative drugs, namely those that act according to the “principle of cure by contraries” (contraria contrariis curentur). Since 1998, we have been bridging the gap between homeopathic and conventional pharmacology through the systematic study of rebound effect of modern drugs, scientifically confirming the homeopathic postulate (primary action of the drug followed by secondary and opposite reaction of the body) and the homeopathic healing principle. Following the homeopathic premises, conventional drugs can be employed according to the principle of therapeutic similitude provided they cause primary symptoms (therapeutic, adverse and side effects) similar to the symptomatic manifestations of sick individuals. Since 2003, we are proposing the use of the rebound effect of modern drugs in a curative manner, administering to patients, in ultra-diluted doses, drugs that cause a set of similar adverse events. Since 2021, these two decades of studies are made available in three free-access digital books.
... Basados en la premisa de Hahnemann, desde 2003 hemos propuesto sistemáticamente emplear los fármacos modernos según el principio homeopático de curación. Este proyecto está detalladamente descrito en varios artículos publicados en diversos periódicos científicos [20][21][22][23][24][25][26][27] , en los que también se indican las bases de los principios homeopáticos. ...
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Homeopathy is based on the law of similarity, which tells us that the use of drugs that produce symptoms similar to those of diseases stimulates the body’s reaction to relieve their own ailments. Homeopathic treatment can use all kinds of substances (natural or synthetic, in weight or infinitesimal doses) provided that this principle is respected. Based on the above, since 2003 we have proposed the use of modern drugs according to the homeopathic healing principle both through research and publications in scientific journals, and the development of a Homeopathic Materia Medica Modern Drugs, which includes the primary effects of 1,250 allopathic drugs, and a Homeopathic Repertory of Modern Drugs. These efforts are part of the New Homeopathic Medicine project: Use of Modern Drugs according to the Principle of Similarity, which can be consulted free of charge, in Portuguese and English, on the website www.newhomeopathicmedicines.com. Now, the clinical and scientific validity of this proposal has begun with the performance of a clinical trial to evaluate the efficacy and safety of energized estrogen in the homeopathic treatment of pelvic pain associated with endometriosis. The result has been positive, but it requires doctors, pharmacists and researchers to join this initiative to strengthen it and boost its growth.//////////// Resumen La Homeopatía se fundamenta en la ley de semejanza, la cual nos dice que el empleo de medicamentos que producen síntomas similares a los de las enfermedades estimula la reacción del organismo para aliviar sus propias dolencias. El tratamiento homeopático puede emplear toda clase de sustancias (naturales o sintéticas, en dosis ponderales o infinitesimales) siempre que se respete dicho principio. Con base en lo anterior, desde 2003 hemos propuesto el uso de fármacos modernos según el principio homeopático de curación tanto a través de investigaciones y publicaciones en revistas científicas, como de la elaboración de una Materia Médica Homeopática de Fármacos Modernos, que incluye los efectos primarios de 1,250 fármacos alopáticos, y un Repertorio Homeopático de Fármacos Modernos. Estos esfuerzos forman parte del proyecto Nuevos Medicamentos Homeopáticos: Uso de Fármacos Modernos según el Principio de Semejanza, que puede consultarse de manera gratuita, en portugués e inglés, en el sitio web www.nuevosmedicamentoshomeopaticos. com. Ahora, la validez clínica y científica de esta propuesta ha comenzado con la realización de un ensayo clínico para evaluar la eficacia y la seguridad del estrógeno dinamizado en el tratamiento homeopático del dolor pélvico asociado a la endometriosis. El resultado ha sido positivo, pero se requiere que médicos, farmacéuticos e investigadores se sumen a esta iniciativa para robustecerla e impulsar su crecimiento.
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Following the pattern of traditional homeopathy, this work proposes to employ modern drugs according to the principle of therapeutic similitude, stimulating the healing rebound effect (vital reaction) of the organism through the administration of substances (in infinitesimal doses) that caused similar symptoms in healthy human. Is worth emphasizing that the pathogenetic effects (primary actions) of classical homeopathic medicines correspond to the therapeutic, adverse and side effects of conventional drugs, which should be similar to totality of the symptoms of the patient to stimulate the curative vital reaction (curative rebound effect) according to the principle of therapeutic similitude. To make this proposal operative, a Homeopathic Materia Medica of Modern Drugs was elaborated (described in another work), where the therapeutic, adverse and side effects of drugs were grouped following the structure of the traditional homeopathic materia medica, while giving particular value to the frequency of the symptoms observed during the phases of study of the drugs. In order to facilitate the selection of the individualized remedy (i.e., similar to the totality of symptoms of the patient), and thus the clinical application of the present proposal, was also elaborated in this work a Homeopathic Repertory of Modern Drugs, where symptoms and remedies are arranged as in the traditional homeopathic repertories.
