Composition

Abstract

The present invention relates to a synthetic composition comprising a first component and a second component. The first and second components are, or are derivable from, one or more extracts, such as lemon balm extract, passionflower extract, ginseng extract, chamomile extract, bacopa extract, valerian extract, black tea extract or ashwagandha extract.

Description

[0001] COMPOSITION FIELD OF THE INVENTION The present invention relates to compositions comprising a first component and a second component, to articles comprising the compositions, as well as to uses, methods and systems for administering the compositions to a user. BACKGROUND It is known that certain active compounds have a pharmacological effect when administered to a user. In some instances, the pharmacological effect may be utilized to influence a medical state of the user, i.e. the active compound is administered as a medicine. In other instances, the pharmacological effect may be utilized to influence a non-medical state of the user, e.g. the active compound is not administered as a medicine. An example of influencing a non-medical state might be the administration of caffeine to modulate alertness. The pharmacological effect of a particular active compound may depend on its ability to interact with one or more biological targets within the body of the user. The extent of the interaction with the one or more targets will influence the extent to which a pharmacological effect is perceived. In some instances, multiple active compounds can be administered to a user. The active compounds may each act on one or more biological targets to a different extent. It would be advantageous to develop improved compositions comprising multiple actives. SUMMARY OF THE INVENTION In one aspect, the present invention relates to a synthetic composition comprising a first component and a second component, wherein the first component comprises at least one compound derivable from lemon balm extract and the second component comprises at least one compound derivable from any of passionflower extract, ginseng extract, chamomile extract, bacopa extract, valerian extract, black tea extract or ashwagandha extract. In a further aspect, the present invention relates to the use of a synthetic composition as defined herein to modulate the neural state of a user. In a further aspect, the present invention relates to a method of modulating the neural state of a user, the method comprising administering to the user a synthetic composition as defined herein. In a further aspect, the present invention relates to an article comprising a synthetic composition as defined herein. These and other aspects of the present invention will now be further described. BRIEF DESCRIPTION OF THE FIGURES Figure 1a provides a concentration-response curve for combination 1 Figure 1b provides a concentration-response curve for combination 1 Figure 2a provides a concentration-response curve for combination 2 Figure 2b provides a concentration-response curve for combination 2 Figure 3a provides a concentration-response curve for combination 3 Figure 3b provides a concentration-response curve for combination 3 Figure 4a provides a concentration-response curve for combination 4 Figure 4b provides a concentration-response curve for combination 4 Figure 5a provides a concentration-response curve for combination 5 Figure 5b provides a concentration-response curve for combination 5 Figure 6a provides a concentration-response curve for combination 6 Figure 6b provides a concentration-response curve for combination 6 Figure 7a provides a concentration-response curve for combination 7 Figure 7b provides a concentration-response curve for combination 7 DETAILED DESCRIPTION

[0002] Synergy

[0003] The concept of “synergy” is generally understood as being present where the effect which results from a combination comprising multiple individual components is greater than the sum of the effect of each individual component in isolation. In the context of the present disclosure, the relevant effect is that which results from the application of the components (in isolation and in combination) to biological targets of interest. To quantify the interaction between the components, the observed combination effect is compared to the expected effect predicted by a reference model. When the combination effect is greater than expected, the combination is classified as synergistic. This is further explained in Yadav et al (2015, Computational and Structural Biotechnology Journal 13 (2015) 504-513).

[0004] Since the presence of synergy depends on the difference between the observed combination effect and the expected effect predicted by a reference model, the choice of the reference model can influence the conclusion as to whether synergy is determined to be present or not.

[0005] Reference models commonly used for the determination of synergy in the context of active components include: the Loewe model (Loewe S. The problem of synergism and antagonism of combined drugs. Arzneimittelforschung. 1953 Jun;3(6):285-90)\ the Bliss model (Bliss Cl. The toxicity of poisons applied jointly. Ann App Biol. 1939; 26: 585-615)', the zero interaction potency (ZIP) model (Yadav B, Wennerberg K, Aittokallio T, Tang J. Searching for Drug Synergy in Complex Dose-Response Landscapes Using an Interaction Potency Model. Comput Struct Biotechnol J. 2015 Sep 25;13:504-13) and the highest single agent (HSA) model (Foucquier J, Guedj M. Analysis of drug combinations: current methodological landscape. Pharmacol Res Perspect. 2015 Jun;3(3):e00149. doi: 10. 1002 / prp2. 149. Epub 2015 May 20. Erratum in: Pharmacol Res Perspect. 2019 Dec;7(6):e00549). These reference models will be referred to throughout the present disclosure as: the Loewe model; the Bliss model; the ZIP model and the HSA model. According to the present invention, the determination of synergy for a particular combination of components involves the step of evaluating which one, or combination, of the above reference models is most applicable.

[0006] Such an approach has resulted in the identification of synergistic synthetic combinations comprising a first component and a second component as defined herein.

[0007] Synthetic Composition

[0008] In one aspect, the present invention relates to a synthetic composition comprising a first component and a second component, wherein the first component comprises at least one compound derivable from lemon balm extract and the second component comprises at least one compound derivable from any of passionflower extract, ginseng extract, chamomile extract, bacopa extract, valerian extract, black tea extract or ashwagandha extract.

[0009] According to the present disclosure, the term “synthetic composition” refers to a composition which is produced by combining multiple individual and / or isolated compounds to form a composition, rather than via an extraction process whereby a starting composition containing multiple compounds is extracted and then purified or otherwise modified to reduce its constituent components. The use of an extract per se is not included in the production of a synthetic composition, it only being required that when an extract is utilized, one or more individual and / or isolated compounds or extracts is combined with the extract.

[0010] The present inventors have determined that such synthetic compositions display synergy or a synergistic behavior when applied in vitro to a biological target, in particular neural cells. The stimulation of neural cells by active components can be used to modulate a particular neural / mood state of the subject. For example, certain active components, such as some cannabinoids, may elicit a feeling of relaxation. Other active components, such as caffeine, may elicit a feeling of stimulation.

