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WO2025137611A1 - Compositions cannabinoïdes pour le traitement de l'épilepsie post-traumatique - Google Patents

Compositions cannabinoïdes pour le traitement de l'épilepsie post-traumatique Download PDF

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Publication number
WO2025137611A1
WO2025137611A1 PCT/US2024/061522 US2024061522W WO2025137611A1 WO 2025137611 A1 WO2025137611 A1 WO 2025137611A1 US 2024061522 W US2024061522 W US 2024061522W WO 2025137611 A1 WO2025137611 A1 WO 2025137611A1
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Prior art keywords
cbd
thc
cbg
composition
cannabinoid
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Inventor
Michael Hunter LAND
Brian Kent BRANDLEY
George Bennett HODGIN
Lucas J. ZUMSTEIN
Justyna KULPA
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Biopharmaceutical Research Co
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Biopharmaceutical Research Co
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/658—Medicinal preparations containing organic active ingredients o-phenolic cannabinoids, e.g. cannabidiol, cannabigerolic acid, cannabichromene or tetrahydrocannabinol

Definitions

  • Post-traumatic epilepsy is a debilitating condition characterized by recurrent seizures that develop as a result of a traumatic brain injury (TBI).
  • TBI traumatic brain injury
  • ASMs antiseizure medications
  • debilitating side effects of medications often impact treatment compliance and quality of life. For this reason, the search for alternative treatments that can offer improved outcomes and quality of life for these patients is of great importance.
  • PTE Post-traumatic epilepsy
  • a method of treating post-traumatic epilepsy (PTE) in a human in need thereof comprises: administering a cannabinoid composition comprising cannabidiol (CBD), cannabigerol (CBG), and tetrahydrocannabinol (THC) present as a major component therein.
  • CBD cannabidiol
  • CBG cannabigerol
  • THC tetrahydrocannabinol
  • 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.
  • BDS botanical drug substances
  • extracts extracts from cannabis plants
  • extracts extracts from cannabis plants blended with additional sources of CBD, CBG and/or THC
  • purified CBD, CBG and/or THC e.g., obtained from purifying the extracts or blended extracts
  • isolates of CBD, CBG and/or THC e.g., obtained from purifying the extracts or blended extracts.
  • the cannabinoid composition further comprises other cannabinoids 1 sf-6205389 776772000640 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 human in need thereof.
  • a vehicle e.g., a lipid vehicle
  • cannabinoids and non-cannabinoids are present from the source from which the composition is obtained.
  • 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.
  • 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.
  • compositions comprising CBD in combination with CBG and THC have an improved therapeutic efficacy for treating seizures in post-traumatic epilepsy (PTE).
  • PTE post-traumatic epilepsy
  • cannabinoid compositions comprising a combination of CBD, CBG and THC, which are collectively present as the major components of the cannabinoids in the compositions.
  • 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.
  • 2 sf-6205389 776772000640 extracts from genetically identical clones of three different cultivars e.g., high CBD cultivars, high CBG cultivars, and high THC cultivars
  • the components of the cannabinoid compositions provided herein are described in further detail below.
  • 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 9%; 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.
  • the cannabinoid compositions may include other cannabinoids as well as non- cannabinoids formulated in a vehicle, such as a lipid vehicle, as described in further detail below.
  • a vehicle such as a lipid vehicle
  • Such other cannabinoids as well as non-cannabinoids are present from the cannabis plant from which the compositions are obtained.
  • 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.
  • the structures of CBD, CBG and THC are well understood in the art.
  • the THC present in the compositions herein is primarily in the form of (–)- delta-9-trans-tetrahydrocannabinol ( ⁇ 9-THC).
  • 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.
  • the CBD and CBG are present in a molar ratio between about 100:1 and about 1:1.
  • the molar ratio of CBD and THC is between about 50:1 and about 1:1.
  • 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 1:0.016- 0.15:0.003-0.03. 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 weight ratio of CBD to THC is between about 50:1 and about 1:1. In certain variations, the weight ratio of CBD to CBG is 3 sf-6205389 776772000640 between about 1:0.016-0.15. In certain variations, the weight ratio of CBD to THC is between about 1:0.003-0.03.
  • 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.
