IE960511A1 - Nicotine-containing homeopathic dilution and its use in¹restoring neuronal function - Google Patents

Abstract

Use of homeopathic dilution of a nicotine-containing extract of the plant Nicotiana tabacum in the manufacture of a medicament for use in a method of restoring neuronal function in a subject whose normal neuronal function has been impaired. Thus, the medicament can be used to induce normal neuronal function in a subject whose normal neuronal function has been impaired by exposure to and tolerance of nicotine. Accordingly, the medicament can be used as a palliative to relieve the withdrawal symptoms experienced by habitual users of tobacco products when the consumption of such products is interrupted. The final homeopathic dilution will preferably contain a nicotine-potentiating agent to amplify the effects of the original solute. Such nicotine-potentiating agents include organic acids such as acetic acid and alkaloids such as caffeine.

Description

Nicotine-containing homeopathic dilution and its use in restoring neuronal function This invention relates to a homeopathic dilution of extracts of the plant Nicotiana tabacum including nicotine and its use in a method of restoring neuronal function in a subject whose normal neuronal function has been impaired.

The plant Nicotiana tabacum has been grown and used as a source of the drug nicotine for several centuries. The dried leaves and stalks of the tobacco plant support a substantial global commercial activity based on the social and recreational use of tobacco in various forms including a fine powder intended for sniffing, a moist wad intended for chewing and chopped or rolled leaves in cigarettes, cigars and pipes from which the smoke of smouldering tobacco is inhaled. In each form the active ingredient, nicotine, is absorbed systemically through mucous membranes of the nose, mouth, throat and lungs. Nicotine itself is recognised as an extremely addictive substance creating both a physical and psychological dependency resulting in habitual consumption of tobacco products. The health risks associated with tobacco consumption are well publicised by the world medical authorities and include mouth, throat and lung cancer, gastric and duodenal ulceration, cardiac and respiratory debilitation and predisposition to infectious disease.

The health authorities of most countries have a keen awareness of the need to encourage the population to stop consumption of tobacco 25 products, but, due to the addictive nature of the principal drug substances, tobacco consumption continues largely unabated despite the associated health risks. The pharmaceutical industry has recognised the need to provide some substance to ameliorate the withdrawal symptoms and to help in overcoming the addiction. To date, apart from filters 30 and other devices intended to reduce the nicotine content of the tobacco during consumption the major products available to the addict are nicotine chewing gum and nicotine transdermal patches. Each of these 1 ’ ' ' il quantities of pure nicotine (greater *it. .......OF 860511 than 1 mg) and is designed to allow the user to absorb nicotine into the systemic circulation through the skin, or mucous membranes of the mouth or nose, as appropriate. Both nicotine gum and nicotine transdermal delivery systems alleviate the major withdrawal symptoms by supplying pharmacologically detectable levels of nicotine to the systemic system, albeit generally at reduced levels in comparison with the consumption of tobacco itself; the mode of action is the same as that of nicotine absorbed from tobacco.

Nicotine exhibits a broad spectrum of activity on the central nervous system. The drug directly affects nicotinic cholinergic receptor sites. In low doses nicotine stimulates the autonomic ganglia and the respiratory process, it promotes the release of vasopressin and adrenaline and affects the serotonergic system. In low doses, it is also known to activate dopaminergic pathways, and, by stimulating the cholinergic neurones acting via the cortex on the hippocampus, it may improve the memory function; these low (or very low) dose effects may present beneficial properties particularly in Parkinson’s and Alzheimer’s disease, and conditions where cerebral insufficiency is generally present in geriatric senility.

In high doses nicotine inhibits neural impulses at autonomic ganglia and the neuromuscular junction ultimately resulting in respiratory paralysis and death.

