EP4287853A1

EP4287853A1 - Vaporizable liquid composition comprising at least nicotine and a cannabinoid for an electronic cigarette

Info

Publication number: EP4287853A1
Application number: EP22708196.5A
Authority: EP
Inventors: Sébastien OMBE
Original assignee: Versevrage
Current assignee: Versevrage
Priority date: 2021-02-08
Filing date: 2022-02-08
Publication date: 2023-12-13
Also published as: FR3119517B1; FR3119517A1; WO2022167773A1

Abstract

The present invention is directed to the combination of a cannabinoid, advantageously cannabidiol (CBD), and nicotine for managing withdrawal, advantageously from tobacco, nicotine and/or vaping products, using an electronic cigarette.

Description

VAPORIZABLE LIQUID COMPOSITION FOR ELECTRONIC CIGARETTE CONTAINING AT LEAST NICOTINE AND ONE CANNABINOID

FIELD OF THE INVENTION

The present invention relates to the combination of a cannabinoid and nicotine, and advantageously of at least one diol, for use in the conduct of smoking, nicotine and vapor withdrawal. This combination, which may additionally contain an acid, flavorings and/or terpenes, is contained in a vaporizable liquid composition for an electronic cigarette.

PRIOR STATE OF THE TECHNIQUE

The electronic cigarette is an existing and democratized market since 2010 in France and around the world. It is now a market regulated and framed by the tobacco directive, although its use is based on an alternative to tobacco linked to healthier and less harmful consumption than that of conventional tobacco, as has been demonstrated in numerous studies ( https://helveticvape.ch/le-rapport-de-public-health-england).

Its operation is simple: an electronic cigarette is an electromechanical or electronic device generating an aerosol intended to be inhaled. It produces “vapor” or “artificial smoke” visually resembling the smoke produced by burning tobacco. This vapor can be flavored with different kinds of aromas: blond tobacco, brown, fruit, mint, gourmet flavors, . . . It may or may not contain nicotine.

Unlike the smoke produced by a traditional cigarette, this vapor (gaseous state) does not have the smell of burnt tobacco and, according to the first scientific studies, contains much lower quantities or even thousands of particles and carcinogenic substances or toxic.

The operation of an electronic cigarette is made possible thanks to two components which are the electronic cigarette and the liquid composition it contains, called "e-liquid" in the field, which will be vaporized.

The electronic cigarette is composed of three main elements:

- a battery or battery; an atomizer containing the resistor;

- a tank containing the e-liquid which will be vaporized. The operation of these three elements consists in vaporizing the e-liquid thanks to the heating of the resistance by pressing or not a button.

The battery is the bulkiest part of an electronic cigarette. It contains a battery or an accumulator commonly called "accu" in the field.

The atomizer is the part that is used to heat the e-liquid present in the tank, in order to transform it into vapor. The atomizers contain a resistive wire that surrounds a wick, the wick having the function of storing the liquid and bringing it by capillary action to the resistance so that it is heated and vaporized.

The tank is the part that contains the e-liquid. It is most often cylindrical in shape, made of polyethylene, glass or stainless metal, but can also be in the form of a cartridge. The tank has two openings: an air inlet and a steam outlet. The outlet is usually equipped with an interchangeable mouthpiece, commonly referred to as a "drip tip" in the field.

The composition of the e-liquid which is used in electronic cigarettes most often includes the following elements: propylene glycol representing 50% to 80% by weight of the e-liquid; vegetable glycerin representing 20% to 50% by weight of the e-liquid; nicotine at a concentration ranging from 0 mg/ml to 20 mg/ml;

- an aroma representing from 0% to 20% by weight of the e-liquid; water and/or alcohol representing 0% to 20% by weight of the e-liquid.

Propylene glycol (PG) or 1,2 -propanediol (CAS = 57-55-6) promotes the rendering of the aroma and thins the liquid, allowing better vaporization of the latter. It also brings a "hit in the throat", namely a tingling sensation in the throat reminiscent of the contraction made when the smoke of a tobacco cigarette passes through the throat. However, too much propylene glycol can bother and irritate the throat when inhaling e-liquid.

Vegetable glycerin, on the other hand, makes it possible to have a rounder vape (i.e. the action of vaping) in the mouth, lessens this irritation during inhalation, with a strong visible vapor emerging during exhalation and reminiscent of the classic cigarette. On the other hand, glycerin, which is a viscous compound, does not favor the rendering of the aroma and causes certain difficulties during vaporization when it is used in large quantities, forcing use of the electronic cigarette at higher temperatures to allow to the product to vaporize and thus favoring, during the degradation of the product, the appearance of undesirable by-products such as acrolein.

Consequently, the market currently favors compositions comprising an equivalent proportion of propylene glycol and vegetable glycerin, advantageously 50% propylene glycol and 50% vegetable glycerin.

However, propylene glycol is derived from petrochemicals, with all the resulting disadvantages, particularly concerning the environmental footprint, resulting in high energy consumption and significant production of volatile organic compounds and waste. Indeed, studies have proven that after purification of propylene glycol, minor organic impurities as well as propylene glycol oxide appear. Also, some users have been shown to be allergic to this product, with irritation beyond normal when inhaled.

