Cannabinoid compositions for treatment of complex regional pain syndrome

Abstract

Cannabinoid compositions formulated for use in the treatment of complex regional pain syndrome (CRPS) are disclosed. The compositions include cannabidiol (CBD), cannabigerol (CBG), and tetrahydrocannabinol (THC) as the major components therein, which may be isolated, purified or extracted from cultivars and blended together. The compositions include CBD, CBG and THC in certain ratios, formulated for the use in the treatment of CRPS.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 614,437, filed December 22, 2023, which is incorporated herein by reference in its entirety. FIELD

[0002] The present disclosure relates generally to treatment of complex regional pain syndrome (CRPS), and more specifically to the use of certain cannabinoid compositions for treating CRPS. BACKGROUND

[0003] Complex Regional Pain Syndrome (CRPS) is a debilitating and perplexing chronic pain condition that produces incalculable suffering to millions of individuals worldwide. The United States alone has a reported 200,000 individuals living with CRPS. The enigmatic nature of CRPS has left it difficult to treat. CRPS is characterized by a constellation of pain, sensory, autonomic, motor, and symptoms that cannot be explained by the initial injury. Although unclear, a common cause of CRPS are radial fractures that demonstrate aberrant processing 4-6 weeks after injury. These include degeneration of primary afferents, high central and peripheral inflammation, and psychological factors such as anxiety and depression are associated with CRPS exhibition and exacerbation. Thus, what is needed in the art are alternative treatments that can be used to directly to attenuate chronic pain resulting from CRPS. BRIEF SUMMARY

[0004] In some aspects, provided is a method of treating complex regional pain syndrome (CRPS) in a subject in need thereof. In some embodiments, the method comprises: administering a cannabinoid composition comprising cannabidiol (CBD), cannabigerol (CBG), and tetrahydrocannabinol (THC) present as a major component therein.

[0005] In certain embodiments, the CBD, CBG and / or THC may be provided as: (i) one or more botanical drug substances (“BDS”); (ii) one or more extracts from cannabis plants (“extracts”); (iii) one or more extracts from cannabis plants blended with additional sources of CBD, CBG and / or THC (“blended extracts”); (iv) purified CBD, CBG and / or THC, e.g., obtained from purifying the extracts or blended extracts; or (v) isolates of CBD, CBG and / or THC. In some variations, the cannabinoid composition further comprises other cannabinoids and non-cannabinoids (e.g., terpenes) formulated in a vehicle (e.g., a lipid vehicle) to yield the final product composition that may be administered to a subject in need thereof. Such other cannabinoids and non-cannabinoids (e.g., terpenes) are present from the source from which the composition is obtained. DETAILED DESCRIPTION

[0006] The following description sets forth exemplary compositions, methods, parameters and the like. It should be recognized, however, that such description is not intended as a limitation on the scope of the present disclosure but is instead provided as a description of exemplary embodiments.

[0007] Cannabinoids are compounds structurally or pharmacologically related to the constituents of the cannabis plant or to the endogenous agonists (endocannabinoids) of the cannabinoid receptors CB1 or CB2. Cannabinoids may be naturally derived from cannabis plants or synthetically derived. Cannabis plants comprise a highly complex mixture of compounds, and hundreds of such compounds have been identified.

[0008] Traditionally, crude extracts from cannabis plants containing CBD have been used by patients suffering from various diseases and disorders. However, such crude products are generally unsuitable for use in pharmaceutical formulations. Those seeking to prepare more consistent CBD formulations for use in treating diseases or disorders have made an effort to either prepare CBD synthetically or attempt to remove all compounds other than CBD, particularly psychoactive compounds such as THC, from plant derived cannabinoids.

[0009] The present invention encompasses the surprising discovery that particular compositions comprising CBD in combination with CBG and THC have an improved therapeutic efficacy for treating pain and health in complex regional pain syndrome (CRPS). Cannabinoid Compositions

[0010] In some aspects, provided are cannabinoid compositions comprising a combination of CBD, CBG and THC, which are collectively present as the major components of the cannabinoids in the compositions. In certain embodiments, the compositions herein, including the compositions administered in the methods herein, are drug formulations that comprise a combination of extracts or isolated compounds from one or more cultivars that are blended to achieve certain ratios of CBD, CBG and THC. For example, in some variations, extracts from genetically identical clones of three different cultivars (e.g., high CBD cultivars, high CBG cultivars, and high THC cultivars) may be used to produce the drug formulations. The components of the cannabinoid compositions provided herein are described in further detail below.

[0011] In some variations, the CBD, CBG and THC are collectively greater than 50%, greater than 60%, greater than 70%, greater 80%, greater than 85%, greater than 90%, greater than 95%, greater than 96%, greater than 97%, greater than 98%, or greater than 99%; or between 50% and 99.9%, between 60% and 99%, between 70% and 99%, between 80% and 99%, between 85% and 99%, between 85% and 95%, or between 90% and 99% by weight of the cannabinoids present in the composition.

[0012] It should be understood that in addition to the cannabinoids, in some embodiments, the cannabinoid compositions may include other cannabinoids as well as noncannabinoids formulated in a vehicle, such as a lipid vehicle, as described in further detail below. Such other cannabinoids as well as non-cannabinoids are present from the cannabis plant from which the compositions are obtained. Thus, in some variations, the composition comprises CBD, CBG and THC in the ratios and amounts as described herein, as well as other components, such as terpenes, and lipid excipients.

[0013] The structures of CBD, CBG and THC are well understood in the art. In some embodiments, the THC present in the compositions herein is primarily in the form of (-)-delta-9-trans-tetrahydrocannabinol (A9-THC).

[0014] In some variations, the CBD, CBG and THC are present in a molar ratio between about 100:100:1 and about 1:1:1; or between about 100:50:1 and about 20:1:1. In certain variations, the CBD and CBG are present in a molar ratio between about 100:1 and about 1:1. In certain variations, the molar ratio of CBD and THC is between about 50:1 and about 1:1.

[0015] In some variations, the CBD, CBG and THC are present in a weight ratio between about 100:100:1 and about 1:1:1; or between about 100:50:1 and about 20:1:1. In some variations, the CBD, CBG and THC are present in a weight ratio between about 1:0.06- 0.6:0.005-0.045. In certain variations, the CBD and CBG are present in a weight ratio between about 100:1 and about 1:1. In certain variations, the CBD and CBG are present in a weight ratio between about 1:0.06-0.6. In certain variations, the weight ratio of CBD to THC is between about 50:1 and about 1:1. In certain variations, the weight ratio of CBD to THC is between about 1:0.005-0.045.

[0016] In some variations, the weight ratio of CBD to CBG is 1:0.06-0.6. In certain variations, the weight ratio of CBD to CBG is 1:0.1-0.3. In some variations, the weight ratio of CBD to THC is 1:0.005-0.045. In certain variations, the weight ratio of CBD to THC is 1:0.005-0.045.

[0017] In some variations, the CBD is greater than half of the cannabinoids present in the composition by weight. In certain variations, the CBD is greater than 49% by weight, or between 49% and 98% by weight of the cannabinoids present in the composition. In other variations, the combination of CBD and CBG is greater than half of the cannabinoids present in the composition by weight.

[0018] In some variations, the CBD is greater than 5 mg / ml, between about 50 mg / ml and 150 mg / ml, or between about 5 mg / ml and 500 mg / ml in the total composition; and the CBG is between about 5 mg / ml and 95 mg / ml, between about 5 mg / ml and 50 mg / ml, between about 5 mg / ml and 20 mg / ml, or between about 10 mg / ml and 30 mg / ml in the total composition. In certain variations, the CBD is between about 50 mg / ml and 150 mg / ml. In a variation of the foregoing, the “total composition” includes cannabinoids, non-cannabinoids (e.g., terpenes, if present), and a vehicle (e.g., lipid vehicle).

[0019] In some variations, the CBG is between about 10 mg / ml and 30 mg / ml in the total composition. In certain variations, CBG is between 18 mg / ml and 22 mg / ml.

[0020] It should be understood that any suitable methods and techniques known in the art may be employed to measure the amounts of the components in the compositions. For example, gravimetric or volumetric methods may be employed to quantify the components present in the composition. One of skill in the art would appreciate how to convert the mg / ml units to other suitable units, such as mg / g.

[0021] In other variations, the CBD is greater than 1% by weight, or between 1% and 90% by weight of the total composition; and the CBG is greater than 0.3% by weight, or between 0.3% and 49% by weight of the total composition. In a variation of the foregoing, the “total composition” includes cannabinoids, non-cannabinoids (e.g., terpenes, if present), and a vehicle (e.g., lipid vehicle).

[0022] In some variations, the THC is present in an amount less than the limit set forth by the appropriate regulatory agencies, including for example, the U.S. Food and Drug Administration (FDA) or the U.S. Drug Enforcement Administration (DEA) or the United States Department of Agriculture (USDA) (e.g., with respect to the 2018 Farm Bill for Hemp products). In certain variations, the THC is less than 0.3% by weight, or between 0.05 % and 0.3% by weight of the cannabinoids present in the composition. In certain variations, the THC is less than 2 mg / ml, between about 0.75 mg / ml and 2.25 mg / ml, or between about 0.5 mg / ml and 1.5 mg / ml in the total composition. In a variation of the foregoing, the “total composition” includes cannabinoids, non-cannabinoids (e.g., terpenes, if present), and a vehicle (e.g., lipid vehicle).

[0023] In some embodiments, the CBD is about 100 mg / ml, the CBG is about 20 mg / ml, and the THC is about 1.5 mg / ml. In some variations of the foregoing, the THC is less than 0.3% by weight of the cannabinoids present in the composition. In certain variations, the minor cannabinoids are less than about 5% or less than about 2.5% by weight of the cannabinoids present in the composition.

