WO2022024096A1 - Compositions and methods for promoting weight loss and for treatment of obesity - Google Patents

Abstract

Compositions and methods are provided for treating obesity or promoting weight loss. The compositions generally comprise at least one edible or medicinal mushroom or extract thereof, at least one cannabinoid, curcuminoid, and terpene, and optionally one more of a flavonoid and a phenolic antioxidant. Methods for optimizing compositions using artificial intelligence algorithms are also provided.

Description

COMPOSITIONS AND METHODS FOR PROMOTING WEIGHT LOSS AND FOR TREATMENT OF OBESITY

CROSS-REFERENCE TO RELATED APPLICATIONS

[1] This claims the benefit of United States Provisional Patent Application No. 63/059,942 filed July 31, 2020, the entirety of which is incorporated herein by reference.

BACKGROUND

Field of the Invention

[2] This relates generally to compositions and methods useful to promote weight loss and in the treatment of obesity. More particularly this relates to nutraceutical and/or pharmaceutical compositions comprising mushrooms or extracts thereof, cannabis extracts, terpenes, and flavonoids, and the like.

Description of Related Art

[3] Obesity is a worldwide problem, particularly in developed nations and more particularly in the United States and Mexico, where obesity has reached epidemic proportions. Obesity is defined as a body mass index (BMI) of greater than 30; severe obesity is defined as a BMI of 40 or greater. Curiously perhaps, the wealth of a nation is not necessarily a predictor of its obesity and obesity is actually on the rise in certain middle income and even poorer nations, such as India, Brazil, and China.

[4] Obesity and excess weight in general are associated with increased health problems, particularly increased risks of chronic diseases such as cardiovascular disease (e.g. coronary artery disease, carditis, cardiomyopathy, cardiac arrhythmia, end-stage renal disease, stroke, and obstructive sleep apnea), atherosclerosis, metabolic syndrome, hyperinsulinemia, hyperlipidemia, type 2 diabetes, hypertension and related disorders, and certain cancers. Obesity is closely associated with metabolic malfunctions involving lipid and glucose metabolism and influences organ dysfunction involving the heart, liver, intestines, lungs, hormones, and reproductive functions. Hormonal cancers and tumor development are positively correlated with obesity. These many effects are likely effectuated through a variety of biological pathways such as excess secretion of bioactive molecules and immunomodulators from adipose tissue (including secretion of inflammatory adipokines including cytokines (TNF-a, IL- 1, and IL-6), complement proteins and growth factors, which generate local steatonecrosis in the vascular system and cause inflammation and endothelial dysfunction), and aromatase action leading to excess presence of estrogens (produced by converting the androgens A4-androstenedione and testosterone). The excess estrogens (particularly in post-menopausal women) ultimately inhibit apoptosis and promote cellular proliferation in the breast epithelium and endometrium. Obesity is also coupled with numerous other pathological effects due to the extra body weight (i.e., worsening of osteoarthritis, sleep apnea, gout, and pain of the vertebral column).

[5] By some accounts, obesity is directly or indirectly responsible for 18% of deaths among Americans 40-85 years of age. Some believe that obesity problem is so grave that it has surpassed both cigarette smoking and the opioid epidemic as a public health concern. Moreover, it is clear that generally, obesity is completely preventable.

[6] In addition to the critical public health concerns in connection with obesity, there are also large economic losses associated with obesity. Estimates of the costs of prevention, diagnostics, and treatment alone approach $150 billion dollars (in 2008 terms). In addition to those direct costs, there are costs such as lost time from work and reduced productivity, enhanced susceptibility to other (secondary) illnesses (colds, flu, infections, etc.), increased risk of physical injuries (biomechanical / movement injuries, back injuries, falls, knee and hip injuries, and the like). Obesity has also been associated with an increase in autoimmune disease because adipose tissue generates inflammatory factors.

[7] Strategies for addressing the obesity problem include a multi-billion dollar diet industry, psychotherapy, counseling and support groups, taxing high caloric foods or beverages, restricting portions sizes that can be sold to consumers, surgical interventions, drugs (both prescription and over the counter), supplements, and more. While any of these strategies may be effective for specific individual cases, none these have proven broadly effective oir capable of resolving this recalcitrant problem. [8] Childhood obesity is of particular concern as it has been on the rise over the last few decades, although it has plateaued from time to time. Children who suffer from obesity may face a lifetime of health struggles, including biomechanical issues, diabetes, psychological problems, self-esteem issues, and more. The spread of childhood obesity can have multigenerational impact on a society, the costs of which are enormous on many levels individually, within families and/or communities, and nationally.

[9] Mushrooms have long been used as a healthy and low-calorie food source, and in connection with weight loss. Among the multitude of potentially therapeutic compounds present in mushrooms are complex sugars and polysaccharides (substituted or not) (e.g. glucans, glycosides, glycopeptides, and glycoproteins), terpenes and/or terpenoids, sterols, peptides, amino acids, and other small and large molecules. More recently, psilocybin, a psychedelic from mushrooms has been used in conjunction with psychotherapy to help with weight loss. It is not presently known if there have been any reported results from such studies that have been adequately tested and reproduced.

[10] Cannabis spp. have also been used in connection with weight loss or obesity. The discovery of the endogenous endocannabinoid system originally believed to be primarily directed to neurological and psychiatric effects. However, based improved understanding of endocannabinoid biology, naturally occurring and exogenous cannabinoids are increasingly recognized as having possible role(s) in both inflammation and obesity. A role for endocannabinoids in inflammatory processes suggested by studying exogenous cannabinoids, particularly naturally occurring cannabinoids from Cannabis sativa, as well as synthetic compounds that can interact with CB1 and CB2 receptors.

[11] The ongoing discovery of less abundant cannabinoids continues to broaden our knowledge about the range of cannabinoids in plants, and their ability to function in regulation of the endocannabinoid system in humans. Our understanding of the role and potential therapeutic value of such compounds is ongoing. Thus, the use of exogenous cannabinoids and their ability to regulate (particularly upregulate) the endocannabinoid system as a therapeutic approach present possibilities for addressing obesity. [12] Other compounds such as terpenes, flavonoids, phenolic antioxidants and various botanicals are known to provide beneficial and healthful functions when consumed or administered.

[13] Obesity and weight loss are a topic of ongoing concern. There is an ongoing need for new compositions and methods that are useful for promoting weight loss, treating obesity, or promoting healthy body weight.

SUMMARY

[14] In a first of the several aspects of this disclosure, the inventor has discovered that certain pharmaceutical and/or nutraceutical compositions generally comprising combinations of one or more edible or medicinal mushrooms or an extract, fraction, or isolate thereof, one or more cannabinoids, one or more curcuminoids, one or more terpenes, and optionally, one or more flavonoids or phenolic antioxidants.

[15] The mushroom or mushroom extract present in the compositions is from any edible or medicinal mushroom species. The edible or medicinal mushroom in various embodiments comprises one or more of these species Agaricus blazei, A. bisporus, A. subrufescens, Agrocybe aegerita, A. cylindracea, Albatrellus caeruleoporus, Amanita muscaria, Boletus edulis, Cantharellus cibarius, C. tubaeformis, Cordyceps militaris, C. pruinose, Caripia montagnei, Coriolus versicolor, Cyathus africanus, C. hookeri, Daldinia childiae, Dictyophora indusiata (synonym: Phallus indusiatus), Elaphomyces granulatus, Flammulina velutipes, Fomitopsis pinicola, Grifola frondosa, Ganoderma lucidum, Geastrum saccatum, Inonotus oblu uus, Lactarius deliciosus, L. rufus, Lentinus edodes, L. polychrous, Lyophyllum decastes, Phellinus linteus, Pholiota nameko, Pleurotus pulmonarius, Pleurotus tuber-regium, Poria cocos, and Termitomyces albuminosus, Tremella fuciformis.

[16] The cannabinoids can be derived from any Cannabis spp. The terpenes and flavonoids can be derived from Cannabis or from any natural or synthetic source. The compositions optionally include other nutraceutical or botanical compounds to provide additional functionality or support. In one embodiment the citrus- derived flavonoid naringenin is useful herein.

[17] The inventor has surprisingly discovered that a composition comprising one or more edible or medicinal mushrooms, one or more cannabinoids, one or more curcuminoids, one or more terpenes, and at least one flavonoid and / or phenolic antioxidant with has many benefits for treatment of obesity or severe obesityes, and the compositions provide certain useful properties, such as effectiveness including over a long period of time, low toxicity, no serious side effects, and good tolerance on the part of a wide range of subjects.

[18] In another of its several aspects, provided are methods of treating a subject suffering from obesity or severe obesity. The methods generally comprise administering a therapeutically effective dose of a composition to the subject. The compositions generally comprise one or more edible or medicinal mushrooms or an extract, fraction, or isolate thereof, one or more cannabinoids, one or more curcuminoids, one or more terpenes, and optionally, one or more flavonoids or phenolic antioxidants. Additional components can also be included, such as S- adenosylmethionine, methylfolate, omega-3 fatty acids, or a B vitamin, vitamin D or a compound providing a biologically available form thereof. Other components can include fish oil, primrose oil, or an extract of one or more of black cumin, ginger, fenugreek, licorice, coriander, tomato, carrot, sweet potato, broccoli, green tea, rosemary, hazelnut, walnut, wheat germ, or date, or any combination thereof. Garlic extract, alpha lipoic acid (ALA), niacin, and/or nicotinamide may also be useful herein. The methods are generally applicable to obesity, severe obesity, and obesity-related diseases. Generally, an obesity- related disease comprising an inflammatory condition, chronic inflammation, metabolic syndrome, cardiovascular disease, hypertension, diabetes, or hyperlipidemia, or any other disease or condition caused directly or indirectly by obesity, or associated with obesity by the ordinarily skilled artisan such as a medical doctor, nutritionist, psychologist, or the like.

[19] In various embodiments, the methods result in body weight loss ranging from 5% to 25% or more of a subject's body weight.

