Methods and compositions for potentiating stem cell therapies

Abstract

To provide methods and compositions that can potentiate the function of stem cell therapies.SOLUTION: An aspect of the present disclosure provides a method for potentiating function of a stem cell in a subject, comprising the steps of (a) administering to said subject said stem cell; (b) administering to said subject a pharmaceutical composition comprising an encapsulated cannabinoid compound. Here, the step (b) takes place prior to, concurrent with, or subsequent to the step (a). In some embodiments, the step (b) further comprises at least one terpene compound. In some embodiments, the treatment with the step (b) reduces the side effects usually associated with the step (a). In some embodiments, the steps (a) and (b) exhibit a synergetic effect on a process in the subject.SELECTED DRAWING: None

Description

[Technical Field]

[0001] cross reference This application claims the benefit of U.S. Provisional Application No. 62 / 350,708, filed June 15, 2016, which is incorporated herein by reference in its entirety. [Background technology]

[0002] background Stem cells are involved in both the generation of tissue during development and regeneration after tissue injury. Stem cells exhibit two important properties: the ability to self-renew and to generate more specialized cell types.

[0003] Research on stem cells has shown promise for treating many diseases. One of the most established forms of stem cell therapy is bone marrow transplantation, in which a patient's hematopoietic stem cells are replaced with donor stem cells. The donor stem cells reside in the patient's bone marrow and regenerate the hematopoietic system. Another well-established type of stem cell therapy is the use of epithelial stem cells in the treatment of large skin wounds, such as those in burn patients. Cell-cultured epithelial autografts allow small grafts from unaffected skin to be expanded in culture, allowing coverage of large wounds. Stem cell therapy has also been successful in treating arthritis, autoimmune diseases, vision and hearing loss, diabetes, and orthopedics. The use of stem cells in neurological disorders is an area of active research, and promising results have been seen in disease models of stroke and multiple sclerosis.

[0004] Many challenges remain for stem cell therapy. The use of autologous adult stem cells is limited by their limited replicative potential. The use of embryonic stem cells can alleviate this concern, but donor stem cells must be carefully matched to minimize immune rejection, and immunosuppressive drugs may still be required. Integration remains a challenge, as stem cell-derived tissues must be able to function alongside existing structures. Control of differentiation and replication is important, as stem cells also have the ability to promote unwanted proliferation. Summary of the Invention [Means for solving the problem]

[0005] Abstract There is a great need for methods and compositions that can enhance the function of stem cell therapy. The inventions described in this disclosure address this need and provide other related advantages as well.

[0006] One aspect of the present disclosure provides a method for enhancing stem cell function in a subject, comprising: (a) administering to the subject stem cells; and (b) administering to the subject a pharmaceutical composition comprising an encapsulated cannabinoid compound, wherein (b) occurs before, simultaneously with, or after step (a). In some embodiments, step (b) further comprises at least one terpene compound. In some embodiments, treatment with step (b) reduces side effects typically associated with step (a). In some embodiments, steps (a) and (b) exhibit a synergistic effect on a process in the subject.

[0007] In some embodiments, the subject has or is suspected of having a disease selected from the group consisting of acute leukemia, chronic leukemia, and lymphoma, inherited platelet disorders, plasma cell disorders, autoimmune diseases, myeloproliferative disorders, lymphoproliferative disorders, phagocytic disorders, myelodysplastic syndromes, histiocytic disorders, congenital immune system disorders, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, and multiple sclerosis, stroke, diabetes, infertility, vision loss or other eye diseases, lysosomal storage diseases, peripheral arterial disease, ischemic limb injury, diabetes, heart disease, liver disease, bone disease, muscular dystrophy, dental disease, and cancer.

[0008] In some embodiments, the subject has suffered from an injury selected from the group of spinal column and spinal cord injury, a wound, a thermal or chemical burn, a sports injury, an occupational injury, or a brain injury.

[0009] In some embodiments, the stem cells are derived from stem cells that are induced pluripotent stem cells, embryonic stem cells, fetal stem cells, or adult stem cells.