To overcome the drawbacks of synthetic propylene glycol, the use of vegetable propylene glycol, obtained by the catalytic hydrogenation of sorbitol itself derived from corn, has been proposed. However, vegetable propylene glycol associated with vegetable glycerin does not allow to obtain a good aromatic rendering nor a consequent volume of vapor sought by many vapers and always clogs the material in a consequent way.

To replace synthetic or vegetable propylene glycol, the use of 1,3-propanediol (CAS=504-63-2), called “propanediol” in the following description, was preferred. It has been shown during in-depth studies of the product placed on the market, Végétol® (www.vegetol.fr), that propanediol used alone or accompanied by vegetable glycerin allowed a reinforcement of the aromatic power, an improvement vapor draw, denser vapour, a greater tingling sensation in the throat ("hit") without irritation, as well as an improvement in the bioavailability of nicotine and the constant delivery of the latter.

The performance of propanediol, proven when used in a liquid composition for electronic cigarettes containing nicotine, has been reported in connection with other components, in particular cannabidiol (CBD) recently used in electronic cigarette liquids.

Cannabidiol (CBD) is a cannabinoid, namely a group of chemicals that activate cannabinoid receptors found in the human body. It is one of the molecules extracted from the Cannabis sativa plant (or cultivated hemp). Its many virtues therapeutics have been proven, as has its non-psychoactive effect. It is currently used in different forms (www.cbd-france.fr), such as oil, food, creams, crystals and now in e-liquids vaporized using electronic cigarettes. It should be noted that to satisfy the French legislation currently in force in particular, cannabidiol (CBD) is advantageously in the form of pure crystals from authorized varieties and parts of plants and making it possible to exclude any trace of delta-9 tetrahydrocannabinol ( THC) in the finished product. Alternatively, CBD is in oil form.

The current composition of e-liquids containing CBD is as follows: cannabidiol at 0 mg to 1000 mg per 10 ml in the form of oil or pure crystals, i.e. a CBD concentration ranging from 0 mg/ml to 100 mg/ml; propylene glycol representing 80% and up to 100% by weight of the e-liquid; vegetable glycerin representing from 0% to 20% by weight of the e-liquid;

- an aroma representing from 0% to 20% by weight of the e-liquid; possibly terpenes.

It has been proven that the bioavailability of CBD is increased when CBD is inhaled: from 20% up to 65% bioavailability against 8% by ingestion (https://fr.vapingpost.com/e-liquide-cbd). The optimized release of CBD makes it possible to accentuate its effects thanks to a diffusion of the product in the body in greater proportion.

However, it has been proven that pure CBD crystals are difficult to dissolve in vegetable glycerin, because they are too viscous, which leads manufacturers to use a composition containing 80% propylene glycol and 20% vegetable glycerin in order to dissolve them more easily. CBD crystals. As mentioned previously, propylene glycol presents a more fluid basic solution than that of vegetable glycerin and allows better dissolution and fixation of CBD like aromas.

However, and as seen above, such a composition (80% propylene glycol / 20% vegetable glycerin) generates many discomforts when inhaled, with irritation at the level of the passage in the throat, as well as slight impurities and propylene oxide potentially harmful to the skin. 'final user. Added to this is a difficulty in using the liquid for those allergic to propylene glycol, as well as earlier clogging of the equipment. To improve the dissolution of CBD, some products on the market contain 100% propylene glycol but they cannot be inhaled directly and must be mixed with existing e-liquids containing propylene glycol but also glycerin. vegetable. In this case, the CBD concentration is reduced, resulting in a loss of effectiveness.

The combination of propanediol with cannabidiol overcomes these difficulties. Propanediol is more fluid than propylene glycol and is an organic solvent allowing better dissolution of CBD, including at high concentrations of up to 1500 mg per 10 ml (150 mg/ml). Thus, the CBD can be dissolved in a base composed of 100% propanediol and free of any other product. The dissolution of the CBD is then greater, thus improving the bioavailability of the product by inhalation, the composition then being able to be inhaled as it is. The use of propanediol associated with CBD also makes it possible to reduce the fouling of resistors and equipment. A composition based on propanediol with little vegetable glycerin (around 1% to 20% or better 0%) allows an increase in the bioavailability of CBD by inhalation, beyond 20%, inducing an increase in the effects for a decrease in intake. Added to this is a better deliverability of CBD at a constant rate, for vaporization at the same temperature between propanediol and CBD (about 190°C).

In addition, it is an entirely natural combination, with no waste after product degradation linked to heating, even at high temperatures, because neither propanediol nor CBD degrades, even at high heating temperatures. The combination of Propanediol and CBD enhances the hit even without nicotine, as Propanediol has been proven to bring out a natural hit without nicotine and CBD has also been shown to bring out a natural hit, the combination of the two leading to an increase in this hit. without the addition of nicotine or any other product simulating this effect, for example Flavor Art's "Flash" aroma.