  • the CBD is greater than 5 mg/ml, between about 50 mg/ml and 150 mg/ml, or between about 5mg/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 2.5 mg/l and 7.5 mg/ml in the total composition.
  • the CBD is between about 50 mg/ml and 150 mg/ml.
  • the CBG is between about 2.5 mg/ml and 7.5 mg/ml in the total composition.
  • the “total composition” includes cannabinoids, non-cannabinoids (e.g., terpenes, if present), and a vehicle (e.g., lipid vehicle).
  • a vehicle e.g., lipid vehicle.
  • 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.
  • the “total composition” includes cannabinoids, non-cannabinoids (e.g., terpenes, if present), and a vehicle (e.g., lipid vehicle).
  • 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.
  • 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.
  • the 4 sf-6205389 776772000640 THC is less than 2 mg/ml, or between about 0.5 mg/ml and 1.5 mg/ml in the total composition.
  • the “total composition” includes cannabinoids, non-cannabinoids (e.g., terpenes, if present), and a vehicle (e.g., lipid vehicle).
  • the CBD is about 100 mg/ml
  • the CBG is about 5 mg/ml
  • the THC is about 1 mg/ml.
  • the THC is less than 0.3% by weight of the cannabinoids present in the composition.
  • the minor cannabinoids are less than about 5%, less than about 2.5%, or less than about 1% by weight of the cannabinoids present in the composition.
  • the cannabinoid compositions provided herein further comprise additional components, including other cannabinoids and/or non-cannabinoids.
  • 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, terpnolene, and valencene).
  • CBDA cannabidiolic acid
  • THCA tetrahydrocannabinolic acid
  • CBC cannabichromene
  • terpenes such as alpha-bisabolol, guaiol, beta-caryophyllene
  • 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.
  • CBN cannabinol
  • CBC cannabichromene
  • THCV cannabigerolic acid
  • CBDA cannabichromene acid
  • CBCA cannabichromene acid
  • THCA tetrahydrocannabinolic acid
  • CBDDA cannabidiolic acid
  • 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), Cannabinerolklare A ((Z)-CBGA C-5A), Cannabigerovarin (((e)-BGV C-3), Cannabigerolklare A(e)-CBGA C-5A), A Cannabigerolklare monomethyl ether ((e)-CBGAM C-5A), Cannabigerovarinklare A ((e)-CBGVA-C3A); • Cannabichromene-type compounds: cannabichromene (CBC-C5), Cannabichromen discoursere A (CBCA C-5A), Cannabichromevarin (CBCVC-3), Cannabichromevarinklare A (CBCVA-C3A); 5 sf-6205389
  • 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. [0026] In some variations, minor cannabinoids present are collectively less than about 5% or less than about 2.5% by weight of the total composition.
  • the “total composition” includes cannabinoids, non-cannabinoids (e.g., terpenes, if present), and a vehicle (e.g., lipid vehicle).
  • the compositions further comprise terpenes.
  • 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, terpnolene, and valencenealpha-bisabolol, beta-caryophyllene oxide, and guaiol.
  • 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 terpenes may be found.
  • 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. 7 sf-6205389 776772000640 [0029] 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.
  • the CBD, CBG and THC are provided as a combination of extracts or isolated from at least two cannabis cultivars.
  • 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.
  • CBD, CBG and THC are provided in the form a botanical drug substance (BDS).
  • BDS botanical drug substance
  • the CBD, CBG and THC are each in the form of BDS.
  • 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.
  • 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.
  • 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”.
  • the CBD, CBG and THC are provided as a combination of cannabis extracts or isolated from 2-4 cannabis cultivars.
  • the CBD, CBG and THC are provided as a combination of cannabis extracts from genetically identical clones of 3 different cannabis cultivars.
  • the 3 different cultivars are a high CBD cultivar, a high CBG cultivar and a high THC cultivar.
  • the cannabis cultivars are Cannabis sativa cultivars.
  • the compositions provided herein further include terpenes.
  • the compositions provided herein further include terpenes and flavonoids.
  • Blended Extracts 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.
  • 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 [0038] 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.
  • the extract or blended 9 sf-6205389 776772000640 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.
  • the purified extracts are oils.
  • 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.
  • 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 [0040]
  • 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.
  • 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.
  • the isolates are powders.
  • 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.