A characteristic feature of all homeopathic dilutions is that they contain little or none of the original active constituent and rely on the derived properties of the succussed solvent to effect their therapeutic action. The exact mode of action of any homeopathic remedy is still unresolved in the scientific community. That homeopathic remedies work is a matter of accepted fact among both conventional (orthodox) and alternative medical practitioners and is illustrated by the scientific publications and reported therapeutic successes, from establishments such as The Royal London Homeopathic Hospital and as reported in articles such as “Clinical Trials in Homeopathy: The British Medical Journal, Kleignen et al. 1991. 302:316”. Contemporary scientific 9685 1 1 research on the mode of action and therapeutic principle of homeopathic remedies is growing in intensity and has resulted in a variety of postulation and hypotheses from such eminent scientists as Dr. Colin B. Lessell: The Infinitesimal Dose’. C.W. Daniels & Co. 1994.

The fact that homeopathic remedies, in general, contain little or none of the original solute is the single most important feature which differentiates them from ‘orthodox’ remedies. The Avogadro Number quantifies the fact that the molecular weight, in grams, of any substance will contain 6.022 x 1023 molecules of that substance. Thus, the gram molecular weight of any substance when dissolved in one litre of water will by definition give a solution containing one mole, i.e. 6.022 x 10 molecules in one litre. If this solution is then subjected to serial dilutions such that 1 ml of the solution (i.e. 6.022 x IO20 molecules) is dissolved in 9 ml of water to give 10 ml and after thorough mixing 1 ml of this is dissolved in 9 ml of water and so on until the 1:10 dilutions have been repeated twenty times then the twentieth sequential dilution will, by mathematical extrapolation, contain, on average, just 6.022 molecules of the substance in 10 ml of water. If this twentieth dilution is subjected to a further 1:10 dilution then the resulting solution will contain less than 1 molecule of the substance (on average 0.6022 molecules by mathematical extrapolation).

When using 1:10 dilutions, the homeopathist will frequently go beyond the twenty third dilution thereby obtaining a 'solution' which by the ‘Avogadro’ definition cannot contain any molecules of the original solute. Homeopathic dilutions are produced from 'mother tinctures' prepared according to the dictates of a homeopathic pharmacopoeia. While these mother tinctures are seldom prepared in anyway designed to give a defined molar concentration, their actual content of active ingredient has been measured by conventional analytical technique, and using this as a starting point, the subsequent serial dilutions are shown theoretically to result in a solution frequently containing none of the original solute. 605 1 1 There are three commonly used scales for serial dilution in homeopathy, these being 'X' or 1:10 dilution, 'C' or 1:100 dilution and ‘LM’ or 1:50,000. There are other less commonly used scales and variations on the theme of each, some of which combine 'X' dilutions initially followed by 'C' dilutions. The most common solvents are water, or a water solution of ethanol. Insoluble material is triturated by grinding with lactose in a pestle and mortar, initial dilution being effected by mixing dry powder and triturating with lactose. After a specified number of triturations , the serial dilution of lactose is dissolved in water or water:ethanol and liquid dilutions carried out thereafter. Just as dry powder (lactose) can be used in trituration to extract the homeopathic potency from an insoluble source, so too can liquid homeopathic potencies be used to endow the same property onto (or into) a dry powder final dose.

After each dilution the solution is succussed i.e. is shaken in an 'up and down' fashion, the downward stroke of each shake ending abruptly by impacting on a firm (but not brittle) surface. The number of shakes and the vigour of each is critical in developing the potency of each dilution. Succussion is proclaimed by the homeopathist to endow the solvent with some intangible aspect of the solute such that the solvent adopts the properties of the solute, and amplifies and reflects these properties when subjected to multiple serial dilutions and succussions.

The homeopathist describes the process of serial dilution as ‘dynamisation’ or ‘potentisation’ of the remedy and the administered dose regimen as posology; the potency of each dose being measured by the number of serial dilutions and labelled with that number and the scale of dilution used. For example a 15 ‘C’ remedy has been potentised by serial dilution 1:100, fifteen times with succussion after each dilution. The preparation of homeopathic remedies varies between practitioners and even between different National Formularies. There is almost universal acceptance in modern homeopathic practice that the process of succussion is fundamental to potentisation. The number of strokes, the frequency and vigour of each, contributing to 'better' 605 1 1 potentisation is often standardised by utilising a mechanical device to effect the potentisation.