[0024] In some embodiments, the cannabinoid compositions provided herein further comprise additional components, including other cannabinoids and / or non-cannabinoids. For example, in some variations, the composition further comprises one or more of the following: cannabidiolic acid (CBDA), tetrahydrocannabinolic acid (THCA), cannabichromene (CBC), and terpenes (such as alpha-bisabolol, guaiol, beta-caryophyllene, caryophyllene oxide, alpha-humulene or alpha-caryophyllene, limonene, linalool, beta-myrcene, trans-nerolidol, (E)-b-ocimene, alpha-pinene, beta-pinene, terpineols, terpinolene, and valencene).

[0025] In other variations, the composition further comprises one or more of the following: cannabinol (CBN), cannabichromene (CBC), tetrahydrocannabivarin (THCV), cannabigerolic acid (CBGA), cannabichromene acid (CBCA), cannabichromene acid (CBCA), tetrahydrocannabinolic acid (THCA), and cannabidiolic acid (CBDA), or any derivatives thereof.

[0026] In other embodiments, the composition may further comprise one or more of the following compounds: • Cannabigerol-type compounds: cannabigerol ((E)-CBG C-5), cannabigerol monomethyl ether ((E)-CBGM C-5A), Cannabinerol saure A ((Z)-CBGA C-5A), Cannabigerovarin (((e)-BGV C-3), Cannabigerol saure A(e)-CBGA C-5A), A Cannabigerol saure monomethyl ether ((e)-CBGAM C-5A), Cannabigerovarinsaure A ((e)-CBGVA-C3 A); • Cannabichromene-type compounds: cannabichromene (CBC-C5), Cannabichromensaure A (CBCA C-5A), Cannabichromevarin (CBCVC-3), Cannabichromevarinsaure A (CBCVA-C3 A); • Cannabidiol-type compounds: cannabidiol (CBD-C5), cannabidiol monomethyl (CBDM-C5), cannabidiol-C4 (CBD-C4), Cannabidivarin (CBDV-C3), Cannabidiorcol (CBD-C1), cannabidiolic (CBDA C-5), Cannabidivarinsaure (CBDVA C-3); • Cannabinodiol-type compounds: Cannabinodiol (CBND C-5), Cannabinodivarin (CBND C-3); • Tetrahydrocannabinol-type compounds: A9-tetrahydrocannabinol (A9-THC-C5), A9-tetrahydrocannabinol-C4 (A9-THC-C4), A9-tetrahydrocannabivarin (A9-THCV-C3), A9-Tetrahydrocannabiorcol (A9-THCO C-l), A9-Tetrahydrocannabinolsaure (A9 THCA-C-5A), A9-Tetrahydrocannabinol saure B (A9 THCA-C-5B), A9-Tetrahydrocannabinolsaure-C4 (A9 THCA-C-4A and / or B), A9-Tetrahydrocannabivarinsaure A (A9-THCVA-C3A), A9-Tetrahydrocannabiorcolsaure (A9-THCOA-C1 A and / or B), (-)-A8-trans-(6aR, 10aR)-8-tetrahydrocannabinol (A8-THC-C5), (-)-A8-trans-(6aR, 10aR)-Tetrahydrocannabinolsaure A (A8-THCA-C 5A); (-)-(6a S, 10a R)-A9-tetrahydrocannabinol ((-)-cis-A9-THC-C5); • Cannabinol-type compounds: Cannabinol CBN-C5, cannabinol C4 (CBN-C4), Cannabivarin (CBN-C3), cannabinol C2 (CBN-C2), Cannabiorcol (CBN-C1), Cannabinolsaure A (C5 CBNA-A), Cannabinolmethylether (CBNM C-5); • Cannabitriol-type compounds: (-)-(9R,10R)-trans-Cannabitriol ((-)-trans-CBT-C5), (+)-(9S,10S)-Cannabitriol ((+)-trans-CBT C-5), (±)-(9R, 10S / 9S, 10R)-Cannabitriol ((±)-cis-CBT-C5), (-)-(9R,10R)-trans [10-0-thyl-cannabitriol] ((-)-trans-CBT-OEt-C5), (±)-(9R, 10R / 9S, 10S)-Cannabitriol-C3 ((±)-trans-CBT-C3), 8,9-dihydroxy-A6a (10a) tetrahydrocannabinol (8,9-di-OH-CBT-C5), cannabidiolic A (CBDA C-59-OH-CBT-C5 ester), (-)-(6aR, 9S, IOS, 10aR)-9,10-dihydroxy-hexahydrocannabinol, Cannabiripsol Cannabiripsol-C5, (-)-6a,7, lOa-trihydroxy-A9-tetrahydrocannabinol ((-)-Cannabitetrol), 10-oxo-A6a (10a) tetrahydrocannabinol (OTHC); • Cannabielsoin-type compounds: (5aS, 6S, 9R, 9aR)-C5-Cannabielsoin (CBEC-5), (5aS, 6S, 9R, 9aR)-C3-Cannabielsoin (CBE C-3), ( 5aS, 6S, 9R, 9aR)-Cannabielsoinsaure A (CBEA-C5 A), (5aS, 6S, 9R, 9aR)-Cannabielsoinsaure B (CBEA-C5 B), (5aS, 6S, 9R, 9aR)-C3 Cannabielsoinsaure B (CBEA-C3 B), Cannabiglendol-C3 (OH-iso-HHCV C-3), Dehydrocannabifuran (DCBF C-5), Cannabifuran (CBF-C5); • Isocannabinoide-type compounds: (-)-A7-trans-(lR, 3R, 6R)Isotetrahydrocannabinol, (±) -A7-l,2-cis- (1R, 3R, 6S / 1S, 3S, 6R)-Isotetrahydrocannabivarin, (-)-A7-trans-(lR, 3R, 6R)-Isotetrahydrocannabivarin; • Cannabicyclol-type compounds: (±)-(laS, 3aR, 8bR, 8Cr-cannabicyclol (CBL-C), (±)-(laS, 3aR, 8bR, 8Cr-Cannabicyclolsaure A (CBLA-C5A) (±)-(laS, 3aR, 8bR, 8Cr-Cannabicyclovarin (CBLV C-3); • Cannabicitran-type compounds: Cannabicitran (CBT-C5); and • Cannabichromanon-type compounds: Cannabichromanon (CBCN C-5), Cannabichromanon-C3 (CBCN C-3), Cannabicoumaronon (CBCON C-5).

[0027] In addition to the above cannabinoids, the carboxylic acids which are biosynthetic precursors of each are contemplated as cannabinoids that may be present in the compositions described herein. In such instances, such cannabinoids are present as a minor component in the composition. In some variations, the cannabinoid precursors are not present in a detectable amount in the composition.

[0028] In some variations, minor cannabinoids present are collectively less than about 5% or less than about 2.5% by weight of the total composition. In a variation of the foregoing, the “total composition” includes cannabinoids, non-cannabinoids (e.g., terpenes, if present), and a vehicle (e.g., lipid vehicle).

[0029] In other variations, the compositions further comprise terpenes. Examples of terpenes that may be detected in the compositions include, for example, alpha-bisabolol, guaiol, beta-caryophyllene, caryophyllene oxide, alpha-humulene or alpha-caryophyllene, limonene, linalool, beta-myrcene, trans-nerolidol, (E)-b-ocimene, alpha-pinene, beta-pinene, terpineols, terpinolene, and valencene, alpha-bisabolol, beta-caryophyllene oxide, and guaiol. In one variation, depending on the source of the cannabinoids as described in further detail below, no detectable amounts of terpenes may be found.

[0030] In yet other variations, the composition further comprises flavonoids. In one variation, depending on the source of the cannabinoids as described in further detail below, no detectable amounts of flavonoids may be found.

[0031] It should be understood that the minor cannabinoids, terpenes and flavonoids, if present in the composition, may be from the BDS and / or extracts used to provide the CBD, CBG and THC, and such sources are described in further detail below. Source of CBD, CBG and THC

[0032] In some embodiments of the cannabinoid compositions provided herein, the CBD, CBG and THC are provided as a combination of extracts or isolated from at least two cannabis cultivars.

[0033] In some variations when the compositions comprise a combination of BDS, extracts or blended extracts (as described in further detail below), such compositions are polymodal compositions that include multiple active components that affect multiple targets and implicate multiple mechanisms of action simultaneously. The polymodality of such compositions may positively affect efficacy and safety profile. Such polymodal compositions may be viewed as distinct from fixed dose combinations (“FDCs”) that typically will use highly purified or isolated cannabinoid components. BDS

[0034] In some embodiments, one or more of CBD, CBG and THC are provided in the form a botanical drug substance (BDS). In some variations, the CBD, CBG and THC are each in the form of BDS. In some variations, a 'botanical drug substance” or ‘ BDS” is defined in the Guidance for Industry Botanical Drug Products Draft Guidance, August 2000, US Department of Health and Human Services, Food and Drug Administration Centre for Drug Evaluation and Research as: “A drug derived from one or more plants, algae, or microscopic fungi. It is prepared from botanical raw materials by one or more of the following processes: pulverisation, decoction, expression, aqueous extraction, ethanolic extraction or other similar processes.” A botanical drug substance does not include a highly purified or chemically modified substance derived from natural sources. Thus, in the case of cannabis, BDS derived from cannabis plants do not include highly purified pharmaceutical grade cannabinoids.

[0035] In some embodiments, the cannabinoid composition consists essentially of CBD, CBG and THC, in the form of botanical drug substance, wherein CBD, CBG and THC collectively a major component of the cannabinoids present in the composition, in the ratios and amounts as described herein. Extracts

[0036] In other embodiments, one or more of CBD, CBG and THC are provided as extracts from the cannabis plant. Such extracts may be obtained using any suitable methods and techniques known in the art. For example, dried cannabis flowers are soaked in water or alcohol to obtain the trichomes from the plant. The trichomes undergo solvent extraction and optionally additional purification steps to obtain a cannabinoid-rich oil, also referred to as an “extract”.