[20] The disclosure also provides a plurality of dosing regimens that utilize the compositions, and variations thereof, on various schedules as dictated by the physiological or psychological health of the subject, and the status of the person having obesity or an obesity-related disease.

[21] In yet another aspect, methods are provided for optimizing a composition for use in treatment of a subject suffering from obesity or severe obesity. The methods generally employ the use of artificial intelligence algorithms, such as classification algorithms, regression algorithms, clustering algorithms, or a combination thereof.

[22] The methods generally comprise:

[23] a) providing data on the therapeutic effect on the obesity or severe obesity of each of:

[24] i) a plurality of edible or medicinal mushrooms, mushroom extracts, or components thereof;

[25] ii) a plurality of cannabinoids or combinations thereof;

[26] iii) a plurality of curcuminoids or combinations thereof;

[27] iv) a plurality of terpenes or combinations thereof;

[28] v) a plurality of flavonoids or combinations thereof;

[29] vi) a plurality of phenolic antioxidants or combinations thereof and optionally,

[30] vii) a plurality of combinations of compositions comprising one or more of mushrooms or extracts thereof, cannabinoids, curcuminoids, terpenes, and flavonoids; or

[31] viii) a plurality of optional ingredients comprising ALA or conjugated ALA, S-adenosylmethionine, methylfolate, omega-3 fatty acids, or a B vitamin or vitamin D or a compound providing a biologically-available form thereof, fish oil, primrose oil, or an extract of one or more of black cumin, ginger, fenugreek, licorice, coriander, tomato, carrot, sweet potato, broccoli, green tea, rosemary, hazelnut, walnut, wheat germ, date, or any combination thereof, garlic extract, alpha lipoic acid (ALA), niacin, and/or nicotinamide;

[32] b) using an artificial intelligence algorithm to analyze the data for the mushrooms or extracts, cannabinoids, curcuminoids, terpenes, and flavonoids; and

[33] c) generating one or more base profiles of compositions optimized for therapeutic treatment of the obesity or severe obesity;

[34] d) optionally, using the artificial intelligence algorithm to analyze the data for the combination compositions and the optional ingredients, and [35] e) generating one or more complete profiles of compositions with and without the optional ingredients.

[36] .

[37] The data for use in the artificial intelligence algorithm can be obtained from original experiments or literature review.

[38] In a final aspect, this disclosure provides methods for treating obesity or severe obesity in a patient in need thereof. The methods generally comprise the step of administering a composition comprising at least one edible or medicinal mushroom or extract thereof, in combination with at least one cannabinoid, at least one curcuminoid, at least one terpene, and at least one flavonoid. The at least one cannabinoid, at least one curcuminoid, at least one terpene, and at least one flavonoid are conveniently administered separately from, sequentially to, or simultaneously with the edible or medicinal mushroom. The at least one edible or medicinal mushroom or extract thereof is also administered separately from, sequentially to, or simultaneously with the cannabinoid, curcuminoid, terpene, and flavonoid.

[39] These and/or further aspects, features, and advantages of the present invention will become apparent to those skilled in the art in view of this disclosure.

BRIEF DESCRIPTION OF THE DRAWINGS

DETAILED DESCRIPTION

[40] Provided herein are compositions and methods for treating obesity or severe obesity. The methods are applicable to obesity, sever obesity, as well as obesity related diseases in a subject. Surprisingly, the compositions allow a modern practitioner to combine the benefits of certain compounds found in edible and medicinal mushrooms (such as used for centuries in Chinese and other traditional medicine practices, and by e.g. herbalists throughout the world), with the positive benefits of another natural substance, cannabis, also used for centuries. The compositions further utilize certain beneficial terpenes and flavonoids derived from Cannabis and other natural or synthetic sources, such as citrus, and other nutraceutical or pharmaceutical compounds. Used properly, these compositions have little risk, few side effects, and are effective for producing measurable and lasting results in patients suffering from obesity, or obesity-related diseases.

Definitions & Abbreviations

[41] Unless expressly defined otherwise, all technical and scientific terms, terms of art, and acronyms used herein have the meanings commonly understood by one of ordinary skill in the art in the field(s) of the invention, or in the field(s) where the term is used. In accordance with this description, the following abbreviations and definitions apply.

[42] The term "obesity" as used herein includes both the general sense of a person who is there ideal body mass index (BMI) and needs to lose weight, and specifically to a person with a body mass index of 30 or greater. "Severe obesity" as used herein means that a person has a BNI of 40 or greater.

[43] As the skilled artisan will appreciate, as used herein the term "edible" does not mean merely capable of being eaten. In that overly broad sense, even poisonous or toxic mushrooms are 'edible' however lethal or sickening or the like. In contrast "edible mushrooms" is used herein in the sense of mushrooms that are used traditionally or in modern times as sources of food, nutrients, nutraceuticals, flavors, and the like. Edible mushrooms are neither toxic nor poisonous as consumed.

[44] "Medicinal mushrooms" as used herein means any mushroom species that has been used traditionally or in modern times as a source of medicinal or therapeutic benefits, healing properties, and / or healthful compounds. It should be noted that the medicinal mushrooms may not be edible in all embodiments herein, and may in fact be poisonous if eaten, however, one or more extracts therefrom or components extracted or isolated therefrom may be perfectly useful herein.

[45] Notwithstanding the foregoing exception(s), generally, mushrooms that are edible or medicinal may be grouped together, as there may be many crossovers and it may be difficult to clearly distinguish between the two groups. Examples of edible and / or medicinal mushrooms useful herein include mushrooms of the genera Agaricus, Agrocybe, Albatrellus, Amanita, Auricularia, Boletus, Cantharellus, Cordyceps, Caripia, Cyathus, Daldinia, Dictyophora, Elaphomyces, Elammulina, Fomitopsis, Grifola, Ganoderma, Geastrum, Hericium, Inonotus, Lactarius, Lentinus, Lyophyllum, Phellinus, Pholiota, Pleurotus, Poria, Termitomyces, Trametes, and Tremeda. Species of particular interest include Agaricus blazei, A. bisporus, A. subrufescens, Agrocybe aegerita, A. cylindracea, Albatrellus caeruleoporus, Amanita muscaria, Boletus edulis, Cantharellus cibarius, C. tubaeformis, Cordyceps militaris, C. pruinose, Caripia montagnei, Cyathus africanus, C. hookeri, Daldinia childiae, Dictyophora indusiata (synonym: Phallus indusiatus), Elaphomyces granulatus, Flammulina velutipes, Fomitopsis pinicola, Grifola frondosa, Ganoderma lucidum, Geastrum saccatum, Inonotus obliquus, Eactarius deliciosus, L. rufus, Eentinus edodes, L. polychrous, Eyophyllum decastes, Phellinus linteus, Pholiota nameko, Pleurotus pulmonarius, Poria cocos, and Termitomyces albuminosus.

[46] More generally edible and / or medicinal mushrooms can be useful in connection with the current disclosure for treating obesity, severe obesity, or obesity-related diseases, directly or indirectly. For example, the therapeutic uses may include: preventing and/or treating obesity, helping recover from large gains of weight due to a variety of factor, promoting healthy weight loss, stimulating and / or supporting the immune system, reducing or mitigating the psychological affects (e.g. stress, anxiety, or the like) of obesity, generally promoting of health, providing antioxidant functionality, reducing metabolic syndrome, reducing adipocyte formation or activation, stimulating or promoting immune system health, or the like.

[47] Reishi mushrooms have been reported to aid in weight loss. Cordyceps has been reported to have adaptagenic properties and stimulate the adrenals glands and modulates the nervous system. Many other mushrooms may be useful herein, including mushrooms that help mitigate the inflammatory effects of obesity. For purposes herein, the publication by Elsayed, Elsayed A et al. entitled "Mushrooms: a potential natural source of anti-inflammatory compounds for medical applications." (Mediators of Inflammation Vol. 2014 (2014): 805841. doi:10.1155/2014/805841) provides a list of anti-inflammatory mushrooms and active components therein. Any of the mushrooms or anti-inflammatory components described in the publication, which is incorporated herein by reference, may be useful herein. [48] "Cannabis" or "Cannabis spp." as used herein refers to any plant of the genus Cannabis, including plants that may be classified as Cannabis sativa, Cannabis indica, or Cannabis ruderalis. It is well known that despite the foregoing list, some experts believe that there are only 2 species, and still others consider that there is only a single species (generally, C. sativa). Whatever nomenclature is used, for purposes of this disclosure, “Cannabis" includes all possible members of the genus, without regard to the species to which they are assigned.

[49] As used herein 'cannabinoids' means any of a class of compounds that generally can interact with one or more cannabinoid receptors, including the receptors of the endocannabinoid system, in particular, CB1 and CB2. Cannabinoids include e.g., phytocannabinoids and synthetic cannabinoids. Phytocannabinoids are found in several plant species, especially Cannabis spp. Among the most prevalent and most studied cannabinoids are tetrahydrocannabinol (THC), and cannabidiol (CBD). However, there are at least ~120 known cannabinoids that have been identified in Cannabis within certain classes including the tetrahydrocannabinols, cannabidiols, cannabigerols, cannabinols, cannabichromenes, and cannabinodiol. Other cannabinoids, such as cannabicyclol, cannabieslsoin, and cannabitriol are currently classed as 'miscellaneous' by some researchers. THC is not only a major cannabinoid in Cannabis spp., it is generally the compound responsible for the psychoactive effects of consuming Cannabis. However, other cannabinoids, such as cannabinol may also be at least mildly psychoactive. Certain other cannabinoids such as CBD may help regulate or attenuate the psychoactive effects of other cannabinoids. For purposes herein, compositions may be created with various ratios of cannabinoids, such as the ratio of CBD to THC or other ratios depending the specific person or the specific condition being treated.