Thus, and as described in document FR 3 078 702, a composition mixing CBD and propanediol offers the possibility of relieving smoking cessation, thanks to the stimulation of certain CB1 and CB2 receptors (https://elixinol.com/ fr/blog/how-does-cannabidiol-cbd-work/) reconsolidating the memory of the smoker. This reduces the harmful effects associated with quitting smoking such as anxiety, insomnia, nervousness and concentration problems related to a lack due to nicotine addiction. In this document, the possibility of adding nicotine or a nicotine substitute to the composition is mentioned, but only in the case where the user also needs nicotine to relieve another pathology such as Parkinson's disease.

There is nevertheless a persistent need to propose vaporizable liquid compositions for electronic cigarettes and withdrawal protocols making it possible to quit smoking. DISCLOSURE OF THE INVENTION

The present invention thus relates to the use of the combination of a cannabinoid, advantageously cannabidiol (CBD), and nicotine in the conduct of withdrawal using an electronic cigarette. The invention also relates to the use of a vaporizable liquid composition for an electronic cigarette containing such a combination and advantageously a diol such as propanediol, a kit and an electronic cigarette comprising such a composition, as well as an associated withdrawal protocol which reverses the two molecules to the benefit of the non-addictive (CBD).

Remarkably, the possibility of combining nicotine and CBD, as well as advantageously propanediol, in an electronic cigarette composition with the aim of weaning oneself from conventional cigarettes has never been described. However, the present application reports below the many advantages associated with such an association.

Indeed and in the electronic cigarette business sector in the broad sense, all the players have assumed that we do not mix nicotine and CBD because the two principles would cancel each other out. The present invention is based on the observation that this principle is certainly true in terms of "physical" feelings by using CBD at high concentration, nicotine limiting the feelings. On the other hand, this principle is not valid in the conduct of nicotine withdrawal because the receptors involved are not the same and in the end, the action of one and the other complement each other.

Indeed, CBD has been described to act as an antagonist at the CB1 and CB2 endocannabinoid receptors. As a result, it acts as an inhibitor of the FAAH enzyme, responsible for the degradation of anandamide, an endogenous neurotransmitter in the brain that generates the feeling of pleasure and calm. By promoting the preservation of anandamide, CBD improves the transmission of serotonin which, via the activation of its receptors, leads to physiological reactions of calming, anti-stress and other important benefits in quitting smoking.

Nicotine, on the other hand, activates the diffusion of dopamine in the brain and thus contributes to addiction to this molecule. However, there are other addiction activating links such as the noradrenergic system, which has the role of making the environment more attractive, and the serotonergic system, which has the role of modulating a response and/or an impulse. (https://www.futura-sciences.com/sante/dossiers/medecine-arreter-lumer-enfranchise-tabac-1164/page/10/). It is the relationship between these two systems that determines the release of dopamine. However, when nicotine activates these two systems simultaneously, there is a confusion at the level of the response which will no longer be appropriate to an impulse, a strong attraction towards a physiological need for nicotine, in the case of nicotine dependence.

In addition, the nicotine in tobacco smoke generates MAOIs (monoamine oxidase inhibitors) which prevent the breakdown of dopamine and thus reinforce the addiction. It has been proven that nicotine alone does not develop MAOIs but it is the sugar contained in a cigarette to improve the taste and the inhalation which, by degrading, will generate MAOIs and accentuate the dependence. Currently, some e-liquids contain sweetening additives which, when vaporized, would cause this same process in addition to the natural addiction associated with e-liquids with sweet flavors and notes.

Cannabidiol, which acts on serotonin, could thus restore the appropriate response during an impulse, a solicitation of the body with nicotine and thus provide physiological responses as to an appeasement and reduction of stress linked to lack.

In addition, CBD would play a role in the process of "reconsolidation of memory", that is to say the reactivation of the brain when viewing an image or other recalling the well-being linked to the consumption of cigarettes, including after a long abstinence. Studies (www.researchgate.net/publication/292677178_Cannabidiol_disrupts_the_reconsolidation_of _contextual_drug-associated_memories_in_Wistar_rats) have shown that the use of pure CBD, in inhaled form, would act on this memory reconsolidation process by breaking the bridge between memories ( good or bad) and the vision of an image or any other reminder in any other form. Notably, a single dose of CBD would act on this principle in the long term and even if the nicotine is reintroduced into the body.

Finally, if nicotine has a half-life of 2 hours on average (elimination in the body after 8 hours), that of CBD would be at least 3 times greater. Thus, the action of the two molecules would complement each other: thanks to the inhalation of a nicotine/CBD product, the drop in nicotine in the body would be compensated by the action of the CBD, making it possible to slow down the immediate need for nicotine. . Especially during the sleep phase when the "craving" (impulsive need) is most felt on waking, when the body has no more nicotine but the action of CBD continues, the body craving for nicotine could thus be reduced with an easier nicotine withdrawal process. DETAILED DESCRIPTION OF THE INVENTION

According to a first aspect, the invention relates to the combination of a cannabinoid and nicotine for use in the conduct of withdrawal, advantageously smoking, nicotine and/or vapology, using an electronic cigarette. Preferably, this combination is contained or enclosed in a vaporizable liquid composition for an electronic cigarette, which may contain other ingredients detailed below.