[0037] In some variations, the CBD, CBG and THC are provided as a combination of cannabis extracts or isolated from 2-4 cannabis cultivars. In certain variations, the CBD, CBG and THC are provided as a combination of cannabis extracts from genetically identical clones of 3 different cannabis cultivars. In one variation for the foregoing, the 3 different cultivars are a high CBD cultivar, a high CBG cultivar and a high THC cultivar. In some variations, the cannabis cultivars are Cannabis sativa cultivars.

[0038] In some variations, when the CBD, CBG and THC are provided as extracts, the compositions provided herein further include terpenes. In certain variations, when the CBD, CBG and THC are provided as extracts, the compositions provided herein further include terpenes and flavonoids. Blended Extracts

[0039] In other embodiments, one or more of the CBD, CBG and THC are provided as a blend of the extracts described above in combination with additional CBD, CBG and / or THC obtained from other sources to achieve the particular ratios and amounts of CBD, CBG and THC as described herein. For example, in some variations, the composition comprises CBD, CBG and THC provided as extracts from the cannabis plants, blended with additional CBD provided in a purified form or as an isolate to achieve the ratios and amounts of CBD, CBG and THC as described herein. Purified Forms

[0040] In yet other embodiments, one or more of the CBD, CBG and THC are provided in a purified form. Such purified forms of the cannabinoids may be obtained using any suitable methods and techniques known in the art. For example, the extract or blended extracts described above may undergo distillation (e.g., molecular distillation) to remove certain constituents, such as terpenes and lipids, that are non-cannabinoids, and also separate out specific cannabinoids. In some variations, the purified extracts are oils.

[0041] In certain variations, the CBD, CBG and THC are a combination of highly purified CBD, highly purified CBG and highly purified THC, wherein each of which are extracted from a cannabis plant and purified to the extent that other cannabinoids and a majority of non-cannabinoid components that are co-extracted with the cannabinoids have been removed. In one variation, the highly purified CBD is greater than or equal to 90% (w / w) pure; the highly purified CBG is greater than or equal to 90% (w / w) pure; and the highly purified THC is greater than or equal to 90% (w / w) pure. Isolates

[0042] In some variations, one or more CBD, CBG and THC are provided as isolates. Such isolates may be obtained using any suitable methods and techniques known in the art. For example, the isolates may be obtained by crystallization or precipitation of a purified extract as described above to isolate a specific cannabinoid, followed by filtration to yield a powder that is essentially a pure cannabinoid with excess solvent removed. In some variations the isolates are powders. In one variation, the CBD isolate is greater than or equal to 99% (w / w) pure; the CBG isolate is greater than or equal to 99% (w / w) pure; and the THC isolate is greater than or equal to 99% (w / w) pure.

[0043] In certain variations, CBD, CBG and THC are provided a combination of isolates, which may be with or without BDS, extracts or blended extracts. In one variation, the CBD, CBG and THC are provided as a combination of isolates and BDS. Natural vs. Synthetic Sources

[0044] In some variations, the CBD, CBG and THC are all naturally derived. In other variations, at least a portion of the CBD, CBG and / or THC is naturally derived, and the other portion is synthetic and / or biosynthetic. Synthetic cannabinoids may include compounds that have a cannabinoid-like structure and are manufactured using chemical processes rather than by the plant. Biosynthetic cannabinoids may include compounds that have a cannabinoid-like structure and are produced using biological processes rather than by the plant. In certain embodiments, at least a portion of CBD present in the composition is prepared synthetically or biosynthetically. In certain embodiments, at least a portion of CBG present in the composition is prepared synthetically or biosynthetically. In certain embodiments, at least a portion of THC present in the composition is prepared synthetically or biosynthetically.

[0045] It should be understood that the compositions provided herein may include CBD, CBG and THC provided in a combination of different forms described above. For example, in certain variations, the CBD, CBG and THC are provided in the form of BDS in combination with additional refined or synthetic or biosynthetic CBD, CBG and THC to achieve the ratios and amounts described herein. Lipid Vehicles

[0046] In some embodiments, the combination of cannabinoids described herein are formulated in lipid vehicles to yield the compositions, e.g., the drug formulation. In some variations, the compositions herein may further comprise at least one lipid excipient. In certain variations, suitable excipients may include glyceryl monolinoleate.

[0047] In some variations, the lipid vehicle comprises a winterized oil composed of long-chain mono-, di-, and triglycerides. In certain variations, the lipid vehicle comprises mono-, di- and triglycerides of mainly linoleic (Ci8:2) and oleic (Ci8:i) acids. In one variation of the foregoing, the diester fraction is predominant.

[0048] In other embodiments, the lipid vehicle comprises self-emulsifying drug delivery systems. Other Components

[0049] In other embodiments, the compositions provided herein may further include or more additional components. For example, in some variations, the compositions further comprise at least one fatty acid. In certain variations, the compositions further comprise long-chain omega-3 polyunsaturated fatty acids (0-3s). In one variation, the compositions further comprise docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA).

[0050] In some embodiments, the drug substance compositions comprise (i) CBD, CBG and THC, collectively a major component of the cannabinoids present in the composition, in the ratios and amounts as described herein; (ii) fats and fatty acids; and (iii) terpenes. In certain embodiments, the drug substance compositions consists essentially of (i) CBD, CBG and THC, collectively a major component of the cannabinoids present in the composition, in the ratios and amounts as described herein; (ii) fats and fatty acids; and (iii) terpenes.

[0051] In some variations, the drug substance compositions comprise between 70% and 90% cannabinoids, including CBD, CBG and THC, collectively a major component of the cannabinoids present in the composition, in the ratios and amounts as described herein; between 10% and 15% fats and fatty acids; and between 1% and 5% terpenes. For example, in one variation, the composition comprises about 80% cannabinoids in the ratios and amounts as described herein, about 15% fats and fatty acids, and about 5% terpenes. In certain variations, the drug substance compositions consist essentially of (i) between 70% and 90% cannabinoids in the ratios and amounts as described herein, (ii) between 10% and 15% fats and fatty acids, and (iii) between 1% and 5% terpenes.

[0052] In some embodiments, the drug product compositions comprise CBD, CBG and THC, collectively a major component of the cannabinoids present in the composition, in the ratios and amounts as described herein; fats and fatty acids; terpenes; and at least one lipid, such as a winterized oil composed of long-chain mono-, di-, and triglycerides. In certain embodiments, the drug product compositions consist essentially of (i) CBD, CBG and THC, collectively a major component of the cannabinoids present in the composition, in the ratios and amounts as described herein, (ii) fats and fatty acids, (iii) terpenes, and (iv) at least one lipid, such as a winterized oil composed of long-chain mono-, di-, and triglycerides. Preparation Methods

[0053] The cannabinoid compositions provided herein may be obtained from combining plant-derived, synthetic and / or biosynthetic CBD, CBG and THC, in order to achieve the appropriate amounts and ratios of these components.

[0054] As discussed above, when CBD, CBG and THC are plant-derived, they may be obtained from a cannabis plant. Various methods, techniques and conditions to cultivate, harvest and process cannabis plants are generally known in the art. Further, the resulting cannabis extract may be characterized using methods known in the art. Any suitable processes known in the art may be employed to obtain the CBD, CBG and THC used herein.

[0055] For example, bulk plant material is isolated from dried cannabis flower. The bulk plant material is separated from the botanical starting material. The botanical starting materials are weighed and stored in an amber jar. The botanical starting material are added to an extraction vessel with solvent. The solvent is removed via vacuum distillation until only refined cannabis oil is present, with a low solvent concentration. The crude cannabis oil is then heated to for a suitable time to convert the THCA to THC to yield a refined cannabis oil. The main cannabinoids, THCA, CBDA and CBGA are converted to the base molecule THC, CBD and CBG, respectively.

[0056] The cannabinoid extracts described above may undergo further purification using methods and techniques known in the art to obtain purified extracts or isolates. The purified extracts are typically in oil form, whereas the isolates are typically in powder form. In some variations, cannabis extracts may undergo distillation to remove certain constituents, such as terpenes and lipids, that are non-cannabinoids, and also separate out specific cannabinoids to yield a purified extract. In other variations, such purified extract may undergo crystallization or precipitation to isolate a specific cannabinoid, followed by filtration to yield a powder that is essentially a pure cannabinoid with excess solvent removed.

[0057] The cannabinoid compositions provided herein are pharmaceutical cannabinoid compositions, formulated based on the mode of intended administration. For example, in some embodiments, administration may be ocular, oral, parenteral, topical, etc. In one variation, the cannabinoid composition is formulated for oral administration. In some embodiments, the cannabinoid composition is formulated as a solution for oral administration. In some embodiments, the composition may further comprise one or more flavoring or masking agents, including agents that may mask bitterness of the composition (e.g., any bitterness from the BDS).

[0058] In some embodiments, the cannabinoid compositions may be formulated with one or more excipients to increase stability, increase shelf-life, or increase efficacy. Cannabinoid compositions disclosed herein may be formulated for administration according to methods known in the art. Treatment Methods

[0059] In some aspects, provided is a method for treating complex regional pain syndrome (CRPS) in a subject in need thereof. In some variations of the foregoing aspects, the subject is a human. In one variation, the subject is an adult human.

[0060] In some embodiments of the foregoing aspects, the method comprises administering to the subject the compositions described herein, e.g., comprising CBD, CBG and THC as the major components therein. In some variations of the foregoing aspects, the terms “treating” or “treatment”, as used herein, refer to a method or procedure for obtaining beneficial or desired results—for example, clinical results. Beneficial or desired results may include: (1) alleviating one or more symptoms caused by or associated with a disease, disorder, or condition; (2) reducing the extent of the disease, disorder, or condition; (3) slowing or stopping the development or progression of one or more symptoms caused by or associated with the disease, disorder, or condition (for example, stabilizing the disease, disorder, or condition); and (4) relieving the disease, for example, by causing the regression of one or more clinical symptoms (e.g., ameliorating the disease state, enhancing the effect of another medication, delaying or stopping the progression of the disease, increasing the quality of life, and / or prolonging survival rates).