[50] As used herein, "curcuminoids" means any of the compounds associated with turmeric or curcumin, as derived rhizome of the plant Curcuma longa, or synthetic versions or derivative thereof. Curcuminoids include but are not limited to curcumin (aka diferuloylmethane), analogs of curcumin such as demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC), turmerones, and turmeric oil. Also include are metabolites of curcumin such as tetrahydrocurcumin (THCU), hexahydrocurcumin, and octahydrocurcumin. Conjugates, such as curcumin glucuronide and curcumin sulfate, are also included herein. Conjugation may also provide opportunities for improved delivery of curcumins herein, for example, conjugation to peptide carriers, or polylactic-co-gly colic acid [PLGA]; as well as complexation with essential oils; coadministration with piperine; and encapsulation into nanoparticles, liposomes, phytosomes, polymeric micelles, and cyclodextrins may also be useful herein.

[51] As used herein, "terpenes" means any of the organic compounds commonly known as terpenes or terpenoids. Terpenes are generally aromatic compounds classified as isoprene derivatives. Terpenes suitable for use herein include hemiterpenes, monoterpenes, sesquiterpenes, diterpenes, sesterterpenes, triterpenes, sesquaterpenes, tetraterpenes, polyterpenes, and norisoprenoids. Exemplary terpenes that are particularly useful herein include alpha bisabolol, alpha pinene, beta caryophyllene, beta pinene, borneol, camphor, camphene, caryophyllene oxide, cineole, delta-3 carene, eucalyptol, farnesenes, farnesol, fenchol, fenchone, geraniol, guaiol, humulene, isopulegol, limonene, linalool, menthol, myrcene, nerol, nerolidol, ocimene, pinene, phytol, pulegone, terpinene, terpineol, terpinolene, and valencene.

[52] As used herein "phenolic antioxidants" means any antioxidant compound that is useful as a pharmacological agent or a food component, and which comprises a phenol or polyphenol. Examples include quercetin, curcumin, resveratrol, and ergothioneine. For purposes herein, curcumin is separately included as a curcuminoid. These phenolics may work to treat obesity based on their ability to protect against intracellular oxidative stress, increase metabolism, reduce chronic inflammation (perhaps by inhibiting TNF and IL production and secretion), stimulate lipolysis, inhibit adipogenesis, and / or interfere with the ability of preadipocytes to mature into adipocytes. Various other related polyphenols, such as biologically active antioxidant derivatives of quercetin, curcumin, resveratrol, and ergothioneine are also contemplated for use herein. Both synthetic and natural phenolic antioxidant compounds may be used, and at present phenolic antioxidants from natural sources such as plants or mushrooms are preferred.

[53] As used herein, "flavonoids" includes any of the class of polyphenolic molecules containing 15 carbon atoms that are naturally produced in plants and are soluble in water. Also included herein as "flavonoids" are natural or synthetic derivative or analogs thereof that have biological activity. Flavonoids of use herein can generally be divided in to 6 groups of structurally related compounds: chaicones, flavones, isoflavonoids, flavanones, anthoxanthins, and anthocyanins. Also useful are flavanols and catechins, as well as glucosides or other derivatives or analogs of any of the foregoing. The flavonoids are found in most fruits and vegetables, particular colorful ones. They are also prevalent in legumes (including soybeans), grains, green and black teas, as well as red wine.

[54] Flavonoids have numerous functions in plants, and act as important cell messengers. Various flavonoids are believed to provide healthful benefits and functions to humans such as anti-viral, anti-cancer, anti-inflammatory, antiallergic, and anti-oxidant properties. They may also be cardio-protective, cholesterol lowering, and anti-atherosclerotic. Natural or synthetic flavonoids from any source may be used herein. Generally natural flavonoids are preferred. Flavonoids isolated from Cannabis, such as cannaflavins A, B, and or C, are of interest in certain applications, as are vitexin, isovitexin, apigenin, kaempferol, quercetin, orientin, and luteolin, as well as the catechins found in Cannabis. In some presently preferred embodiments, the flavonoid, naringenin, from citrus is particularly useful herein.

[55] "Traditional Jamaican medicinal plants" means any plant that has been used in traditional or indigenous medicine or herbalism practices in Jamaica or other Caribbean states. The book, “Common Medicinal Plants of Portland, Jamaica" by Thomas and Austin, provides a useful list of a number of such plants. The book was published in its second edition in 2010 by CIEER. For purposes herein, the definition of such traditional Jamaican medicinal plants" expressly excludes Cannabis spp.

[56] As used herein, the singular form of a word includes the plural, and vice versa, unless the context clearly dictates otherwise. Thus, the references "a", "an", and "the" are generally inclusive of the plurals of the respective terms. For example, reference to "a composition" or "a mushroom extract" includes a plurality of such "compositions" or "mushroom extracts."

[57] The words "comprise", "comprises", and "comprising" are to be interpreted inclusively rather than exclusively. Likewise, the terms "include", "including" and "or" should all be construed to be inclusive, unless such a construction is clearly prohibited from the context. Further, forms of the terms "comprising" or "including" are intended to include embodiments encompassed by the phrases "consisting essentially of" and "consisting of". Similarly, the phrase "consisting essentially of" is intended to include embodiments encompassed by the phrase "consisting of".

[58] Where used herein, ranges are provided in shorthand, so as to avoid having to list and describe each and every value within the range. Any appropriate value within the range can be selected, where appropriate, as the upper value, lower value, or the terminus of the range.

[59] The methods and devices and/or other advances disclosed here are not limited to particular methodology, protocols, and/or structures described herein because, as the skilled artisan will appreciate, they may vary. Further, the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to, and does not, limit the scope of that which is disclosed or claimed.

[60] Although any devices, methods, articles of manufacture, or other means or materials similar or equivalent to those described herein can be used in the practice of the present invention, the preferred compositions, methods, articles of manufacture, or other means or materials are described herein.

[61] All patents, patent applications, publications, technical and/or scholarly articles, and other references cited or referred to herein are in their entirety incorporated herein by reference to the extent permitted under applicable law. Any discussion of those references is intended merely to summarize the assertions made therein. No admission is made that any such patents, patent applications, publications or references are prior art, or that any portion thereof is either relevant or material to the patentability of what is claimed herein.

Applicant specifically reserves the right to challenge the accuracy and pertinence of any assertion that such patents, patent applications, publications, and other references are prior art, or are relevant, and/or material.

Abbreviations

[62] The following abbreviations apply unless indicated otherwise: ALA: alpha lipoic acid;

APM: "Apollon Medical" strain of C. sativa;

BDMC; bisdemethoxycurcumin;

CBD: cannabidiol;

CBG: cannabigerol;

CBN: cannabinol;

CLA: conjugated linoleic acid;

DMC: demethoxycurcumin;

DMT: N,N-Dimethyl tryptamine;

5-HT: 5-hydroxytryptamine;

KNN: K Nearest Neighbor;

NK: natural killer cells;

NS AID: nonsteroidal anti-inflammatory drugs;

OCD: obsessive compulsive disorder;

PKC0: protein kinase C theta;

PLGA: polylactic-co-glycolic acid;

SVM: Support Vector Machines;

THC: tetrahydrocannabinol;

THCU: tetrahydrocurcumin; and

THCV: tetrahydrocannabi varin.

Detailed Description of Illustrative Embodiments

[63] In a first of its several aspects, compositions generally comprising one or more edible or medicinal mushrooms or extracts, fractions, isolates, or components thereof are provided. The compositions further generally comprise one or more cannabinoids, one or more terpenes, and optionally, one or more flavonoids.

[64] In various embodiments, the edible or medicinal mushroom(s) comprise one or more of Agaricus, Agrocybe, Albatrellus, Amanita, Auricularia, Boletus, Cantharellus, Cordyceps, Caripia, Cyathus, Daldinia, Dictyophora, Elaphomyces, Flammulina, Fomitopsis, Grifola, Ganoderma, Geastrum, Hericium, Inonotus, Lactarius, Lentinus, Lyophyllum, Phellinus, Pholiota, Pleurotus, Poria, Termitomyces, Trametes, and Tremella. [65] These mushrooms are all well-known edible and/or medicinal mushrooms with a long history of use. Without limiting the invention to any particular theory of operation, mushrooms, such as Reishi, Chaga, Turkey Tail, Lion's Head, shitake, maitake, and many others have a plethora of beneficial and potentially therapeutic compounds present in them. For example, the polysaccharides, peptides, and/or other small molecules in various mushrooms have been shown to regulate the production of certain molecular mediators of inflammation and functions of immune cells (e.g. B- and/or T-cells) as well as pro-inflammatory lymphocytes, T-helper cells, T-killer cells, and macrophages. These processes may be related to obesity in a number of ways and share some of the same mediator molecules and pathways. The same glycan has also been shown to be involved with suppressing tumor necrosis factor (TNF-a). Phenolics like betulin and betulinic acid in Chaga are believed to have anti-inflammatory properties.

[66] Regardless of the mechanism(s) responsible, the compositions preferably comprise the benefits of such edible or medicinal mushroom(s) as described above.

[67] The mushroom(s) in certain presently preferred embodiments comprises one or more species such as Agaricus blazei, Albatrellus confluens, Antrodia camphorate, Boletus badius, Clitocybe maxima, Cordyceps militaris, Cordyceps sinensis, Cordyceps liangshanensis, Cordyceps gunnii, Cordyceps cicadicola, Flanulina velutipes, Pomes fomentarius, Punalia trogii, Ganoderma lucidum, Grifoloa fondosa, Hericium erinaceus, Inocybe umbrinella, lonatus olbiquus, Lactarius flavidulus, Lentinula edodes, Phellinus linteus, Pleurotus ostreatus, Schizophyllum commune, Suillus placidus, or Trametes versicolor. In other embodiments, presently preferred species include Agaricus blazei, A. bisporus, A. subrufescens, Agrocybe aegerita, A. cylindracea, Albatrellus caeruleoporus, Amanita muscaria, Boletus edulis, Cantharellus cibarius, C. tubaeformis, Cordyceps militaris, C. pruinose, Caripia montagnei, Cyathus africanus, C. hookeri, Daldinia childiae, Dictyophora indusiata (synonym: Phallus indusiatus), Elaphomyces granulatus, Plammulina velutipes, Fomitopsis pinicola, Grifola frondosa, Ganoderma lucidum, Geastrum saccatum, Inonotus obliquus, Lactarius deliciosus, L. rufus, Lentinus edodes, L. polychrous, Lyophyllum decastes, Phellinus linteus, Pholiota nameko, Pleurotus pulmonarius, Poria cocos, and Termitomyces albuminosus. [68] The edible or medicinal mushrooms or extracts can be present as fresh mushrooms, or as a dried mushroom or extract thereof, a lyophilized mushroom preparation, a mushroom powder, or an aqueous or alcohol extract (e.g. an ethanolic or other alcohol extract) of mushroom. Extracts for purposes herein can include hot- or cold-water extracts. Mushroom concentrates, or partially purified or even extensively purified mushroom fractions, or fully purified components or isolates from a mushroom are also useful herein.

