WO2023092079A1 - Use of cannabinoid compounds to treat gastrointestinal disorders - Google Patents

Abstract

Methods of treating gastrointestinal disorders using cannabinoid compounds are described herein. The cannabinoid compounds can include one or more of tetrahydrocannabivarin ("THCV"), cannabicyclol ("CBL"), cannabichromene ("CBC"), cannabidol ("CBD"), cannabinol ("CBN"), (+)-cannabidiol ("(+)-CBD"), cannabigerol butyl ("CBG-C4"), cannabidivarinic acid ("CBDVA"), and cannabicyclolic acid ("CBLA"). The methods can be used to treat Inflammatory Bowel Disease ("IBD"), Crohn's disease, ulcerative colitis, and Irritable Bowel Syndrome. Compositions and articles including the cannabinoid compounds are further disclosed.

Description

USE OF CANNABINOID COMPOUNDS TO TREAT GASTROINTESTINAL

DISORDERS

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims the priority benefit of U.S. Provisional Patent App. Serial No. 63/264,337, filed November 19, 2021, which is hereby incorporated herein by reference in its entirety.

TECHNICAL FIELD

[0002] The present disclosure generally relates to the use of cannabinoid compounds to treat gastrointestinal disorders.

BACKGROUND

[0003] The gastrointestinal tract (“GI tract”) is a vital system of organs which includes the mouth, esophagus, the stomach, small intestine, large intestine, rectum, and anus. In addition to the organs, the GI tract also includes a diverse collection of microflora. Collectively, the organs and the microflora in the GI tract function as the human digestive system. Disruption of the organs, the microflora, or the signaling pathways in the GI tract can result in numerous gastrointestinal disorders (“GI disorders”) including various types of colitis. Inflammation of the GI tract is a principal component of autoimmune disorders including inflammatory bowel disease, ulcerative colitis, and Crohn’s disease. Other GI disorders include irritable bowel syndrome related to disruptions of the gut-brain signaling. Treatment of GI disorders can be difficult because the disorders can present similar symptoms despite being caused by different, complex, disruptions of the GI tract.

DETAILED DESCRIPTION

[0004] GI disorders are debilitating diseases that range in severity from uncomfortable to potentially life-threatening. The disorders can be transient or can require lifelong treatment and management of symptoms that are disruptive to normal life behaviors. Traditional treatment of GI disorders is complex as it requires the identification of the underlying cause of the GI disorder and treatment plans that addresses the underlying cause. However, similarities in the symptoms of GI disorders as well as the overall complexity of the GI tract can make GI disorders difficult to both diagnose and treat.

[0005] The present application describes the novel use of cannabinoid compounds to treat various GI disorders. As will be appreciated, cannabinoid compounds can provide desirable benefits for the treatment of GI disorders due to the strong regulation of the GI tract by the endocannabinoid receptor system as well as the ability of cannabinoid compounds to mediate the response of other G protein-coupled receptors (“GPC receptors”) present within the GI tract. The ability of cannabinoid compounds to regulate multiple receptor pathways within the GI tract enables cannabinoid compounds to treat GI disorders that are otherwise difficult to treat using known methods as the cannabinoid compounds have effective mechanisms of treatment, can allow for treatments that are effective against the underlying cause of multiple GI disorders, and which can be easily supplied to, and tolerated by, patients.

[0006] As can be appreciated, endocannabinoid receptors are GPC receptors found throughout the human body including in the brain, central nervous system, and GI tract. In addition to their other roles, endocannabinoid receptors 1 and 2 (CBiR and CB2R respectively) are known to be associated with the regulation of the GI tract with activation of the endocannabinoid receptors inhibiting peristalsis and gastric acid secretion and enhancing food intake. Additionally, studies have suggested that dysregulation of the endocannabinoid system can worsen several GI disorders including inflammatory bowel disease, irritable bowel syndrome, and obesity.