[0061] In some variations, treating CRPS comprises treating pain and health associated with CRPS. In some variations, the treatment produces improved analgesia as measured on the CRPS scale. In some variations, the treatment attenuates pain sensitivity and increase pain tolerance. In some variations, the treatment reduces ecological momentary assessment pain reports. In some variations, the treatment improves one or more CRPS related comorbidities. In certain variations, the treatment improves a spectrum CRPS related comorbidities. In certain variations, the CRPS related comorbidities comprises depression or anxiety, or a combination thereof. In other variations, the treatment improves neural processing in the human that will be associated with significant improvements in pain. In other variations, the treatment reduces inflammatory pain markers, wherein these reductions are associated with CRPS relief. In other variations, the subject suffers from persistent pain, swelling, changes in skin temperature or color, or limited range of motion, or any combination thereof. In other variations, treating CRPS comprises improving fracture healing or increased biomarkers related to bone healing in the subject.

[0062] In certain aspects, provided is a method for treating CRPS in a human in need thereof, comprising: a) administering a cannabinoid composition as described herein to the human; and b) treating pain and health associated with CRPS. In certain aspects, provided is a method for treating CRPS in a human in need thereof, comprising: a) administering a cannabinoid composition as described herein to the human; and b) improving analgesia as measured on the CRPS scale. In certain aspects, provided is a method for treating CRPS in a human in need thereof, comprising: a) administering a cannabinoid composition as described herein to the human; and b) attenuating pain sensitivity and increasing pain tolerance. In certain aspects, provided is a method for treating CRPS in a human in need thereof, comprising: a) administering a cannabinoid composition as described herein to the human; and b) reducing ecological momentary assessment pain reports. In certain aspects, provided is a method for treating CRPS in a human in need thereof, comprising: a) administering a cannabinoid composition as described herein to the human; and b) improving one or more CRPS related comorbidities. In certain aspects, provided is a method for treating CRPS in a human in need thereof, comprising: a) administering a cannabinoid composition as described herein to the human; and b) improving a spectrum CRPS related comorbidities, such as depression and / or anxiety. In certain aspects, provided is a method for treating CRPS in a human in need thereof, comprising: a) administering a cannabinoid composition as described herein to the human; and b) improving neural processing in the human that will be associated with significant improvements in pain. In certain aspects, provided is a method for treating CRPS in a human in need thereof, comprising: a) administering a cannabinoid composition as described herein to the human; and b) reducing inflammatory pain markers, wherein these reductions are associated with CRPS relief. In certain aspects, provided is a method for treating CRPS in a human in need thereof, comprising: a) administering a cannabinoid composition as described herein to the human; and b) improving fracture healing or increased biomarkers related to bone healing in the human.

[0063] In some variations of the foregoing aspects, CRPS is also referred to herein as reflex sympathetic dystrophy (RSD). In certain variations, CRPS is in the form of CRPS Type 1 (also referred to as “CRPS-I”). CRPS Type 1 occurs after an injury or illness but is not associated with nerve damage. In other variations s, CRPS is in the form of CRPS Type 2 (also referred to as “CRPS-II”). CRPS Type 2 is known as causalgia and is associated with damage to a specific nerve. In some variations of the foregoing aspects, provided is a method for treating CRPS Type 1 and / or CRPS Type 2 using the cannabinoid compositions as described herein.

[0064] In some variations, the cannabinoid composition is administered once daily. In some variations, the cannabinoid composition is administered twice daily. In some variations, the cannabinoid composition is administered with food. In some variations, the cannabinoid composition is administered without food.

[0065] In some variations of the foregoing aspects, a therapeutically effective amount of the cannabinoid composition is administered. In certain variations, the term “therapeutically effective amount” applied to dose or amount refers to that quantity of a composition or formulation, such as those described herein, that is sufficient to result in a desired clinical benefit after administration to a subject in need thereof. It is to be understood that the amount may be in one or more doses, e.g., a single dose or multiple doses may be needed to achieve the desired treatment endpoint. In some variations, the cannabinoid composition is administered at a dose of greater than 100 mg total daily dose, including e.g., between 100 mg and 1500 mg total daily dose. It should be understood here that the “total daily dose” is measured against the amount of CBD.

[0066] In some embodiments, the cannabinoid composition is administered at a therapeutically effective dose or amount. In some variations, the term “therapeutically effective” applied to dose or amount refers to that quantity of the cannabinoid composition, such as those described elsewhere herein, that is sufficient to result in a desired clinical benefit after administration to a subject in need thereof. It is to be understood that an effective amount may be in one or more doses, e.g., a single dose or multiple doses may be needed to achieve the desired treatment endpoint.

[0067] In some variations, provided is a composition as described herein, e.g., comprising CBD, CBG and THC as the major components therein, for use in a method of treating CRPS, wherein analgesia as measured on the CRPS scale is improved, pain sensitivity and increase pain tolerance is attenuated, ecological momentary assessment pain reports is reduced, one or more CRPS related comorbidities is improved, spectrum CRPS related comorbidities, such as depression and / or anxiety, is improved, or any combination of the foregoing outcomes. In some variations, provided is a composition as described herein, e.g., comprising CBD, CBG and THC as the major components therein, for use in a method of treating CRPS, wherein neural processing in the human that will be associated with significant improvements in pain is improved, inflammatory pain markers is reduced, or any combination of the foregoing outcomes. In some variations, provided is a composition as described herein, e.g., comprising CBD, CBG and THC as the major components therein, for use in a method of treating CRPS, wherein fracture healing or increased biomarkers related to bone healing in the subject is improved.

[0068] In certain aspects, provided is a composition as described herein, e.g., comprising CBD, CBG and THC as the major components therein, for use in a method of CRPS. In some variations, provided is a composition as described herein, e.g., comprising CBD, CBG and THC as the major components therein, for use in a method of treating CRPS in any of the doses described herein, including in a dose between 50 mg and 1,000 mg, a 400 mg daily dose, a 400 mg twice daily dose, a 500 mg daily dose, or a 500 mg twice daily dose. It should be understood that dose here is measured against the amount of CBD.

[0069] The terms “treating” or “treatment”, as used herein, refer to a method or procedure for obtaining beneficial or desired results—for example, clinical results. Beneficial or desired results may include: (1) alleviating one or more symptoms caused by or associated with a disease, disorder, or condition; (2) reducing the extent of the disease, disorder, or condition; (3) slowing or stopping the development or progression of one or more symptoms caused by or associated with the disease, disorder, or condition (for example, stabilizing the disease, disorder, or condition); and (4) relieving the disease, for example, by causing the regression of one or more clinical symptoms (e.g., ameliorating the disease state, enhancing the effect of another medication, delaying or stopping the progression of the disease, increasing the quality of life, and / or prolonging survival rates).

[0070] In some variations, the cannabinoid composition is administered at an initial dose between about 50 mg and about 300 mg, wherein the dose is measured against the amount of CBD in the composition. In one variation, the initial dose administered is about 50 mg of the cannabinoid composition. In certain variations, the aforementioned initial doses may be administered once a day or twice a day.

[0071] In some embodiments, the initial dose of the cannabinoid composition is between 100 mg and 600 mg total daily dose. In certain embodiments, the initial dose of the cannabinoid composition is 100 mg total daily dose. In some variations, the subject is monitored for clinical response and tolerability of the cannabinoid composition administered. In some variations, the dose of the cannabinoid composition administered to the subject is increased up to a maximum total daily dose of about 1500 mg, about 1000 mg, about 800 mg, about 700 mg, about 600 mg, about 500 mg, about 400 mg, about 300 mg, or about 200 mg. The dose may be titrated up based on safety and desired effect experienced by the subject. In some variations of the foregoing, the total daily dose noted above may be administered once a day, or twice a day.

[0072] In one aspect, provided is a method treating CRPS in a human in need thereof that comprises administering a cannabinoid composition as described herein at a therapeutically effect amount. In one embodiment, the method comprises administering a cannabinoid composition as described herein at a total daily dose between about 100 mg and about 600 mg; monitoring safety and effect on CRPS, or the symptoms of CRPS, experienced by the subject; and administering an increased dose of the cannabinoid composition, wherein the increased dose is up to a maximum total daily dose of about 1500 mg, about 1000 mg, about 800 mg, about 700 mg, about 600 mg, about 500 mg, about 400 mg, about 300 mg, or about 200 mg. In one variation of the foregoing, the total daily dose is administered in one daily dose. In another variation of the foregoing, the total daily dose is administered twice a day (e.g., in two doses). Kits and Articles of Manufacture

[0073] In other aspects, the present disclosure further provides kits for carrying out the methods of the invention. The kits may comprise the cannabinoid compositions described herein and suitable packaging. In some embodiments, provided is a kit, comprising: (i) any of the cannabinoid compositions described herein; and (ii) a label and / or instructions for use in treating CRPS. In some variations of the foregoing, the kit may further comprise a bottle adaptor and / or oral dosing syringe.