[69] In certain embodiments, preferably, various extracts, concentrates, or partially purified fractions, or the like, are enriched for one or more advantageous mushroom component, or compounds with desirable effects on treatment of obesity, severe obesity, or obesity-related diseases, immune status, or general health. In one embodiment, the extract, concentrate, partially purified fraction, or the like are enriched for one or more phenolic acids, flavonoids, triterpenes, carotenoids, stilbenes, sterols, fatty acids, lignans, chitosan, polyphenols, polysaccharides, glycosides, glucans, polysaccharide-protein complexes, glycoproteins, polysaccharopeptide, krestin, tocopherols, peptides, cyclic peptides, or other amino compounds found in the mushroom.

[70] While certain edible and / or medicinal mushrooms have been explored for their use in the therapeutic treatment of obesity, severe obesity, or obesity-related diseases, the inventors have discovered that by providing mushroom extracts with additional compounds such as cannabinoids, terpenes, flavonoids, and other components, the benefits for treating obesity can be derived from the treatments with better outcomes and fewer side effects. In certain embodiments herein, lentinan, eritadenine, and other mushrooms compounds are useful whether present in crude extracts, partially purified, purified, or substantially purified.

[71] The compositions in various embodiments therefor also include cannabinoids, comprising one or more of cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), tetrahydrocannabinol (THC) or tetrahydrocannabivarin (THCV).

[72] In certain embodiments, the cannabinoids are derived from hemp, or the THC content is removed from the cannabinoids such that THC is present in the composition at less than about 0.3 percent. In various embodiments, the THC content may be less than 0.2, or even less than 0.1% of the composition.

[73] In other embodiments, the ratio of cannabinoids is set in the compositions. For example, in certain embodiments, the ratio of CBD to THC ranges from about 1:5 to about 30:1 or more. In other embodiments the ration may range from about 1:2 to about 10:1. In still other embodiments, the ratio of CBD to THC may be about 1:1 to 5:1. In other cases, the ration of e.g. CBD to CBG or CBN may be set based on any of a variety of factors, including the health status of the subject being treated, the symptoms of the subject, the condition(s) being treated, and or one or more physiological or genetic criteria.

[74] In certain embodiments the compositions may be provided in completely customized or personalized formulations for each person being treated - i.e. as personalized medicines. In such cases, the compositions may be adjusted based on initial or subsequent blood work, enzyme test results, bioinformatic data (including measurements of e.g. the genome, transcriptome, proteome, metabolome, or any portion thereof, for a subject), the nature of the obesity, severe obesity, or obesity-related diseases, specific markers, antigen, or mediators present, specific symptomology, or the like. The formulation of the compositions may also be changed based on the results from an initial treatment, subsequent treatment, or based on subsequent tests.

[75] In various presently preferred embodiments, the cannabinoids are derived from Cannabis spp. or an extract thereof. Cannabis can generally be concentrated or extracted (e.g. via mechanical or chemical means) to obtain cannabinoids. Mechanical means of extracting oils from plants, such as pressing, have been used for centuries, and may be suitable for use herein. Extraction via chemical means includes extraction with various volatile solvents that range from hydrocarbon solvents such as butane, hexane, or propane, to supercritical fluids, alcohol (e.g. isopropanol, butanol, or ethanol), steam, or even water. Two very common methods are extraction with supercritical carbon dioxide, or ethanol, both of which are particularly useful herein. Extracts can be also be distilled e.g. to remove additional compounds of interest, or to concentrate them. Certain components can be removed, e.g. by treatment with steam to strip certain volatiles, which can be captured as an additional component from the Cannabis. [76] In various embodiments, cannabinoids present in an ethanolic extract or supercritical CO₂ extract of Cannabis sativa are preferred for use herein. The extract comprises one or more of Girl Scout Cookie, Jack the Ripper, Ringo's Gift, Willie Nelson, Tangie, Skunk #1, Doug's Varin, Dutch Treat, or Durban Poison strains of Cannabis sativa, or strains of their lineage. "Apollon Medical" ("APM"), a proprietary strain commercially available from Apollon Formularies, is also useful herein. Presently preferred are strains relatively high in THCV content. THCV is believed to be an appetite suppressing cannabinoid.

[77] In one embodiment, the curcuminoids in the composition comprise one or more of curcumin, demethoxy curcumin (DMC), bisdemethoxycurcumin (BDMC), turmerones, turmeric oil, or a natural or synthetic metabolites, conjugates, or derivatives thereof. In certain preferred embodiments, the curcuminoids presents are derived from rhizomes of Curcuma longa. They may be for example, in the form of crude extract or they be in an enriched fractions, semi, or partially purified, or they be substantially purified compounds.

[78] The compositions in various embodiments include terpenes comprising one or more monoterpenes, one or more sesquiterpenes, or a combination thereof. The terpenes comprise one or more of alpha bisabolol, alpha pinene, beta caryophyllene, beta pinene, borneol, camphor, camphene, caryophyllene oxide, cineole, delta-3 carene, eucalyptol, farnesenes, farnesol, fenchol, fenchone, geraniol, guaiol, humulene, isopulegol, limonene, linalool, menthol, myrcene, nerol, nerolidol, ocimene, pinene, phytol, pulegone, terpinene, terpineol, terpinolene, or valencene.

[79] In one embodiment, the terpenes comprise phytol, limonene, humulene, camphene, myrcene, phellandrene, caryophyllene, linalool, pinene, or a combination thereof. In other embodiments, the terpenes preferably comprise one or more of limonene, humulene, camphene, myrcene, beta-caryophyllene, linalool, alpha pinene, or a combination thereof.

[80] In presently preferred embodiments, the terpenes are derived from Cannabis spp. or an extract thereof. The terpenes can be derived from any source and in certain embodiments; they can be present in steam distillate or an ethanolic extract of Cannabis sativa. [81] The compositions in certain embodiments include extracts of Cannabis spp, such as C. sativa as a source of cannabinoids and/or terpenes. In various embodiments, the C. sativa comprises one or more Girl Scout Cookie, Jack the Ripper, Ringo's Gift, Willie Nelson, Tangie, Skunk #1, Doug's Varin, Dutch Treat, or Durban Poison strains. In other embodiments, the C. sativa comprises the proprietary Apollon Formularies strain, APM.

[82] In various other embodiments, the compositions may further comprise one or more flavonoids. The flavonoids can comprise chaicones, flavones, isoflavonoids, flavanones, anthoxanthins, anthocyanins, flavonols, or glucosides or other biologically active derivatives or analogs thereof, and combinations of any number of the foregoing. In certain embodiments, flavonoids are included in the compositions are isolated or derived from a plant, e.g. cannabis or citrus, a mushroom, or other natural source.

[83] In another embodiment, the composition still further comprises an extract or fraction from one or more traditional Jamaican medicinal plants other than Cannabis spp. Any of the traditional Jamaican or Carribbean medicinal plants may be useful herein. Examples of Jamaican plants useful herein include ackee, aloe vera, avocado, breadflower, ginger, leaf of life, soursop, tamarind, and trumpet. In a presently preferred embodiments, the compositions include a whole plant extract, or an extract from any parts or portion thereof including but not limited to leaves (dried, fresh, or extracted), stems, flowers, roots, fruit, seeds, or the like.

[84] In terms of compounding the compositions, the skilled artisan will appreciate that methods of maximizing the efficacy of the composition such as by enhancing the bioavailability of one or more components, or by providing the components in optimized ratios, for example one component to another with which it interacts, or each component to the others in ratio(s) that optimize the absorption into the gut or bloodstream, or enhance the therapeutic effect of the composition. The skilled artisan will also understand that some information useful in improving the compounding may be obtained empirically.

[85] In various embodiments, the compositions, or one or more components thereof, may be solubilized, micronized, provided as, for example, extracts, powders, lyophilized powders, concentrates, tinctures, essential oils, aqueous or lipid suspensions, emulsions, microemulsions, or nano-emulsions, or in whole or part as liposomal, vesicular, or other delivery systems. As described below, the compounding or formulation of any of the compositions provided herein may be optimized for the intended delivery route.

[86] The compositions may be administered and delivered as pharmaceuticals, however, it is also contemplated that one or more of the compositions may be formulated for administration and delivery by oral routes that include as food and beverages, including solid, semisolid, and liquid foods, such as smoothies, shakes, pudding, broths, teas, and soups. The food and or beverage compositions can also include hot, cold, or even frozen foods (such as frozen desserts).

[87] In another aspect of the disclosure, provided are methods of treating a subject suffering from obesity or severe obesity. The methods generally comprise administering a therapeutically effective dose of a composition to the subject. The composition typically comprises one or more edible or medicinal mushrooms, or an extract, fraction, or isolate thereof, one or more cannabinoids, one or more curcuminoids, one or more terpenes, and optionally, one or more flavonoids.

[88] The composition for use in the methods is generally as described above for the first aspect. The description of the compositions above is incorporated by reference herein for purposes of the present methods.