In the present application, the expression "electronic cigarette" refers to any electromechanical or electronic device generating an aerosol intended to be inhaled producing a "vapor" or "artificial smoke", visually reminiscent of the smoke associated with the combustion of tobacco. This definition therefore includes all models of personal vaporizer, as well as electronic devices delivering nicotine called ENDS (“Electronic Nicotine Delivery System”) or ENDD (“Electronic Nicotine Delivery Device”), as well as tobacco-based cigarettes heated.

The term "withdrawal" refers to deprivation for the purpose of detoxification. In the context of the present invention, it is both a smoking cessation (vis-à-vis traditional tobacco), nicotinic (vis-à-vis nicotine) and / or vapological (vis-à-vis -Vis de la vape, that is to say the action of inhaling using an electronic cigarette).

The first component of the combination is a cannabinoid. According to a preferred embodiment, the cannabinoid used in the context of the invention is not delta-9 tetrahydrocannabinol (THC) or does not contain THC.

Preferably, it is cannabidiol (CBD). This molecule can come from the Cannabis sativa plant (https://dumas.ccsd.cnrs.fr/dumas-00983072/document), or hemp, a plant derivative with a very low THC content, or hops.

Even more preferably, the CBD is in the form of pure crystals, derived from authorized varieties and parts of plants and making it possible to exclude any trace of THC in the finished product, thus meeting legal standards, in particular in France. Indeed, CBD is not classified as a narcotic in France if the cannabinoid is extracted from authorized hemp varieties with a THC content of less than 0.3% and if the finished product after processing is free of any trace of THC (http://www.drogues.gouv.fr/ actualites/cannabidiol-cbd-point-legislation). More generally, CBD can be used in different forms such as pure crystals, powder, distillate (CBD concentrate containing other cannabinoids) or oil. Advantageously, the CBD comes from a totally organic culture. Thus, crystals containing no trace of pesticides or heavy metals can be obtained from organic European hemp, authorized plant varieties that are regulated and listed in the Public Health Code under French legislation, and offered in this form following the crystallization of pure hemp extract to obtain a 99.5% pure product. It is thus possible to obtain a composition which, once diluted in propanediol, allows the inhalation via a personal vaporizer of a 100% vegetable composition free of any impurity after the degradation of these two molecules, even after heating at high temperature.

The cannabinoid, advantageously cannabidiol (CBD), can represent from 1% to 30% by weight of the composition, preferably from 1% to 20% and even more preferably from 1% to 15% of the total weight of said composition. According to another particular embodiment, the cannabinoid, advantageously cannabidiol (CBD), is present in the composition at a concentration of at least 1 mg/ml and possibly up to 50 mg/ml, 100 mg/ml or even 200 mg/ml, for example 5, 10, 15, 20 or 25 mg/ml.

The second component of the combination according to the invention is nicotine or a nicotine substitute, of synthetic or natural (plant) origin: Nicotine can be extracted from tobacco leaves or obtained by chemical or biological synthesis. Advantageously, the nicotine meets the purity criteria described in the American (USP) and European (EU) pharmacopoeias in force.

According to a particular embodiment, the nicotine is used in the form of nicotine base, that is to say at basic pH, or even more advantageously in the form of nicotine salt, that is to say nicotine - base to which an acid is added. Several acids can be used: benzoic acid (classified CMR), lauric acid, salicylic acid or lactic acid. Preferably, lactic acid is used because of its lower toxicity, its greater efficiency (there is a need to put less of it in the composition to achieve the same result), and the fact that it does not degrade not at the vaporization temperature of an e-liquid.

The use of nicotine salts makes it possible to respond to the problem of inhaling high concentrations of nicotine: in fact, this form of nicotine is associated with a more acidic pH, around 5 to 6, which favors inhalation in reducing the hit perceived during passage through the throat. More generally, the use of nicotine base and nicotine salt at concentrations different allows to obtain a feeling of constant hit, whatever the concentrations of nicotine and CBD used.

The nicotine concentration is advantageously between 0 mg/ml and 50 mg/ml of the composition, preferably less than or equal to 20 mg/ml. Likewise, the acid can be present at a concentration of between 0 mg/ml and 50 mg/ml, preferably between 0 and 20 mg/ml.

According to a particular embodiment, the mass proportion between cannabinoid, advantageously CBD, and nicotine in the combination or in the composition according to the invention is between 20% and 80%, for example 20%, 40%, 60% and 80 %. Thus, and by way of example, in the case where the sum of the nicotine and CBD concentrations is constant and equal to 25mg/ml of composition, the composition may include:

5 mg/ml of CBD (20%) and 20 mg/ml of nicotine (80%);

10 mg/ml of CBD (40%) and 15 mg/ml of nicotine (60%);

15 mg/ml of CBD (60%) and 10 mg/ml of nicotine (40%); Where

20 mg/ml of CBD (80%) and 5 mg/ml of nicotine (20%).