[0074] In yet other aspects, the present disclosure further provides an article of manufacture, comprising any of the cannabinoid compositions described herein in a suitable container. In some variations of the foregoing, the article of manufacture may further comprise a bottle adaptor and / or oral dosing syringe. ENUMERATED EMBODIMENTS

[0075] The following enumerated embodiments are representative of some aspects of the invention. 1 A.      A method of treating Complex Regional Pain Syndrome (CRPS) in a human in need thereof, comprising: administering a cannabinoid composition comprising: cannabidiol (CBD), cannabigerol (CBG), and tetrahydrocannabinol (THC), collectively a major component of the cannabinoids present in the composition, wherein the CBD, CBG and THC are provided as a combination of extracts or isolated from at least two cannabis cultivars. 2A. The method of embodiment 1 A, wherein the CBD, CBG and / or THC are provided as botanical drug substances (BDS). 3 A.      The method of embodiment 2A, wherein the cannabinoid composition further comprises other cannabinoid and / or non-cannabinoid components that are present from the BDS. 4A. The method of embodiment 2A, wherein the cannabinoid composition further comprises terpenes that are present from the BDS. 5 A.      The method of any one of embodiments 2A to 4A, wherein the cannabinoid composition further comprises flavonoids that are present from the BDS. 6A. The method of embodiment 1 A, wherein the CBD, CBG and THC are provided as a combination of cannabis extracts. 7A. The method of embodiment 1 A, wherein the CBD, CBG and THC are provided as a combination of extracts from 2-4 cannabis cultivars. 8A. The method of embodiment 1 A, wherein the CBD, CBG and THC are provided as a combination of extracts from genetically identical clones of 3 different cannabis cultivars. 9A. The method of embodiment 8A, wherein the 3 different cannabis cultivars are a high CBD cultivar, a high CBG cultivar and a high THC cultivar. 10A. The method of any one of embodiments 7A to 9A, wherein cannabis cultivars are Cannabis sativa cultivars. 11 A.     The method of any one of embodiments 6A to 10A, wherein the cannabinoid composition further comprises other cannabinoid and / or non-cannabinoid components that are present from the extracts. 12A.     The method of any one of embodiments 6A to 10A, wherein the cannabinoid composition further comprises terpenes that are present from the extracts. 13A. The method of any one of embodiments 6A to 11 A, wherein the cannabinoid composition further comprises flavonoids that are present from the extracts. 14A. The method of any one of embodiments 2A to 13A, wherein the cannabinoid composition further comprises additional CBD, CBG and / or THC provided in purified form. 15 A.     The method of any one of embodiments 2A to 13 A, wherein the cannabinoid composition further comprises additional CBD, CBG and / or THC isolates. 16A. The method of embodiment 1 A, wherein the CBD, CBG and THC are provided as a combination of purified CBD, CBG and THC cannabis extracts. 17A. The method of embodiment 1 A, wherein the CBD, CBG and THC are provided as a combination of CBD, CBG and THC isolates. 18A. The method of embodiment 1A, wherein the CBD, CBG and THC are provided as a combination of BDS and CBD, CBG and / or THC isolates. 19A. The method of embodiment 1 A, wherein the CBD, CBG and THC are provided as a combination of BDS, and purified CBD, CBG and / or THC cannabis extracts. 20A. The method of embodiment 1 A, wherein the CBD, CBG and THC are provided as a combination of BDS, and CBD, CBG and / or THC isolates. 21 A.     The method of embodiment 1 A, wherein the CBD, CBG and THC are provided as BDS in combination with refined or synthetic CBD, CBG and / or THC. 22A. The method of embodiment 1 A, wherein the CBD, CBG and THC are a combination of highly purified CBD, highly purified CBG and highly purified THC, wherein each of which are extracted from a cannabis plant and purified to the extent that other cannabinoids and a majority of non-cannabinoid components that are co-extracted with the cannabinoids have been removed. 23 A.      The method of embodiment 22A, wherein the highly purified CBD is greater than or equal to 90% (w / w) pure; the highly purified CBG is greater than or equal to 90% (w / w) pure; and the highly purified THC is greater than or equal to 90% (w / w) pure. 24A. The method of embodiment 1 A, wherein the CBD, CBG and THC are all naturally derived. 25 A.     The method of embodiment 1 A, wherein at least a portion of the CBD, CBG and / or THC is naturally derived, and the other portion is synthetic and / or biosynthetic. 26A. The method of any one of the preceding embodiments, wherein the THC is present primarily in the form of (-)-delta-9-trans-tetrahydrocannabinol (A9-THC). 27A. The method of any one of the preceding embodiments, wherein the CBD, CBG and THC are collectively greater than 50% by weight of the cannabinoids present in the composition. 28A. The method of embodiment 27A, wherein the CBD, CBG and THC are collectively greater than 60% by weight of the cannabinoids present in the composition. 29A. The method of any one of the preceding embodiments, wherein the CBD, CBG and THC are present in a molar ratio between about 100:100:1 and about 1:1:1. 30A. The method of embodiment 29A, wherein the CBD, CBG and THC are present in a molar ratio is between about 100:50:1 and about 20:1:1. 31 A.     The method of any one of the preceding embodiments, wherein the CBD and CBG are present in a molar ratio between about 100:1 and about 1:1. 32A. The method of any one of the preceding embodiments, wherein the molar ratio of CBD and THC is between about 50:1 and about 1:1. 33A. The method of any one of the preceding embodiments, wherein the cannabinoid composition further comprises at least one lipid excipient. 34A. The method of embodiment 33A, wherein at least one lipid excipient is a winterized oil comprising long-chain mono-, di-, and triglycerides. 3 5 A.      The method of any one of the preceding embodiments, wherein the cannabinoid composition further comprises docosahexaenoic acid (DHA), or eicosapentaenoic acid (EPA), or a combination thereof. 36A. The method of any one of the preceding embodiments, wherein the composition is formulated for oral delivery, and optionally wherein the composition further comprises one or more flavoring or masking agents. 3 7 A.     The method of any one of the preceding embodiments, wherein treating CRPS comprises treating pain and health associated with CRPS. 3 8 A.      The method of any one of the preceding embodiments, wherein the treatment produces improved analgesia as measured on the CRPS scale. 3 9 A.      The method of any one of the preceding embodiments, wherein the treatment attenuates pain sensitivity and increase pain tolerance. 40A. The method of any one of the preceding embodiments, wherein the treatment reduces ecological momentary assessment pain reports. 41 A.      The method of any one of the preceding embodiments, wherein the treatment improves one or more CRPS related comorbidities. 42A.     The method of embodiment 41 A, wherein the treatment improves a spectrum CRPS related comorbidities. 43 A.     The method of embodiment 41A or 42A, wherein the CRPS related comorbidities comprises depression or anxiety, or a combination thereof. 44A. The method of any one of the preceding embodiments, wherein the treatment improves neural processing in the human that will be associated with significant improvements in pain. 45 A.      The method of any one of the preceding embodiments, wherein the treatment reduces inflammatory pain markers, wherein these reductions are associated with CRPS relief. 46A. The method of any one of the preceding embodiments, wherein the human suffers from persistent pain, swelling, changes in skin temperature or color, or limited range of motion, or any combination thereof. 47A. The method of any one of embodiments 1A to 46A, wherein the pharmaceutical cannabinoid composition is administered once daily. 48A. The method of any one of embodiments 1A to 46A, wherein the pharmaceutical cannabinoid composition is administered twice daily. 49A. The method of any one of the preceding embodiments, wherein the pharmaceutical cannabinoid composition is administered with food. 50A. The method of any one of the preceding embodiments, wherein the pharmaceutical cannabinoid composition is administered at a dose between 100 mg and 1500 mg total daily dose. 51 A.     A cannabinoid composition, comprising: cannabidiol (CBD), cannabigerol (CBG), and tetrahydrocannabinol (THC), collectively a major component of the cannabinoids present in the composition, wherein the CBD is between about 90 mg / ml and 110 mg / ml, and the CBG is between about 18 mg / ml and 22 mg / ml, and wherein the CBD, CBG and THC are provided as a combination of extracts or isolated from at least two cannabis cultivars. 52A. The composition of embodiment 51 A, wherein the CBD, CBG and / or THC are provided as botanical drug substances (BDS). 53 A.      The composition of embodiment 52A, further comprising other cannabinoid and / or non-cannabinoid components that are present from the BDS. 54A. The composition of embodiment 52A, further comprising terpenes that are present from the BDS. 55 A.     The composition of any one of embodiments 51A to 54A, further comprising flavonoids that are present from the BDS. 56A. The composition of embodiment 51 A, wherein the CBD, CBG and THC are provided as a combination of cannabis extracts. 57A. The composition of embodiment 51 A, wherein the CBD, CBG and THC are provided as a combination of extracts from 2-4 cannabis cultivars. 58A. The composition of embodiment 51 A, wherein the CBD, CBG and THC are provided as a combination of extracts from genetically identical clones of 3 different cannabis cultivars. 59A. The composition of embodiment 58A, wherein the 3 different cannabis cultivars are a high CBD cultivar, a high CBG cultivar and a high THC cultivar. 60A. The composition of any one of embodiments 57A to 59A, wherein cannabis cultivars are Cannabis sativa cultivars. 61 A.     The composition of any one of embodiments 56A to 60A, further comprising other cannabinoid and / or non-cannabinoid components that are present from the extracts. 62A. The composition of any one of embodiments 56A to 61 A, further comprising terpenes that are present from the extracts. 63 A.     The composition of any one of embodiments 56A to 62A, further comprising flavonoids that are present from the extracts. 64A. The composition of any one of embodiments 51A to 63 A, further comprising additional CBD, CBG and / or THC provided in purified form. 65 A.     The composition of any one of embodiments 51A to 63 A, further comprising additional CBD, CBG and / or THC isolates. 66A. The composition of embodiment 65 A, wherein the CBD, CBG and THC are provided as a combination of purified CBD, CBG and THC cannabis extracts. 67A. The composition of embodiment 51 A, wherein the CBD, CBG and THC are provided as a combination of CBD, CBG and THC isolates. 68A. The composition of embodiment 51 A, wherein the CBD, CBG and THC are provided as a combination of BDS and CBD, CBG and / or THC isolates. 69A. The composition of embodiment 51 A, wherein the CBD, CBG and THC are provided as a combination of BDS, and purified CBD, CBG and / or THC cannabis extracts. 70A. The composition of embodiment 51 A, wherein the CBD, CBG and THC are provided as a combination of BDS, and CBD, CBG and / or THC isolates. 71 A.     The composition of embodiment 51 A, wherein the CBD, CBG and THC are provided as BDS in combination with refined or synthetic CBD, CBG and / or THC. 72A. The composition of embodiment 51 A, wherein the CBD, CBG and THC are a combination of highly purified CBD, highly purified CBG and highly purified THC, wherein each of which are extracted from a cannabis plant and purified to the extent that other cannabinoids and a majority of non-cannabinoid components that are co-extracted with the cannabinoids have been removed. 73 A.      The composition of embodiment 72A, wherein the highly purified CBD is greater than or equal to 90% (w / w) pure; the highly purified CBG is greater than or equal to 90% (w / w) pure; and the highly purified THC is greater than or equal to 90% (w / w) pure. 74A. The composition of embodiment 51 A, wherein the CBD, CBG and THC are all naturally derived. 75 A.     The composition of embodiment 51 A, wherein at least a portion of the CBD, CBG and / or THC is naturally derived, and the other portion is synthetic and / or biosynthetic. 76A.     The composition of any one of the preceding embodiments, wherein the THC is present primarily in the form of (-)-delta-9-trans-tetrahydrocannabinol (A9-THC). 77A.      The composition of any one of the preceding embodiments, further comprising at least one lipid excipient. 78A.      The composition of embodiment 77A, wherein at least one lipid excipient is a winterized oil comprising long-chain mono-, di-, and triglycerides. 79A.      The composition of any one of the preceding embodiments, further comprising docosahexaenoic acid (DHA), or eicosapentaenoic acid (EPA), or a combination thereof. 80A.     The composition of any one of the preceding embodiments, wherein the THC is present in less than 0.3% by weight of the total composition. 81 A.     The composition of any one of the preceding embodiments, wherein the CBD is about 100 mg / ml, the CBG is about 20 mg / ml, and the THC is about 1.5 mg / ml. 82A.      The composition of any one of the preceding embodiments, wherein the composition is formulated for oral delivery, and optionally wherein the composition further comprises one or more flavoring or masking agents. IB. A method of treating Complex Regional Pain Syndrome (CRPS) in a human in need thereof, comprising: administering a therapeutically effective dose of a cannabinoid composition comprising: cannabidiol (CBD), cannabigerol (CBG), and tetrahydrocannabinol (THC), collectively a major component of the cannabinoids present in the composition, wherein CBD, CBG and THC are provided as a combination of extracts or isolated from at least two cannabis cultivars, and wherein the weight ratio of CBD to CBG is 1 to between 0.06 and 0.6. 2B. The method of embodiment IB, wherein the weight ratio of CBD to CBG is 1:0.10.3. 3B. The method of embodiment IB or 2B, wherein the weight ratio of CBD to THC is 1:0.005-0.045. 4B. The method of embodiment 3B, wherein the weight ratio of CBD to THC is 1:0.01-0.02. 5B. The method of any one of embodiments IB to 4B, wherein CBD, CBG and / or THC are provided as botanical drug substances (BDS). 