[89] In various embodiments, the compositions for use in the methods further comprise one or more optional ingredients comprising S-adenosylmethionine, methylfolate, omega-3 fatty acids, or a B vitamin, vitamin D or a compound providing a biologically-available form thereof. In still other embodiments fish oil, primrose oil, or an extract of one or more of black cumin, ginger, fenugreek, licorice, coriander, tomato, carrot, sweet potato, broccoli, green tea, rosemary, hazelnut, walnut, wheat germ, or date, or any combination thereof, can also be included. Garlic extract, alpha lipoic acid (ALA), conjugated linoleic acid (CLA), niacin, and / or nicotinamide are also contemplated for use herein.

[90] As above the curcuminoids can comprise one or more of curcumin, demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC), turmerones, turmeric oil, or a natural or synthetic metabolites, conjugates, or derivatives thereof. In certain presently preferred embodiments, the curcuminoids presents are derived from rhizomes of Curcuma longa. They may be in the form of crude extract or they be in an enriched fractions, semi, or partially purified, or they be substantially purified compounds.

[91] The terpenes for use with the compositions can comprise one or more monoterpenes, one or more sesquiterpenes, or a combination thereof. In various embodiments, the terpenes comprise one or more of alpha bisabolol, alpha pinene, beta caryophyllene, beta pinene, borneol, camphor, camphene, caryophyllene oxide, cineole, delta-3 carene, eucalyptol, farnesenes, farnesol, fenchol, fenchone, geraniol, guaiol, humulene, isopulegol, limonene, linalool, menthol, myrcene, nerol, nerolidol, ocimene, pinene, phytol, pulegone, terpinene, terpineol, terpinolene, or valencene. In certain preferred embodiments, the terpenes are derived from Cannabis spp. or an extract thereof. The terpenes can be present in steam distillate or an ethanolic extract of Cannabis sativa, and can comprise limonene, humulene, camphene, myrcene, beta-caryophyllene, linalool, alpha pinene, or a combination thereof, in some embodiments. The Cannabis sativa in one embodiment includes one or more of Girl Scout Cookie, Jack the Ripper, Ringo's Gift, Willie Nelson, Tangie, Skunk #1, Doug's Varin, Dutch Treat, or Durban Poison strains.

[92] The compositions for use with the methods also comprise one or more flavonoids that can be chaicones, flavones, isoflavonoids, flavanones, anthoxanthins, anthocyanins, flavonols, or glucosides or other biologically active derivatives or analogs thereof, and preferably they are from a plant, such as a cannabis or citrus plant, a mushroom, or other natural source.

[93] Presently preferred flavonoids include naringenin from citrus, cannaflavin A, cannaflavin B, or cannaflavin C, vitexin, isovitexin, apigenin, kaempferol, quercetin, orientin, luteolin, a catechin found in Cannabis, or a combination of any of the foregoing.

[94] In various embodiments, measure of weight, or decreases in obesity may be measure by a variety of way, including body weight, BMI determination, various methods based on differential conductivity of fat and water, by measuring subcutaneous fate (e.g. with calipers) and the like. In various embodiments, subject may lose from about 5% to about 30% of their body weight using the methods and compositions. More preferably the subject may lose between about 6% to about 25%, or about 7% to about 22%, or about 8% to about 20% or their body weight. In some embodiments, the subject may lose at least about 10%, 12%, 15%, or more of their body weight. Losses of about 10% to about 20%, or about 12% to about 18% are also contemplated herein. BMI reductions for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, or even 10 are achievable over time. BMI reductions of greater than about 10 to about 20 should be done only under medical supervision. Subcutaneous fat deposits may be reduced by about 20% to about 75%, about 25% to about 67%, about 30% to about 60%, or about 33% to about 50% or more. Internal fat (or body cavity fat) may be reduced anywhere from about 10% to about 40%, or about 15% to about 33%, or about 20% to about 30% in various embodiments. Liver fat may be measured and reductions of about 5%, 10%, 15% or more may be achievable. Such changes may provide positive benefits for fatty liver disease. Also, in certain embodiments, the development or status of adipocytes and fatty tissue can be studied and reduction in the size and fat content of adipocytes, or the increase or decrease in new adipocyte maturation or similar measure may be attained.

[95] In various embodiments of the methods, the compositions help to stimulate the development or activity or brown adipose tissue, in addition to or as an alternative to helping to lose fat. The skilled artisan will appreciate that brown adipose tissue is metabolically highly active and can help burn net fat.

[96] In certain embodiments, the methods further comprise one or more steps of administering an additional therapeutically effective dose of the composition.

[97] Preferably the additional administering steps are performed on a periodic basis of any frequency or schedule. For example, the administration or dosing can conveniently be on e.g. a daily, thrice weekly, twice weekly, weekly, biweekly, monthly, bimonthly, quarterly, semi-annual, or annual basis. The administration need not be the same over every period of time. By way of nonlimiting example, administration could be daily for a week, then weekly for a month. Or the administration could be every 4 months for a year, then every 6 months thereafter. Similarly, the actual amount of the composition or dosage administration can vary. For example, a monthly dosage schedule could feature a dose of x for the first dosage each quarter, and a dose of O.lx for the remaining months in each quarter. [98] Just as the composition can be 'personalized', so can the administration or dosing schedule. Thus, in various embodiments, the methods further comprise the step of periodically assessing one or more of the subject's medication levels, enzyme levels, or other indicators of physiological health or status, genetic markers or metabolic markers or mediator presence, or the like, in order to determine the periodic basis for administration.

[99] The methods provide for administration of the compositions via any useful route, including parenteral (intravenous, intra-arterial, intramuscular, intraperitoneal, or subcutaneous), oral, nasal, ocular, transmucosal (buccal, vaginal, or rectal), transdermal, or via inhalation.

[100] It should be noted that the route of dosing or administration of compositions can vary over the course of treating a subject or patient with multiple steps of treatment, as well as from subject to subject, or with different extents of obesity. A severely or morbidly obese person may require a different dosing regimen than a person who is barely obese, or who, e.g., has a BMI of e.g. 25-30. Dosing may be different for a person who is diabetic, as compared to a person who is in an early stage of metabolic syndrome. Also, administration via one route may be useful when administering a larger dose and a different route may be useful for smaller doses. Or, administration via a particular route may be appropriate initially, with subsequent doses conveniently administered through another route. It should be noted that the methods may include an optional exercise or activity regimen to coincide with the regimen of doses of the composition. In certain embodiments, the methods and composition provided herein do not require and psychological therapy or counseling, support groups, or behavior modification to be effective. Again, the skilled artisan will appreciate that exercise, education, and / or behavior modification can certainly be useful herein but are not necessary.

[101] In one embodiment, the method further comprises a step of providing to the subject additional treatment of obesity comprising: i) an exercise regimen; ii) one or more treatments with prescription weight loss drug; iii) one or more other treatments specifically provided to treat obesity or an obesity-related disease; iv) a surgical intervention, particularly for a morbidly obese person, or v) any combination of any of the foregoing.

[102] Methods that further comprise a step of providing to the subject an additional composition are also provided. The additional composition may be administered in between doses of the base compositions, or may be provided on a separate and independent periodic basis. The addition compositions generally comprise any combination of less than four of the following:

[103] i) one or more edible or medical mushrooms or an extract, fraction, or isolate thereof;

[104] ii) one or more cannabinoids;

[105] iii) one or more curcuminoids;

[106] iv) one or more terpenes;

[107] v) one or more phenolic antioxidants, or

[108] v) one or more flavonoids;

[109] The additional compositions further optionally comprise any combination of one or more of S-adenosylmethionine, methylfolate, omega-3 fatty acids, or a B vitamin, vitamin D, or a compound providing a biologically available form thereof. In other embodiments, fish oil, primrose oil, or an extract of one or more of black cumin, ginger, fenugreek, licorice, coriander, tomato, carrot, sweet potato, broccoli, green tea, rosemary, hazelnut, walnut, wheat germ, or date, or any combination thereof can also be included. Also suitable for use herein are garlic extract, alpha lipoic acid (ALA), niacin, CLA, and nicotinamide, or any combination thereof.

[110] In various embodiments of the methods:

[111] i) the one or more edible or medical mushrooms comprise Agaricus, Auricularia, Clitocybe, Ganoderma, Grifola, Hericium, Lentinus, Leucop axillus, Phellinus, Pleurotus, Sarcodona, Frametes, Albatrellus, Antrodia, Calvatia, Cordyceps, Plammulina, Pomes, Funlia, Inocybe, Inonotus, Lactarius, Russula, Schizophyllum, Suillus, or Xerocomus; or the mushrooms comprise Agaricus, Agrocybe, Albatrellus, Amanita, Auricularia, Boletus, Cantharellus, Cordyceps, Caripia, Cyathus, Daldinia, Dictyophora, Elaphomyces, Plammulina, Fomitopsis, Grifola, Ganoderma, Geastrum, Hericium, Inonotus, Lactarius, Lentinus, Lyophyllum, Phellinus, Pholiota, Pleurotus, Poria, Termitomyces, Trametes, and Premella.

[112] ii) the cannabinoids comprise one or more of cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), tetrahydrocannabinol (THC), or tetrahyrdocannabivarin (THCV);

[113] iii) the curcuminoids comprise one or more of curcumin, demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC), turmerones, turmeric oil, or a natural or synthetic metabolites, conjugates, or derivatives thereof;

[114] iv) the terpenes comprise one or more of alpha bisabolol, alpha pinene, beta caryophyllene, beta pinene, borneol, camphor, camphene, caryophyllene oxide, cineole, delta-3 carene, eucalyptol, farnesenes, farnesol, fenchol, fenchone, geraniol, guaiol, humulene, isopulegol, limonene, linalool, menthol, myrcene, nerol, nerolidol, ocimene, pinene, phytol, pulegone, terpinene, terpineol, terpinolene, or valencene;

[115] v) the one or more phenolic antioxidants comprise quercetin or resveratrol; and

[116] vi) the one or more flavonoids comprise chai cones, flavones, isoflavonoids, flavanones, anthoxanthins, anthocyanins, flavonols, or glucosides or other biologically active derivatives or analogs thereof.