According to another preferred embodiment, a vaporizable liquid composition according to the invention advantageously contains a solvent, even more advantageously a diol such as propylene glycol or propanediol. The most suitable and preferred solvent for transporting these two molecules is propanediol, combined or not with advantageously vegetable glycerin. Propanediol can be vegetable or synthetic and allows better dissolution of cannabidiol (CBD). Propanediol can thus be derived from vegetable raw materials and obtained by fermentation of glycerol via a biological process that respects the environment.

The propanediol can represent from 10% to 99%, preferably from 50% to 99%, for example from 70% to 99% relative to the total weight of the composition.

Thus and according to a preferred embodiment, a vaporizable liquid composition comprises a cannabinoid, advantageously cannabidiol (CBD), nicotine, advantageously a nicotine salt, and a diol, advantageously propanediol.

Indeed and to the Applicant's knowledge, there is no disclosure that describes the use, in the presence of nicotine, of propanediol combined as a base with cannabidiol (CBD), making it possible to improve its dissolution in order to obtain the highest bioavailability by inhalation (above 20%) and thus improve the effects related to CBD. In fact, the invention reports for the first time their association with nicotine, allowing interactions with the effects CBD to consider a path towards improved nicotine, smoking and/or vapological withdrawal behavior.

In addition, a composition according to the invention, namely an electronic cigarette liquid, may comprise at least one of the following additives: advantageously vegetable glycerin, propylene glycol, flavorings, terpenes, water and/or an alcohol such as ethanol.

The composition used may or may not contain propylene glycol, whether synthetic or of vegetable origin, that is to say obtained from vegetable raw materials. Propylene glycol is obtained from the reaction of propylene oxide with water to form monopropylene glycol (MPG), or by plant production using biosourced monopropylene glycol.

Propylene glycol, synthetic or of vegetable origin, can thus represent from 0% to 90% by weight of the composition, preferably from 0% to 70% or even from 0% to 50%.

According to a particular embodiment, the composition according to the invention is free of propylene glycol. Indeed and as stated above, synthetic propylene glycol is very irritating and its use in a high proportion in the composition, necessary to facilitate the dissolution of CBD, makes it unsuitable for use in an e-liquid of electronic cigarette. Vegetable propylene glycol, for its part, even if it makes it possible to avoid the aforementioned drawbacks in connection with synthetic propylene glycol, is not as fluid as propanediol and does not allow use up to 100% of the composition: it would remain too dry during the passage in the throat without ensuring a better bioavailability of the CBD.

The composition may or may not contain glycerin, advantageously of vegetable origin. According to a preferred embodiment of the invention, the composition contains little glycerin, advantageously of plant origin. Indeed and as mentioned above, its viscosity hinders the dissolution of CBD, thus reducing its bioavailability and therefore its effects. Its high viscosity also requires a higher heating temperature which, during the degradation of the product, can lead to the appearance of unsuitable impurities during inhalation, such as acrolein which is toxic. The heating temperature of vegetable glycerin, which is 288°C, is significantly higher than that of CBD (approximately 190°C), which requires very significant heating of the composition to be able to vaporize the vegetable glycerin which, as a result , leads to the degradation of the CBD molecule. In addition, vegetable glycerin clogs the material. However, and in small quantities in the composition, it can improve the bioavailability of CBD. Thus and according to a particular embodiment, the glycerin may represent from 0% to 50% by weight of the composition, or even from 0% to 30%, or even from 0% to 20%.

Beyond the aforementioned components, the composition can also contain aromas and/or terpenes to give an aromatic note to the composition.

The flavorings can be synthetic or natural flavorings such as those approved in the food and/or pharmaceutical fields, in particular those listed in EU regulation 872/2012 of October ¹ , 2012 and in the American (USP) and European (EU) pharmacopoeias in vigor.

The concentration of aroma(s) and/or terpene(s) can be from 0% to 20% by weight, preferably from 0% to 15% by weight, more preferably from 0% to 10% by weight of the composition . As mentioned above, terpenes associated with other cannabinoids can provide an entourage effect and therefore enhance the effects of CBD, a phenomenon accentuated by its greater bioavailability due to its association with propanediol.

The composition used may or may not also contain alcohol such as ethanol and/or water and/or at least one colorant.

The alcohol can represent from 0% to 20% by weight, preferably from 0% to 10% by weight, more preferably from 0% to 5% by weight relative to the total weight of the composition. The water can represent from 0% to 10% by weight, preferably from 0% to 5% by weight relative to the total weight of the composition. Dyes can be of synthetic or vegetable origin such as those approved in the food and/or pharmaceutical fields, and in particular those listed in EU regulation No. 1331/2008 and in the American (USP) and European (EU) pharmacopoeias. in force.