6B. The method of embodiment 5B, wherein the cannabinoid composition further comprises other cannabinoid and / or non-cannabinoid components that are present from the BDS. 7B. The method of embodiment 5B, wherein the cannabinoid composition further comprises terpenes that are present from the BDS. 8B. The method of any one of embodiments 5B to 7B, wherein the cannabinoid composition further comprises flavonoids that are present from the BDS. 9B. The method of any one of embodiments IB to 4B, wherein CBD, CBG and THC are provided as a combination of cannabis extracts. 10B. The method of any one of embodiments IB to 4B, wherein CBD, CBG and THC are provided as a combination of extracts from 2-4 cannabis cultivars. 1 IB. The method of any one of embodiments IB to 4B, wherein CBD, CBG and THC are provided as a combination of extracts from genetically identical clones of 3 different cannabis cultivars. 12B. The method of embodiment 1 IB, wherein the 3 different cannabis cultivars are a high CBD cultivar, a high CBG cultivar and a high THC cultivar. 13B. The method of any one of embodiments 10B to 12B, wherein cannabis cultivars are Cannabis sativa cultivars. 14B. The method of any one of embodiments 9B to 13B, wherein the cannabinoid composition further comprises other cannabinoid and / or non-cannabinoid components that are present from the extracts. 15B. The method of any one of embodiments 9B to 14B, wherein the cannabinoid composition further comprises terpenes that are present from the extracts. 16B. The method of any one of embodiments 9B to 14B, wherein the cannabinoid composition further comprises flavonoids that are present from the extracts. 17B. The method of any one of embodiments 5B to 16B, wherein the cannabinoid composition further comprises additional CBD, CBG and / or THC provided in purified form. 18B. The method of any one of embodiments 5B to 16B, wherein the cannabinoid composition further comprises additional CBD, CBG and / or THC isolates. 19B. The method of any one of embodiments IB to 4B, wherein CBD, CBG and THC are provided as a combination of purified CBD, CBG and THC cannabis extracts. 20B. The method of any one of embodiments IB to 4B, wherein CBD, CBG and THC are provided as a combination of CBD, CBG and THC isolates. 21B. The method of any one of embodiments IB to 4B, wherein CBD, CBG and THC are provided as a combination of BDS and CBD, CBG and / or THC isolates. 22B. The method of any one of embodiments IB to 4B, wherein CBD, CBG and THC are provided as a combination of BDS, and purified CBD, CBG and / or THC cannabis extracts. 23B. The method of any one of embodiments IB to 4B, wherein CBD, CBG and THC are provided as a combination of BDS, and CBD, CBG and / or THC isolates. 24B. The method of any one of embodiments IB to 4B, wherein CBD, CBG and THC are provided as BDS in combination with refined or synthetic CBD, CBG and / or THC. 25B. The method of any one of embodiments IB to 4B, wherein CBD, CBG and THC are a combination of highly purified CBD, highly purified CBG and highly purified THC, wherein each of which are extracted from a cannabis plant and purified to the extent that other cannabinoids and a majority of non-cannabinoid components that are co-extracted with the cannabinoids have been removed. 26B. The method of embodiment 25B, wherein the highly purified CBD is greater than or equal to 90% (w / w) pure; the highly purified CBG is greater than or equal to 90% (w / w) pure; and the highly purified THC is greater than or equal to 90% (w / w) pure. 27B. The method of any one of embodiments IB to 4B, wherein CBD, CBG and THC are all naturally derived. 28B. The method of any one of embodiments IB to 4B, wherein at least a portion of CBD, CBG and / or THC is naturally derived, and the other portion is synthetic and / or biosynthetic. 29B. The method of any one of the preceding embodiments, wherein THC is present primarily in the form of (-)-delta-9-trans-tetrahydrocannabinol (A9-THC). 30B. The method of any one of the preceding embodiments, wherein CBD, CBG and THC are collectively greater than 50% by weight of the cannabinoids present in the composition. 3 IB. The method of embodiment 30B, wherein CBD, CBG and THC are collectively greater than 60% by weight of the cannabinoids present in the composition. 32B. The method of any one of the preceding embodiments, wherein the cannabinoid composition further comprises at least one lipid excipient. 33B. The method of embodiment 32B, wherein at least one lipid excipient is a winterized oil comprising long-chain mono-, di-, and triglycerides. 34B. The method of any one of the preceding embodiments, wherein the cannabinoid composition further comprises docosahexaenoic acid (DHA), or eicosapentaenoic acid (EPA), or a combination thereof. 35B. The method of any one of the preceding embodiments, wherein the composition is formulated for oral delivery, and optionally wherein the composition further comprises one or more flavoring or masking agents. 36B. The method of any one of the preceding embodiments, wherein the cannabinoid composition is formulated as a solution. 37B. The method of embodiment 36B, wherein CBD is between about 50 mg / ml and 150 mg / ml. 38B. The method of embodiment 37B, wherein CBD is between about 90 mg / ml and 110 mg / ml. 39B. The method of embodiments any one of embodiments 36B to 38B, wherein CBG is between about 10 mg / ml and 30 mg / ml. 40B. The method of embodiment 39B, wherein CBG is between about 18 mg / ml and 22 mg / ml. 41B. The method of any one of embodiments 36B to 40B, wherein THC is between about 0.75 mg / ml and 2.25 mg / ml. 42B. The method of embodiment 41B, wherein THC is between about 0.5 mg / ml and 1.5 mg / ml. 43B. The method of any one of embodiments 36B to 42B, wherein CBD is about 100 mg / ml, CBG is about 20 mg / ml, and THC is about 1.5 mg / ml. 44B. The method of any one of the preceding embodiments, wherein treating CRPS comprises treating pain and health associated with CRPS. 45B. The method of any one of the preceding embodiments, wherein the treatment produces improved analgesia as measured on the CRPS scale. 46B. The method of any one of the preceding embodiments, wherein the treatment attenuates pain sensitivity and increase pain tolerance. 47B. The method of any one of the preceding embodiments, wherein the treatment reduces ecological momentary assessment pain reports. 48B. The method of any one of the preceding embodiments, wherein the treatment improves one or more CRPS related comorbidities. 49B. The method of embodiment 48B, wherein the treatment improves a spectrum CRPS related comorbidities. 50B. The method of embodiment 48B or 49B, wherein the CRPS related comorbidities comprises depression or anxiety, or a combination thereof. 5 IB. The method of any one of the preceding embodiments, wherein the treatment improves neural processing in the human that will be associated with significant improvements in pain. 52B. The method of any one of the preceding embodiments, wherein the treatment reduces inflammatory pain markers, wherein these reductions are associated with CRPS relief. 53B. The method of any one of the preceding embodiments, wherein the human suffers from persistent pain, swelling, changes in skin temperature or color, or limited range of motion, or any combination thereof. 54B. The method of any one of the preceding embodiments, wherein the cannabinoid composition is administered once daily. 55B. The method of any one of the preceding embodiments, wherein the cannabinoid composition is administered twice daily. 56B. The method of any one of the preceding embodiments, wherein the cannabinoid composition is administered with food. 57B. The method of any one of the preceding embodiments, wherein the cannabinoid composition is administered without food. 58B. The method of any one of the preceding embodiments, wherein the cannabinoid composition is administered at a dose between 100 mg and 1500 mg total daily dose. 59B. A cannabinoid composition, comprising: cannabidiol (CBD), cannabigerol (CBG), and tetrahydrocannabinol (THC), collectively a major component of the cannabinoids present in the composition, wherein CBD, CBG and THC are provided as a combination of extracts or isolated from at least two cannabis cultivars, and wherein the weight ratio of CBD to CBG is 1 to between 0.06 and 0.6. 60B. The composition of embodiment 59B, wherein the weight ratio of CBD to CBG is 1:0.1-0.3. 61B. The composition of embodiment 59B or 60B, wherein the weight ratio of CBD to THCis 1:0.005-0.045. 62B. The composition of embodiment 61B, wherein the weight ratio of CBD to THC is 1:0.01-0.02. 63B. The composition of any one of embodiments 59B to 62B, wherein CBD, CBG and / or THC are provided as botanical drug substances (BDS). 64B. The composition of embodiment 63B, further comprising other cannabinoid and / or non-cannabinoid components that are present from the BDS. 65B. The composition of embodiment 63B, further comprising terpenes that are present from the BDS. 66B. The composition of any one of embodiments 63B to 65B, further comprising flavonoids that are present from the BDS. 67B. The composition of any one of embodiments 59B to 62B, wherein CBD, CBG and THC are provided as a combination of cannabis extracts. 68B. The composition of any one of embodiments 59B to 62B, wherein CBD, CBG and THC are provided as a combination of extracts from 2-4 cannabis cultivars. 69B. The composition of any one of embodiments 59B to 62B, wherein CBD, CBG and THC are provided as a combination of extracts from genetically identical clones of 3 different cannabis cultivars. 70B. The composition of embodiment 69B, wherein the 3 different cannabis cultivars are a high CBD cultivar, a high CBG cultivar and a high THC cultivar. 71B. The composition of any one of embodiments 68B to 70B, wherein cannabis cultivars are Cannabis sativa cultivars. 72B. The composition of any one of embodiments 67B to 71B, further comprising other cannabinoid and / or non-cannabinoid components that are present from the extracts. 73B. The composition of any one of embodiments 67B to 72B, further comprising terpenes that are present from the extracts. 74B. The composition of any one of embodiments 67B to 73B, further comprising flavonoids that are present from the extracts. 75B. The composition of any one of embodiments 59B to 74B, further comprising additional CBD, CBG and / or THC provided in purified form. 76B. The composition of any one of embodiments 59B to 74B, further comprising additional CBD, CBG and / or THC isolates. 77B. The composition of embodiment 76B, wherein CBD, CBG and THC are provided as a combination of purified CBD, CBG and THC cannabis extracts. 78B. The composition of any one of embodiments 59B to 62B, wherein CBD, CBG and THC are provided as a combination of CBD, CBG and THC isolates. 79B. The composition of any one of embodiments 59B to 62B, wherein CBD, CBG and THC are provided as a combination of BDS and CBD, CBG and / or THC isolates. 80B. The composition of any one of embodiments 59B to 62B, wherein CBD, CBG and THC are provided as a combination of BDS, and purified CBD, CBG and / or THC cannabis extracts. 8 IB. The composition of any one of embodiments 59B to 62B, wherein CBD, CBG and THC are provided as a combination of BDS, and CBD, CBG and / or THC isolates. 82B. The composition of any one of embodiments 59B to 62B, wherein CBD, CBG and THC are provided as BDS in combination with refined or synthetic CBD, CBG and / or THC. 83B. The composition of any one of embodiments 59B to 62B, wherein CBD, CBG and THC are a combination of highly purified CBD, highly purified CBG and highly purified THC, wherein each of which are extracted from a cannabis plant and purified to the extent that other cannabinoids and a majority of non-cannabinoid components that are co-extracted with the cannabinoids have been removed. 84B. The composition of embodiment 83B, wherein the highly purified CBD is greater than or equal to 90% (w / w) pure; the highly purified CBG is greater than or equal to 90% (w / w) pure; and the highly purified THC is greater than or equal to 90% (w / w) pure. 85B. The composition of any one of embodiments 59B to 62B, wherein CBD, CBG and THC are all naturally derived. 86B. The composition of any one of embodiments 59B to 62B, wherein at least a portion of the CBD, CBG and / or THC is naturally derived, and the other portion is synthetic and / or biosynthetic. 87B. The composition of any one of the preceding embodiments, wherein the THC is present primarily in the form of (-)-delta-9-trans-tetrahydrocannabinol (A9-THC). 88B. The composition of any one of the preceding embodiments, further comprising at least one lipid excipient. 89B. The composition of embodiment 88B, wherein at least one lipid excipient is a winterized oil comprising long-chain mono-, di-, and triglycerides. 90B. The composition of any one of the preceding embodiments, further comprising docosahexaenoic acid (DHA), or eicosapentaenoic acid (EPA), or a combination thereof. 91B. The composition of any one of the preceding embodiments, wherein THC is present in less than 0.3% by weight of the total composition. 92B. The composition of any one of the preceding embodiments, wherein the composition is formulated for oral delivery, and optionally wherein the composition further comprises one or more flavoring or masking agents. 93B. The composition of any one of the preceding embodiments, wherein the composition is formulated as a solution. 94B. The composition of embodiment 93B, wherein CBD is between about 50 mg / ml and 150 mg / ml. 95B. The composition of embodiment 94B, wherein CBD is between about 90 mg / ml and 110 mg / ml. 96B. The composition of embodiments any one of embodiments 93B to 95B, wherein CBG is between about 10 mg / ml and 30 mg / ml. 97B. The composition of embodiment 96B, wherein CBG is between about 18 mg / ml and 22 mg / ml. 98B. The composition of any one of embodiments 93B to 97B, wherein THC is between about 0.75 mg / ml and 2.25 mg / ml. 99B. The composition of embodiment 98B, wherein THC is between about 0.5 mg / ml and 1.5 mg / ml. 100B. The composition of any one of embodiments 93B to 99B, wherein CBD is about 100 mg / ml, the CBG is about 20 mg / ml, and the THC is about 1.5 mg / ml. 101B. A method of treating Complex Regional Pain Syndrome (CRPS) in a human in need thereof, comprising: administering an initial dose of a cannabinoid composition comprising: cannabidiol (CBD), cannabigerol (CBG), and tetrahydrocannabinol (THC), collectively a major component of the cannabinoids present in the composition, wherein CBD, CBG and THC are provided as a combination of extracts or isolated from at least two cannabis cultivars, wherein the weight ratio of CBD to CBG is 1 to between 0.06 and 0.6, wherein the initial dose is between about 100 mg and about 600 mg total daily dose, monitoring safety and effect on CRPS, or the symptoms of CRPS, experienced by the human in need thereof, and administering an increased dose of the cannabinoid composition, wherein the increased dose is up to a maximum total daily dose of between about 200 mg and 1500 mg. 102B. A composition of any one of embodiments 59B to 101B for use in treating Complex Regional Pain Syndrome (CRPS). EXAMPLES