[0011] In the context of the present invention, eliciting relaxation extends to one or more of reducing stress, increasing sleep, and reducing muscle tension. Moreover, the present invention is generally aimed at eliciting a response which is not curative in the medical sense. Accordingly, the composition and uses described herein are for non-medical uses. In one embodiment, the composition is not used to treat pain. By determining the synergistic effect with respect to the stimulation of neural cells, it is possible to identify synergistic synthetic combinations that can be used to modulate the mood state of a user. According to the present invention, the synthetic composition comprises a first component, wherein the first component comprises at least one compound derivable from lemon balm extract. Lemon balm (Melissa officinalis) is a perennial herbaceous plant in the mint family. Extracts from lemon balm contain a range of active compounds. In this regard, the main active constituents of lemon balm are: volatile compounds such as geranial, neral, citronellal and geraniol; triterpenes, such as ursolic acid and oleanolic acid; phenolic acids, such as rosmarinic acid, caffeic acid and chlorogenic acid; and flavonoids such as quercetin, rhamnocitrin, and luteolin. In one embodiment, the first component comprises at least two compounds derivable from lemon balm extract. In one embodiment, the first component comprises at least three compounds derivable from lemon balm extract. In one embodiment, the first component comprises at least four compounds derivable from lemon balm extract. In one embodiment, the first component comprises at least five compounds derivable from lemon balm extract. In one embodiment, the first component comprises at least rosmarinic acid. In one embodiment, the first component comprises lemon balm extract. In one embodiment, the first component consists of lemon balm extract. In one embodiment, the first component comprises lemon balm extract comprising rosmarinic acid. In one embodiment, the first component comprises lemon balm extract comprising rosmarinic acid in an amount of least 3%wt based on the total weight of the extract. In one embodiment, the first component comprises lemon balm extract comprising rosmarinic acid in an amount of least 4.5%wt based on the total weight of the extract. In one embodiment, the first component comprises lemon balm extract comprising rosmarinic acid in an amount of least 5%wt based on the total weight of the extract. In one embodiment, the first component comprises lemon balm extract comprising rosmarinic acid in an amount of least 5.5%wt based on the total weight of the extract. In one embodiment, the first component comprises lemon balm extract comprising rosmarinic acid in an amount of least 5.8%wt based on the total weight of the extract. In one embodiment, the first component comprises lemon balm extract comprising rosmarinic acid in an amount of least 6%wt based on the total weight of the extract. When present as a lemon balm extract, the first component may be present in the synthetic composition in a range of from 0.1µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in a range of from 0.5µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in a range of from 1µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in a range of from 2µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in a range of from 3µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in a range of from 4µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in a range of from 5µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in a range of from 6µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in a range of from 7µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in a range of from 8µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in a range of from 9µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in a range of from 10µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in a range of from 0.1µg / ml to 24µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in a range of from 0.1µg / ml to 23µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in a range of from 0.1µg / ml to 22µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in a range of from 0.1µg / ml to 21µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in a range of from 0.1µg / ml to 20µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in a range of from 0.1µg / ml to 19µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in a range of from 0.1µg / ml to 18µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in a range of from 0.1µg / ml to 17µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in a range of from 0.1µg / ml to 16µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in a range of from 0.1µg / ml to 15µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 1µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 2µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 3µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 4µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 5µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 6µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 7µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 8µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 9µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 10µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 11µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 12µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 13µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 14µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 15µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 16µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 17µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 18µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 19µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 20µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 21µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 22µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 23µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 24µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in an amount of about 6.25µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in a range of from 0.39µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the lemon balm extract may be present in the synthetic composition in a range of from 1.56µg / ml to 6.25µg / ml based on the total volume of the synthetic composition. In a preferred embodiment, the lemon balm extract may comprise rosmarinic acid in an amount of at least 5%wt and be present in the synthetic composition in a range of from 1.56µg / ml to 6.25µg / ml based on the total volume of the synthetic composition. In a preferred embodiment, the lemon balm extract may comprise rosmarinic acid in an amount of at least 5%wt and be present in the synthetic composition in an amount of about 0.39µg / ml based on the total volume of the synthetic composition. In a preferred embodiment, the lemon balm extract may comprise rosmarinic acid in an amount of at least 5%wt and be present in the synthetic composition in an amount of about 25µg / ml based on the total volume of the synthetic composition. According to the present invention, the synthetic composition comprises a second component. According to the present invention, the second component comprises at least one compound derivable from any of passionflower extract, ginseng extract, chamomile extract, bacopa extract, valerian extract, black tea extract or ashwagandha extract. In one embodiment, the second component comprises at least two compounds derivable from any of passionflower extract, ginseng extract, chamomile extract, bacopa extract, valerian extract, black tea extract or ashwagandha extract. Passionflower (Passiflora incarnate) is an indigenous American vine with white and blue or purple flowers and an edible fruit. Extracts of passionflower contain a range of active compounds, including flavonoids. In one embodiment, the second component comprises at least one flavonoid derivable from passionflower extract. In one embodiment, the second component comprises at least two flavonoids derivable from passionflower extract. In one embodiment, the second component comprises at least three flavonoids derivable from passionflower extract. In one embodiment, the second component comprises at least four flavonoids derivable from passionflower extract. In one embodiment, the second component comprises at least five flavonoids derivable from passionflower extract. In one embodiment, the second component comprises passionflower extract. In one embodiment, the second component consists of passionflower extract. In one embodiment, the passionflower extract may be present in the synthetic composition in a range of from 0.5µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the passionflower extract may be present in the synthetic composition in a range of from 1µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the passionflower extract may be present in the synthetic composition in a range of from 2µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the passionflower extract may be present in the synthetic composition in a range of from 3µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the passionflower extract may be present in the synthetic composition in a range of from 4µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the passionflower extract may be present in the synthetic composition in a range of from 5µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the passionflower extract may be present in the synthetic composition in a range of from 6µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the passionflower extract may be present in the synthetic composition in a range of from 7µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the passionflower extract may be present in the synthetic composition in a range of from 8µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the passionflower extract may be present in the synthetic composition in a range of from 9µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the passionflower extract may be present in the synthetic composition in a range of from 10µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the passionflower extract may be present in the synthetic composition in a range of from 0.1µg / ml to 24µg / ml based on the total volume of the synthetic composition. In one embodiment, passionflower extract may be present in the synthetic composition in a range of from 0.1µg / ml to 23µg / ml based on the total volume of the synthetic composition. In one embodiment, the passionflower extract may be present in the synthetic composition in a range of from 0.1µg / ml to 22µg / ml based on the total volume of the synthetic composition. In one embodiment, the passionflower extract may be present in the synthetic composition in a range of from 0.1µg / ml to 21µg / ml based on the total volume of the synthetic composition. In one embodiment, the passionflower extract may be present in the synthetic composition in a range of from 0.1µg / ml to 20µg / ml based on the total volume of the synthetic composition. In one embodiment, the passionflower extract may be present in the synthetic composition in a range of from 0.1µg / ml to 19µg / ml based on the total volume of the synthetic composition. In one embodiment, the passionflower extract may be present in the synthetic composition in a range of from 0.1µg / ml to 18µg / ml based on the total volume of the synthetic composition. In one embodiment, the passionflower extract may be present in the synthetic composition in a range of from 0.1µg / ml to 17µg / ml based on the total volume of the synthetic composition. In one embodiment, the passionflower extract may be present in the synthetic composition in a range of from 0.1µg / ml to 16µg / ml based on the total volume of the synthetic composition. In one embodiment, the passionflower extract may be present in the synthetic composition in a range of from 0.1µg / ml to 15µg / ml based on the total volume of the synthetic composition. Chamomile is a member of the daisy family (Asteraceae or Compositae) and its extract contains a number of active compounds, including -bisabolol, bisabolol oxides A and B, chamazulene, azulenesse, farnesene and spiro-ether quiterpene lactones, glycosides, hydroxycoumarins, flavonoids such as apigenin, luteolin, patuletin, and quercetin, coumarins such as herniarin and umbelliferone, terpenoids, and mucilage. In one embodiment, the second component comprises at least one compound derivable from chamomile extract. In one embodiment, the second component comprises at least two compounds derivable from chamomile extract. In one embodiment, the second component comprises at least three compounds derivable from chamomile extract. In one embodiment, the second component comprises at least four compounds derivable from chamomile extract. In one embodiment, the second component comprises at least five compounds derivable from chamomile extract. In one embodiment, the second component comprises apigenin. In one embodiment, the second component comprises chamomile extract comprising at least apigenin. In one embodiment, the second component consists of chamomile extract comprising at least apigenin. In one embodiment, the second component comprises chamomile extract comprising at least apigenin in an amount of at least 0.5%wt. In one embodiment, the second component comprises chamomile extract comprising at least apigenin in an amount of at least 0.6%wt. In one embodiment, the second component comprises chamomile extract comprising at least apigenin in an amount of at least 0.7%wt. In one embodiment, the second component comprises chamomile extract comprising at least apigenin in an amount of at least 0.8%wt. In one embodiment, the second component comprises chamomile extract comprising at least apigenin in an amount of at least 0.9%wt. In one embodiment, the second component comprises chamomile extract comprising at least apigenin in an amount of at least 1.0%wt. In one embodiment, the second component comprises chamomile extract comprising at least apigenin in an amount of at least 1.1%wt. In one embodiment, the second component comprises chamomile extract comprising at least apigenin in an amount of at least 1.2%wt. In one embodiment, the chamomile extract may be present in the synthetic composition in a range of from 0.5µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the chamomile extract may be present in the synthetic composition in a range of from 1µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the chamomile extract may be present in the synthetic composition in a range of from 2µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the chamomile extract may be present in the synthetic composition in a range of from 3µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the chamomile extract may be present in the synthetic composition in a range of from 4µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the chamomile extract may be present in the synthetic composition in a range of from 5µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the chamomile extract may be present in the synthetic composition in a range of from 6µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the chamomile extract may be present in the synthetic composition in a range of from 7µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the chamomile extract may be present in the synthetic composition in a range of from 8µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the chamomile extract may be present in the synthetic composition in a range of from 9µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the chamomile extract may be present in the synthetic composition in a range of from 10µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the chamomile extract may be present in the synthetic composition in a range of from 0.1µg / ml to 24µg / ml based on the total volume of the synthetic composition. In one embodiment, chamomile