There is also variation in the solvent; the solvent will always contain water, and mostly a water:ethanol mix. The serial dilutions are frequently carried out using a 14% v/v ethanol: water, and the final potency in 95% v/v ethanol:water. The variation in concentration of ethanol may reflect commercial considerations more than actual physical or chemical pre-requisites. The use of ethanol is commonly interpreted as being for the purpose of preservation. More recent research indicates however, that ethanol contributes to the potency of the dilution and this is thought to reflect the polar -OH group on the ethanol molecule which mimics (or is better than) the -OH polar water molecule in transferring and amplifying the endowed property of the original solute. Very little, if any, use is made of solvents other than water:ethanol, a fact which reflects the lack of exploratory research in homeopathy.

A comprehensive review of the current hypotheses on the mode of action of homeopathic remedies can be found in Dr. C. Lessell’s book, The Infinitesimal Dose, published by Daniel & Co., London 1994. Basically there are three levels of complexity in which most theories are rooted: a) The geometrical level, at which polymers of molecular water are proposed to take up some conformity of shape which mimics the original solute. b) The dynamic level in which electromagnetic vibration is in some way transferred from the solute to the solvent. c) The submolecular level, where the concept of a chemical imprint being left in the water by the solute is postulated.

In accepting the fact that homeopathic remedies do work based on empirical medical evidence it is necessary then to understand the 96051 T principles upon which each remedy is based. Hahneman’s principle is that of Similia Similibus Curentur” or the law of similars; substances which produce a defined physiological symptom in healthy individuals can be used to cure similar symptoms produced by disease, if administered in the form of (very dilute) homeopathic potencies.

There are over 200 standard homeopathic remedies described in various homeopathic pharmacopoeias. Each remedy has been 'proven' by administering it - in undiluted form - to healthy individuals and carefully observing the symptoms it produces, fever, nausea, dizziness, pain, etc. A drug picture is then established and this is used to match as closely as possible - the symptomatic picture of a disease state. The fundamental principle in homeopathic prescription is the similimum or most similar in terms of correspondence between the symptomatological picture of the disease and that produced in healthy individuals during 'proving' of the homeopathic remedy.

Homeopathic remedies are frequently based on a drug substance which bears little or no relationship to the disease state; and the same disease (as categorised by orthodox medicine) may manifest itself in different symptoms in different individuals necessitating different homeopathic remedies.

A variation of classical homeopathy was developed by Wilhelm Lux (1831-1833) which is based on the principle of 'sameness' (Aequalia Aequalibus Curentur) as distinct from similars and is termed 'isopathy'. The principle is based on the use of a homeopathic dilution of the agent causing the disease as a treatment for the disease itself.

In classical homeopathy the remedy is based (generally) on some toxic substance which when administered undiluted causes similar symptoms in healthy people to those symptoms seen in sick people, (this is described as 'proving'). The high serial dilution of the same toxic substance can be considered to have been 'negatively charged' in comparison to its 'positively charged' undiluted origin such that when administered to sick people it acts to quench the 'positive' symptoms and thus cure the disease. (The terms 'negatively charged' and 6 05 1 1 'positively charged' are used only as a means of illustrating the principle involved and have no relation to the electric charges of the substance used.) In classical isopathy the dilution can again be considered to have been 'negatively charged' such that it re-balances an unwanted 'positive charge' e.g. allergic reaction to pollen (positive charge) which is quenched by the 'negatively charged' homeopathic potentisation of pollen.