[0007] Other studies have specifically focused on activation of the endocannabinoid receptors CBiR and CB2R. Such studies have further found that activation of the endocannabinoid receptors can control cholinergic neurotransmission in the GI tract, can reduce peristalsis, and can control gastric secretions. Other such studies have found that CBiR and CB2R agonists can reduce colitis caused by inflammatory bowel disease. The benefits of activating the endocannabinoid receptors CBiR and CB2R have also been found to generally provide pain relief, reduce nausea, and reduce diarrhea.

[0008] As can be appreciated, compounds which can act as agonists to the endocannabinoid receptors CBiR and CB2R would be useful to treat various GI disorders and to reduce the symptoms of such disorders. Certain cannabinoid compounds described herein can act as such agonists including tetrahydrocannabivarin (“THCV”), cannabichromene (“CBC”), (+)- cannabidiol (“(+)-CBD”), and cannabigerol — C4 (“CBG-C4”). Other cannabinoid compounds can act as agonists to CB1R and CB2R to a lesser degree including cannabidiol (“CBD”), cannabidivarinic acid (“CBDVA”), cannabicyclol (“CBL”), and cannabicyclolic acid (“CBLA”).

[0009] In addition to the general benefits of using cannabinoid compounds as agonists to the endocannabinoid receptors CBiR and CB2R, cannabinoid compounds can further have strong GPC receptor mediation of other receptors known to play a role in the regulation of the GI tract. For example, certain cannabinoid compounds have been shown to regulate the inflammatory response of the GI tract, help regulate the gut-brain signaling associated with Irritable Bowel Syndrome (“IBS”), and have been linked to regulation of intestinal motility.

[0010] As can be appreciated, inflammation of the GI tract is associated with multiple GI disorders including Inflammatory Bowel Disease (“IBD”), Crohn’s disease, and ulcerative colitis. Each of IBD, Crohn’s disease, and ulcerative colitis are related GI disorders with some differences in the underlying pathology and location of distress in the GI tract. The compositions and methods described herein can be effective against each of these GI disorders because the GPC receptor targets targeted by the cannabinoid compounds are located throughout the GI tract and because of the common symptoms such as inflammation expressed by each of the disorders.

[0011] Cannabinoid compounds have been demonstrated in various studies to help reduce inflammation both directly and by mediation of various GPC receptors. Studies have found that corticotrophin releasing hormone receptor 1 (“CRHR1”) antagonists as well as corticotrophin releasing hormone receptor 2 (“CRHR2”) agonists can reduce inflammation in the GI tract and can be used to treat lower GI tract inflammatory diseases such as chronic inflammatory bowel syndromes and ulcerative colitis in various mouse studies.

[0012] Inflammation of the GI tract can also be caused by activation of the immune response of epithelial cells on the lining of the GI tract. Such activation is normally caused by extracellular nucleotides, such as UDP, which signal the release of CXCL8. Experimental studies have determined that that activation of the P2 receptor system, and specifically, the P2RY6 receptor, can initiate the immune response thereby causing such inflammation. Cannabinoid compounds which act as agonists to the P2RY6 receptor can decrease inflammation caused by an overactive immune response and can be used to treat various GI disorders such as IBD, Crohn’s disease, and ulcerative colitis.

[0013] It has been further found that cannabinoid compounds can further treat other GI disorders. For example, Irritable Bowel Syndrome (“IBS”) is a group of symptoms associated with dysregulation of the gut-brain link that causes various issues including visceral and abdominal pain, constipation and diarrhea, and nausea. Studies have shown that certain cannabinoid compounds and receptors mediated by cannabinoid compounds, can help manage IBS. For example, CBD, cannabinol (“CBN”), and CBC have demonstrated the ability to normalize intestinal motility and reduce visceral pain in various studies.