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Seguindo a mesma dinâmica da homeopatia clássica, essa obra sistematiza uma proposta para empregar os fármacos modernos segundo o princípio da similitude terapêutica, estimulando o efeito rebote (reação vital) curativo do organismo através da administração de substâncias (em doses dinamizadas) que despertaram sintomas semelhantes no estado de saúde humano. Vale ressaltar que os efeitos patogenéticos (ações primárias) dos medicamentos homeopáticos clássicos correspondem aos efeitos terapêuticos, adversos e colaterais dos fármacos modernos, os quais devem apresentar uma totalidade sintomática semelhante ao do paciente para estimular a reação vital curativa (efeito rebote curativo), de acordo ao princípio da similitude terapêutica. Para viabilizar essa proposta, foi necessário elaborar uma Matéria Médica Homeopática dos Fármacos Modernos (descrita em outra obra), agrupando os efeitos terapêuticos, adversos e colaterais das drogas conforme a disposição anátomo-funcional dos capítulos das matérias médicas homeopáticas tradicionais, valorizando a frequência de manifestação dos sintomas observadas nas fases de estudo da droga. Como segundo passo, para facilitar a seleção do medicamento individualizado (semelhança com a totalidade de sintomas do paciente) e a aplicação clínica da proposta, foi elaborado nessa obra um Repertório Homeopático dos Fármacos Modernos, dispondo os sintomas e seus respectivos medicamentos de forma análoga aos repertórios homeopáticos tradicionais, descrito nesta obra.
Chapter
The high efficacy of CAM therapies is globally acknowledged; however, their scientific validations are yet to be determined. Currently, CAM therapies are applied for treating influenza, Japanese encephalitis, inflammatory diseases, and breast cancer. These nonconventional therapies strengthen whole immune system with minimal side effects and are also cost effective. CAM is a personalized medication which alleviates the disease by treating the underlying causes coupled with it. The usefulness of CAM has been increased recently and considered as a healthcare system, product, and practice that are not a part of conventional medicine. The name CAM (complementary and alternative medicine) has been recently changed to complementary and integrative health (CIH) in Australia and other Western countries.
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Apesar da secular eficácia terapêutica da homeopatia, fator imprescindível na manutenção deste método de tratamento até os dias atuais, o meio acadêmico e científico exige comprovações segundo os seus parâmetros de pesquisa e avaliação. Essa é sempre a tônica das discussões entre homeopatas e 'alopatas', pois esses dois métodos de tratamento estão fundamentados em paradigmas opostos, possuindo metodologias distintas e divergindo sobre inúmeros fatores: verificação dos poderes curativos das drogas utilizando a experimentação em indivíduos humanos sadios ou em doentes (animais); valorização de aspectos psíquicos, emocionais e gerais nessas experimentações; escolha do medicamento através dos princípios da semelhança ou dos contrários; utilização de doses infinitesimais ou ponderais; administração de medicamentos únicos ou combinados, etc. Essa obra foi idealizada na tentativa de aproximar o modelo homeopático à racionalidade médica atual, buscando nas publicações e pesquisas científicas modernas o substrato para fundamentar os principais conceitos da homeopatia, em especial, o princípio terapêutico pela similitude. Em diversas áreas do conhecimento humano, da física à fisiologia humana, assim como em centenas de medicamentos empregados pela farmacologia clássica, encontramos a confirmação dos pressupostos homeopáticos, semelhantemente ao citado por Hahnemann há mais de dois séculos. Buscando a aproximação científica da medicina homeopática com a medicina convencional, esperamos num futuro próximo poder participar conjuntamente na formação de uma Medicina única, na qual o benefício ao paciente esteja acima de qualquer outro objetivo. Principais tópicos O método de cura homeopático reiterado pelo conhecimento científico moderno. O princípio terapêutico homeopático observado na história da medicina. Relatos de curas homeopáticas por médicos de todas as épocas. Estudo minucioso dos pilares fundamentais da homeopatia: lei dos semelhantes e experimentação no homem são. O princípio da similitude segundo a racionalidade científica dos séculos XVI a XIX: lei dos semelhantes como lei natural. O princípio da semelhança evidenciado em outras áreas do conhecimento humano (física, psicoterapia). Conceitos homeopáticos abordados segundo os fundamentos da fisiologia moderna. O mecanismo de ação das drogas homeopáticas evidenciado pela farmacologia clínica e experimental: fundamentação dos preceitos homeopáticos na observação dos efeitos secundários de centenas de fármacos modernos. Sugestões de pesquisa homeopática com drogas convencionais. Available at: http://homeozulian.med.br/homeozulian_visualizarlivroautor.asp?id=3