According to a particular embodiment, a composition according to the invention contains neither alcohol (ethanol) nor water, in particular when the latter contains at least one diol, preferably propanediol. Indeed, the fluidity of propanediol is sufficient to avoid having to add water, which is likely to promote the development of pathogenic microorganisms of microbial origin and then requiring the use of preservatives or the performance of sterilizing microfiltration. Furthermore, since CBD is not soluble in water, the combination of propanediol, CBD and nicotine will be more effective in the absence of water and ethanol by maximizing CBD/nicotine interactions, and healthier. by inhalation for weaning. According to a particular embodiment, a composition according to the invention comprises: a cannabinoid, advantageously cannabidiol (CBD); nicotine, advantageously in the form of nicotine salt, that is to say combined with an acid, advantageously lactic acid;

- a diol, advantageously propanediol; and optionally glycerin, preferably vegetable glycerin.

According to another particular embodiment, it corresponds to one of the compositions described in point 1 of the embodiment examples, in particular to a composition according to stages #2 to #5.

Remarkably, such a combination, in particular of CBD, propanediol, nicotine or even lactic acid, or composition allows:

- to improve the dissolution and the bioavailability by inhalation of the cannabinoid, in particular of CBD;

- to promote interactions related to nicotine and the cannabinoid, in particular CBD, and thus to promote withdrawal;

- to promote the delivery of nicotine and cannabinoids, in particular CBD;

- to reinforce the aromatic power;

- to reduce the fouling of the equipment and generally of the electronic cigarette;

- to reduce the hit in the throat or the tingling sensation in the throat felt during the vape; and or

- to facilitate the inhalation of the vaporizable liquid composition, in particular when it contains high concentrations of nicotine.

According to another aspect, the invention relates to a kit intended for smoking, nicotine and/or vapor withdrawal comprising at least one composition as defined above.

Advantageously, such a kit comprises an electronic cigarette intended to receive or contain said composition. An electronic cigarette is as known to those skilled in the art, and can for example be a disposable electronic cigarette.

According to one particular embodiment, such a kit comprises at least two compositions as defined above. Advantageously, the at least two compositions have different nicotine concentrations. According to another particular embodiment, the at least two compositions have different cannabinoid concentrations. Advantageously, the sum of the nicotine and cannabinoid concentrations is equal in each of the compositions.

According to another aspect, the invention relates to a process for smoking, nicotine and/or vapor withdrawal, advantageously implemented using a kit as defined above.

Such a process comprises taking compositions as defined above in stages, comprising decreasing concentrations of nicotine, advantageously ranging from 20 mg/ml to 5 mg/ml, even more advantageously 20, 15, 10 and 5 mg/ml .

Preferably, the compositions used in the context of weaning comprise increasing cannabinoid concentrations, advantageously ranging from 5 mg/ml to 20 mg/ml, even more advantageously 5, 10, 15 and 20 mg/ml, so as to compensate for the decrease in nicotine concentration.

According to other aspects, the invention relates to:

- an electronic cigarette liquid composition containing at least one diol as well as nicotine and at least one cannabinoid compound except delta-9 tetrahydrocannabinol (THC) in the conduct of smoking and nicotine withdrawal;

- an electronic cigarette liquid composition containing at least one diol as well as nicotine and at least one cannabinoid compound except delta-9 tetrahydrocannabinol (THC) for its use in the conduct of smoking and nicotine withdrawal;

- the use of the composition containing at least one diol, preferably 1.3 propanediol with nicotine base or nicotine salt, that is to say nicotine base to which an acid and cannabidiol are added (CBD) preferably in the form of pure crystals derived from authorized varieties and parts of plants and making it possible to exclude any trace of delta-9 tetrahydrocannabinol (THC) in the finished product, with or without vegetable glycerin to improve the dissolution and bioavailability of CBD by inhalation and maximizing CBD-nicotine interactions;

- the use of the composition containing at least one diol, preferably 1.3 propanediol with nicotine salt, that is to say nicotine-base to which an acid is added, and cannabidiol preferably under the form of pure crystals from authorized varieties and parts of plants and making it possible to exclude any trace of delta-9 tetrahydrocannabinol (THC) in the finished product, in order to reduce the hit in the throat, the sensation of tingling in the throat felt by a vaper and/or facilitating inhalation of the composition representing the electronic cigarette liquid; - the use of the composition containing at least one diol, preferably 1.3 propanediol, with nicotine salt, that is to say nicotine-base to which an acid is added and cannabidiol preferably under the form of pure crystals from authorized varieties and parts of plants and allowing to exclude any trace of delta-9 tetrahydrocannabinol (THC) in the finished product as an electronic cigarette liquid allowing and facilitating the inhalation of a high concentration nicotine to smoking cessation;

- the use of the composition containing at least one diol, preferably 1.3 propanediol, nicotine base or nicotine salt, that is to say nicotine base to which an acid is added with cannabidiol preferably in the form of pure crystals derived from authorized varieties and parts of plants and making it possible to exclude any trace of delta-9 tetrahydrocannabinol (THC) in the finished product, allowing less fouling of the equipment;