[117] In one embodiment of the methods, the composition further comprises an extract or fraction from one or more traditional Jamaican medicinal plants other than Cannabis spp. The traditional medicinal plants comprise ackee, aloe vera, avocado, breadflower, ginger, leaf of life, soursop, tamarind, and/or trumpet in certain embodiments.

[118] The skilled artisan will appreciate that the methods are flexible as set forth herein, an aspect which is particularly useful given the varied and nature of the disorders which they are intended to treat.

[119] In yet another aspect of the disclosure, methods of optimizing a composition for use in treatment of a subject suffering from obesity and/or an obesity- related disease process using artificial intelligence are provided herein. The methods generally comprise, for each subject in need of therapeutic compositions for obesity or an obesity-related disease: [120] a) providing data on the therapeutic effect on the obesity or an obesity- related disease of each of:

[121] i) a plurality of edible or medicinal mushrooms, mushroom extracts, or components thereof;

[122] ii) a plurality of cannabinoids or combinations thereof;

[123] iii) a plurality of curcuminoids or combinations thereof;

[124] iv) a plurality of terpenes or combinations thereof;

[125] v) a plurality of phenolic antioxidants or combinations thereof;

[126] vi) a plurality of flavonoids or combinations thereof; and optionally,

[127] vii) a plurality of combinations of compositions comprising one or more of mushrooms or extracts thereof, cannabinoids, curcuminoids, terpenes, and flavonoid; or

[128] viii) a plurality of optional ingredients comprising S-adenosylmethionine, methylfolate, omega-3 fatty acids, or a B vitamin or vitamin D or a compound providing a biologically-available form thereof, or combinations thereof, or fish oil, primrose oil, or an extract of one or more of black cumin, ginger, fenugreek, licorice, coriander, tomato, carrot, sweet potato, broccoli, green tea, rosemary, hazelnut, walnut, wheat germ, date, or any combination thereof, garlic extract, alpha lipoic acid (ALA), niacin, or nicotinamide;

[129] b) using an artificial intelligence algorithm to analyze the data for the mushrooms or extracts, cannabinoids, curcuminoids, terpenes, and flavonoids; and

[130] c) generating one or more base profiles of compositions optimized for therapeutic treatment of the obese condition including any underlying obesity- related diseases;

[131] d) optionally, using the artificial intelligence algorithm to analyze the data for the combination compositions and the optional ingredients, and

[132] e) generating one or more complete profiles of compositions with and without the optional ingredients.

[133] In certain embodiments, the subject /person may be suffering from an obesity related disease such as an inflammatory condition or even chronic inflammation, metabolic syndrome, cardiovascular disease, hypertension, diabetes, hyperlipidemia, or the like.

[134] Generally, the data for the method are obtained from original experiments and/or reviews of the relevant scientific literature.

[135] The artificial intelligence algorithm can comprise any useful software or algorithm approach capable of making the distinctions required. In various embodiments, the algorithm comprises a classification algorithm, a regression algorithm, a clustering algorithm, or a combination thereof.

[136] In one embodiment, the methods comprise a classification algorithm that is a naive Bayes algorithm, decision tree, random forest algorithm, Support Vector Machines, or K Nearest Neighbor algorithm.

[137] In another embodiment, the methods comprise a regression algorithm that is a liner regression, lasso regression, logistic regression, or multivariate regression.

[138] In yet another embodiment, the methods comprise a clustering algorithm that is a K-means clustering, fuzzy C-means algorithm, expectation-maximization algorithm, or hierarchical clustering algorithm.

[139] The skilled artisan will appreciate that the methods are designed to optimize the compositions, and that such optimization as set forth above can be with respect to each particular inflammatory disease process or even each particular variant of such a condition. However, the compositions can also be optimized for, and a profile of relevant compositions generated for each particular subject, e.g. for a 'personalized medicine' approach.

[140] Thus, also provided herein are the methods comprising the additional step of providing subject-specific data comprising, e.g. initial or subsequent blood work, enzyme test results, bioinformatic data (including measurements of e.g. the genome, transcriptome, proteome, metabolome, or any portion thereof, for a subject), specific symptomology, or the like. The artificial intelligence algorithm is then used to further optimize the composition based on those data in addition to the disorder-specific data. The optimized formulation of the compositions may also be changed based on data from the results from an initial treatment, subsequent treatment, or based on subsequent tests of the subject.

[141] In certain embodiments, the person may be suffering from an obesity related disease such as an inflammatory condition or chronic inflammation, metabolic syndrome, cardiovascular disease, hypertension, diabetes, hyperlipidemia, or the like.

[142] The plurality of edible or medicinal mushrooms, mushroom extracts, or components for which data are analyzed generally comprise one or more of the species Agaricus blazei, Albatrellus confluens, Antrodia camphorate, Boletus badius, Clitocybe maxima, Cordyceps militaris, Cordyceps sinensis, Cordyceps liangshanensis, Cordyceps gunnii, Cordyceps cicadicola, Flanulina velutipes, Fames f omentar ius, Funalia trogii, Ganoderma lucidum, Grifoloa fondosa, Hericium erinaceus, Inocybe umbrinella, lonatus olbiquus, Lactarius flavidulus, Lentinula edodes, Phellinus linteus, Pleurotus ostreatus, Schizophyllum commune, Suillus placidus, or Trametes versicolor. In other embodiments the species comprise one or more of Agaricus blazei, A. bisporus, A. subrufescens, Agrocybe aegerita, A. cylindracea, Albatrellus caeruleoporus, Amanita muscaria, Boletus edulis, Cantharellus cibarius, C. tubaeformis, Cordyceps militaris, C. pruinose, Caripia montagnei, Cyathus africanus, C. hookeri, Daldinia childiae, Dictyophora indusiata (synonym: Phallus indusiatus), Elaphomyces granulatus, Flammulina velutipes, Fomitopsis pinicola, Grifola frondosa, Ganoderma lucidum, Geastrum saccatum, Inonotus obliquus, Lactarius deliciosus, L. rufus, Lentinus edodes, L. polychrous, Lyophyllum decastes, Phellinus linteus, Pholiota nameko, Pleurotus pulmonarius, Poria cocos, and Termitomyces albuminosus.

[143] A further aspect of the invention provides methods for the treatment of obesity or severe obesity. The patient may also have an obesity-related disease. The methods generally comprise the step of administering to a patient in need thereof a composition comprising at least one edible or medicinal mushroom or extract thereof, in combination with at least one cannabinoid, at least one curcuminoid, at least one terpene, at least one phenolic antioxidant, and at least one flavonoid. In one embodiment the at least one cannabinoid, at least one curcuminoid, at least one terpene, and at least one flavonoid are administered separately from, sequentially to, or simultaneously with the edible or medicinal mushroom or extract thereof. In another embodiment, the at least one edible or medicinal mushroom or extract thereof is also administered separately from, sequentially to, or simultaneously with the cannabinoid, curcuminoid, phenolic antioxidant, terpene, and flavonoid. [144] Again, the composition with respect to this aspect of the disclosure can comprise any of the compositions described hereinabove. In one embodiment of the methods:

[145] i) the at least one edible or medicinal mushroom or extract comprise Agaricus blazei, Albatrellus confluens, Antrodia camphorate, Boletus badius, Clitocybe maxima, Cordyceps militaris, Cordyceps sinensis, Cordyceps liangshanensis, Cordyceps gunnii, Cordyceps cicadicola, Flanulina velutipes, Pomes fomentarius, Punalia trogii, Ganoderma lucidum, Grifoloa fondosa, Hericium erinaceus, Inocybe umbrinella, lonatus olbiquus, Lactarius flavidulus, Lentinula edodes, Phellinus linteus, Pleurotus ostreatus, Schizophyllum commune, Suillus placidus, or Trametes versicolor; or the one or more edible or medicinal mushrooms comprise Agaricus blazei, A. bisporus, A. subrufescens, Agrocybe aegerita, A. cylindracea, Albatrellus caeruleoporus, Amanita muscaria, Boletus edulis, Cantharellus cibarius, C. tubaeformis, Cordyceps militaris, C. pruinose, Caripia montagnei, Cyathus africanus, C. hookeri, Daldinia childiae, Dictyophora indusiata (synonym: Phallus indusiatus), Elaphomyces granulatus, Plammulina velutipes, Fomitopsis pinicola, Grifola frondosa, Ganoderma lucidum, Geastrum saccatum, Inonotus obliquus, Lactarius deliciosus, L. rufus, Lentinus edodes, L. polychrous, Lyophyllum decastes, Phellinus linteus, Pholiota nameko, Pleurotus pulmonarius, Poria cocos, and Termitomyces albuminosus; or a combination of any of the foregoing.

[146] ii) the at least one cannabinoid comprises CBD, CBG, CBN, THCV and THC extracted from Cannabis sativa Girl Scout Cookie, Jack the Ripper, Ringo's Gift, Willie Nelson, Tangie, Skunk #1, Doug's Varin, Dutch Treat, or Durban Poison strain;

[147] iii) the at least one curcuminoid comprises one or more of curcumin, demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC), turmerones, turmeric oil, or a natural or synthetic metabolite, conjugate, or derivative thereof;

[148] iv) the at least one terpene comprises limonene, humulene, camphene, myrcene, beta-caryophyllene, linalool, alpha pinene, or a combination thereof;

[149] v) the at least one phenolic antioxidant comprises quercetin or resveratrol, or a biologically-active derivative thereof; and [150] v) the at least one flavonoid comprises a chaicone, flavone, isoflavonoid, flavanone, anthoxanthin, anthocyanin, flavonol, or glucoside or other biologically active derivatives or analogs thereof.

[151] In various embodiments of the methods, one or more of the components have one more of the following functions:

1. induces apoptosis of adipocytes or other cells involved in maintaining the obesity or severe obesity;

2. inhibits oxidative stress;

3. decreases VLDL;

4. decreases the catalytic functions of HMG-CoA reductase;

5. reduces expression of adipogenic transcription factor

6. stimulates transport or storage of glucose and lipids

7. activates AMPK signaling pathways;

8. increases insulin sensitivity or reduces insulin resistance;

9. suppresses appetite; or

10. reduces one or more symptoms of an obesity-related disease.