[0076] The presently disclosed subject matter will be better understood by reference to the following Examples, which are provided as exemplary of the invention, and not by way of limitation. Example 1A EXTRACTION AND ISOLATION OF CANNABINOIDS FROM THE PLANT

[0077] Bulk plant material was isolated from dried cannabis flower. The bulk plant material was separated from the botanical starting material. The botanical starting materials were weighed and stored in an amber jar. The botanical starting material were added to an extraction vessel with solvent. The solvent was removed via vacuum distillation until only refined cannabis oil was present, with a low solvent concentration. The crude cannabis oil was then heated to for a suitable time to convert the THCA to THC to yield a refined cannabis oil. The main cannabinoids, THCA, CBDA and CBGA were converted to the base molecule THC, CBD and CBG, respectively. Example IB CHARACTERIZATION OF AN EXEMPLARY CANNABINOID COMPOSITION

[0078] Exemplary cannabinoid compositions were produced according to Example 1A above, blended with botanical isolates to arrive at the amounts and ratios of CBD, CBG and THC as set forth in Table 1 below, and combined with an oil containing long chain mono, di, and triglycerides as the lipid vehicle. The following Table 1 provides the profile of exemplary drug product compositions, characterized based on cannabinoid content. The compositions were characterized using methods and techniques known in the art, including ultra-performance liquid chromatography (UPLC). Table 1. Exemplary Drug Product Composition mg / mL Ratio CBD 50-150 1.00 CBG 10-30 0.06-0.6 THC 00.75-2.25 0.005-0.045 Example 2 STUDY OF EFFECTS AND MECHANISM OF CANNABINOID COMPOSITION IN THE TREATMENT OF PAIN AND HEALTH IN COMPLEX REGIONAL PAIN SYNDROME

[0079] This study has several specific aims. Specific Aim 1: Identify if Cannabinoid Composition A produces greater pain relief than placebo

[0080] Approach: Multiple psychophysical approaches are being conducted in conjunction with psychological and inflammatory marker testing to determine if and how cannabinoids produce stabilized improvement in CRPS-related pain and comorbidities. Individuals with CRPS report significantly higher pain sensitivity and lower pain tolerance in response to innocuous and noxious heat. Thus, we are using acute pain evocation models in addition with stable assessments of CRPS pain to measure the efficacy of Cannabinoid Composition A.

[0081] Aim la: Examine if Cannabinoid Composition A produces greater pain relief in response to noxious heat (48°C) and innocuous (38°C) when compared to placebo after 2 weeks (Visit 2) and 6 weeks (Visit 3) as compared to baseline (Visit 1).

[0082] Aim lb: Examine if Cannabinoid Composition A produces improvements in pain tolerance (using the established psychophysical method of limits) as compared to placebo after 2 weeks and 6 weeks as compared to baseline (Visit 1).

[0083] Aim 1c: Durable improvements in pain are being assessed before, during and after the cannabinoid intervention using the Brief Pain Inventory Severity and Brief Pain Inventory Interference scales.

[0084] Aim Id: Durable improvements in CRPS severity are being assessed before, during a two-week (using ecological momentary assessments) and after the interventions using the International Association for the Study of Pain (IASP) and Budapest CRPS scales, respectively.

[0085] Aim 1 Secondary outcomes: include but are not limited to the Pain Catastrophizing Scale, Roland-Morris Disability Questionnaire, and other commodities impacted by CRPS (sleep; quality of life). These are administered before, during and after the interventions. Aim 2: Do cannabinoids improve stress and pain-related inflammation markers in CRPS?