- the use of the composition containing at least one diol, preferably 1.3 propanediol with nicotine base or nicotine salt, that is to say nicotine base to which an acid and cannabidiol are added preferably in the form of pure crystals derived from authorized varieties and parts of plants and making it possible to exclude any trace of delta-9 tetrahydrocannabinol (THC) in the finished product and with or without vegetable glycerin as an electronic cigarette liquid for improve the delivery of cannabidiol and nicotine;

- the use of the composition containing at least one diol, preferably 1.3 propanediol, nicotine base or nicotine salt, that is to say nicotine base to which an acid and cannabidiol are added preferably in the form of pure crystals derived from authorized varieties and parts of plants and making it possible to exclude any trace of delta-9 tetrahydrocannabinol (THC) in the finished product with or without vegetable glycerin in the presence of flavoring and/or or terpene as e-cigarette liquid to enhance aromatic power;

- an electronic cigarette containing a composition of any one of claims 1 to 2.

EXAMPLES OF REALIZATION

The invention and the resulting advantages will emerge more clearly from the following embodiments. However, these have no limiting scope. 1/ Compositions

These different compositions can be packaged in glass or plastic bottles (for example PET), generally with a volume of 10 ml, with a tip making it possible to fill an electronic cigarette without losses.

These different compositions can also be packaged in sealed cartridges with an advantageous capacity of 2 ml, intended for electronic cigarettes of the "POD" type, making it possible to exclude any manipulation and any incorporation of foreign bodies into the composition by the end user. .

Said bottles can be sold individually or in a kit comprising all or part of the bearings as defined in the table above.

Such a kit may also contain an electronic cigarette and instructions. These instructions may relate to the use of the electronic cigarette provided and/or the proposed withdrawal protocol, as detailed below. 2/ Sewing protocol

2-1 Principle of weaning in stages

The compositions according to the invention contain at least nicotine base (to which an acid is added) and Cannabidiol (CBD), the aim of the withdrawal protocol being to reverse the two molecules for the benefit of the non-addictive (CBD ) in the conduct of smoking, nicotine and vapor withdrawal.

The formulations are presented in the form of levels, ranging from level 1 (the most dosed in nicotine and free of CBD) to level 6 (100% CBD and free of nicotine), with intermediate levels that present different concentrations of nicotine / CBD .

This system of stages is intended to constitute the path leading to smoking, nicotine and vapological withdrawal with a treatment that will have a start date and an end date of use. It is recommended to use it for 3 to 6 months with the levels containing nicotine (levels 1 to 5), until use of the last level containing exclusively CBD, which can go up to 12 months for complete weaning from nicotine. tool, in this case the electronic cigarette.

The principle of the system of stages in the conduct of a three-dimensional withdrawal (tobacco, nicotine, vapor) aims to no longer worry about the right concentration of nicotine to choose, this work having already been done for smokers who can then focus only on their desire to quit smoking. The innovative method of the different levels, in particular the 6 levels defined below, associated with unique innovative formulations combining nicotine and CBD makes it possible to act on tobacco, nicotine and vapological dependence. The 6 levels defined below are to be respected and passed one after the other, without skipping steps. Only the starting level can vary according to the cigarette consumption of the smoker at the start of withdrawal.

2-2 Definition of levels

Step #1: Smoking cessation step

This is the starting level for heavy smokers (consumption of more than 1 pack of cigarettes per day) who first need to have a product highly concentrated in nicotine to compensate for stopping smoking and the lack of of nicotine associated with this quitting. In this first stage, there is no cannabidiol (CBD): we are tackling nicotine substitution at the level of tobacco dependence. Stages #2 and #3: Stages of smoking and nicotine withdrawal

These intermediate starting levels are intended for smokers who consume less than one pack of cigarettes per day. They allow these more or less moderate smokers to begin the work of smoking cessation via nicotine substitution at concentrations that remain high and appropriate according to the profile of the smoker concerned, while starting the CBD intake via low concentrations allowing to begin the body's assimilation of this molecule gently, while working on nicotine dependence and compensation for the lack, anxiety linked to the drop in nicotine thanks to the interactions of the molecule as previously detailed.

The objective is to stay on the same starting level until you no longer smoke a single cigarette for a period of 15 consecutive days before being able to move on to the next level.

Step #4: Nicotine withdrawal step

Once the starting level has been crossed, you can change levels from 15 days to 15 days, provided you do not smoke a single cigarette during this transition period. If this is the case, it is advisable to start again at the lower level and begin a new period of 15 days at this level. In this level 4, nicotine is no longer predominant, the work takes place on nicotine dependence. The anxiety linked to a lack of nicotine is partly compensated by the CBD which makes it possible to be less receptive to this lack. The hit will also be constant as in the lower levels, making it possible to obtain the same sensation in the throat without having the impression of having decreased in nicotine, a very impacting role in the conduct of smoking cessation.