[152] In yet another embodiment of the methods provided in this aspect of the disclosure, the composition further comprises an extract or fraction from one or more traditional Jamaican medicinal plants other than Cannabis spp. Traditional medicinal plants such as ackee, aloe vera, avocado, breadflower, ginger, leaf of life, soursop, tamarind, and trumpet are contemplated as useful herein.

[153] The scope of the invention is set forth in the claims appended hereto, subject, for example, to the limits of language. Although specific terms are employed to describe the invention, those terms are used in a generic and descriptive sense and not for purposes of limitation. Moreover, while certain presently preferred embodiments of the claimed invention have been described herein, those skilled in the art will appreciate that such embodiments are provided by way of example only. In view of the teachings provided herein, certain variations, modifications, and substitutions will occur to those skilled in the art. It is therefore to be understood that the invention may be practiced otherwise than as specifically described, and such ways of practicing the invention are either within the scope of the claims, or equivalent to that which is claimed, and do not depart from the scope and spirit of the invention as claimed.

Claims

WHAT IS CLAIMED IS:

1. A composition comprising one or more edible or medicinal mushrooms or an extract, fraction, or isolate thereof, one or more cannabinoids, one or more curcuminoids, one or more terpenes, and optionally, one or more flavonoids.

2. The composition of claim 1 wherein the edible or medicinal mushroom comprises one or more of Agaricus, Agrocybe, Albatrellus, Amanita, Boletus, Cantharellus, Cordyceps, Caripia, Cyathus, Daldinia, Dictyophora, Elaphomyces, Flammulina, Fomitopsis, Grifola, Ganoderma, Geastrum, Inonotus, Lactarius, Lentinus, Lyophyllum, Phellinus, Pholiota, Pleurotus, Poria, and Termitomyces.

3. The composition of claim 1 wherein the edible or medicinal mushroom comprises one or more of Agaricus blazei, A. bisporus, A. subrufescens, Agrocybe aegerita, A. cylindracea, Albatrellus caeruleoporus, Amanita muscaria, Boletus edulis, Cantharellus cibarius, C. tubaeformis, Cordyceps militaris, C. pruinose, Caripia montagnei, Cyathus africanus, C. hookeri, Daldinia childiae, Dictyophora indusiata, Elaphomyces granulatus, Flammulina velutipes, Fomitopsis pinicola, Grifola frondosa, Ganoderma lucidum, Geastrum saccatum, Inonotus obliquus, Eactarius deliciosus, L. rufus, Eentinus edodes, L. polychrous, Eyophyllum decastes, Phellinus linteus, Pholiota nameko, Pleurotus pulmonarius, Poria cocos, and Termitomyces albuminosus.

4. The composition of claim 1 wherein the edible or medicinal mushroom comprises fresh mushroom, dried mushroom, lyophilized mushroom, a mushroom powder, an aqueous or ethanolic extract of mushroom, or concentrate thereof, or a partially purified or purified mushroom fraction or component, or an isolate thereof.

5. The composition of claim 5 wherein the aqueous or ethanolic extract of mushroom, or concentrate thereof, or the partially purified or purified mushroom fraction or component, or isolate thereof are enriched for one or more of phenolic acids, flavonoids, triterpenes, carotenoids, stilbenes, sterols, fatty acids, lignans, chitosan, polyphenols, polysaccharides, glycosides, glucans, polysaccharide-protein complexes, glycoproteins, polysaccharopeptide, krestin, tocopherols, peptides, cyclic peptides, or amino compounds found in the mushroom.

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6. The composition of claim 1 wherein the curcuminoid comprises one or more of curcumin, demethoxy curcumin (DMC), bisdemethoxycurcumin (BDMC), turmerones, turmeric oil, or a natural or synthetic metabolite, conjugate, or derivative thereof.

7. The composition of claim 6 wherein the curcuminoid is derived from rhizomes of Curcuma longa.

8. The composition of claim 1 wherein the cannabinoids comprise one or more of cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), or tetrahydrocannabinol (THC), or tetrahyrdocannabivarin (THCV).

9. The composition of claim 8 wherein the THC is present at less than about 0.3 percent.

10. The composition of claim 8 wherein the ratio of CBD to THC is about 1:5 to about 30:1 or more.

11. The composition of claim 1 wherein the cannabinoids are derived from Cannabis spp. or an extract thereof.

12. The composition of claim 11 wherein the cannabinoids are present in an ethanolic extract of Cannabis sativa.

13. The composition of claim 12 wherein the extract comprises one or more of Girl Scout Cookie, Jack the Ripper, Ringo's Gift, Willie Nelson, Tangie, Skunk #1, Doug's Varin, Dutch Treat, or Durban Poison strains of Cannabis sativa.

14. The composition of claim 1 wherein the terpenes comprise one or more monoterpenes, one or more sesquiterpenes, or a combination thereof.

15. The composition of claim 14 wherein the terpenes comprise one or more of alpha bisabolol, alpha pinene, beta caryophyllene, beta pinene, borneol, camphor, camphene, caryophyllene oxide, cineole, delta-3 carene, eucalyptol, farnesenes, farnesol, fenchol, fenchone, geraniol, guaiol, humulene, isopulegol, limonene, linalool, menthol, myrcene, nerol, nerolidol, ocimene, phellandrene, pinene, phytol, pulegone, terpinene, terpineol, terpinolene, or valencene.

16. The composition of claim 15 wherein the terpenes are derived from Cannabis spp. or an extract thereof.

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17. The composition of claim 16 wherein the terpenes are present in steam distillate or an ethanolic extract of Cannabis sativa.

18. The composition of claim 17 wherein the terpenes comprise phytol, limonene, humulene, camphene, myrcene, phellandrene, caryophyllene, linalool, pinene, or a combination thereof.

19. The composition of claim 1 wherein the one or more flavonoids comprise chaicones, flavones, isoflavonoids, flavanones, anthoxanthins, anthocyanins, flavonols, or glucosides or other biologically active derivatives or analogs thereof.

20. The composition of claim 1 wherein the one or more flavonoids are from a plant, mushroom, or other natural source.

21. The composition of claim 21 wherein the one or more flavonoids comprise naringenin, cannaflavin A, cannaflavin B, or cannaflavin C, vitexin, isovitexin, apigenin, kaempferol, quercetin, orientin, luteolin, a catechin found in Cannabis, or a combination of any of the foregoing.

22. The composition of claim 1 further comprising an extract or fraction from one or more traditional Jamaican medicinal plants other than Cannabis spp.

23. The composition of claim 23 wherein the traditional medicinal plants comprise ackee, aloe vera, avocado, breadflower, ginger, leaf of life, soursop, tamarind, and trumpet.

24. The composition of claim 1 further comprising one or more optional ingredients comprising S-adenosylmethionine, methylfolate, omega-3 fatty acids, or a B vitamin, vitamin D, or a compound providing a biologically-available form thereof, fish oil, primrose oil, or an extract of one or more of black cumin, ginger, fenugreek, licorice, coriander, tomato, carrot, sweet potato, broccoli, green tea, rosemary, hazelnut, walnut, wheat germ, or date, or any combination thereof, garlic extract, alpha lipoic acid (ALA), niacin, or nicotinamide.

25. A method of treating a subject suffering from obesity or severe obesity which comprises administering to the subject a therapeutically effective dose of a composition comprising one or more edible or medicinal mushrooms or an extract, fraction, or isolate thereof, one or more cannabinoids, one or more curcuminoids, one or more terpenes, and optionally, one or more flavonoids; wherein the subject is also suffering from an obesity-related disease comprising an inflammatory condition, chronic inflammation, metabolic syndrome, cardiovascular disease, hypertension, diabetes, or hyperlipidemia.

26. The method of claim 26 wherein the composition further comprises one or more optional ingredients comprising S-adenosylmethionine, methylfolate, omega-3 fatty acids, or a B vitamin, vitamin D or a compound providing a biologically-available form thereof, fish oil, primrose oil, or an extract of one or more of black cumin, ginger, fenugreek, licorice, coriander, tomato, carrot, sweet potato, broccoli, green tea, rosemary, hazelnut, walnut, wheat germ, date, or combinations thereof, garlic extract, alpha lipoic acid (ALA), niacin, or nicotinamide.

27. The method of claim 26 wherein the edible or medicinal mushroom comprises one or more of Agaricus, Agrocybe, Albatrellus, Amanita, Boletus, Cantharellus, Cordyceps, Caripia, Cyathus, Daldinia, Dictyophora, Elaphomyces, Flammulina, Fomitopsis, Grifola, Ganoderma, Geastrum, Inonotus, Lactarius, Lentinus, Lyophyllum, Phellinus, Pholiota, Pleurotus, Poria, and Termitomyces.

28. The method of claim 30 wherein the aqueous or ethanolic extract of mushroom, or concentrate thereof, or the partially purified or purified mushroom fraction or component, or isolate thereof are enriched for one or more of phenolic acids, flavonoids, triterpenes, carotenoids, stilbenes, sterols, fatty acids, lignans, chitosan, polyphenols, polysaccharides, glycosides, glucans, polysaccharide-protein complexes, glycoproteins, polysaccharopeptide, krestin, tocopherols, peptides, cyclic peptides, or amino compounds found in the mushroom.

29. The method of claim 26 wherein the cannabinoids comprise one or more of cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), or tetrahydrocannabinol (THC), or tetrahyrdocannabivarin (THCV).

30. The method of claim 26 wherein the THC is present at less than about 0.3 percent.

31. The method of claim 26 wherein the ratio of CBD to THC is about 1:5 to about 30:1 or more.

32. The method of claim 26 wherein the curcuminoid comprises one or more of curcumin, demethoxy curcumin (DMC), bisdemethoxycurcumin (BDMC), turmerones, turmeric oil, or a natural or synthetic metabolite, conjugate, or derivative thereof.

33. The method of claim 26 wherein the terpenes comprise one or more monoterpenes, one or more sesquiterpenes, or a combination thereof.