extract may be present in the synthetic composition in a range of from 0.1µg / ml to 23µg / ml based on the total volume of the synthetic composition. In one embodiment, the chamomile extract may be present in the synthetic composition in a range of from 0.1µg / ml to 22µg / ml based on the total volume of the synthetic composition. In one embodiment, the chamomile extract may be present in the synthetic composition in a range of from 0.1µg / ml to 21µg / ml based on the total volume of the synthetic composition. In one embodiment, the chamomile extract may be present in the synthetic composition in a range of from 0.1µg / ml to 20µg / ml based on the total volume of the synthetic composition. In one embodiment, the chamomile extract may be present in the synthetic composition in a range of from 0.1µg / ml to 19µg / ml based on the total volume of the synthetic composition. In one embodiment, the chamomile extract may be present in the synthetic composition in a range of from 0.1µg / ml to 18µg / ml based on the total volume of the synthetic composition. In one embodiment, the chamomile extract may be present in the synthetic composition in a range of from 0.1µg / ml to 17µg / ml based on the total volume of the synthetic composition. In one embodiment, the chamomile extract may be present in the synthetic composition in a range of from 0.1µg / ml to 16µg / ml based on the total volume of the synthetic composition. In one embodiment, the chamomile extract may be present in the synthetic composition in a range of from 0.1µg / ml to 15µg / ml based on the total volume of the synthetic composition. Ginseng (such as Korean or panax ginseng) is known to contain active compounds referred to as ginsenosides. These ginsenosides include two classes: protopanaxadiols (and derivatives) and protopanaxatriols (and derivatives). In one embodiment, the second component comprises at least one compound derivable from ginseng extract. In one embodiment, the second component comprises at least two compounds derivable from ginseng extract. In one embodiment, the second component comprises at least three compounds derivable from ginseng extract. In one embodiment, the second component comprises at least four compounds derivable from ginseng extract. In one embodiment, the second component comprises at least five compounds derivable from ginseng extract. In one embodiment, the at least one compound derivable from ginseng extract is selected from Rb1, Re, Rd, Rc, Rg1 and Rb3 and mixtures thereof. In one embodiment, the second component comprises ginseng extract. In one embodiment, the second component consists of ginseng extract. In one embodiment, the ginseng extract may be present in the synthetic composition in a range of from 0.5µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the ginseng extract may be present in the synthetic composition in a range of from 1µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the ginseng extract may be present in the synthetic composition in a range of from 2µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the ginseng extract may be present in the synthetic composition in a range of from 3µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the ginseng extract may be present in the synthetic composition in a range of from 4µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the ginseng extract may be present in the synthetic composition in a range of from 5µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the ginseng extract may be present in the synthetic composition in a range of from 6µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the ginseng extract may be present in the synthetic composition in a range of from 7µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the ginseng extract may be present in the synthetic composition in a range of from 8µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the ginseng extract may be present in the synthetic composition in a range of from 9µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the ginseng extract may be present in the synthetic composition in a range of from 10µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the ginseng extract may be present in the synthetic composition in a range of from 0.1µg / ml to 24µg / ml based on the total volume of the synthetic composition. In one embodiment, ginseng extract may be present in the synthetic composition in a range of from 0.1µg / ml to 23µg / ml based on the total volume of the synthetic composition. In one embodiment, the ginseng extract may be present in the synthetic composition in a range of from 0.1µg / ml to 22µg / ml based on the total volume of the synthetic composition. In one embodiment, the ginseng extract may be present in the synthetic composition in a range of from 0.1µg / ml to 21µg / ml based on the total volume of the synthetic composition. In one embodiment, the ginseng extract may be present in the synthetic composition in a range of from 0.1µg / ml to 20µg / ml based on the total volume of the synthetic composition. In one embodiment, the ginseng extract may be present in the synthetic composition in a range of from 0.1µg / ml to 19µg / ml based on the total volume of the synthetic composition. In one embodiment, the ginseng extract may be present in the synthetic composition in a range of from 0.1µg / ml to 18µg / ml based on the total volume of the synthetic composition. In one embodiment, the ginseng extract may be present in the synthetic composition in a range of from 0.1µg / ml to 17µg / ml based on the total volume of the synthetic composition. In one embodiment, the ginseng extract may be present in the synthetic composition in a range of from 0.1µg / ml to 16µg / ml based on the total volume of the synthetic composition. In one embodiment, the ginseng extract may be present in the synthetic composition in a range of from 0.1µg / ml to 15µg / ml based on the total volume of the synthetic composition. Bacopa monnieri is a small perennial herbaceous plant belonging to the family Scrophulariaceae. Extracts of bacopa are known to contain a range of active compounds (Biomolecules.2020 Apr; 10(4): 536). In one embodiment, the second component comprises at least one compound derivable from bacopa extract. In one embodiment, the second component comprises at least two compounds derivable from bacopa extract. In one embodiment, the second component comprises at least three compounds derivable from bacopa extract. In one embodiment, the second component comprises at least four compounds derivable from bacopa extract. In one embodiment, the second component comprises at least five compounds derivable from bacopa extract. In one embodiment, the second component comprises bacopa extract. In one embodiment, the second component consists of bacopa extract. In one embodiment, the bacopa extract may be present in the synthetic composition in a range of from 0.5µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the bacopa extract may be present in the synthetic composition in a range of from 1µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the bacopa extract may be present in the synthetic composition in a range of from 2µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the bacopa extract may be present in the synthetic composition in a range of from 3µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the bacopa extract may be present in the synthetic composition in a range of from 4µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the bacopa extract may be present in the synthetic composition in a range of from 5µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the bacopa extract may be present in the synthetic composition in a range of from 6µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the bacopa extract may be present in the synthetic composition in a range of from 7µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the bacopa extract may be present in the synthetic composition in a range of from 8µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the bacopa extract may be present in the synthetic composition in a range of from 9µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the bacopa extract may be present in the synthetic composition in a range of from 10µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the bacopa extract may be present in the synthetic composition in a range of from 0.1µg / ml to 24µg / ml based on the total volume of the synthetic composition. In one embodiment, bacopa extract may be present in the synthetic composition in a range of from 0.1µg / ml to 23µg / ml based on the total volume of the synthetic composition. In one embodiment, the bacopa extract may be present in the synthetic composition in a range of from 0.1µg / ml to 22µg / ml based on the total volume of the synthetic composition. In one embodiment, the bacopa extract may be present in the synthetic composition in a range of from 0.1µg / ml to 21µg / ml based on the total volume of the synthetic composition. In one embodiment, the bacopa extract may be present in the synthetic composition in a range of from 0.1µg / ml to 20µg / ml based on the total volume of the synthetic composition. In one embodiment, the bacopa extract may be present in the synthetic composition in a range of from 0.1µg / ml to 19µg / ml based on the total volume of the synthetic composition. In one embodiment, the bacopa extract may be present in the synthetic composition in a range of from 0.1µg / ml to 18µg / ml based on the total volume of the synthetic composition. In one embodiment, the bacopa extract may be present in the synthetic composition in a range of from 0.1µg / ml to 17µg / ml based on the total volume of the synthetic composition. In one embodiment, the bacopa extract may be present in the synthetic composition in a range of from 0.1µg / ml to 16µg / ml based on the total volume of the synthetic composition. In one embodiment, the bacopa extract may be present in the synthetic composition in a range of from 0.1µg / ml to 15µg / ml based on the total volume of the synthetic composition. Valeriana officinalis (Valerian) is a perennial flowering plant native to Europe and Asia. Extracts from the root of valerian are known to contain a range of active compounds, including alkaloids, terpenes, organic acids and its derivatives, valepotriates and flavones. In one embodiment, the second component comprises at least one compound derivable from valerian extract. In one embodiment, the second component comprises at least two compounds derivable from valerian extract. In one embodiment, the second component comprises at least three compounds derivable from valerian extract. In one embodiment, the second component comprises at least four compounds derivable from valerian extract. In one embodiment, the second component comprises at least five compounds derivable from valerian extract. In one embodiment, the second component comprises valerian extract. In one embodiment, the second component consists of valerian extract. In one embodiment, the valerian extract may be present in the synthetic composition in a range of from 0.5µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the valerian extract may be present in the synthetic composition in a range of from 1µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the valerian extract may be present in the synthetic composition in a range of from 2µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the valerian extract may be present in the synthetic composition in a range of from 3µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the valerian extract may be present in the synthetic composition in a range of from 4µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the valerian extract may be present in the synthetic composition in a range of from 5µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the valerian extract may be present in the synthetic composition in a range of from 6µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the valerian extract may be present in the synthetic composition in a range of from 7µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the valerian extract may be present in the synthetic composition in a range of from 8µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the valerian extract may be present in the synthetic composition in a range of from 9µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the valerian extract may be present in the synthetic composition in a range of from 10µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the valerian extract may be present in the synthetic composition in a range of from 0.1µg / ml to 24µg / ml based on the total volume of the synthetic composition. In one embodiment, valerian extract may be present in the synthetic composition in a range of from 0.1µg / ml to 23µg / ml based on the total volume of the synthetic composition. In one embodiment, the valerian extract may be present in the synthetic composition in a range of from 0.1µg / ml to 22µg / ml based on the total volume of the synthetic composition. In one embodiment, the valerian extract may be present in the synthetic composition in a range of from 0.1µg / ml to 21µg / ml based on the total volume of the synthetic composition. In one embodiment, the valerian extract may be present in the synthetic composition in a range of from 0.1µg / ml to 20µg / ml based on the total volume of the synthetic composition. In one embodiment, the valerian extract may be present in the synthetic composition in a range of from 0.1µg / ml to 19µg / ml based on the total volume of the synthetic composition. In one embodiment, the valerian extract may be present in the synthetic composition in a range of from 0.1µg / ml to 18µg / ml based on the total volume of the synthetic composition. In one embodiment, the valerian extract may be present in the synthetic composition in a range of from 0.1µg / ml to 17µg / ml based on the total volume of the synthetic composition. In one embodiment, the valerian extract may be present in the synthetic composition in a range of from 0.1µg / ml to 16µg / ml based on the total volume of the synthetic composition. In one embodiment, the valerian extract may be present in the synthetic composition in a range of from 0.1µg / ml to 15µg / ml based on the total volume of the synthetic composition. The tea plant (Camellia sinensis) has been used to produce extracts for human consumption for many years. Black tea (produced via a particular fermentation process) is known to produce extracts containing a variety of active compounds. As well as containing a range of compounds such as polyphenols, black tea extract can contain compounds such as L-theanine. In one embodiment, the second component comprises at least one compound derivable from black tea extract. In one embodiment, the second component comprises at least two compounds derivable from black tea extract. In one embodiment, the second component comprises at least three compounds derivable from black tea extract. In one embodiment, the second component comprises at least four compounds derivable from black tea extract. In one embodiment, the second component comprises at least five compounds derivable from black tea extract. In one embodiment, the second component comprises L-theanine. In one embodiment, L-theanine may be present in the synthetic composition of this aspect in a range of from 0.01µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 19µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 18µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 17µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 16µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 15µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 14µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 13µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 12µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 11µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 10µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 5.