  • CBD, CBG and THC are provided a combination of isolates, which may be with or without BDS, extracts or blended extracts.
  • the CBD, CBG and THC are provided as a combination of isolates and BDS. Natural vs. Synthetic Sources [0042] 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.
  • compositions provided herein may include CBD, CBG and THC provided in a combination of different forms described above.
  • 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.
  • the combination of cannabinoids described herein are formulated in lipid vehicles to yield the compositions, e.g., the drug formulation.
  • the compositions herein may further comprise at least one lipid excipient.
  • suitable excipients may include glyceryl monolinoleate.
  • the lipid vehicle comprises a winterized oil composed of long- chain mono-, di-, and triglycerides.
  • the lipid vehicle comprises mono-, di- and triglycerides of mainly linoleic (C 18:2 ) and oleic (C 18:1 ) acids.
  • the diester fraction is predominant.
  • the lipid vehicle comprises self-emulsifying drug delivery systems.
  • the compositions provided herein may further include or more additional components.
  • the compositions further comprise at least one fatty acid.
  • the compositions further comprise long-chain omega-3 polyunsaturated fatty acids (O-3s).
  • the compositions further comprise docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA).
  • 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.
  • the drug substance consists essentially of (i) CBD, CBG and THC, 11 sf-6205389 776772000640 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.
  • the drug substance compositions comprise (i) 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, (ii) between 10% and 15% fats and fatty acids, and (iii) between 1% and 5% terpenes.
  • the composition comprises (i) about 80% cannabinoids in the ratios and amounts as described herein, (ii) about 15% fats and fatty acids, and (iii) about 5% terpenes.
  • 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.
  • the drug product 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, (iii) terpenes, and (iv) at least one lipid, such as a winterized oil composed of long-chain mono-, di-, and triglycerides.
  • 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; terpenes, (iii) and at least one lipid, such as a winterized oil composed of long-chain mono-, di-, and triglycerides.
  • 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.
  • CBD, CBG and THC when they 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.
  • bulk plant material is isolated from dried cannabis flower. The bulk plant material is separated from the botanical starting material. The botanical starting 12 sf-6205389 776772000640 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • 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 [0057] In some aspects, provided is a method for treating post-traumatic epilepsy (PTE) 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.
  • PTE post-traumatic epilepsy
  • the method comprises administering to the subject the compositions described herein, e.g., comprising CBD, CBG and THC as the major components therein.
  • 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).
  • the treatment decreases the frequency of occurrence of seizures in the human. In some variations, the treatment decreases the severity of seizures in the human.
  • the treatment reduces anxiety in the human. In some variations, the treatment improves mood in the human. In some variations, the treatment improves sleep quality in the human. In certain embodiments, the treatment reduces the amount and/or frequency of antiepileptic drug and/or rescue medication concomitantly administered to the human.
  • PTE post-traumatic epilepsy
  • a method for treating post-traumatic epilepsy (PTE) in a human in need thereof comprising: a) administering to the human a cannabinoid composition as described herein; and b) decreasing the severity of seizures in the human.
  • a method for treating post-traumatic epilepsy (PTE) in a human in need thereof comprising: a) administering to the human a cannabinoid composition as described herein; and b) reducing anxiety in the human.
  • a method for treating post-traumatic epilepsy (PTE) in a human in need thereof comprising: a) administering to the human a cannabinoid composition as described herein; and b) improving mood in the human.
  • a method for treating post-traumatic 14 sf-6205389 776772000640 epilepsy (PTE) in a human in need thereof comprising: a) administering to the human a cannabinoid composition as described herein; and b) improving sleep quality in the human.
  • the human is concomitantly taking an antiepileptic drug and/or rescue medication.
  • the method further comprising concomitantly administering an antiepileptic drug and/or rescue medication to the human.
  • rescue medications are approved as an acute treatment, and given at the time of the seizure or during periods of frequent seizures. They may be used to treat cluster seizures or seizures that are distinct from the person’s usual seizure patterns.
  • suitable rescue medications may include, for example, Diastat AcuDial (rectal diazepam), Nayzilam (intranasal midazolam), and Valtoco (intranasal diazepam).
  • the PTE is refractory PTE.
  • refractory PTE is defined as a failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom for PTE patients.
  • the human suffers from drug-resistant PTE. In certain variations, the human suffers from debilitating drug-resistant PTE.