Homeopathic dilutions of Nicotiana species are known and are referenced in Homeopathic Pharmacopoeias including the Homeopathic Pharmacopoeia of the United States, 7th Edition, published by Boericke & Tafel, 1011 Arch Street, Philadelphia. In this, the History and Authority (i.e. proving of the remedy) is referenced and accredited to ‘Hartlaub & Trinks’ in 1831. The clinical uses of the remedy are given as angina pectoris with coronaritis and high tension. Quite a number of contemporary publications reference the use of nicotine (homeopathic dilution of) as a remedy for travel sickness. See for example The Complete Family Guide to Homeopathy, Dr. Christopher Hammond published by Element Books, Shaftsbury, Dorset SP7 8BP in 1995. In this, as in other recent references, the use of nicotine is indicated for seasickness and for symptoms such as nausea, vomiting, vertigo, palpitations, pallor and sweating such as those which might arise in pregnancy, Meniere's Disease and heart disease. The use of the remedy in overcoming the withdrawal symptoms associated with cessation of tobacco consumption is not known because it does not fall within the classical framework of homeopathy or isopathy, and the symptomatological picture is not generally thought of as a 'disease'.

To date, the use of nicotine in orthodox dosages in the treatment of addiction to tobacco and/or/as a palliative for relieving the withdrawal symptoms associated with cessation of habitual abuse of nicotine-containing products has not proved generally successful for all of those wishing to overcome addiction to tobacco products. 6 05 1 1 The invention overcomes this problem by providing use of a homeopathic dilution of a nicotine-containing extract of the plant Nicotiana tabacum in the manufacture of a medicament for use in a method of restoring neuronal function in a subject whose neuronal function has been impaired.

Thus, the medicament can be used to induce normal neuronal function in a subject whose normal neuronal function has been impaired by exposure to and tolerance of nicotine.

The medicament for use in accordance with the invention can also be used to correct a condition characterised by cerebral insufficiency. Such conditions include Alzheimer's disease, Parkinson's disease and geriatric senility.

In particular, the medicament for use in accordance with the invention can be used as a palliative to relieve the withdrawal symptoms experienced by habitual users of tobacco products when the consumption of such products is interrupted.

By nicotine-containing extract of the plant Nicotiana tabacum herein is meant purified or partially purified constituents thereof, including nicotine.

The homeopathic dilution of nicotine is prepared according to the established procedures of serial dilution and succussion first described by Dr. Samuel Hahneman in his seminal text Essay on New Curative Principle in 1796.

According to the invention the disease state is the symptomatological picture presented on removal of a toxic substance to which the addict has become tolerant. For example: inhalation of smoke from a cigarette will have very unpleasant effects on a nonsmoker, inducing dizziness, disorientation, nausea, and cardiac palpitations. Over a period the individuals nervous system becomes tolerant to the toxin, learning to use it for its 'stimulating' effects on β 6 OS 1 1 cholinergic receptor sites, the nervous system then becomes addicted to it, developing a need for the toxin in order to function adequately.

On removal of the toxic substance, nicotine, the tolerant nervous system tries to recover its original functionality and reflects this relearning as withdrawal symptoms not unlike those associated with nicotine itself, in the non-addict; dizziness, disorientation, nausea, lack of concentration, sleeplessness, irritability.

In this situation the 'positively charged' symptoms were those first produced by exposure to nicotine, which over the course of time have become hidden by the induction of tolerance to the toxin. The application of a 'negatively charged' homeopathic dilution of the same toxin acts as a rapid re-induction of normal neuronal and cerebral function and so relieves the withdrawal symptoms. In this case the therapeutic principal is neither classical homeopathy or isopathy as nicotine withdrawal the disease state is not generally recognised as a disease, and this remedy differs totally from the orthodox approach which is to present nicotine in pharmacologically detectable amounts from an alternative source (chewing gum/transdermal patch). This invention utilises the homeopathic potentisation technique to extract from, and endow the solvent with, the ‘negative charge’ properties of the tolerated toxin, which is then used to affect normal intolerance of the toxin and normal neuronal functionality. Should any trace level of the original solute remain in the dose it is several orders of magnitude below that which is usually considered to be pharmacologically detectable, (i.e. the orthodox dose as administered in gum or transdermal patches).

Preferably, a mother tincture used to prepare the medicament contains nicotine or a salt thereof.

In most preferred embodiment the dilution of mother tincture used to prepare the medicament contains nicotine base. 605 1 1 ίο The mother tincture used to prepare the medicament for use in accordance with the invention may contain an amount of an alkali.