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The homeopathic method of healing is grounded on the application of the principle of therapeutic similitude (similia similibus curentur) by using medicines that cause effects similar to the symptoms of disease in order to stimulate the reaction of the organism against its own disturbs. Such vital, homeostatic or paradoxical reaction of the organism can be scientifically explained on the basis of the rebound effect of modern drugs. This article presents the conclusion of a study aiming at a method to use modern drugs with homeopathic criteria. This claim is epistemologically justified by the fact that a definite class of adverse events described by experimental pharmacology represents actual pathogenetic symptoms of drugs. On these grounds it was possible to elaborate a homeopathic materia medica and repertory comprising 1,251 modern drugs to be employed according to the principle of similitude and the individualizing symptomatic totality. Besides supplying a basis for homeopathy as a medical rationality regarding scientific pharmacology, this study makes available a method that may broaden the scope of intervention of homeopathy in present day diseases. (www.newhomeopathicmedicines.com)
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When Samuel Hahnemann systematized homeopathy and the effects of drugs on the state of human health, he described the primary action of drugs and the following secondary and opposite reaction of the organism. Seeking to apply this secondary action or vital reaction of the organism as therapeutic method, he postulated the principle of similitude, i.e. the prescription to ill individuals of drugs that cause similar symptoms in the healthy (similia similibus curentur). In modern pharmacology, secondary action (vital reaction) of drugs is known as rebound effect or paradoxical reaction of the organism. It has been observed after discontinuation of several classes of palliative (enantiopathic) drugs, namely those that act according to the principle of contraries (contraria contrariis curentur). Although in this case it is associated with severe and fatal iatrogenic events, rebound effect might awaken a healing reaction when the very same drug is employed according to the principle of similitude. The validity of the principle of similitude is proved by scientific evidence on rebound effect, whereas conventional drugs primary (therapeutic, adverse and side) effects might be equated to pathogenetic manifestations and thus be homeopathically applied. For this purpose a homeopathic materia medica and repertory comprising 1,251 modern drugs was elaborated using the monographs described in The United States Pharmacopeia Dispensing Information as source (www.newhomeopathicmedicines.com). Thus, the therapeutic range of homeopathy is broadened through the addition of hundreds of new medicines that might be employed in every kind of disease including countless modern clinical syndromes.
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The homeopathic model applies the secondary action or vital reaction of the organism as a therapeutic method and thus prescribes treatment by similitude, which consists in administering to ill individuals substances that cause similar symptoms in healthy individuals. The vital, homeostatic or paradoxical reaction of the organism might be explained scientifically by means of the rebound effect of modern drugs, which might cause fatal iatrogenic events after discontinuation of antipathic (a term used in alternative medicine for palliative treatment, also known as enantiopathic) treatment. Although the rebound effect is studied by modern pharmacology, it is poorly communicated to and discussed among healthcare professionals, who are thus deprived of information needed for the safe management of modern drugs. This article presents an up-to-date review on the rebound effect of modern drugs that grounds the homeopathic principle of healing and calls the attention of doctors to this type of adverse effect that is usually unnoticed. The rebound effect of modern palliative drugs, which was pointed out by Hahnemann more than two centuries ago, might cause fatal adverse events and is illustrated by the examples of acetylsalicylic acid, anti-inflammatory agents, bronchodilators, antidepressants, statins, proton-pump inhibitors, etc. Although the rebound effect is expressed by a small fraction of (susceptible) individuals and might be avoided by gradual tapering of antipathic drugs, it exhibits epidemiologic importance as a function of the massive use of such palliative drugs and the lack of knowledge in its regard.