  • the pharmaceutical cannabinoid composition is administered daily. In other variations, the pharmaceutical 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.
  • a therapeutically effective amount of the cannabinoid composition is administered.
  • 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 pharmaceutical may be needed to achieve the desired treatment endpoint.
  • the cannabinoid composition is administered at a dose between 100 mg and 1500 mg. In certain variations, the cannabinoid composition is administered at a dose of 200 mg daily or 100 mg twice daily.
  • the cannabinoid composition is administered at a dose of 800 mg daily or 15 sf-6205389 776772000640 400 mg twice daily. In yet other variations, the cannabinoid composition is administered at a dose of 1500 mg daily or 750 mg twice daily. It should be understood that dose here is measured against the amount of CBD. [0066] In some embodiments, the cannabinoid composition is administered at a therapeutically effective dose. 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.
  • 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.
  • a composition as described herein e.g., comprising CBD, CBG and THC as the major components therein, for use in a method of treating post- traumatic epilepsy (PTE).
  • compositions as described herein e.g., comprising CBD, CBG and THC as the major components therein, for use in a method of treating post-traumatic epilepsy (PTE) in any of the doses described herein, including in a dose between 100 mg and 1500 mg, a 200 mg daily dose, a 100 mg twice daily dose, a 800 mg daily dose, a 400 mg twice daily dose, 1500 mg daily dose, or a 750 mg twice daily dose. It should be understood that dose here is measured against the amount of CBD.
  • PTE post-traumatic epilepsy
  • compositions as described herein e.g., comprising CBD, CBG and THC as the major components therein, for use in a method of treating post- traumatic epilepsy (PTE), wherein the frequency of occurrence of seizures is decreased, the severity of seizures is decreased, anxiety is reduced, mood improves, or sleep quality improves, or any combination of the foregoing outcomes.
  • PTE post- traumatic epilepsy
  • the method comprises administering the composition concomitantly with an antiepileptic drug and/or rescue medication.
  • compositions as described herein e.g., comprising CBD, CBG and THC as the major components therein, for use in a method of 16 sf-6205389 776772000640 treating post-traumatic epilepsy (PTE) in a specific patient population suffering from refractory PTE.
  • PTE post-traumatic epilepsy
  • a composition as described herein e.g., comprising CBD, CBG and THC as the major components therein, for use in a method of treating post-traumatic epilepsy (PTE) in a specific patient population suffering from drug- resistant PTE, or in one variation, suffering from debilitating drug-resistant PTE.
  • PTE post-traumatic epilepsy
  • the cannabinoid composition is administered at an initial dose between about 100 mg and about 150 mg, wherein the dose is measured against the amount of CBD in the composition.
  • the initial dose administered is about 100 mg of the cannabinoid composition.
  • the aforementioned initial doses may be administered once a day or twice a day.
  • the initial dose of the cannabinoid composition is between 200 mg and 300 mg total daily dose. In certain embodiments, the initial dose of the cannabinoid composition is 200 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 1000 mg, about 800 mg, about 700 mg, about 600 mg, about 500 mg, about 400 mg, or about 300 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.
  • a method of treating post-traumatic epilepsy (PTE) in a human in need thereof comprises administering a cannabinoid composition as described herein at a therapeutically effect amount.
  • the method comprises administering a cannabinoid composition as described herein at an initial dose of about 100 mg; monitoring safety and effect on PTE, or the symptoms of PTE, 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 1000 mg, about 1000 mg, about 800 mg, about 700 mg, about 600 mg, about 500 mg, about 400 mg, or about 300 mg.
  • the total daily dose is administered in one daily dose.
  • kits for carrying out the methods of the invention may comprise the cannabinoid compositions described herein and suitable packaging.
  • a kit comprising: (i) any of the cannabinoid compositions described herein; and (ii) a label and/or instructions for use in treating PTE.
  • the total daily dose is administered in one daily dose.
  • the total daily dose is administered twice a day (e.g., in two doses).
  • the present disclosure further provides an article of manufacture, comprising any of the cannabinoid compositions described herein in a suitable container.
  • the total daily dose is administered in one daily dose.
  • the total daily dose is administered twice a day (e.g., in two doses).