Step #5: Nicotinic and vapor withdrawal step

At this level, consumption should naturally have decreased, the frequency of use of the electronic cigarette should be reduced. The CBD present compensates for the drop in nicotine, a hit is present and a sensation in the throat that persists a little more than in the previous levels contributes to less soliciting the use of the electronic cigarette. This level also begins to act on vapological dependence and habits related to gestures. The higher concentration of CBD, via physiological interactions as detailed above, gradually erases the psychological link of the notion of well-being in the face of tobacco addiction.

Step #6: Vaping weaning step

At this level, the objective is to be free of nicotine, the use of the electronic cigarette having to be done only at the end of the day or evening. This stage focuses on vapological weaning, that is to say weaning from the tool that made it possible to quit smoking. With the exclusive use of CBD, i.e. the non-addictive molecule, at a high concentration, it is to break the memory bridges linking the user to the attachment he had with tobacco and the associated notion of pleasure. After a few weeks at this last stage, the objective is to be able to stop everything up to the device used for weaning.

2-3 Conclusions

The different stages defined serve as a benchmark to help in a weaning process but can be adapted to each profile of smokers.

Two elements remain essential to ensure the best conduct of weaning for which the said composition has been studied and developed: these are nicotine and the "hit" in the throat, in particular adjusted thanks to the use of CBD.

Nicotine remains a very important and essential tool for the purpose of quitting smoking. Nicotine is not carcinogenic, is not responsible for lung or other diseases related to smoking. It remains addictive, just like caffeine for example. It is an ally to cross the first stages of starting, the following stages allowing to act on the dependence on nicotine, then vapological for a complete weaning via the use of the composition and the association nicotine / CBD.

The hit in the throat (sensation of passage in the throat) is very important for a smoker and in his participation in weaning. The hit of the said composition has been specially studied to best satisfy the smoker in his transition and differs from the hits that can be found in traditional e-liquids. The differentiated hit of the formulations has the particularity of being composed of a primary hit, which is felt at the level of the pharynx immediately when passing through the throat, and of a secondary hit, which extends more deeply after inhalation at the level of the larynx through the use of CBD. The combination of these two hits makes it possible to obtain a general hit that is as close as possible to inhaling a tobacco cigarette and thus promoting withdrawal. In practice, during the passage to the next level, the primary hit will be less intense but the secondary hit will be prolonged, making it possible to reduce the desire to consume while being satiated at the level of the sensation of the passage in the throat.

Claims

1. Combination of a cannabinoid, advantageously cannabidiol (CBD), and nicotine for use in the conduct of withdrawal, advantageously smoking, nicotine and/or vapology, using an electronic cigarette.

2. Combination for its use according to claim 1, in which the nicotine is in the form of nicotine salt.

3. Combination for its use according to claim 1 or 2, in which the combination is contained in a vaporizable liquid composition for an electronic cigarette.

4. Combination for its use according to claim 3, in which the nicotine is at a concentration less than or equal to 50 mg/ml of composition.

5. Combination for its use according to claim 3 or 4, in which the cannabinoid representing from 1 to 30% by weight of the composition.

6. Combination for its use according to one of claims 3 to 5, in which the composition further comprises an acid advantageously chosen from benzoic acid, lauric acid, salicylic acid and lactic acid, even more advantageously lactic acid.

7. Combination for its use according to one of claims 3 to 6, in which the composition further comprises a diol advantageously chosen from propylene glycol and propanediol, even more advantageously propanediol.

8. Combination for its use according to one of claims 3 to 7, in which the composition further comprises glycerin, advantageously vegetable, even more advantageously at a content less than or equal to 50% by weight of the composition.

9. Combination for its use according to one of claims 3 to 8, in which the composition further comprises at least one aroma and/or one terpene.

10. Combination for its use according to one of claims 3 to 9, in which the composition allows:

- to improve the dissolution and the bioavailability by inhalation of the cannabinoid, in particular of CBD; - promote interactions related to nicotine and cannabinoids, in particular CBD;

- to promote the delivery of nicotine and cannabinoids, in particular CBD;

- to reinforce the aromatic power;

- to reduce the fouling of the electronic cigarette;

- to reduce the tingling sensation in the throat felt when using the electronic cigarette; and or

- to facilitate its inhalation, in particular when it contains high concentrations of nicotine.

11. Kit comprising at least one composition as defined in one of claims 4 to 10, and possibly an electronic cigarette.

12. Kit comprising at least two compositions as defined in one of claims 3 to 10, advantageously kit according to claim 11, in which the at least two compositions have different nicotine concentrations.

13. Kit according to claim 12, in which the at least two compositions have different cannabinoid concentrations, advantageously with the sum of the nicotine and cannabinoid concentrations constant.

14. Smoking, nicotine and/or vapor withdrawal process comprising taking compositions as defined in one of claims 3 to 10 in stages, comprising decreasing concentrations of nicotine, advantageously ranging from 20 mg/ml to 5 mg/ml , even more advantageously 20, 15, 10 and 5 mg/ml.

15. Process according to claim 14, in which the compositions comprise increasing concentrations of cannabinoid, advantageously ranging from 5 mg/ml to 20 mg/ml, even more advantageously 5, 10, 15 and 20 mg/ml.