In order to stabilise the free base nicotine during the succussion process it may be desirable to introduce a suitable alkali such as ammoniun ion, thus minimising any interaction with, for example, a carbonium ion from dissolved CO2.

Preferably the homeopathic dilution is a 2'C'- 15'C' dilution of mother tincture.

Homeopathic remedies increase in potency as they are diluted, in this invention the lowest potency applicable is a 2'C' dilution containing less than 1 nanogram of the original active ingredient, there is no known or theoretical maximum potency (dilution) but potencies greater than 15'C' should be administered with extreme caution.

The medicament in accordance with the invention can be administered in various forms. Preferably, the formulation is administered in the form of oral drops, a solid oral dose, as an intranasal spray or as a suppository designed for administration per rectum.

The medicament can also be administered orally using sustained release formulations such as a chewing gum or as a muco-adhesive polymer. Other suitable formulations include sustained release formulation administered by way of a transdermal delivery system.

Preferably, the final dilution of the homeopathic dilution contains a nicotine-potentiating agent.

In one embodiment, the nicotine-potentiating agent is an organic acid or a polymer or co-polymer which contains an organic acid as a repeating monomeric unit.

Suitably the organic acid is selected from acetic acid, ascorbic acid, citric acid, lactic acid, glycolic acid or a mixture thereof.

Most especially the organic acid is acetic acid.

In accordance with the invention one can utilise acetic acid as a final diluent with water and/or ethanol: the initial low potency dilutions having been prepared in water only. In preliminary trials acetic acid was found to dramatically amplify the empirical effects of 15'C' potency of nicotine. Although not wishing to be bound by any theoretical explanation of the invention, this effect probably results from the presence of the terminal -OH moiety in the -COOH acetate group in acetic and other organic acids.

Nicotine is a weak base and readily forms salts with any organic acid. It is known that salts of nicotine are less toxic and do not penetrate the mucous membranes as easily as the free base. For this reason, only the final dose is diluted in ethanokacetic acid:water, all preliminary serial dilutions (l'C - 14'C') being in water only.

In preliminary trials a 50:50 ethanol: IN acetic acid solution was used to prepare a final '15C' potentisation of pure nicotine. In a single volunteer this potency gave substantially greater effects than a similar ' 15C' potency prepared at the same time using 50:50 ethanol:water.

As indicated above, the dissociation of acetic acid in water and ethanol may increase the relative polarity of the ethanol and this may or may not be a contributing factor in 'locking up' the endowed properties of the original solute. Further development of the solvent characteristics would be possible by introducing electron withdrawing or donating groups on the ethanol or acetic acid to improve the overall electronegativity of the solvent.

In a further embodiment, the nicotine-potentiating agent is an alkaloid.

Suitably, the potentiating agent is caffeine. The use of caffeine has been found to amplify the effects of the original solute.

The use of low background concentrations of caffeine as a weak base was evaluated. A 0.1 % w/v solution of caffeine in water was used as the diluent throughout all potencies to arrive at 15'C' homeopathic dilutions of nicotine in 0.1 % w/v caffeine. Again this method was subjectively judged to have greatly enhanced the therapeutic effect of the nicotine.

The invention also provides a homeopathic dilution of a nicotinecontaining extract of the plant Nicotiana tabacum wherein the final dilution contains a nicotine-potentiating agent.

As indicated above, the nicotine-potentiating agent is suitably an organic acid or a polymer or co-polymer which contains an organic acid as a repeating monomeric unit.

The organic acid is suitably selected from acetic acid, ascorbic acid, citric acid, lactic acid, glycolic acid or a mixture thereof, especially acetic acid.