[0014] The ability of the cannabinoid compounds to treat multiple causes of GI disorders can allow the compositions and methods described herein to treat a variety of GI disorders without necessarily knowing the exact underlying cause of the disorders. In certain embodiments however, the compositions and methods can be tailored to specific GI disorders. For example, in certain embodiments, only cannabinoid compounds which treat inflammation can be included.

[0015] As can be appreciated, cannabinoid compounds are further known to exhibit other more general effects on the human body including general pain relief and nausea relief. Such effects can further facilitate treatment of GI disorders by providing general symptom relief in addition to the specific role of the cannabinoid compounds to regulate the underlying GI tract issues and GI disorders. In certain embodiments, regulation of the GI tract can act as treatments of GI disorders.

[0016] In certain embodiments, one or more cannabinoid compounds can be used to treat GI disorders including IBD, IBS, Crohn’s disease, and ulcerative colitis. Such cannabinoid compounds can exhibit one or more of: agonist effects on the endocannabinoid system, antagonist effects on the CRHR1 receptor, agonist effects on the CRHR2 receptor, and agonist effects on the P2RY6 receptor. According to certain embodiments, the one or more cannabinoid compounds demonstrating activity against one or more of these targets includes: THCV, cannabicyclol (“CBL”), CBC, CBD, CBN, (+)-cannabidiol (“(+)-CBD”), and cannabigerol butyl (“CBG-C4”). [0017] Other cannabinoid compounds however were not found to be effective at exhibiting effects against any of the listed receptors such as cannabidivarin (“CBDV”), cannabidiorcol (“CBD-C1”), cannabidiethanol (“CBD-C2”), cannabidiolic acid (“CBDA”), cannabigerolic acid (“CBGA”), cannabigerolic acid butyl (“CBGA-C4”), cannabigerol (“CBG”), Cannabigerovarin (“CBGV”), cannabigerovarinic acid (“CBGV A”), and cannabichromenic acid (“CBCA”).

[0018] Prior to the present discovery, it was not appreciated that cannabinoid compounds could target multiple GI disorders through the pathways identified herein, nevertheless which specific cannabinoid compounds could act to treat such GI disorders. By selecting the cannabinoid compounds with multiple modalities, the present disclosure provides improved methods of treating GI disorders.

[0019] The present discovery was facilitated by the Applicant’s unique methods of producing hereto rare cannabinoid compounds in appreciable quantities including through chemical synthesis reactions and growth in yeast cultures. Prior to the Applicant’s research, the lack of viable production of individual cannabinoid compounds obviated the ability to identify cannabinoid compounds which exhibited the receptor activity necessary to treat GI disorders. Additional details about the production of producing rare cannabinoid compounds are described in PCT Patent Application Nos. WO 2020/069142 Al, WO 2020/069214 A2, WO 2021/05597 Al; and WO 2020/236789 Al, each of which is incorporated herein by reference.

[0020] Prior to the Applicant’s process of isolating specific and unique cannabinoid compounds from non-horti cultural sources, cannabinoid compounds were extracted and isolated only from naturally grown marijuana plants which drastically limited the volume of the rarer cannabinoid compounds available for research or use. Thus, these non-horticulturally derived cannabinoid compounds offer benefits in regard to the treatment of GI disorders not previously contemplated. As used herein, non-horticulturally derived cannabinoid compounds refers to cannabinoid compounds not grown in plants (e.g., not through horticulture or agriculture).

[0021] Additionally, isolated cannabinoid compounds extracted from marijuana plants can also suffer from purity issues as certain unavoidable containments (such as other natural marijuana plant compounds, irremovable amounts of other cannabinoid compounds, etc.) can remain present in isolated cannabinoid compounds extracted from marijuana plants. Such unavoidable containments can impact the quality of the data or even alter the apparent functioning of the cannabinoid compounds. Compositions and methods of treating GI disorders that use horticulturally derived cannabinoid compounds may not exhibit the same effects as compositions and methods using purer cannabinoid compounds such as the cannabinoid compounds contemplated herein. As can be appreciated however, horticulturally derived cannabinoid compounds can be used in certain embodiments of the disclosure if the horticulturally derived cannabinoid compounds are sufficiently pure and/or if any containments are sufficiently well understood.