  • ENUMERATED EMBODIMENTS [0076] The following enumerated embodiments are representative of some aspects of the invention. 1A.
  • a method of treating post-traumatic epilepsy (PTE) 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.
  • CBD, CBG and THC are provided as botanical drug substances (BDS).
  • the cannabinoid composition further comprises other cannabinoid and/or non-cannabinoid components that are present from the BDS. 18 sf-6205389 776772000640 4A.
  • the method of embodiment 2A, wherein the cannabinoid composition further comprises terpenes that are present from the BDS. 5A.
  • 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 1A, wherein the CBD, CBG and THC are provided as a combination of cannabis extracts. 7A.
  • 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 11A, 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. 15A.
  • the cannabinoid composition further comprises additional CBD, CBG and/or THC isolates.
  • 16A The method of embodiment 1A, wherein the CBD, CBG and THC are provided as a combination of purified CBD, CBG and THC cannabis extracts. 19 sf-6205389 776772000640 17A.
  • 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 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.
  • 23A 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 1A, wherein the CBD, CBG and THC are all naturally derived.
  • 25A The method of embodiment 1A, 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 ( ⁇ 9-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. 20 sf-6205389 776772000640 28A.
  • 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.
  • 31A 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 cannabinoid composition further comprises at least one lipid excipient.
  • at least one lipid excipient is a winterized oil comprising long-chain mono-, di-, and triglycerides.
  • 35A 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.
  • DHA docosahexaenoic acid
  • EPA eicosapentaenoic acid
  • composition is formulated for oral delivery, and optionally wherein the composition further comprises one or more flavoring or masking agents.
  • the PTE is refractory PTE.
  • 38A The method of any one of the preceding embodiments, wherein the treatment decreases the frequency of occurrence of seizures in the human.
  • 39A The method of any one of the preceding embodiments, wherein the treatment decreases the severity of seizures in the human. 21 sf-6205389 776772000640 40A.
  • the treatment reduces anxiety in the human. 41A.
  • 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 4.5 mg/ml and 5.5 mg/ml, and wherein the CBD, CBG and THC are provided as a combination of extracts or isolated from at least two cannabis cultivars.
  • CBD cannabidiol
  • CBG cannabigerol
  • THC tetrahydrocannabinol
  • composition of embodiment 53A further comprising other cannabinoid and/or non-cannabinoid components that are present from the BDS. 56A.
  • the composition of embodiment 53A further comprising terpenes that are present from the BDS. 57A.
  • the composition of embodiment 53A, wherein the CBD, CBG and THC are provided as a combination of cannabis extracts.
  • 59A The composition of embodiment 53A, wherein the CBD, CBG and THC are provided as a combination of extracts from 2-4 cannabis cultivars. 60A.
  • composition of embodiment 53A wherein the CBD, CBG and THC are provided as a combination of extracts from genetically identical clones of 3 different cannabis cultivars.
  • 61A The composition of embodiment 60A, wherein the 3 different cannabis cultivars are a high CBD cultivar, a high CBG cultivar and a high THC cultivar.
  • 62A The composition of any one of embodiments 59A to 61A, wherein cannabis cultivars are Cannabis sativa cultivars.
  • 63A The composition of any one of embodiments 59A to 62A, further comprising other cannabinoid and/or non-cannabinoid components that are present from the extracts. 23 sf-6205389 776772000640 64A.
  • composition of any one of embodiments 59A to 63A further comprising terpenes that are present from the extracts.
  • 65A The composition of any one of embodiments 59A to 64A, further comprising flavonoids that are present from the extracts.
  • 66A The composition of any one of embodiments 53A to 65A, further comprising additional CBD, CBG and/or THC provided in purified form.
  • 67A The composition of any one of embodiments 53A to 65A, further comprising additional CBD, CBG and/or THC isolates.
  • 68A The composition of embodiment 53A, wherein the CBD, CBG and THC are provided as a combination of purified CBD, CBG and THC cannabis extracts. 69A.
  • composition of embodiment 53A, wherein the CBD, CBG and THC are provided as a combination of CBD, CBG and THC isolates.
  • the composition of embodiment 53A, wherein the CBD, CBG and THC are provided as a combination of BDS and CBD, CBG and/or THC isolates.