As indicated above, the nicotine-potentiating agent can also be an alkaloid, preferably a plant alkaloid such as caffeine In order to define dose limits and so differentiate this invention from orthodox remedies it can be stated that the medicament according to the invention is diluted to the point where a single dose will contain less than 1 nanogram of the original active ingredient (nicotine) and that the therapeutic effect is subjectively detectable even when diluted beyond the point where there can be any certainty that any one dose contains even one molecule of the original solute based on the Avogadro Number. If the original 'mother tincture' or solution of extract from Nicotiana species is shown, by conventional analysis, to be 1.0 Molar solution (or any other concentration). And if the process of homeopathic dilution and potentisation results in a volume of (say) 1.0 litre which has been subjected to serial dilution such that the final volume of (say) 1.0 litre contains less than 200 molecules of the original solute (by mathematical reduction of the Avogadro Number), then there is no certainty that a 5 ml dose (1/200 of the final volume) will contain even one molecule of the original solute. In this invention the dose may be an aliquot of a solution where the theoretical number of molecules in the total volume is less than the total number of dose aliquots in that solution, and will always be an aliquot of a solution where the concentration of solute is such that a single dose is less than 1 nanogram of active principal and is produced by serial dilution and succussion.

For example: The formula weight of pure nicotine is 162.2 grams (C10H14N2). The compound is a liquid with a density of 1.02 g per ml. 159 ml of pure nicotine (162.2 /1.02) diluted to 1.0 litre with water will provide a 1 molar solution i.e. 1 gram molecular weight in 1 litre and will by definition contain 6.022 x 10 molecules of pure nicotine.

If this solution is subjected to serial dilution 1:100, ten times, by definition it will contain 6.022 x 10 or 6,022 molecules of nicotine. 1.0 ml will contain 6.022 molecules, 0.1 ml or one drop will contain 0.6022 molecules.

According to the invention the dose may be one drop (0.1 ml) of a 10 ‘C’ or greater dilution of a 1.0 molar solution of nicotine, suitably potentised by homeopathic succussion, or similar dilutions designed to produce a solution from a 'mother tincture' such that the dose administered is less than 1 molecule of the active ingredient.

The following rationale serves to further illustrate the limits of dilution and dose content of active ingredient.

Nicotine: Formula Weight Density 159 ml 162.2 grams 1.02 grams per ml 162.2 grams I4 159 ml made up to 1.0 litre with water = 1 molar solution 1 molar solution contains 6.022 x 1023 molecules of nicotine 1 ml of this 1 molar solution contains 6.022 x 10 molecules (one thousandth of 1 molar) 1 ml also contains 162.2 g/1,000 or 0.162 grams Therefore 1 ml in 99 ml of water = 1/100 or l'C' dilution, contains (per ml) 6.022 x 1018 molecules or 0.001622 grams i.e. 1.622 mg nicotine. ml of the above l’C' dilution in 99 ml of water will give a 2'C' dilution containing (per ml) 6.022 x 1016 molecules or 0.01622 mg i.e. 16.22 nanograms nicotine ml of the above 2'C' dilution will contain 6.022 x 1014 molecules or 0.1622 nanograms nicotine The invention will be further illustrated by the following Examples: Example 1 A mother tincture of Nicotiana tabacum was prepared according to the U.S. Homeopathic Pharmacopoeia as follows: Tabacum in coarse powder (dried tobacco leaves) 100 g. Purified water 200 ml. Strong alcohol 824 ml.

To make 1 litre of mother tincture with a drug strength of 1/10.

In the Pharmacopoeia potencies which may be used are given as '2 x' (2 x 1:10 dilutions) and higher with dispensing alcohol. The prescribed dose is given as the third to thirtieth potency.

Example 2 Smoke from 5 g. of smouldering leaves of Tabacum nicotiana was slowly sparged into 1.0 litre of 50:50 v/v solution of ethanol water. This 'mother tincture' was an acrid brown solution which was considered to contain 5 mg of nicotine in 1 litre. By definition this solution contained 1.856 x 1019 molecules of nicotine in total.

Nicotine Formula Weight = 162.2 g. 162.2 g = 6.022 x 1023 molecules 5 mg = 162.2/0.005 g = 1/32440 6.022 x 1023/32440= 1.856 x 1019 A '20 x' serial solution was prepared from this, 1:10 with succussion after each dilution, using water, the final 20'X' dilution being prepared in 50:50 ethanol:water.