[0022] Generally, the compositions and methods described herein can introduce an effective concentration of one or more of THCV, CBL, CBC, CBD, CBN, (+)-CBD, CBG-C4, CBDVA, and CBLA into the GI tract. The products can be introduced orally, intravenously, or rectally in various embodiments. In certain embodiments, the cannabinoid compounds can be isolated until it reaches the GI tract. For example, the cannabinoid compounds can be included in a pill or capsule that dissolves only a pre-determined pH such as at an acidic pH to release the cannabinoid compounds into the stomach or at a basic pH to release the cannabinoid compounds into the intestines.

[0023] In certain embodiments, the one or more cannabinoid compounds can include THCV, CBL, CBC, CBD, CBN, (+)-CBD, CBG-C4, CBDVA, and CBLA. In certain embodiments, each of the foregoing cannabinoid compounds can be included, while in other embodiments, only a subset of such cannabinoid compounds may be included. In certain embodiments, only a single cannabinoid compound may be included. In certain embodiments, only cannabinoid compounds which exhibit multiple identified treatment modalities can be selected. For example, THCV was found to be an effective modulator of CBiR, CB2R, CRHR1, and CRHR2 and would be expected to exhibit strong anti-inflammatory responses due to the remediation of multiple causes of inflammation.

[0024] The concentration of the selected cannabinoid compound(s) can vary depending on factors such as the desired treatment, the severity and type of the GI disorder, the duration of treatment, and the method of delivering the cannabinoid compound(s) to a subject. For example, in certain embodiments, treatment of an intermittent GI disorder can include a relatively greater amount of the one or more cannabinoid compounds while treatment of an ongoing GI disorder such as Crohn’s disease can include continual dosing with a smaller amount of the one or more cannabinoids. Treatment of GI disorders can also vary depending on the amount of the cannabinoid compounds included in a pill, capsule or food; the frequency the cannabinoid compounds are provided; and the biological half-life of the cannabinoid compounds remaining in the body.

[0025] In certain embodiments, the compositions, products, articles, and methods described herein can be substantially or entirely free of cannabinoid compounds other than THCV, CBL, CBC, CBD, CBN, (+)-CBD, CBG-C4, CBDVA, and CBLA. For example, the compositions, products, articles, and methods can be substantially or entirely free of tetrahydrocannabinol (“THC”). As used herein, substantially free can mean less than about 5%, less than about 4%, less than about 3%, less than about 2%, less than about 1%, less than about 0.5%, less than about 0.1%, or less than about 0.01%. In certain embodiments, the cannabinoid compounds can be produced using non-horticulturally derived methods such as through chemical synthesis (e.g., organic synthesis reactions) or through modification of yeast and/or bacterial cells to produce the cannabinoid compounds in high purity. However, in certain embodiments, cannabinoid compounds can also be a natural product, e.g., an extract of a cannabis plant if sufficiently pure. In certain embodiments, substantially pure means that the isolated cannabinoid compound, when added, includes about 3% or less of contaminants, about 2% or less of contaminants, about 1% or less of contaminants, about 0.5% or less of contaminants, about 0.1% or less of contaminants, or about 0.01% or less of contaminants.

[0026] In certain embodiments, the compositions, products, articles, and methods described herein can be utilized on a predetermined schedule (e.g., nightly, twice daily, etc.) or can be utilized on an as-needed basis. In certain embodiments, the predetermined schedule can be based on the halflife of the cannabinoid compounds as well as the release dynamics of the cannabinoid compounds.

[0027] In certain embodiments, the compositions and methods described herein can be used only by health professionals (e.g., doctors, surgeons, dieticians, etc.) or under their supervision.