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 4.9µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 4.8µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 4.7µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 4.6µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 4.5µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 4.4µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 4.3µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 4.2µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 4.1µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 4.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.02µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.03µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.04µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.05µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.06µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.07µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.08µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.09µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.1µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.2µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.3µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.4µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.5µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.6µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.7µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.8µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.9µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 1.0µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 2.0µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 3.0µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 4.0µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, the second component comprises black tea extract comprising at least L-theanine, wherein the black tea extract is present in the synthetic composition so as to provide the L-theanine in the composition in an amount of from 0.01µg / ml to 20.0µg / ml (or the other amounts as disclosed above) based on the total volume of the synthetic composition. Ashwagandha (Withania somnifera) is a herb. Ashwagandha extract is known to contain a variety of active compounds, including alkaloids such as isopelletierine, anaferine, cuseohygrine, anahygrine, steroidal lactones such as withanolides and withaferins, and saponins. In one embodiment, the second component comprises at least one compound derivable from Ashwagandha extract. In one embodiment, the second component comprises at least two compounds derivable from Ashwagandha extract. In one embodiment, the second component comprises at least three compounds derivable from Ashwagandha extract. In one embodiment, the second component comprises at least four compounds derivable from Ashwagandha extract. In one embodiment, the second component comprises at least five compounds derivable from Ashwagandha extract. In one embodiment, the second component comprises Ashwagandha extract. In one embodiment, the second component consists of Ashwagandha extract. In one embodiment, the Ashwagandha extract may be present in the synthetic composition in a range of from 0.5µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the Ashwagandha extract may be present in the synthetic composition in a range of from 1µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the Ashwagandha extract may be present in the synthetic composition in a range of from 2µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the Ashwagandha extract may be present in the synthetic composition in a range of from 3µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the Ashwagandha extract may be present in the synthetic composition in a range of from 4µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the Ashwagandha extract may be present in the synthetic composition in a range of from 5µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the Ashwagandha extract may be present in the synthetic composition in a range of from 6µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the Ashwagandha extract may be present in the synthetic composition in a range of from 7µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the Ashwagandha extract may be present in the synthetic composition in a range of from 8µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the Ashwagandha extract may be present in the synthetic composition in a range of from 9µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the Ashwagandha extract may be present in the synthetic composition in a range of from 10µg / ml to 25µg / ml based on the total volume of the synthetic composition. In one embodiment, the Ashwagandha extract may be present in the synthetic composition in a range of from 0.1µg / ml to 24µg / ml based on the total volume of the synthetic composition. In one embodiment, Ashwagandha extract may be present in the synthetic composition in a range of from 0.1µg / ml to 23µg / ml based on the total volume of the synthetic composition. In one embodiment, the Ashwagandha extract may be present in the synthetic composition in a range of from 0.1µg / ml to 22µg / ml based on the total volume of the synthetic composition. In one embodiment, the Ashwagandha extract may be present in the synthetic composition in a range of from 0.1µg / ml to 21µg / ml based on the total volume of the synthetic composition. In one embodiment, the Ashwagandha extract may be present in the synthetic composition in a range of from 0.1µg / ml to 20µg / ml based on the total volume of the synthetic composition. In one embodiment, the Ashwagandha extract may be present in the synthetic composition in a range of from 0.1µg / ml to 19µg / ml based on the total volume of the synthetic composition. In one embodiment, the Ashwagandha extract may be present in the synthetic composition in a range of from 0.1µg / ml to 18µg / ml based on the total volume of the synthetic composition. In one embodiment, the Ashwagandha extract may be present in the synthetic composition in a range of from 0.1µg / ml to 17µg / ml based on the total volume of the synthetic composition. In one embodiment, the Ashwagandha extract may be present in the synthetic composition in a range of from 0.1µg / ml to 16µg / ml based on the total volume of the synthetic composition. In one embodiment, the Ashwagandha extract may be present in the synthetic composition in a range of from 0.1µg / ml to 15µg / ml based on the total volume of the synthetic composition. In one embodiment, the second component comprises at least two compounds derivable from any of passionflower extract, ginseng extract, chamomile extract, bacopa extract, valerian extract, black tea extract or ashwagandha extract. For example, in one embodiment the second component comprises a compound derivable from black tea extract and a compound derivable from Ashwagandha extract. In one embodiment, the second component comprises a compound derivable from black tea extract, in particular L-theanine, and Ashwagandha extract. The first component and the second component may be present in the synthetic composition in defined amounts in dependence on the nature of the first and second component. In particular, where the first component comprises lemon balm extract, and the second component comprises at least one compound derivable from chamomile extract, the first component may be present in an amount of from about 1.56 to 6.25µg / ml and the second component may be present in an amount of about 6.25µg / ml. Moreover, the precise amount of each of the first and second component in the synthetic composition can be varied whilst still adhering to a particular ratio of each component on a µg / ml basis. Accordingly, in one embodiment, where the first component comprises lemon balm extract, and the second component comprises at least one compound derivable from chamomile extract, they can be present in the synthetic composition based on a ratio of 1-4 (first component):4 (second component). In particular, where the first component comprises lemon balm extract, and the second component comprises at least one compound derivable from passionflower extract, the first component may be present in an amount of about 6.25µg / ml and the second component may be present in an amount of from about 1.56 to 6.25µg / ml. Moreover, the precise amount of each of the first and second component in the synthetic composition can be varied whilst still adhering to a particular ratio of each component on a µg / ml basis. Accordingly, in one embodiment, where the first component comprises lemon balm extract, and the second component comprises at least one compound derivable from chamomile extract, they can be present in the synthetic composition based on a ratio of 4 (first component):1-4 (second component). In particular, where the first component comprises lemon balm extract, and the second component comprises at least one compound derivable from ashwagandha extract, the first component may be present in an amount of from about 6.25 to 25µg / ml and the second component may be present in an amount of from about 0.39 to 25µg / ml. Moreover, the precise amount of each of the first and second component in the synthetic composition can be varied whilst still adhering to a particular ratio of each component on a µg / ml basis. Accordingly, in one embodiment, where the first component comprises lemon balm extract, and the second component comprises at least one compound derivable from chamomile extract, they can be present in the synthetic composition based on a ratio of 16-64 (first component):1-64 (second component). In particular, where the first component comprises lemon balm extract, and the second component comprises at least one compound derivable from valerian extract, the first component may be present in an amount of about 6.25µg / ml and the second component may be present in an amount of from about 1.56 to 6.25µg / ml. Moreover, the precise amount of each of the first and second component in the synthetic composition can be varied whilst still adhering to a particular ratio of each component on a µg / ml basis. Accordingly, in one embodiment, where the first component comprises lemon balm extract, and the second component comprises at least one compound derivable from chamomile extract, they can be present in the synthetic composition based on a ratio of 4 (first component):1-4 (second component). In particular, where the first component comprises lemon balm extract, and the second component comprises at least one compound derivable from black tea extract, in particular L-theanine, the first component may be present in an amount of about 25µg / ml and the second component may be present in an amount of about 0.07 to 4.4µg / ml. Moreover, the precise amount of each of the first and second component in the synthetic composition can be varied whilst still adhering to a particular ratio of each component on a µg / ml basis. Accordingly, in one embodiment, where the first component comprises lemon balm extract, and the second component comprises at least one compound derivable from chamomile extract, they can be present in the synthetic composition based on a ratio of 357 (first component): 1-63 (second component). In particular, where the first component comprises lemon balm extract, and the second component comprises L-theanine and Ashwagandha extract, the first component may be present in an amount of about 25µg / ml and the Ashawgandha extract may be present in an amount of 3.125 6.25 µg / mL and the L-theanine may be present in an amount 0.391 100 µM (0.07 17.4 µg / mL) L-theanine. A preferred molar ratio of Ashwagandha extract (A): L-theanine (LT): lemon balm extract (LB) is 45 89 : 1 249 : 357 (A : LT : LB). Accordingly, the first component may be present in the synthetic composition relative to the second component according to the following mass per ml ratios: 1-4 (first component):4 (second component); 4 (first component):1-4 (second component); 16-64 (first component):1-64 (second component); or 357 (first component): 1-63 (second component). According to a further aspect, there is also provided a synthetic composition comprising at least one compound derivable from black tea extract and at least one compound derivable from ashwagandha extract. In one embodiment, the at least one compound derivable from black tea is at least L-theanine. The ashwagandha extract and the L- theanine can be present in the composition in a molar ratio of 714 : 1 - 249 (Ashwagandha:L-theanine). In one embodiment, L-theanine may be present in the synthetic composition of this aspect in a range of from 0.01µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 19µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 18µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 17µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 16µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 15µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 14µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 13µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 12µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 11µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 10µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 5.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 4.9µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 4.8µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 4.7µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 4.6µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 4.5µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 4.4µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 4.3µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 4.2µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 4.1µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 4.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.01µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.02µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.03µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.04µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.05µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.06µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.07µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.08µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.09µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.1µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.2µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.3µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.4µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.5µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.6µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.7µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.8µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 0.9µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 1.0µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 2.0µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 3.0µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, L-theanine may be present in the synthetic composition in a range of from 4.0µg / ml to 20.0µg / ml based on the total volume of the synthetic composition. In one embodiment, the second component comprises black tea extract comprising at least L-theanine, wherein the black tea extract is present in the synthetic composition so as to provide the L-theanine in the composition in an amount of from 0.01µg / ml to 20.0µg / ml (or the other amounts as disclosed above) based on the total volume of the synthetic composition. In one embodiment of this aspect, in addition to the at least one compound derivable from black tea outlined above, the composition comprises at least one compound derivable from Ashwagandha extract. In one embodiment, the composition comprises at least two compounds derivable from Ashwagandha extract. In one embodiment, the composition comprises at least three compounds derivable from Ashwagandha extract. In one embodiment, the composition comprises at least four compounds derivable from Ashwagandha extract. In one embodiment, the composition comprises at least five compounds derivable from Ashwagandha extract.