The resulting solution contained 0.185 molecules of nicotine. This '20 x' potency was tested for efficacy in relieving nicotine withdrawal symptoms, in a single volunteer nicotine addict (i.e. habitual user of tobacco). After a period of 12 hours abstinence from nicotine one drop of this '20 x' potency was applied to the tongue and held in the mouth for 30 seconds before swallowing. After approximately one minute the volunteer reported a sense of tightness at the back of the neck, this was followed shortly by a sense of elation and ‘giddiness’ which lasted for about one hour. There was no desire to obtain nicotine from tobacco for a period of about six hours, thereafter.

Example 3 In order to obtain a standardised ‘mother tincture’ a 98% - 100% pure preparation of a naturally occurring isomer of (-) nicotine was obtained from The Sigma Company, Poole, Dorset, U.K. The compound has a formula weight of 162.2 grams and a density of 1.02g/ml. 159 ml of this made up to a volume of 1.0 litre representing a 1 molar solution. 1:100 centessimal or 'C' dilutions were carried out using water as a diluent. After each dilution the solution was subjected to 100 succussion strokes. Ί2Ο and '150 potencies were prepared i.e. 12 x 1:100 dilutions and 15 x 1:100 dilutions, both of which were used to test the efficacy of the remedy in alleviating the symptoms of nicotine withdrawal.

By mathematical extrapolation the ' 12C' potency of this solution contains 0.6022 molecules in the total volume of 1 litre; the '15C' dilution contains 0.0000006 molecules - (none). The dose was chosen arbitrarily using a medicine dropper designed to deliver 2.0 ml (in homeopathy the dose volume is not critical). Each dose was dropped onto the back of the tongue and held there without swallowing for 30 seconds.

Volunteer 1 Healthy teenage (17) female casual smoker.

The volunteer had refrained from smoking for 12 hours and expressed a mild desire to smoke. On application of the ‘12 C’ remedy the volunteer reported giddiness, elation and a feeling of well being; the desire to smoke was absent until a further 12 hours had elapsed.

Volunteer 2 Healthy teenage (15) male had never smoked and disliked the habit in others. On administration of the ‘12C’ remedy the volunteer reported a sense of bad taste in the remedy and experienced no tangible symptoms other than some irritability in his throat.

Volunteer 3 Healthy 43 year old female smoking cigarettes for over 25 years, showing no physical symptoms of disease other than a mild infrequent cough.

On application of the ‘15C’ remedy the volunteer reported a bad taste followed by a sense of lightness and relaxation; the desire to smoke was absent for over 6 hours.

Volunteer 4 Healthy 44 year old male, smoking cigarettes for over twenty years with a few periods of abstinence 6 05 1 1 in that time. The remedy ‘15C’ was administered on wakening in the morning and the volunteer refrained from the normal habit of smoking during the early part of the day. The volunteer reported that the normal urge to smoke was absent and there was a feeling of lightness and well being. Further administrations of the same remedy at four hourly intervals during the day provided a sustained sense of well being and elation. The normal urge to smoke was not experienced in anything like the intensity normally felt by an addict opting for temporary suspension of the drug.

Example 4 Using the same procedure as in Example 3 except replacing the water at the 15 'C' dilution with 50:50 ethanol:IN acetic acid.

Volunteer 4 compared the effects of the ‘15C’ ethanol:acetic acid potency with the 15'C' water potency on two successive days.

The day after the water remedy had been tested the exact same procedure was used this time utilising the ethanol:acetic acid dilution. The empirical effects were much greater, more immediate and seemed to last longer. The effects were the same, lightness and elation and loss of a desire to smoke. The only observation which was different was a ‘sour taste’ which was accounted for by the acetic acid.