  • the composition of embodiment 53A, wherein the CBD, CBG and THC are provided as a combination of BDS, and purified CBD, CBG and/or THC cannabis extracts.
  • 72A. The composition of embodiment 53A, wherein the CBD, CBG and THC are provided as a combination of BDS, and CBD, CBG and/or THC isolates.
  • composition of embodiment 53A wherein the CBD, CBG and THC are provided as BDS in combination with refined or synthetic CBD, CBG and/or THC.
  • 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.
  • 24 sf-6205389 776772000640 75A 75A.
  • composition of embodiment 74A 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.
  • 76A The composition of embodiment 53A, wherein the CBD, CBG and THC are all naturally derived.
  • 77A The composition of embodiment 53A, wherein at least a portion of the CBD, CBG and/or THC is naturally derived, and the other portion is synthetic and/or biosynthetic. 78A.
  • 79A The composition of any one of the preceding embodiments, further comprising at least one lipid excipient.
  • 81A. The composition of any one of the preceding embodiments, further comprising docosahexaenoic acid (DHA), or eicosapentaenoic acid (EPA), or a combination thereof.
  • DHA docosahexaenoic acid
  • EPA eicosapentaenoic acid
  • 83A The composition of any one of the preceding embodiments, wherein the CBD is about 100 mg/ml, the CBD is about 5 mg/ml, and the THC is about 1 mg/ml.
  • 84A 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.
  • 85A. A composition of any one of embodiments 53A to 84A for use in treating post- traumatic epilepsy (PTE).
  • 86A The composition of embodiment 85A, for use in treating refractory PTE.
  • 87A 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.
  • 83A The composition of any one of the preceding embodiments, wherein the CBD is about 100 mg/ml, the CBD is about 5
  • composition of embodiment 85A or 86A wherein: the frequency of occurrence of seizures is decreased; or 25 sf-6205389 776772000640 the severity of seizures is decreased; or anxiety is reduced; or mood is improved; or sleep quality is improved; or any combination of the foregoing.
  • 88A The composition of any one of embodiments 85A to 87A, wherein the method comprises administering the composition concomitantly with an antiepileptic drug and/or rescue medication.
  • 89A. The composition of embodiment 88A, wherein the amount and/or frequency of the antiepileptic drug and/or rescue medication concomitantly administered is reduced. 90A.
  • a method of treating post-traumatic epilepsy (PTE) 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 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 0.016 and 0.15. 2B.
  • the method of embodiment 1B, wherein the weight ratio of CBD to THC is 1:0.003- 0.03. 3B.
  • CBD, CBG and/or THC are provided as botanical drug substances (BDS). 4B.
  • the method of embodiment 3B, wherein the cannabinoid composition further comprises other cannabinoid and/or non-cannabinoid components that are present from the BDS. 26 sf-6205389 776772000640 5B.
  • the method of embodiment 3B, wherein the cannabinoid composition further comprises terpenes that are present from the BDS. 6B.
  • the method of any one of embodiments 3B to 5B, wherein the cannabinoid composition further comprises flavonoids that are present from the BDS. 7B.
  • the cannabinoid composition further comprises other cannabinoid and/or non-cannabinoid components that are present from the extracts. 13B.
  • the method of any one of embodiments 7B to 12B, wherein the cannabinoid composition further comprises terpenes that are present from the extracts. 14B.
  • the method of any one of embodiments 7B to 13B, wherein the cannabinoid composition further comprises flavonoids that are present from the extracts. 15B.
  • the cannabinoid composition further comprises additional CBD, CBG and/or THC provided in purified form. 16B.
  • the cannabinoid composition further comprises additional CBD, CBG and/or THC isolates.
  • 17B The method of embodiment 1B or 2B, wherein CBD, CBG and THC are provided as a combination of purified CBD, CBG and THC cannabis extracts. 27 sf-6205389 776772000640 18B.
  • CBD, CBG and THC are provided as a combination of CBD, CBG and THC isolates.
  • 19B The method of embodiment 1B or 2B, wherein CBD, CBG and THC are provided as a combination of BDS and CBD, CBG and/or THC isolates. 20B.
  • CBD, CBG and THC are provided as a combination of BDS, and purified CBD, CBG and/or THC cannabis extracts.
  • 21B The method of embodiment 1B or 2B, wherein CBD, CBG and THC are provided as a combination of BDS, and CBD, CBG and/or THC isolates.