[0012] In one embodiment, the composition comprises Ashwagandha extract. In one embodiment, the second component consists of Ashwagandha extract.

[0013] In one embodiment of this aspect, the Ashwagandha extract may be present in the synthetic composition in a range of from 45pg / ml to 55pg / ml based on the total volume of the synthetic composition. In one embodiment, the Ashwagandha extract may be present in the synthetic composition in a range of from 47.5pg / ml to 52.5pg / ml based on the total volume of the synthetic composition. In one embodiment, the Ashwagandha extract may be present in the synthetic composition about 50pg / ml based on the total volume of the synthetic composition.

[0014] The synthetic composition of the present invention may be formulated as a delivery vehicle for delivery of the first and second components to a user. In this regard, the synthetic compositions defined herein may be formulated to deliver the first and second components to a user orally, nasally, respiratorily or transdermally.

[0015] In one embodiment, the synthetic composition is formulated to deliver the first and second components to a user respiratorily. In this regard, the synthetic composition may be formulated so as to be capable of forming an aerosol (either via condensation or atomization) for inhalation.

[0016] One example of such a formulation is as an aerosolisable liquid, gel or solid. In the context of the present disclosure, such a formulation is referred to as an aerosolgenerating material. Thus, in the context of this formulation of the synthetic composition, the terms “synthetic composition” and “aerosol-generating material” may be used interchangeably.

[0017] In one embodiment, the aerosol-generating material may comprise one or more aerosol former materials. The one or more aerosol-former materials may be selected from one or more of glycerol, propylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, 1 ,3-butylene glycol, erythritol, meso-Erythritol, ethyl vanillate, ethyl laurate, a diethyl suberate, triethyl citrate, triacetin, a diacetin mixture, benzyl benzoate, benzyl phenyl acetate, tributyrin, lauryl acetate, lauric acid, myristic acid, and propylene carbonate.

[0018] In the context of being formulated to deliver the first and second components to a user respiratorily, the aerosol-generating material may be used in a non-combustible aerosol provision system that releases compounds from an aerosol-generating material without combusting the aerosol-generating material, such as electronic cigarettes, tobacco heating products, and hybrid systems to generate aerosol using a combination of aerosol-generating materials.

[0019] According to the present disclosure, a “non-combustible” aerosol provision system is one where the aerosol-generating material of the aerosol provision system (or component thereof) is not combusted or burned in order to facilitate delivery of at least one substance to a user.

[0020] In some embodiments, the delivery system is a non-combustible aerosol provision system, such as a powered non-combustible aerosol provision system.

[0021] In some embodiments, the non-combustible aerosol provision system is an electronic cigarette, also known as a vaping device or electronic nicotine delivery system (END), although it is noted that the presence of nicotine in the aerosol-generating material is not a requirement.

[0022] In some embodiments, the non-combustible aerosol provision system is an aerosolgenerating material heating system, also known as a heat-not-burn system. An example of such a system is a tobacco heating system (wherein the aerosol-generating material comprises tobacco or a component derived therefrom).

[0023] In some embodiments, the non-combustible aerosol provision system is a hybrid system to generate aerosol using a combination of aerosol-generating materials, one or a plurality of which may be heated. In particular, each of the aerosol-generating materials may be, for example, in the form of a solid, liquid or gel and may or may not contain nicotine. In some embodiments, the hybrid system comprises a liquid or gel aerosol- generating material and a solid aerosol-generating material. The solid aerosol- generating material may comprise, for example, tobacco or a non-tobacco product. Typically, the non-combustible aerosol provision system may comprise a non- combustible aerosol provision device and a consumable for use with the non- combustible aerosol provision device. In some embodiments, the disclosure relates to consumables comprising aerosol- generating material and configured to be used with non-combustible aerosol provision devices. These consumables are sometimes referred to as articles throughout the disclosure. In some embodiments, the non-combustible aerosol provision system, such as a non- combustible aerosol provision device thereof, may comprise a power source and a controller. The power source may, for example, be an electric power source or an exothermic power source. In some embodiments, the exothermic power source comprises a carbon substrate which may be energised so as to distribute power in the form of heat to an aerosol-generating material or to a heat transfer material in proximity to the exothermic power source. In some embodiments, the non-combustible aerosol provision system may comprise an area for receiving the consumable, an aerosol generator, an aerosol generation area, a housing, a mouthpiece, a filter and / or an aerosol-modifying agent. In some embodiments, the consumable for use with the non-combustible aerosol provision device may comprise aerosol-generating material, an aerosol-generating material storage area, an aerosol-generating material transfer component, an aerosol generator, an aerosol generation area, a housing, a wrapper, a filter, a mouthpiece, and / or an aerosol-modifying agent. In one embodiment, the synthetic composition is formulated to deliver the first and second components to a user orally. In this regard, the synthetic composition may be formulated so as to be capable of delivering the first and second components to the buccal cavity of a user and / or the gastrointestinal tract of a user. In one embodiment, the synthetic composition may take the form of a lozenge, tablet, gum, gel, powder, chew, melt, liquid, or semi-solid lozenges, or article comprising inhalable powders, and oral products such as oral tobacco which includes snus or moist snuff, wherein the synthetic composition may or may not comprise nicotine. Such synthetic compositions are configured to release the first and second components to the buccal cavity of a user and / or the gastrointestinal tract of a user. The synthetic composition may be present in a pouch or capsule for buccal or GI release. When formulated for oral delivery, the synthetic composition can comprise the first and second components, and one or more fillers. The one or more fillers may generally comprise a sugar alcohol or a combination of sugar alcohols. In any of the above synthetic compositions which are formulated to deliver the first and second components orally or respiratorily, the synthetic composition may comprise one or more further constituents. In particular, one or more further constituents may be selected from one or more physiologically and / or olfactory active constituents, and / or one or more functional constituents. In some embodiments, the active constituent is an olfactory active constituent and may be selected from a "flavour" and / or "flavourant" which, where local regulations permit, may be used to create a desired taste, aroma or sensation in a product for adult consumers. In some instances such constituents may be referred to as flavours, flavourants, cooling agents, heating agents, or sweetening agents, and may include one or more of flavour enhancers, bitterness receptor site blockers, sensorial receptor site activators or stimulators, sugars and / or sugar substitutes (e.g., sucralose, acesulfame potassium, aspartame, saccharine, cyclamates, lactose, sucrose, glucose, fructose, sorbitol, or mannitol), and other additives such as charcoal, chlorophyll, minerals, botanicals, or breath freshening agents. They may be imitation, synthetic or natural ingredients or blends thereof. They may be in any suitable form, for example, oil, liquid, or powder. The flavor may be added to the aerosolisable material as part of a so- aerosolisable material. In some embodiments, the active constituent may be or derived from plants.

[0024] In one embodiment, the synthetic composition is formulated to deliver the first and second components to a user transdermally. In this regard, the synthetic composition may be formulated as an ointment, cream, gel, or rub.

[0025] In one embodiment, the synthetic composition is formulated to deliver the first and second components to a user nasally. In this regard, the synthetic composition may be formulated as a powder, liquid, or semi-solid.

[0026] As described generally herein, there is provided a synthetic composition comprising a synergistic combination of a first component and a second component. Whilst the first and second components have been described above as being present in the composition in certain concentrations and / or molar ratios, it will be appreciated to one skilled in the art that when an active component is present in a composition which is to be delivered to a user, certain factors may lead to less than 100% of the component present in the composition being available at the site of the biological target. Such factors include the “release” of the component from the composition (this may also include “transfer” of the component from one phase to another), as well as the bioavailability of the component once administered to a user.