Example 5 Using the 1 molar solution of nicotine in water from Example 3 as 'The Mother Tincture' a 15'C' remedy was prepared using a 0.1% w/v aqueous solution of caffeine as the diluent. By subjective analysis Volunteer 4 considered the caffeine/nicotine potency to be superior in effect to either the 15'C' water or the 15'C' ethanol:IN acetic acid potencies. At present there is no known analytical technique which can be used to compare the potencies of these homeopathic remedies, therefore subjective analysis awaits confirmation in large scale clinical trials.

The in-vivo testing carried out to date is limited to a small number of volunteers because of Regulatory Authority controls on preapproval for clinical trials.

The small population study described above contained some 10 reported anomalies such as the 'bad taste' from Volunteers 2 and 3, and the fact that the remedy had little or no reported effect on Volunteer 3. These are not unusual effects in homeopathic remedies; the bad taste is frequently remarked on and is one of the indications that some aspect of the solute has remained in the solvent even though the process of dilution is known to have exceeded the molecular concentration. The lack of any specific effect in the one volunteer who had never smoked is also characteristic of homeopathic remedies; because the body systems are in equilibrium there is nothing to restore and the harmonisation or inductive properties of the homeopathic dose have no effect. The dose effect is experienced only where there is some physiological or symptomatological disruption of normal functionality.

Claims (23)

Claims

1. Use of a homeopathic dilution of a nicotine-containing extract of the plant Nicotiana tabacum in the manufacture of a medicament for use in a method of restoring neuronal function in a subject whose neuronal function has been impaired.

2. Use according to Claim 1, wherein the medicament is used to induce normal neuronal function in a subject whose normal neuronal function has been impaired by exposure to and tolerance of nicotine.

3. Use according to Claim 2, wherein the medicament is used as a palliative to relieve the withdrawal symptoms experienced by habitual users of tobacco products when the consumption of such products is interrupted.

4. Use according to Claim 1, wherein the medicament is used to correct a condition characterised by cerebral insufficiency.

5. Use according to Claim 4, wherein the condition is selected from Alzheimer's disease, Parkinson's disease and geriatric senility.

6. Use according to any preceding claim, wherein a mother tincture used to prepare the medicament contains nicotine or a salt thereof.

7. Use according to Claim 6, wherein a mother tincture used to prepare the medicament contains nicotine base.

8. Use according to Claim 6 or 7, wherein a mother tincture used to prepare the medicament contains an amount of an alkali.

9. Use according to any preceding claim, wherein the homeopathic dilution is a 2'C'-15'C' dilution of mother tincture. 9 6 05 1 1

10. Use according to any preceding claim, wherein the final dilution of the homeopathic dilution contains a nicotine-potentiating agent.

11. Use according to Claim 10, wherein the nicotinepotentiating agent is an organic acid or a polymer or co-polymer which contains an organic acid as a repeating monomeric unit.

12. Use according to Claim 11, wherein the organic acid is selected from acetic acid, ascorbic acid, citric acid, lactic acid, glycolic acid or a mixture thereof.

13. Use according to Claim 11 or 12, wherein the organic acid is acetic acid.

14. Use according to Claim 10, wherein the nicotinepotentiating agent is an alkaloid.

15. Use according to Claim 14, wherein the alkaloid is caffeine.

16. A homeopathic dilution of a nicotine-containing extract of the plant Nicotiana tabacum wherein the final dilution contains a nicotine-potentiating agent.

17. A homeopathic dilution according to Claim 16, wherein the nicotine-potentiating agent is an organic acid or a polymer or copolymer which contains an organic acid as a repeating monomeric unit.

18. A homeopathic dilution according to Claim 17, wherein the organic acid is selected from acetic acid, ascorbic acid, citric acid, lactic acid, glycolic acid or a mixture thereof.

19. A homeopathic dilution according to Claim 17 or 18, wherein the organic acid is acetic acid.

20. A homeopathic dilution according to Claim 16, wherein the nicotine-potentiating agent is an alkaloid.

21. A homeopathic dilution according to Claim 20, wherein the alkaloid is caffeine. 5

22. Use according to Claim 1, substantially as hereinbefore described

23. A homeopathic dilution according to Claim 16, substantially as hereinbefore described.