34. The method of claim 33 wherein the terpenes comprise one or more of alpha bisabolol, alpha pinene, beta caryophyllene, beta pinene, borneol, camphor, camphene, caryophyllene oxide, cineole, delta-3 carene, eucalyptol, farnesenes, farnesol, fenchol, fenchone, geraniol, guaiol, humulene, isopulegol, limonene, linalool, menthol, myrcene, nerol, nerolidol, ocimene, pinene, phytol, pulegone, terpinene, terpineol, terpinolene, or valencene.

35. The method of claim 26 wherein the terpenes are derived from Cannabis spp. or an extract thereof.

36. The method of claim 26 wherein the one or more flavonoids comprise chaicones, flavones, isoflavonoids, flavanones, anthoxanthins, anthocyanins, flavonols, or glucosides or other biologically active derivatives or analogs thereof.

37. The method of claim 26 wherein the one or more flavonoids comprise naringenin, cannaflavin A, cannaflavin B, or cannaflavin C, vitexin, isovitexin, apigenin, kaempferol, quercetin, orientin, luteolin, a catechin found in Cannabis, or a combination of any of the foregoing.

38. The method of claim 26 further comprising one or more steps of administering an additional therapeutically effective dose of the composition on a periodic basis.

39. The method of claim 26 further comprising a step of providing to the subject additional treatment of the obesity or severe obesity comprising: i) one or more doses of an NS AID; ii) one or more treatments with a corticosteroid; iii) one or more other treatments specifically provided to treat the obesity or severe obesity; or iv) any combination of any of the foregoing.

36

40. The method of claim 26 further comprising a step of providing to the subject an additional composition comprising any combination of less than three of the following: a) one or more edible or medical mushrooms or an extract, fraction, or isolate thereof; b) one or more curcuminoids; c) one or more cannabinoids; d) one or more phenolic antioxidants; e) one or more terpenes; or f) one or more flavonoids; and optionally, any combination of one or more of S-adenosylmethionine, methylfolate, omega-3 fatty acids, or a B vitamin, vitamin D, or a compound providing a biologically-available form thereof, fish oil, primrose oil, or an extract of one or more of black cumin, ginger, fenugreek, licorice, coriander, tomato, carrot, sweet potato, broccoli, green tea, rosemary, hazelnut, walnut, wheat germ, date, or combinations thereof, garlic extract, alpha lipoic acid (ALA), niacin, or nicotinamide.

41. The method of claim 40 wherein: a) the one or more edible or medical mushrooms comprise Agaricus, Agrocybe, Albatrellus, Amanita, Boletus, Cantharellus, Cordyceps, Caripia, Cyathus, Daldinia, Dictyophora, Elaphomyces, Flammulina, Fomitopsis, Grifola, Ganoderma, Geastrum, Inonotus, Lactarius, Lentinus, Lyophyllum, Phellinus, Pholiota, Pleurotus, Poria, and Termitomyces; b) the cannabinoids comprise one or more of cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), or tetrahydrocannabinol (THC), or tetrahyrdocannabivarin (THCV); c) the curcuminoids comprise one or more of curcumin, demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC), turmerones, turmeric oil, or a natural or synthetic metabolite, conjugate, or derivative thereof; d) the phenolic antioxidants comprise quercetin, resveratrol, or a biologically active derivative thereof;

37 e) the terpenes comprise one or more of alpha bisabolol, alpha pinene, beta caryophyllene, beta pinene, borneol, camphor, camphene, caryophyllene oxide, cineole, delta-3 carene, eucalyptol, farnesenes, farnesol, fenchol, fenchone, geraniol, guaiol, humulene, isopulegol, limonene, linalool, menthol, myrcene, nerol, nerolidol, ocimene, pinene, phytol, pulegone, terpinene, terpineol, terpinolene, or valencene; and f) the one or more flavonoids comprise chaicones, flavones, isoflavonoids, flavanones, anthoxanthins, anthocyanins, flavonols, or glucosides or other biologically active derivatives or analogs thereof.

42. The method of claim 40 wherein the composition further comprises an extract or fraction from one or more traditional Jamaican medicinal plants other than Cannabis spp.

43. The method of claim 42 wherein the traditional medicinal plants comprise one or more of ackee, aloe vera, avocado, breadflower, ginger, leaf of life, soursop, tamarind, and trumpet.

44. A method of optimizing a composition for use in treatment of obesity or severe obesity in a subject suffering therefrom, such optimization performed using artificial intelligence comprising, for each obesity or severe obesity: a) providing data on the therapeutic effect on the obesity or severe obesity of each of: i) a plurality of edible or medicinal mushrooms, mushroom extracts, or components thereof; ii) a plurality of cannabinoids or combinations thereof; iii) a plurality of curcuminoids or combinations thereof; iv) a plurality of terpenes or combinations thereof; v) a plurality of flavonoids or combinations thereof; and optionally,

38 vi) a plurality of combinations of compositions comprising one or more of mushrooms or extracts thereof, cannabinoids, curcuminoids, terpenes, and flavonoid; or vi) a plurality of optional ingredients comprising S- adenosylmethionine, methylfolate, omega-3 fatty acids, or a B vitamin or vitamin D or a compound providing a biologically-available form thereof, fish oil, primrose oil, or an extract of one or more of black cumin, ginger, fenugreek, licorice, coriander, tomato, carrot, sweet potato, broccoli, green tea, rosemary, hazelnut, walnut, wheat germ, date, or combinations thereof, garlic extract, alpha lipoic acid (ALA), niacin, or nicotinamide; b) using an artificial intelligence algorithm to analyze the data for the mushrooms or extracts, cannabinoids, curcuminoids, terpenes, and flavonoids; and c) generating one or more base profiles of compositions optimized for therapeutic treatment of the obesity or severe obesity; d) optionally, using the artificial intelligence algorithm to analyze the data for the combination compositions and the optional ingredients, and e) generating one or more complete profiles of compositions with and without the optional ingredients; wherein the obesity or severe obesity comprises an obesity-related disease comprising an inflammatory condition, chronic inflammation, metabolic syndrome, cardiovascular disease, hypertension, diabetes, or hyperlipidemia; and wherein the data are obtained from original experiments or literature review.

45. The method of claim 44 wherein the artificial intelligence algorithm comprises a classification algorithm, regression algorithm, clustering algorithm, or a combination thereof.

46. The method of claim 45 wherein the classification algorithm comprises a naive Bayes algorithm, decision tree, random forest algorithm, Support Vector Machines, or K Nearest Neighbor algorithm.

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47. The method of claim 45 wherein the regression algorithm comprises liner regression, lasso regression, logistic regression, or multivariate regression.

48. The method of claim 45 wherein the clustering algorithm comprises K- means clustering, fuzzy C-means algorithm, expectation-maximization algorithm, or hierarchical clustering algorithm.

49. A method for the treatment of obesity or severe obesity comprising the step of administering to a patient in need thereof a composition comprising at least one edible or medicinal mushroom or extract thereof, in combination with at least one cannabinoid, at least one curcuminoid, at least one terpene, and at least one flavonoid; wherein the at least one cannabinoid, at least one terpene, and at least one flavonoid is administered separately from, sequentially to, or simultaneously with the edible or medicinal mushroom; and wherein the at least one edible or medicinal mushroom or extract thereof is also administered separately from, sequentially to, or simultaneously with the cannabinoid, terpene, and flavonoid.

50. The method of claim 49 wherein: i) the at least one edible or medicinal mushroom or extract comprises comprise Agaricus blazei, A. bisporus, A. subrufescens, Agrocybe aegerita, A. cylindracea, Albatrellus caeruleoporus, Amanita muscaria, Boletus edulis, Cantharellus cibarius, C. tubaeformis, Cordyceps militaris, C. pruinose, Caripia montagnei, Cyathus africanus, C. hookeri, Daldinia childiae, Dictyophora indusiata (synonym: Phallus indusiatus), Elaphomyces granulatus, Flammulina velutipes, Fomitopsis pinicola, Grifola frondosa, Ganoderma lucidum, Geastrum saccatum, Inonotus oblu uus, Lactarius deliciosus, L. rufus, Lentinus edodes, L. polychrous, Lyophyllum decastes, Phellinus linteus, Pholiota nameko, Pleurotus pulmonarius, Poria cocos, and Termitomyces albuminosus; ii) the at least one cannabinoid comprises CBD, CBG, CBN, THCV, and THC extracted from Cannabis sativa Girl Scout Cookie, Jack the Ripper, Ringo's Gift, Willie Nelson, Tangie, Skunk #1, Doug's Varin, Dutch Treat, or Durban Poison strains; iii) the at least one curcuminoid comprises comprises one or more of curcumin, demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC),

40 turmerones, turmeric oil, or a natural or synthetic metabolite, conjugate, or derivative thereof. iv) the at least one terpene comprises limonene, humulene, camphene, myrcene, beta-caryophyllene, linalool, alpha pinene, or a combination thereof; and v) the at least one flavonoid comprises a chaicone, flavone, isoflavonoid, flavanone, anthoxanthin, anthocyanin, flavonol, or glucoside or other biologically active derivatives or analogs thereof.

51. The method of claim 49 wherein one or more of the components have one more of the following functions: a) induces apoptosis of adipocytes or other cells involved in maintaining the obesity or severe obesity; b) inhibits oxidative stress; c) decreases VLDL; d) decreases the catalytic functions of HMG-CoA reductase; e) reduces expression of adipogenic transcription factor f) stimulates transport or storage of glucose and lipids g) activates AMPK signaling pathways; h) increases insulin sensitivity or reduces insulin resistance; i) reduces one or more symptoms of an obesity-related disease; or j) suppresses appetite.

52. The method of claim 49 wherein the composition further comprises an extract or fraction from one or more traditional Jamaican medicinal plants other than Cannabis spp.

53. The method of claim 52 wherein the traditional medicinal plants comprise one or more of ackee, aloe vera, avocado, breadflower, ginger, leaf of life, soursop, tamarind, and trumpet.

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