[0027] One skilled in the art is able to perform routine testing to determine the “release” of the component from a particular formulation. For example, considering a liquid formulation which is to be delivered to the user via inhalation, one skilled in the art can determine the concentration of the relevant component in the formulation (since the formulation can be made and tested according to known chemical techniques) and then the amount of the relevant component present in an aerosol produced from the formulation can be tested by capturing the aerosol on, for example, a Cambridge filter pad and performing an analysis of the of the component captured (using standard analytical techniques). It is then possible to calculate the efficiency of the transfer from the liquid composition to the aerosol. An appropriate release scaling factor (Freiease) can then be applied to the amounts or ratios (such as molar ratios for individual compounds) of the components in the composition. The scaling factor represents the extent to which the amount or ratio of a particular component needs to be increased so as to approximate the composition amount or ratio in the formulated composition. Where there is 100% release, Freleaseis 1. Where there is 50% release, Frelease is 2. According to the present invention, Freleasefor any given synthetic formulation may be 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 9.0, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, 10.0, 11, 12, 13, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300, 350, 400, 450, or 500. With respect to oral bioavailability of a released component, a similar approach can be taken. For example, if the first component has a bioavailability of 100% and the second component has a bioavailability of 50% and the calculated ratio in order to achieve synergy in vitro are 2 (first component):1 (second component), then the synthetic composition formulated for delivery would have a ratio of 1 (first component):1 (second component), since twice as much of the second component would needed to achieve the desired ratio in vivo. According, when formulating the synthetic composition for a particular mode of administration, a bioavailability scaling factor (Favailability) can also be applied to the amounts or ratios of the components in the composition. The skilled person is aware of suitable software which can be used to predict bioavailability of various actives. A particular example in this regard is ADMET Predictor® from SimulationsPlus (https: / / www.simulations-plus.com / software / admetpredictor / ) In the context of the present disclosure, Favailabilityfor following first and second components as determined ADMET Predictor® are as follows: rosmarinic acid: about 0.97 apigenin: about 1 Accordingly, the concentrations and / or ratio of each component may need to be adjusted to account for said factors Frelease and / or Favailability. The extent of the adjustment will depend on the formulation used for delivery. For example, when the synthetic composition is formulated for delivery via inhalation, account can be taken firstly of the transfer of the component from the composition to an aerosol (if not already present as an aerosol), and secondly the bioavailability of the component once administrated respiratorily. The skilled person is able to determine both the transfer and bioavailability of each of the first and second component and adjust the concentration and / or ratio accordingly. Thus, in one embodiment, the synthetic composition is formulated to deliver the first and second components in a synergistic amount to a user. Use and method for modulating the relaxation state of a user In a further aspect, the present invention relations to the use of a synthetic composition as defined herein to modulate the neural state, e.g. relaxation state, of a user. Accordingly, in respect of the use, the specific first and second components, and their amounts in the composition, may be as outlined for the synthetic composition above. In a further aspect, the present invention relations to a method of modulating the neural state, e.g. relaxation state, of a user, the method comprising administering to the user a synthetic composition as defined herein. Accordingly, in respect of the method, the specific first and second components, and their amounts in the composition, may be as outlined for the synthetic composition above. Said modulation for the use or the method may be to increase the relaxation state of the user. In one embodiment of the use or method to modulate the relaxation state of a user, the synthetic composition is administered one, twice, three, four, five or more times per day. In one embodiment of the use or method to modulate the relaxation state of a user, the synthetic composition is administered one or two hours before the user goes to sleep. Method for determining the extent of synergy between a first component and a second component The present disclosure utilizes a method for determining the extent of synergy between a first component and a second component when applied to a target together via a synthetic composition.

[0028] The method comprises the steps of: i) performing an in vitro [Ca2+]i FLIPR Assay on the target using a first component at a plurality of concentrations of the first component to generate a raw data set in respect of the first component; ii) performing an in vitro [Ca2+]i FLIPR Assay on the target using a second component at a plurality of concentrations of the second component to generate a raw data set in respect of the second component; iii) performing an in vitro [Ca2+]i FLIPR Assay on the target using compositions comprising the first component and the second component at a plurality of concentrations to generate a raw data set in respect of the compositions; iv) evaluating the raw data in respect of the first and the second component to categorize each raw data set as being effect-based or concentration-based; v) applying one or more reference models of synergy to the raw data set in respect of the compositions based on the categorization of the raw data for the first and the second component; and vi) based on the application of the one or more reference models of synergy to raw data set in respect of the compositions, determining the extent of synergy between the first component and second component in the compositions.

[0029] The target can be a collection of cells, for example, neural cells.

[0030] The reference models can be selected from the Loewe model, the Bliss model, the ZIP model and / or the HSA model.

[0031] In one embodiment, step iv) includes the step of identifying and excluding positive outliers in the data. A suitable methodology for this may be Tukey’s test.

[0032] At least two of steps i), ii) or iii) can be performed using the same test cell source. This can result in improved accuracy of the assay. Synergy can be determined based on the statistical significance of at least one reference model producing a synergistic result for at least concentration combination. The raw data for each component can be categorized as being effect-based or concentration-based, dependent on its concentration-response curve profile. Typically, when the concentration-response curve for the first component is not sigmoidal, the reference model applied for step v) can comprise the Bliss and / or the HSA model. When the concentration-response curve for the second component is not sigmoidal, the reference model applied for step v) can comprise the Bliss and / or the HSA model. When the concentration-response curve for both the first and the second component is not sigmoidal, the reference model applied for step v) can comprise the Bliss and / or the HSA model. When the concentration-response curve for the first component is different to the concentration-response curve for the second, the reference model applied for step v) can comprise the Bliss and / or the HSA model. When the normalized response for at least one compound is above 100%, the reference model can be selected from the Loewe model and / or the HSA model. When the majority of the normalized responses are above 100%, the reference model can be selected from the Loewe model, the ZIP model and / or the HSA model. When the first component and the second component demonstrate different concentration response behaviors, the reference model can be selected from the Bliss model and / or the HSA model. An example of the first component and the second components demonstrating different concentration response behaviors, would be when the two components possess discordant slopes (a positive concentration-response trend for one and a negative concentration-response trend for the other). The first component for the method can be as described above with respect to the synthetic composition. The second component for the method can be as described above with respect to the synthetic composition. The compositions comprising the first and second components for the method are the synthetic compositions described herein. EXAMPLES Example 1 Evaluation of component mixtures on rat cortical culture using intracellular calcium oscillation 1.1 Introduction Rat primary brain cortical culture was selected as a system to investigate the effect of a list of compounds on intracellular calcium and cell viability. 2 Test items 2.1 Test items 2.2 Test mixtures

[0033] 2.3 - Test Item Formulation

[0034] Test items were dissolved in DMSO, at a concentration of 50 mM, and then stored at - 20°C until use.

[0035] 2.3.1. Test Item Assay Plate Preparation

[0036] Test compound stock solutions (50 mM in neat DMSO) were 4- fold serial diluted in DMSO using a Biomek NX to generate 7-point concentration response curves (ORC) at a concentration which is 250-fold the final assay concentration. Of this compound plate, appropriate volume of each well were stamped into V-bottom drug plates and diluted prior to the experiment with assay buffer to obtain 0.4% DMSO final concentration and the following test item final concentrations in the assay plate: 10 pM, 2.5 pM, 0.625 pM, 0.156 pM, 0.039 pM, 0.0 pM for cannabidiol (CBD); 100 pM, 25 pM, 6.25 pM, 1.56 pM, 0.39 pM, 0.0 pM for remaining test items when MW was available; 100 pg / ml, 25 pg / ml, 6.25 pg / ml, 1.56 pg / ml, 0.39 pg / ml, 0.0 pg / ml, when MW was not available (i.e. for extracts).

[0037] 3. EQUIPMENT

[0038] 3.1. FLIPR Tetra

[0039] FLIPR Tetra (Molecular Devices, San Jose, CA, USA) was used to detect intracellular calcium levels. The instrument is provided with excitation led at 470-495 nm wavelength and emission filter at 515-575 nm wavelength. The instrument is equipped with an automated 384-tips head which allows simultaneous compound dispensing and fluorescence reading. Temperature controller was set at 37°C for the duration of the experiment.

[0040] 4 - EXPERIMENTAL DESIGN

[0041] The experimental design aimed to assess the effect of test items on rat brain cortical culture using intracellular calcium oscillations.

[0042] The combination studies were performed in 384 wells plates. Each combination was performed in triplicate, in the same plate.

[0043] 5 - METHODS AND PROCEDURES

[0044] Rat cortical cell culture derived using the methodology described below was used at 14 DIV for the assays.

[0045] 5.1 - Rat Cortical Culture

[0046] Rat cortical neurons were obtained from rat (Sprague-Dawley) foetuses at embryonic day 18. After the pregnant rat sacrifice, foetuses were decapitated and cortices isolated. Cortices were enzymatically digested with Neuron Isolation Enzyme (ThermoFisher), following manufacturer’s instructions. Isolated cortical neurons were counted and suspended in complete neuronal medium containing Neurobasal Plus (ThermoFisher) supplemented with 2% B27 Plus (ThermoFisher) and 1 % Pen / Strep. Plating into 384- wells plates coated with 50 pg / mL poly-D-lysine (Sigma) was performed at a density of 7000 cells / well for calcium and viability assays. The cells were cultured in a 37 °C humidified incubator with 5% CO2. Half volume medium was removed and replenished with fresh medium once a week.