[0028] In certain embodiments, the cannabinoid compounds can alternatively be administered to individuals via food products and other comestibles. By way of illustration and not as a limitation, the selected cannabinoid compounds can be incorporated into a beverage, a “smoothie” (fruit, vegetable, nut oil, or yogurt based), a frozen desert (e.g., ice cream or sorbet), a food bar, a nutrition bar, a dressing, a snack, into a flour- or flour-alternative-based product, a rice-based product, pastes, gels, powders, gums, etc. Incorporation into food products can facilitate consumption of the cannabinoid compounds and increase palatability.

[0029] As can be appreciated, the exact nature of the food article can influence the bioavailability of the cannabinoid compounds. For example, a cannabinoid included in a large food article may take more time to become bioavailable than the same amount of cannabinoid compounds in a single pill or capsule. Generally, the remainder of the composition or article can constitute any suitable non-bioactive component such as filler, food, or water.

[0030] In certain embodiments, the compositions or articles including the cannabinoid compounds described herein can include indicia and/or packaging to convey to end users the amount of the cannabinoid compounds contained therein. For example, a small nutrient bar may be individually labeled and packaged to express to the end user that only a single bar should be consumed.

[0031] As will be appreciated, a wide variety of different compositions and articles can be prepared which include the one or more cannabinoid compounds of the present disclosure including compositions and articles not listed here. All such compositions and articles are contemplated herein as they are within the ordinary skill of artisans based on the guidance provided in the present disclosure.

[0032] Generally, all of the compositions and articles described herein can be manufactured and produced as known in the art. For example, in certain embodiments, the cannabinoid compounds can be dissolved in a suitable solvent such as an alcohol or oil and then added to the composition or article.

Examples

[0033] To evaluate the role specific cannabinoid compounds can have in modulating the GI tract, a GPCR reactivity assay was performed to determine the reactivity of 19 cannabinoid compounds to each of CBiR, CB2R, CRHR1, CRHR2, and PSRY6. The evaluated cannabinoid compounds were: (+)-CBD, CBD, CBDV, CBD-C2, CBD-C1, CBG, CBG-C4, CBGV, CBC, CBL, CBN, THCV, CBDA, CBDVA, CBGA, CBGA-C4, CBGVA, CBCA, and CBLA. CP55940 (a synthetic THC analogue) was used as the control for CBiR and CB2R; sauvagine was used as the control for CRHR1 and CRHR2; and uracil triphosphate was used as the control for P2YR6.

[0034] To perform the GPCR reactivity assay, a commercial GPCR assay, PathHunter® P- Arrestin from Eurofins DiscoverX Products (Fremont, CA), was used. In the PathHunter® P- Arrestin GPCR assay, an inactive peptide fragment is fused to the targeted GPCR receptor and a complementary peptide fragment is fused to P-arrestin. At activation of the GPCR receptor and recruitment of P-arrestin, complementation of the peptide fragments occurs and restores P- galactosidase activity. The amount of P-galactosidase activity is then measurable using chemiluminescent reagents.

[0035] A total of five assays were run. Specifically, agonist assays were run for each of CBiR, CB2R, CRHR2, and PSRY6 and an antagonist assay was run for CRHR1. In each of the agonist assays, PathHunter® cell lines were removed from a freezer stock and seeded at a volume of 20 pL into white walled, 384-well microplates and incubated at 37 °C. Each cell was incubated with a sample to induce a response and then diluted to generate a 5x sample in assay buffer. 5 pL of the 5x sample was then added to cells and incubated at 37 °C for 90 or 180 minutes. The final assay concentration was 1%. The assay signal was generated through addition of 12.5 pL or 15 pL (50% V/V) of a detection reagent cocktail followed by a one hour incubation time at room temperature. Microplates were read following signal generation with a PerkinElmer Envision™ (PerkinElmer Inc., Waltham, MA) for chemiluminescent signal detection. Reactivity was analyzed using the CBIS data analysis suite (Chemlnnovation, CA) where RLU refers to the raw measured values. The percent activity was then calculated using the formula: % Activity = 100% * (mean RLU of test sample - mean RLU of control) / (mean max control ligand - mean RLU of vehicle control).