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Apesar da secular eficácia terapêutica da homeopatia, fator imprescindível na manutenção deste método de tratamento até os dias atuais, o meio acadêmico e científico exige comprovações segundo os seus parâmetros de pesquisa e avaliação. Essa é sempre a tônica das discussões entre homeopatas e 'alopatas', pois esses dois métodos de tratamento estão fundamentados em paradigmas opostos, possuindo metodologias distintas e divergindo sobre inúmeros fatores: verificação dos poderes curativos das drogas utilizando a experimentação em indivíduos humanos sadios ou em doentes (animais); valorização de aspectos psíquicos, emocionais e gerais nessas experimentações; escolha do medicamento através dos princípios da semelhança ou dos contrários; utilização de doses infinitesimais ou ponderais; administração de medicamentos únicos ou combinados, etc. Essa obra foi idealizada na tentativa de aproximar o modelo homeopático à racionalidade médica atual, buscando nas publicações e pesquisas científicas modernas o substrato para fundamentar os principais conceitos da homeopatia, em especial, o princípio terapêutico pela similitude. Em diversas áreas do conhecimento humano, da física à fisiologia humana, assim como em centenas de medicamentos empregados pela farmacologia clássica, encontramos a confirmação dos pressupostos homeopáticos, semelhantemente ao citado por Hahnemann há mais de dois séculos. Buscando a aproximação científica da medicina homeopática com a medicina convencional, esperamos num futuro próximo poder participar conjuntamente na formação de uma Medicina única, na qual o benefício ao paciente esteja acima de qualquer outro objetivo. Principais tópicos O método de cura homeopático reiterado pelo conhecimento científico moderno. O princípio terapêutico homeopático observado na história da medicina. Relatos de curas homeopáticas por médicos de todas as épocas. Estudo minucioso dos pilares fundamentais da homeopatia: lei dos semelhantes e experimentação no homem são. O princípio da similitude segundo a racionalidade científica dos séculos XVI a XIX: lei dos semelhantes como lei natural. O princípio da semelhança evidenciado em outras áreas do conhecimento humano (física, psicoterapia). Conceitos homeopáticos abordados segundo os fundamentos da fisiologia moderna. O mecanismo de ação das drogas homeopáticas evidenciado pela farmacologia clínica e experimental: fundamentação dos preceitos homeopáticos na observação dos efeitos secundários de centenas de fármacos modernos. Sugestões de pesquisa homeopática com drogas convencionais.
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Supported in the Hippocratic aphorism primum non nocere, the bioethical principle of non-maleficence pray that the medical act cause the least damage or injury to the health of the patient, leaving it to the doctor to assess the risks of a particular therapy through knowledge of possible adverse events of drugs. Among these, the rebound effect represents a common side effect to numerous classes of modern drugs, may cause serious and fatal disorders in patients. This review aims to clarify the health professionals on clinical and epidemiological aspects of rebound phenomenon. A qualitative, exploratory and bibliographic review was held in the PubMed database using the keywords 'rebound', 'withdrawal', 'paradoxical', 'acetylsalicylic acid', 'anti-inflammatory', 'bronchodilator', 'antidepressant', 'statin', 'proton pump inhibitor' and 'bisphosphonate'. The rebound effect occurs after discontinuation of numerous classes of drugs that act contrary to the disease disorders, exacerbating them at levels above those prior to treatment. Regardless of the disease, the drug and duration of treatment, the phenomenon manifests itself in a small proportion of susceptible individuals. However, it may cause serious and fatal adverse events should be considered a public health problem in view of the enormous consumption of drugs by population. Bringing together a growing and unquestionable body of evidence, the physician needs to have knowledge of the consequences of the rebound effect and how to minimize it, increasing safety in the management of modern drugs. On the other hand, this rebound can be used in a curative way, broadening the spectrum of the modern therapeutics. http://ramb.elsevier.es/pt/linkresolver/efeito-rebote-dos-farmacos-modernos/90259384/
Article
Homeopathic treatment is based on the principle of similitude ('like cures like') administering to sick individuals substances that cause similar symptoms in healthy individuals, employing the paradoxical or biphasic action of the organism as therapeutic response. This homeostatic, vital or secondary action of the organism is scientifically explained by the rebound effect of drugs, resulting in worsening of symptoms after enantiopathic treatment withdrawal. Natalizumab reduces relapses in patients with active multiple sclerosis (MS), but recent studies report severe worsening of MS after suspension of treatment, as a consequence of the rebound effect. Extending this source of evidence, this work reviews research that demonstrates secondary worsening of MS after discontinuation of natalizumab, a human monoclonal antibody that suppresses the disease inflammatory activity as primary action. Several studies refer to the immune reconstitution inflammatory syndrome (IRIS) as a plausible explanation of reactivation of MS after withdrawal of natalizumab: a rebound effect or secondary action of the organism in response to the primary immunosuppression caused by the drug. Relapses of MS after discontinuation of natalizumab treatment indicate rebound of disease activity, supporting the homeopathic principle and warning healthcare professionals about this serious iatrogenic event.