[0047] 5.2 - [Ca2+]i FLI PR Assay

[0048] 5.2.1 - FLIPR Solutions

[0049] Assay buffer was prepared, containing 145 mM NaCI, 5 mM KCI, 2 mM CaCI2, 1 g / litre D-(+)-glucose, 20 mM HEPES (pH 7.4).

[0050] Compound buffer was prepared from assay buffer, by addition of 0.05% Pluronic F-127 (Sigma).

[0051] Loading solution was prepared from assay buffer, by addition of 5 pM Cal-520 (Abeam), a cytoplasmic calcium indicator in the acetoxy I methyl (AM) ester form and 2.5 mM probenecid (Sigma). Probenecid, an inhibitor of organic anion transport, was added to calcium sensitive dye efflux. 5.2.2 FLIPR Protocol Compound assay ready plate preparation: preparation was performed as described in FLIPR compound addition: both fluorescent dye loaded cell plate and compound assay heated FLIPR chamber, for automated compound addition and simultaneous fluorescence reading. Cell plate fluorescence was read for 2 were dispensed by FLIPR in cell plate (0.4% final DMSO concentration), and fluorescence reading continued for additional 22 minutes. 6 ANALYSIS 6.1 - FLIPR Data Analysis FLIPR peak analysis: [Ca2+]ipeaks were measured during a 2 minute time-frame at 21- 22 min (20 min). [Ca2+]i peak detection and count was performed by Peak Pro software (Molecular Devices). 6.2. SynergyFinder Analysis Analysis was conducted to assess which mixtures were synergistic. The data from the 20 minutes time point were considered. An outlier analysis was performed on the thresholds based on the quartiles of the data. An extreme outlier is defined as values more than 1.5 times the interquartile range from the quartiles. Once the extreme observations were excluded, the response was normalized on the mean of positive and negative controls and expressed in percentage. For each drug, the concentration-response curve was estimated fitting a four-parameter logistic function. The test item interaction was evaluated performing the 4-reference models: Loewe additivity model, the Bliss model, the Zero Interaction Potency model (ZIP) and the Higher Single Agent model (HSA) (Yadav B et al, 2015; Foucquier J et al, 2015). The synergy score matrix was presented in the heat map and graphically represented with a surface plot. The heatmap reported the overall average of synergy scores and the single scores estimated, with 95% confidence interval, for each combination. An additional T-Test analysis was performed on bootstrapped estimated synergy scores under the null hypothesis of no-interaction. P-values lower than 0.05 were considered statistically significant. Data elaboration was performed with SAS V.9.4 and RStudio V.1.4.1717; drug interaction assessment was performed with the SynergyFinder package V.3.0.13. 7 RESULTS 7.1 [Ca2+]i FLIPR Assays on Compounds Mixtures Spontaneous calcium oscillations were present in 14 DIV cultures, before test item addition. Time matched vehicle controls data were used for statistical analysis. The results derived from the ZIP, HSA, Bliss and Loewe model were evaluated simultaneously to define the interaction of each drug in combination. The most appropriate model was considered to evaluate the interaction according to model assumptions. Effect-based models, such as Bliss and HSA, were preferred when the single agents concentration-response curves were not sigmoidal or had different concentration-response behaviour. The Bliss model was not suggested when most of normalized responses were above 100%. Otherwise, the dose-effect based Loewe model was preferred. Each combination was analysed by applying the models to the three replicates not averaged and the evaluation of the effects (Synergy / No effect / Antagonism) was performed after an accurate comparison with the concentration-response matrices. Table 1 summarizes the effects of the compounds mixtures on calcium oscillations, the chosen models and the concentration ranges where the effects were observed. Table 1

[0052] Combination 1 Lemon balm extract vs L-theanine: The compounds exhibited different concentration-response curves. A clear synergy was observed at 25 pg / ml for lemon balm extract and in a range of 0.39 - 25 pM for L-theanine. In addition, strong antagonism peaks were detected but not consistent in the context of the models matrices and in comparison with the concentration-response matrix. HSA model was applied for the estimation of the combinations effects with the results shown in Table 2. Concentration-responseCurves for the individual components are given in Figure 1a and Figure 1 b.

[0053] Table 2 Combination 2 Lemon balm extract vs chamomile extract: The compounds exhibited a similar trend in the concentration-response curves. Synergy was observed at 6.25 pg / ml for lemon balm extract and in a range of 1 .56 - 100 pg / ml for chamomile extract. The LOEWE model was applied for the estimation of the combinations effects, because of the nice fitting of the concentration-response curves, with the results shown in Table 3. Concentration-responseCurves for the individual components are given in Figure 2a and Figure 2b.

[0054] Table 3 Combination 3 Lemon balm extract vs passiflora incarnata extract: The compounds exhibited an opposite trend in the concentration-response curves. Strong synergism was observed at 6.25 pg / ml for lemon balm extract and in a range of 1 .56 - 6.25 pg / ml for passiflora incarnata extract. In addition, strong antagonism peaks were detected but not consistent in the context of the models matrices and in comparison with the dose- reponse matrix. BLISS and HSA models were applied for the estimation of the combinations effects with the results shown in Table 4. Concentration-responseCurves for the individual components are given in Figure 3a and Figure 3b.

[0055] Table 4 Combination 4 Ashwagandha extract vs lemon balm extract: The compounds exhibited a similar trend in the concentration-response curves. Synergism was observed in a range of 0.39 - 25 pg / ml for ashwagandha extract and 6.25 - 25 pg / ml for lemon balm extract. LOEWE model was applied for the estimation of the combinations effects, because of the nice fitting of the concentration-response curves, with the results shown in Table 5. Concentration-responseCurves for the individual components are given in Figure 4a and Figure 4b.

[0056] Table 5 Combination 5 Lemon balm extract strong vs powdered valerian extract: The compounds exhibited different concentration-response curves. Synergy was observed at 6.25 pg / ml for Lemon Balm extract strong and in a range of 1 .56 - 6.25 pg / ml for powdered valerian extract. HSA model was applied for the estimation of the combinations effects with the results shown in Table 6. Concentration-response Curves for the individual components are given in Figure 5a and Figure 5b.

[0057] Table 6 Combination 6 Lemon balm extract vs L-theanine and ashwagandha extract: The compounds exhibited different concentration-response curves. A clear synergy was balm extract and in a range of 0.39 100 µM of L- theanine 3.125 6.25 µg / mL of Ashawgandha extract. HSA model was applied for the estimation of the combination effects with the results shown in Table 7. Concentration- response curves for the Ashwagandha extract and L-theanine are given in Figure 6a and Figure 6b. Table 7 Combination 7 L-theanine vs ashwagandha extract: The compounds exhibited different concentration-response curves. A clear synergy was observed at 50 Ashawgandha exract and in a range of 0.39 100 µM of L-theanine. HSA model was applied for the estimation of the combinations effects with the results shown in Table 8. Concentration-response curves for the Ashwagandha extract and L-theanine are given in Figure 7a and Figure 7b. Table 8