  • 22B The method of embodiment 1B or 2B, wherein CBD, CBG and THC are provided as BDS in combination with refined or synthetic CBD, CBG and/or THC. 23B.
  • 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.
  • 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.
  • CBD, CBG and THC are collectively greater than 60% by weight of the cannabinoids present in the composition.
  • the cannabinoid composition further comprises at least one lipid excipient.
  • 31B The method of embodiment 30B, wherein at least one lipid excipient is a winterized oil comprising long-chain mono-, di-, and triglycerides.
  • 32B 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. 33B.
  • DHA docosahexaenoic acid
  • EPA eicosapentaenoic acid
  • composition is formulated for oral delivery, and optionally wherein the composition further comprises one or more flavoring or masking agents.
  • 34B The method of any one of the preceding embodiments, wherein the cannabinoid composition is formulated as a solution.
  • 35B The method of embodiment 34B, wherein CBD is between about 50 mg/ml and 150 mg/ml. 36B.
  • CBD is between about 90 mg/ml and 110 mg/ml.
  • CBG is between about 2.5 mg/ml and 7.5 mg/ml. 38B.
  • THC is between about 0.5 mg/ml and 1.5 mg/ml.
  • 39B The method of any one of embodiments 34B to 38B, wherein CBD is about 100 mg/ml, CBG is about 5 mg/ml, and THC is about 1 mg/ml.
  • 40B The method of any one of the preceding embodiments, wherein the PTE is refractory PTE. 29 sf-6205389 776772000640 41B.
  • the method of any one of the preceding embodiments, wherein the treatment decreases the frequency of occurrence of seizures in the human. 42B.
  • the method of any one of the preceding embodiments, wherein the treatment decreases the severity of seizures in the human. 43B.
  • the treatment reduces anxiety in the human. 44B.
  • 47B. The method of embodiment 46B, wherein the treatment reduces the amount and/or frequency of the antiepileptic drug and/or rescue medication concomitantly administered to the human.
  • 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 0.016 and 0.15.
  • 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 0.016 and 0.15.
  • 57B The composition of embodiment 56B, wherein the weight ratio of CBD to THC is 1:0.003-0.03.
  • 58B The composition of embodiment 56B or 57B, wherein CBD, CBG and/or THC are provided as botanical drug substances (BDS). 59B.
  • composition of embodiment 58B further comprising other cannabinoid and/or non-cannabinoid components that are present from the BDS. 60B.
  • the composition of embodiment 58B further comprising terpenes that are present from the BDS. 61B.
  • the composition of embodiment 56B or 57B, wherein CBD, CBG and THC are provided as a combination of cannabis extracts.
  • composition of embodiment 56B or 57B, wherein CBD, CBG and THC are provided as a combination of extracts from 2-4 cannabis cultivars. 64B.
  • 66B The composition of any one of embodiments 63B to 65B, wherein cannabis cultivars are Cannabis sativa cultivars.
  • composition of embodiment 56B or 57B, wherein CBD, CBG and THC are provided as BDS in combination with refined or synthetic CBD, CBG and/or THC. 32 sf-6205389 776772000640 78B.
  • composition of embodiment 56B or 57B, 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. 79B.
  • composition of embodiment 78B 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.
  • 80B The composition of embodiment 56B or 57B, wherein CBD, CBG and THC are all naturally derived.
  • 83B The composition of any one of the preceding embodiments, further comprising at least one lipid excipient.
  • DHA docosahexaenoic acid
  • EPA eicosapentaenoic acid
  • the composition of any one of the preceding embodiments, wherein the cannabinoid composition is formulated as a solution. 90B.
  • composition of embodiment 89B wherein CBD is between about 50 mg/ml and 150 mg/ml. 91B.
  • a method of treating post-traumatic epilepsy (PTE) 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 0.016 and 0.15.
  • CBD cannabidiol
  • CBG cannabigerol
  • THC tetrahydrocannabinol
  • the initial dose is between about 200 mg and 300 mg total daily dose, monitoring safety and effect on PTE, or the symptoms of PTE, 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 about 1000 mg.
  • 96B A composition of any one of embodiments 56B to 94B for use in treating post- traumatic epilepsy (PTE). 97B. The composition of embodiment 96B for use in treating refractory PTE. 34 sf-6205389 776772000640 98B.