[0036] In each of the antagonist assays, PathHunter® cell lines were removed from a freezer stock and seeded at a volume of 20 pL into white walled, 384-well microplates and incubated at 37 °C. Each cell was pre-incubated with an antagonist followed by an agonist challenge at the EC80 concentration. Cells were then diluted to generate a 5x sample in assay buffer. 5 pL of the 5x sample was then added to cells and incubated at 37 °C for 30 minutes. Finally, 5 pL of 6x EC80 agonist in assay buffer were added to the cells and incubated at 37 °C for 90 minutes or 180 minutes. The assay signal was generated through addition of 12.5 pL or 15 pL (50% V/V) of a detection reagent cocktail followed by a one hour incubation time at room temperature. Microplates were read following signal generation with a PerkinElmer Envision™ (PerkinElmer Inc., Waltham, MA) for chemiluminescent signal detection. Reactivity was analyzed using the CBIS data analysis suite (Chemlnnovation, CA) where RLU refers to the raw measured values. The percent inhibition was calculated using the formula: % Inhibition = 100% * (1 - mean RLU of test sample - mean RLU of control) / (mean RLU of EC80 control - mean RLU of vehicle control).

[0037] As will be appreciated, CP55940 is a synthetic THC analogue that exhibits stronger activation of the endocannabinoid receptors CBiR and CB2R than actual THC. Accordingly, the percent activity values of the evaluated cannabinoid compounds can appear relatively small for acceptable activation of the endocannabinoid receptors.

[0038] The results of the GCPR reactivity screen are depicted in Table 1. For agonist activity, the percent activity is depicted while for antagonist activity, the percent inhibition is depicted.

TABLE 1

TABLE 1 (Continued)

[0039] As depicted in Table 1, certain cannabinoids demonstrated consistent results against the various GPC receptors including THCV, CBL, CBC, CBD, CBN, (+)-CBD, CBG-C4, CBDVA, and CBLA. Other cannabinoids including CBDV, CBD-C2, CBD-C1, CBG, CBGV, CBD A, CBDVA, CBGA, CBGA-C4, CBGV A, CBCA, and CBLA did not demonstrate effective agonist or antagonist activity against the GPC receptors associated with the treatment of GI disorders described herein.

[0040] The dimensions and values disclosed herein are not to be understood as being strictly limited to the exact numerical values recited. Instead, unless otherwise specified, each such dimension is intended to mean both the recited value and a functionally equivalent range surrounding that value.

[0041] It should be understood that every maximum numerical limitation given throughout this specification includes every lower numerical limitation, as if such lower numerical limitations were expressly written herein. Every minimum numerical limitation given throughout this specification will include every higher numerical limitation, as if such higher numerical limitations were expressly written herein. Every numerical range given throughout this specification will include every narrower numerical range that falls within such broader numerical range, as if such narrower numerical ranges were all expressly written herein.

[0042] Every document cited herein, including any cross-referenced or related patent or application, is hereby incorporated herein by reference in its entirety unless expressly excluded or otherwise limited. The citation of any document is not an admission that it is prior art with respect to any invention disclosed or claimed herein or that it alone, or in any combination with any other reference or references, teaches, suggests, or discloses any such invention. Further, to the extent that any meaning or definition of a term in this document conflicts with any meaning or definition of the same term in a document incorporated by reference, the meaning or definition assigned to that term in the document shall govern.

[0043] The foregoing description of embodiments and examples has been presented for purposes of description. It is not intended to be exhaustive or limiting to the forms described. Numerous modifications are possible in light of the above teachings. Some of those modifications have been discussed and others will be understood by those skilled in the art. The embodiments were chosen and described for illustration of various embodiments. The scope is, of course, not limited to the examples or embodiments set forth herein, but can be employed in any number of applications and equivalent articles by those of ordinary skill in the art. Rather it is hereby intended the scope be defined by the claims appended hereto.