[0058] The present disclosure will now be further described with reference to the following numbered paragraphs: 1. A synthetic composition comprising a first component and a second component, wherein the first component comprises at least one compound derivable from lemon balm extract and the second component comprises at least one compound derivable from any of passionflower extract, ginseng extract, chamomile extract, bacopa extract, valerian extract, black tea extract or ashwagandha extract. 2. The synthetic composition according to paragraph 1, the first component comprises lemon balm extract. 3. The synthetic composition according to paragraph 2, wherein the lemon balm extract comprises rosmarinic acid in an amount of least 3%wt based on the total weight of the extract. 4. The synthetic composition according to any one of paragraphs 1 to 3, wherein the second component comprises at least one compound derivable from passionflower extract. 5. The synthetic composition according to any one of paragraphs 1 to 3, wherein the second component comprises at least one compound derivable from chamomile extract. 6. The synthetic composition according to any one of paragraphs 1 to 3, wherein the second component comprises at least one compound derivable from black tea extract, wherein the compound is preferably L-theanine. 6a. The synthetic composition according to any one of paragraphs 1 to 3, wherein the second component comprises at least one compound derivable from black tea extract, wherein the compound is preferably L-theanine, and at least one compound derivable from ashwagandha extract, preferably ashwagandha extract. 7. The synthetic composition according to any one of paragraphs 1 to 3, wherein the second component comprises at least one compound derivable from ashwagandha extract. 8. The synthetic composition according to any one of paragraphs 1 to 3, wherein the second component comprises at least one compound derivable from valerian extract. 9. The synthetic composition according to any one of preceding paragraphs, wherein the composition is formulated to deliver the first and second components to a user orally, nasally, respiratorily or transdermally. 10. The synthetic composition according to paragraph 9, wherein the composition is formulated to deliver the first and second components to a user respiratorily and is an aerosol generating material. 11. The synthetic composition according to paragraph 10, wherein the aerosol generating material comprises one or more aerosol former materials. 12. The synthetic composition according to paragraph 11, wherein the one or more aerosol-former materials may comprise one or more of glycerol, propylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, 1,3-butylene glycol, erythritol, meso-Erythritol, ethyl vanillate, ethyl laurate, a diethyl suberate, triethyl citrate, triacetin, a diacetin mixture, benzyl benzoate, benzyl phenyl acetate, tributyrin, lauryl acetate, lauric acid, myristic acid, and propylene carbonate. 13. The synthetic composition according to paragraph 9, wherein the composition is formulated to deliver the composition to a user orally, nasally, or transdermally. 14. The synthetic composition according to paragraph 13, wherein the delivery system is configured to deliver the composition orally and takes the form of a lozenge, tablet, gum, gel, powder, chew, melt, liquid, or semi-solid lozenges, or article comprising inhalable powders, and oral products such as oral tobacco which includes snus or moist snuff, wherein the synthetic composition may or may not comprise nicotine. 15. The synthetic composition according to paragraph 13, wherein the delivery system is configured to deliver the composition transdermally and takes the form of an ointment, cream or rub. 16. The synthetic composition according to paragraph 13, wherein the delivery system is configured to deliver the composition nasally and takes the form of a powder, liquid, or semi-solid. 17. The synthetic composition according to any of the preceding paragraphs, wherein the µg / ml ratio of first component to second is in a range selected from: 1-4 (first component):4 (second component); 4 (first component):1-4 (second component); 16-64 (first component):1-64 (second component); or 357 (first component): 1-63 (second component). 18. The synthetic composition according to any one of the preceding paragraphs, where the first component comprises lemon balm extract, and the second component comprises at least one compound derivable from chamomile extract, the first component may be present in an amount of from about 1.56 to 6.25µg / ml and the second component may be present in an amount of about 6.25µg / ml. 19. The synthetic composition according to any one of paragraphs 1 to 17, where the first component comprises lemon balm extract, and the second component comprises at least one compound derivable from passionflower extract, the first component may be present in an amount of about 6.25µg / ml and the second component may be present in an amount of from about 1.56 to 6.25µg / ml. 20. The synthetic composition according to any one of paragraphs 1 to 17, where the first component comprises lemon balm extract, and the second component comprises at least one compound derivable from ashwagandha extract, the first component may be present in an amount of from about 6.25 to 25µg / ml and the second component may be present in an amount of from about 0.39 to 25µg / ml. 21. The synthetic composition according to any one of paragraphs 1 to 17, where the first component comprises lemon balm extract, and the second component comprises at least one compound derivable from valerian extract, the first component may be present in an amount of about 6.25µg / ml and the second component may be present in an amount of from about 1.56 to 6.25µg / ml. 22. The synthetic composition according to any one of paragraphs 1 to 17, where the first component comprises lemon balm extract, and the second component comprises at least one compound derivable from black tea extract, in particular L-theanine, the first component may be present in an amount of about 25µg / ml and the second component may be present in an amount of about 0.07 to 4.4µg / ml. 23. The use of a synthetic composition as defined in any one of paragraphs 1 to 22 to modulate the neural state of a user, preferably the relaxation state. 24. The use according to paragraph 23, wherein the relaxation state of the user is increased following administration to a user. 25. A method of modulating the relaxation state of a user, the method comprising administering to the user a synthetic composition as defined in any one of paragraphs 1 to 22. 26. An article comprising a synthetic composition as defined in any one of paragraphs 1 to 22. 27. The article according to paragraph 26, wherein the article contains the synthetic composition, and wherein the article comprises a container, a pouch, a patch, or a capsule. 28. The article according to paragraph 27, wherein the container is for use with an aerosol provision system. In conclusion, in order to address various issues and advance the art, this disclosure shows by way of illustration various embodiments in which the claimed invention(s) may be practiced. The advantages and features of the disclosure are of a representative sample of embodiments only, and are not exhaustive and / or exclusive. They are presented only to assist in understanding and to teach the claimed invention(s). It is to be understood that advantages, embodiments, examples, functions, features, structures, and / or other aspects of the disclosure are not to be considered limitations on the disclosure as defined by the claims or limitations on equivalents to the claims, and that other embodiments may be utilised and modifications may be made without departing from the scope of the claims. Various embodiments may suitably comprise, consist of, or consist essentially of, various combinations of the disclosed elements, components, features, parts, steps, means, etc. other than those specifically described herein. The disclosure may include other inventions not presently claimed, but which may be claimed in future.

Claims

CLAIMS 1. A synthetic composition comprising a first component and a second component, wherein the first component comprises at least one compound derivable from lemon balm extract and the second component comprises at least one compound derivable from any of passionflower extract, ginseng extract, chamomile extract, bacopa extract, valerian extract, black tea extract or ashwagandha extract.

2. The synthetic composition according to claim 1, the first component comprises lemon balm extract.

3. The synthetic composition according to claim 2, wherein the lemon balm extract comprises rosmarinic acid in an amount of least 3%wt based on the total weight of the extract.

4. The synthetic composition according to any one of claims 1 to 3, wherein the second component comprises at least one compound derivable from passionflower extract.

5. The synthetic composition according to any one of claims 1 to 3, wherein the second component comprises at least one compound derivable from chamomile extract.

6. The synthetic composition according to any one of claims 1 to 3, wherein the second component comprises at least one compound derivable from black tea extract, wherein the compound is preferably L-theanine.

7. The synthetic composition according to any one of claims 1 to 3, wherein the second component comprises at least one compound derivable from ashwagandha extract.

8. The synthetic composition according to any one of claims 1 to 3, wherein the second component comprises at least one compound derivable from valerian extract.

9. The synthetic composition according to any one of preceding claims, wherein the composition is formulated to deliver the first and second components to a user orally, nasally, respiratorily or transdermally.

10. The synthetic composition according to claim 9, wherein the composition is formulated to deliver the first and second components to a user respiratorily and is an aerosol generating material.

11. The synthetic composition according to claim 10, wherein the aerosol generating material comprises one or more aerosol former materials.

12. The synthetic composition according to claim 11, wherein the one or more aerosol-former materials may comprise one or more of glycerol, propylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, 1,3-butylene glycol, erythritol, meso-Erythritol, ethyl vanillate, ethyl laurate, a diethyl suberate, triethyl citrate, triacetin, a diacetin mixture, benzyl benzoate, benzyl phenyl acetate, tributyrin, lauryl acetate, lauric acid, myristic acid, and propylene carbonate.

13. The synthetic composition according to claim 9, wherein the composition is formulated to deliver the composition to a user orally, nasally, or transdermally.

14. The synthetic composition according to claim 13, wherein the delivery system is configured to deliver the composition orally and takes the form of a lozenge, tablet, gum, gel, powder, chew, melt, liquid, or semi-solid lozenges, or article comprising inhalable powders, and oral products such as oral tobacco which includes snus or moist snuff, wherein the synthetic composition may or may not comprise nicotine.

15. The synthetic composition according to claim 13, wherein the delivery system is configured to deliver the composition transdermally and takes the form of an ointment, cream or rub.

16. The synthetic composition according to claim 13, wherein the delivery system is configured to deliver the composition nasally and takes the form of a powder, liquid, or semi-solid.

17. The synthetic composition according to any of the preceding claims, wherein the µg / ml ratio of first component to second is in a range selected from: 1-4 (first component):4 (second component); 4 (first component):1-4 (second component); 16-64 (first component):1-64 (second component); or 357 (first component): 1-63 (second component).

18. The synthetic composition according to any one of the preceding claims, where the first component comprises lemon balm extract, and the second component comprises at least one compound derivable from chamomile extract, the first component may be present in an amount of from about 1.56 to 6.25µg / ml and the second component may be present in an amount of about 6.25µg / ml.

19. The synthetic composition according to any one of claims 1 to 17, where the first component comprises lemon balm extract, and the second component comprises at least one compound derivable from passionflower extract, the first component may be present in an amount of about 6.25µg / ml and the second component may be present in an amount of from about 1.56 to 6.25µg / ml.

20. The synthetic composition according to any one of claims 1 to 17, where the first component comprises lemon balm extract, and the second component comprises at least one compound derivable from ashwagandha extract, the first component may be present in an amount of from about 6.25 to 25µg / ml and the second component may be present in an amount of from about 0.39 to 25µg / ml.

21. The synthetic composition according to any one of claims 1 to 17, where the first component comprises lemon balm extract, and the second component comprises at least one compound derivable from valerian extract, the first component may be present in an amount of about 6.25µg / ml and the second component may be present in an amount of from about 1.56 to 6.25µg / ml.

22. The synthetic composition according to any one of claims 1 to 17, where the first component comprises lemon balm extract, and the second component comprises at least one compound derivable from black tea extract, in particular L-theanine, the first component may be present in an amount of about 25µg / ml and the second component may be present in an amount of about 0.07 to 4.4µg / ml.

23. The use of a synthetic composition as defined in any one of claims 1 to 22 to modulate the neural state of a user, preferably the relaxation state.

24. A method of modulating the relaxation state of a user, the method comprising administering to the user a synthetic composition as defined in any one of claims 1 to 22.

25. An article comprising a synthetic composition as defined in any one of claims 1 to 22.

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