[0086] This study aims to determine if and how cannabinoids impact chronic pain-related comorbidities and corresponding inflammatory markers. Plasma is being collected from participants at baseline, 2 weeks, and 6 weeks to determine if Cannabinoid Composition A is associated with greater reductions in inflammatory markers, including interleukin 6, as compared to baseline (Visit 1). Regression analyses are being used to assess if pain changes are predictive of changes in inflammatory markers. Aim 3: Do cannabinoids produce significant reductions in depression and anxiety?

[0087] We are administering several validated psychological assessments to participants including but not limited to the Beck Depression Inventory, Cohen Perceived Stress Scale, Spielberger State-Trait Anxiety Inventory and Pittsburgh Sleep Index. Exploratory analyses are being used to examine the relationship between brain mechanisms, pain, stress, and biomarkers, respectively. Aim 4: Can Cannabinoids remediate central mechanisms supporting CRPS-pain and comorbidities?

[0088] In a subset of participants, we are testing the effects of cannabinoids on CRPS during fMRI acquisition to identify changes in functional connectivity. Participants

[0089] Participants aged 18 years and above with CRPS (CRPS-I; CRPS-II) for at least 3 months. Females are three times as likely to be impacted by CRPS, thus, we are overrecruiting female participants. Participants are being randomly assigned to Cannabinoid Composition A or placebo group. Participants are required to meet specific diagnostic criteria for CRPS, which include symptoms such as persistent pain, swelling, changes in skin temperature or color, and limited range of motion.

[0090] Study outcomes being measured include: 1. Ecological Momentary Assessment of CRPS Pain (delivered via a smartphone application) 2. CRPS Scale (Budapest Criteria) 3. CRPS Scale (IASP Criteria) 4. Pain sensitivity (heat): apply noxious heat (48°C) 5. Pain Tolerance (heat) 6. Depression 7. Anxiety 8. Calcitonin-gene-related peptide 9. TNFa 10. Skin temperature 11. Blood Oxygen Level Dependent Signal (BOLD) fMRI images 12. Beck Depression Inventory 13. Brief Pain Inventory 14. Pittsburgh Sleep Quality Index 15. Cohen Perceived Stress Scale 16. Spi elb erger Anxi ety Inventory 17. Pain Catastrophizing Scale Study Drug: Cannabinoid Composition

[0091] The study drug is referred to herein as “Cannabinoid Composition A”, which is produced in accordance with the procedures set forth above in Examples 1A and IB. For example, the study drug may include 100 mg / ml CBD, 20 mg / ml CBG, and 1.5 mg / ml A9-THC. The study drug is a botanically derived extract that contains less than 0.3% THC and other minor plant components in the lipid vehicle composed of mono-, di-, and triglycerides. The THC content is below the 0.3% THC allowable limit established by the United States Department of Agriculture (USDA) 2018 Farm Bill for Hemp products. The study drug is formulated for oral use in a lipid vehicle. Dosing and Titration

[0092] Dosing will be administered orally. A flexible dosing regimen was considered in the study, starting at 50-300 mg of Cannabinoid Composition A or matching placebo two times a day (bid) and up-titrated based on clinical response and tolerability over 2 weeks to a maximum of 1500 mg total daily dose or starting at a fixed dose of up to 1500 mg daily.

[0093] In the ongoing study, participants are receiving an initial dose of 50 mg of Cannabinoid Composition A, with a maximum initial daily dose of 100 mg of Cannabinoid Composition A, or matching placebo bid and up-titrating based on safety and desired effect. The highest allowable dose in the ongoing study is 500 mg, with a maximum daily dose of 1,000 mg, of Cannabinoid Composition A per day.

[0094] Analyses and Interpretation: Across all behavioral and blood-inflammatory marker outcomes, separate, 2 (group: active vs. placebo cannabinoids) X 2 (pre-rest vs. post-cannabinoids / placebo) X 3 (Visits) linear mixed effect model is employed to determine if Cannabinoid Composition A produces greater analgesia. Simple effects test is used to examine significant main effects and interactions. Age, sex and baseline VAS pain are entered as covariates in all relevant analyses. Exploratory analyses are used to determine the effects of Cannabinoid Composition A on follow-up and EMA changes.

[0095] Functional MRI: After standard preprocessing steps, the following are performed to test study hypotheses. A 2 (active vs. placebo THC group) X 2 (rest vs. THC) ANOVA is conducted on 4D CBF data, using fMRI, in response to noxious heat (48°C) stimulation to determine if cannabinoids produce greater activation in prefrontal areas and the caudate nucleus when compared to placebo. Significant interactions are investigated with planned post-hoc analyses.

[0096] Interim Results: In the ongoing study based on the clinical protocol as set forth herein, one participant who completed the 6-week period of the study reported no adverse events. This participant also reported a 5-point decrease in pain scores based on the CRPS Scale, and provided comments that reflected improvements in quality-of-life. Recruitment in the clinical study remains ongoing, and the results to be reported will be unblinded at the completion of the study.

Claims

1. A method of treating Complex Regional Pain Syndrome (CRPS) in a human in needthereof, comprising:administering a therapeutically effective dose of a cannabinoid composition comprising: cannabidiol (CBD), cannabigerol (CBG), and tetrahydrocannabinol (THC), collectively a major component of the cannabinoids present in the composition,wherein CBD, CBG and THC are provided as a combination of extracts or isolated from at least two cannabis cultivars, andwherein the weight ratio of CBD to CBG is 1:0.06-0.6.

2. The method of claim 1, wherein the initial dose is between about 100 mg and about 600 mg total daily dose,wherein the method further comprises:monitoring safety and effect on CRPS, or the symptoms of CRPS, experienced by the human, andadministering an increased dose of the cannabinoid composition, wherein the increased dose is up to a maximum total daily dose of between about 200 mg and 1500 mg.

3. The method of claim 1 or 2, wherein the weight ratio of CBD to CBG is 1:0.1-0.3.

4. The method of any one of claims 1 to 3, wherein the weight ratio of CBD to THC is1:0.005-0.045.

5. The method of claim 4, wherein the weight ratio of CBD to THC is 1:0.01-0.02.

6. The method of any one of claims 1 to 5, wherein CBD, CBG and / or THC areprovided as botanical drug substances (BDS).

7. The method of claim 6, wherein the cannabinoid composition further comprises othercannabinoid and / or non-cannabinoid components that are present from the BDS.

8. The method of any one of claims 1 to 5, wherein CBD, CBG and THC are provided as a combination of cannabis extracts.

9. The method of any one of claims 1 to 5, wherein CBD, CBG and THC are provided as a combination of extracts from 2-4 cannabis cultivars.

10. The method of any one of claims 1 to 5, wherein CBD, CBG and THC are provided as a combination of extracts from genetically identical clones of 3 different cannabis cultivars.

11. The method of claim 10, wherein the 3 different cannabis cultivars are a high CBD cultivar, a high CBG cultivar and a high THC cultivar.

12. The method of any one of the preceding claims, wherein CBD, CBG and THC are collectively greater than 50% by weight of the cannabinoids present in the composition.

13. The method of any one of the preceding claims, wherein the composition is formulated for oral delivery.

14. The method of any one of the preceding claims, wherein the cannabinoid composition is formulated as a solution.

15. The method of claim 14, wherein CBD is between about 90 mg / ml and 110 mg / ml.

16. The method of claim 14 or 15, wherein CBG is between about 18 mg / ml and 22mg / ml.

17. The method of any one of claims 14 to 16, wherein THC is between about 0.5 mg / ml and 1.5 mg / ml.

18. The method of any one of claims 14 to 17, wherein CBD is about 100 mg / ml, CBG is about 20 mg / ml, and THC is about 1.5 mg / ml.

19. The method of any one of the preceding claims, wherein treating CRPS comprises treating pain and health associated with CRPS.

20. The method of any one of the preceding claims, wherein the treatment:(i) produces improved analgesia as measured on the CRPS scale; or(ii) attenuates pain sensitivity and increase pain tolerance; or(iii) reduces ecological momentary assessment pain reports; or(iv) improves one or more CRPS related comorbidities; or(v) improves a spectrum CRPS related comorbidities, wherein the CRPS related comorbidities comprises depression or anxiety, or a combination thereof; or(vi) improves neural processing in the human that will be associated with significant improvements in pain; or(vii) reduces inflammatory pain markers, wherein these reductions are associated with CRPS relief21. The method of any one of the preceding claims, wherein the human suffers from persistent pain, swelling, changes in skin temperature or color, or limited range of motion, or any combination thereof.

22. The method of any one of the preceding claims, wherein the cannabinoid composition is administered at a dose between 100 mg and 1500 mg total daily dose.

23. A cannabinoid composition, comprising:cannabidiol (CBD), cannabigerol (CBG), and tetrahydrocannabinol (THC), collectively a major component of the cannabinoids present in the composition,wherein CBD, CBG and THC are provided as a combination of extracts or isolated from at least two cannabis cultivars, andwherein the weight ratio of CBD to CBG is 1 to between 0.06 and 0.6.

24. The composition of claim 23, wherein the weight ratio of CBD to CBG is 1:0.1-0.3.

25. The composition of claim 23 or 24, wherein the weight ratio of CBD to THC is1:0.005-0.045.

26. The composition of claim 25, wherein the weight ratio of CBD to THC is 1:0.01-0.02.

27. The composition of any one of claims 23 to 26, wherein CBD, CBG and / or THC areprovided as botanical drug substances (BDS).

28. The composition of claim 27, further comprising other cannabinoid and / or noncannabinoid components that are present from the BDS.

29. The composition of any one of claims 23 to 26, wherein CBD, CBG and THC are provided as a combination of cannabis extracts.

30. The composition of any one of claims 23 to 29, wherein CBD is about 100 mg / ml, the CBG is about 20 mg / ml, and the THC is about 1.5 mg / ml.

31. The composition of any one of claims 23 to 30, for use in treating Complex RegionalPain Syndrome (CRPS).