[0044] It should be understood that certain aspects, features, structures, or characteristics of the various embodiments can be interchanged in whole or in part. Reference to certain embodiments mean that a particular aspect, feature, structure, or characteristic described in connection with certain embodiments can be included in at least one embodiment and may be interchanged with certain other embodiments. The appearances of the phrase “in certain embodiments” in various places in specification are not necessarily all referring to the same embodiment, nor are certain embodiments necessarily mutually exclusive of other certain embodiments. It should also be understood that the steps of the methods set forth herein are not necessarily required to be performed in the orders described, and the order of the steps of such methods should be understood to be merely exemplary. Likewise, additional steps can be included in such methods, and certain steps may be omitted or combined, in methods consistent with certain embodiments.

Claims

WHAT IS CLAIMED IS:

1. A composition comprising one or more cannabinoid compounds, wherein the composition regulates the gastrointestinal tract.

2. The composition of any preceding claim, wherein the composition therapeutically treats one or more of Inflammatory Bowel Disease (“IBD”), Crohn’s disease, ulcerative colitis, and Irritable Bowel Syndrome.

3. The composition of any preceding claim, wherein the one or more cannabinoid compounds comprise tetrahydrocannabivarin (“THCV”), cannabicyclol (“CBL”), cannabichromene (“CBC”), cannabidol (“CBD”), cannabinol (“CBN”), (+)-cannabidiol (“(+)-CBD”), cannabigerol butyl (“CBG-C4”), cannabidivarinic acid (“CBDVA”), and cannabicyclolic acid (“CBLA”).

4. The composition of any preceding claim comprises about 100 mg or less of the one or more cannabinoid compounds.

5. The composition of any preceding claim is a liquid.

6. The composition of any preceding claim is a food or beverage.

7. The composition of any of claims 1 to 4 is a pill or capsule.

8. The composition according to claim 7 is a delayed-release pill or capsule.

9. The composition according to claim 7 or claim 8 dissolves in the stomach or intestines.

10. The composition of any preceding claim, wherein the one or more cannabinoid compounds are non-horticulturally derived cannabinoid compounds.

11. The composition of any preceding claim, wherein the one or more cannabinoid compounds exhibit one or more of: agonist activity to the CB1R receptor; agonist activity to the CB2R receptor; antagonist activity to the CRHR1 receptor; agonist activity to the CRHR2 receptor; and agonist activity to the P2RY6 receptor.

12. The composition of any preceding claim reduces inflammation of the gastrointestinal tract.

13. The composition of any preceding claim intestinal motility.

14. An article comprising the composition of any of the preceding claims.

15. A method of treating a gastrointestinal disorder, the method comprising administering a therapeutically effective amount of one or more cannabinoid compounds selected from the group comprising tetrahydrocannabivarin (“THCV”), cannabicyclol (“CBL”), cannabichromene (“CBC”), cannabidol (“CBD”), cannabinol (“CBN”), (+)-cannabidiol (“(+)-CBD”), cannabigerol butyl (“CBG-C4”), cannabidivarinic acid (“CBDVA”), and cannabicyclolic acid (“CBLA”).

16. The method of claim 15, wherein the gastrointestinal disorder comprises Inflammatory Bowel Disease (“IBD”), Crohn’s disease, ulcerative colitis, and Irritable Bowel Syndrome.

17. The method of claim 15 or claim 16, wherein the one or more cannabinoid compounds exhibit one or more of: agonist activity to the CB1R receptor; agonist activity to the CB2R receptor; antagonist activity to the CRHR1 receptor; agonist activity to the CRHR2 receptor; and agonist activity to the P2RY6 receptor.

18. The method of any of claims 15 to 17, wherein the one or more cannabinoid compounds are administered in a food, a liquid, or a pill or capsule.