  • composition of embodiment 96B or 97B wherein: the frequency of occurrence of seizures is decreased; or the severity of seizures is decreased; or anxiety is reduced; or mood is improved; or sleep quality is improved; or any combination of the foregoing.
  • 99B The composition of any one of embodiments 96B to 98B, wherein the method comprises administering the composition concomitantly with an antiepileptic drug and/or rescue medication.
  • 100B The composition of embodiment 99B, wherein the amount and/or frequency of the antiepileptic drug and/or rescue medication concomitantly administered is reduced.
  • PTE post- traumatic epilepsy
  • Example 1A EXTRACTION AND ISOLATION OF CANNABINOIDS FROM THE PLANT
  • 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.
  • Example 1B CHARACTERIZATION OF AN EXEMPLARY CANNABINOID COMPOSITION
  • 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.
  • 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 Example 2 A RANDOMIZED CONTROLLED TRIAL INVESTIGATING THE SAFETY AND EFFICACY OF CANNABINOID COMPOSITION IN REFRACTORY POST- TRAUMATIC EPILEPSY (PTE) [0080] This study seeks to evaluate the safety and efficacy of Cannabinoid Composition A in the treatment of refractory PTE.
  • 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 1B.
  • the study drug may include 100 mg/ml CBD, 5 mg/ml CBG, and 1 mg/ml ⁇ 9-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 36 sf-6205389 776772000640 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.
  • Study Objectives [0082] Primary Objective(s): • To evaluate the safety and tolerability of Cannabinoid Composition A in adults with refractory PTE. • To evaluate the efficacy of Cannabinoid Composition A on seizure frequency in adults with refractory PTE. [0083] Secondary Objective(s): • To evaluate the efficacy of Cannabinoid Composition A on seizure severity. • To evaluate the efficacy of Cannabinoid Composition A on anxiety. • To evaluate the efficacy of Cannabinoid Composition A on mood. • To evaluate the efficacy of Cannabinoid Composition A on sleep quality. • To evaluate the efficacy of Cannabinoid Composition A on quality of life.
  • the duration of study medication use will be 12 weeks. Fifty (50) enrolled participants; ten (10) in Part A and forty (40) in Part B. [0086] Dosage: 100 mg/mL, titrated based on safety and efficacy [0087] Dosing Schedule: Twice daily (q12h) for 12 consecutive weeks 37 sf-6205389 776772000640 [0088] Mode of administration: Oral [0089] Endpoints: [0090] Primary Endpoint(s): [0091] Safety will be assessed in terms of: • Adverse events (AEs) and serious AEs (SAEs) • Vital signs • Laboratory assessments [0092] Efficacy will be assessed in terms of: • Change from baseline to 12 weeks (post-treatment) in number of PTE-associated seizures [0093] Key Secondary Endpoint(s): • Number of patients considered treatment responders defined as those with a ⁇ 50% reduction in PTE-associated seizure frequency.
  • SSQ Seizure Severity Questionnaire
  • PROMIS Patient-Reported Outcomes Measurement Information System

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Abstract

L'invention concerne des compositions de cannabinoïdes formulées pour être utilisées dans le traitement de l'épilepsie post-traumatique (EPT). Les compositions comprennent du cannabidiol (CBD), du cannabigérol (CBG) et du tétrahydrocannabinol (THC) en tant que composants principaux, qui peuvent être isolés, purifiés ou extraits de cultivars et mélangés. Les compositions comprennent du CBD, du CBG et du THC dans certains rapports, formulés pour être utilisés dans le traitement de l'EPT.
PCT/US2024/061522 2023-12-22 2024-12-20 Compositions cannabinoïdes pour le traitement de l'épilepsie post-traumatique Pending WO2025137611A1 (fr)

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AYCHMAN MACKENZIE M., GOLDMAN DAVID L., KAPLAN JOSHUA S.: "Cannabidiol's neuroprotective properties and potential treatment of traumatic brain injuries", FRONTIERS IN NEUROLOGY, FRONTIERS RESEARCH FOUNDATION, vol. 14, XP093333757, ISSN: 1664-2295, DOI: 10.3389/fneur.2023.1087011 *

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