[0010] In some embodiments, the stem cells are selected from the group consisting of AA4, AA4.1, P-gp (CD243), ABCB5, ABCG2 (CDw338), ALDH, alkaline phosphatase, alpha6-integrin, WNT2B, antithrombin III (AT), asialoGM1, Bcl-2, beta1-integrin, bromodeoxyuridine, c-kit (CD117), c-Met, C1qR(p), END (CD105), PROM1 (CD133), ALCAM (CD166), ITGB1 (CD29), TNFRSF8 (CD30), PECAM-1 (CD31), Siglec-3 (CD33), CD34, CD44, NCAM (CD56), CD73, CD9, CD90, CDCP1, circulating anticoagulant protein C (PC), CK19, CLV3, cyclic CMP, ECMA-7, EDR1, EEC, FGF-4, Flk-2, Flk1(+), Flt3 / Flk2, FMS (CD115), FORSE-1, Gamma-anticoagulant protein C (Gamma-anticoagulant protein C ... LUFA16, GDF3, GFPM, Gli2, Gli3, glial fibrillary acidic protein, glycoprotein IB, GSTA1, HAS2 gene expression, Her5, hMYADM, HSA, hsp25, Id2, IL-3R alpha, integrin, interleukin-3 receptor alpha chain, iron oxide nanoparticles, KDR, keratin 15 (also known as CK15, cytokeratin 15), keratin 19 (also known as CK19, cytokeratin 19, K19), Kit, L-selectin (CD 62L), lamin A / C, Lewis X antigen (Le(X)), LeX, Lgr5, Lrp4, MCM2, MCSP, metallothionein (MT) crypt-restricted immunopositive index (MTCRII), monosomy 7, mouse ortholog of ARX, MRP4, Msi-1, Musashi, Musashi-1, mutant BCRP, nestin, neurofilament-microtubule-associated protein 2, neuron-glial antigen 2 (NG2), Notch 1, nrp-1, nucleostemin, OC.3, Oct-4, OST-PTP, P-gp / MDR1, p21, p63, p75, PCLP, PCNA, PECAM, PgP-1, phosphorylated-p38, podocalyxin, procalcitonin (PCT), PSC, pSV2gpt, PTPRC, purified LRC, rat liver fatty acid binding protein / human growth hormone transgene (Fabpl / hGH), RC1 antigen, Rex-1, Sca-1, SCF, sialyl-lactotetra, side population (SP), SOX 10, SOX2, SOX9, SP phenotype, SSEA-1, SSEA-3, SSEA-4, Stat3, Stat5, Stella, Stra8, Stro-1, tartrate-resistant acid phosphatase (TRAcP), TdT, telomerase reverse transcriptase, hemoglobin electrophoretic pattern, thrombomucin, Thy-1, Tra-1-60, TWIST1, VEGFR-2, vimentin, X-smoothened, XKrk1, or Zac1.

[0011] In some embodiments, the stem cells are derived from stem cells that exhibit totipotency, pluripotency, bipotency, or unipotency.

[0012] In some embodiments, the stem cells are selected from the group consisting of fibroblasts, keratinocytes, melanocytes, cold-sensitive primary sensory neurons, auditory inner hair cells or organs of Corti, Merkel cells, photoreceptor cells, taste bud cells, cholinergic neurons, adrenergic neurons, peptidergic neurons, hepatocytes, adipocytes, liver adipocytes, kidney glomerular podocytes, pancreatic duct cells, gallbladder epithelial cells, pericytes, corneal fibroblasts, skeletal muscle cells, cardiac myocytes, Purkinje fibrocytes, erythrocytes, megakaryocytes, monocytes, Langerhans cells, osteoclasts, osteoblasts, dendritic cells, and the like. The cells are derived from stem cells that give rise to ovarian cells, microglial cells, neutrophil granulocytes, hybridoma cells, mast cells, helper T cells, suppressor T cells, cytotoxic T cells, natural killer T cells, B cells, oocytes, sperm cells, follicle cells, Schwann cells, satellite glial cells, enteric glial cells, astrocytes, neuronal cells, oligodendrocytes, anterior lens epithelial cells, crystallin-containing lens fiber cells, growth hormone-producing cells, adrenocorticotropic cells, melanocyte-stimulating hormone-producing cells, thyroid cells, or odontocytes.

[0013] In some embodiments, the stem cells are derived from stem cells delivered via intravenous infusion, intradermal, transplanted microvascular beds of bone marrow, subcutaneous, oral (e.g., ingested or inhaled), transdermal (topical), transmucosal, rectal administration, engineered monolayer tissue transplant, intraarterial, intramuscular, intratracheal, intraperitoneal, intravitreal, or direct injection into the target site.

[0014] In some embodiments, the pharmaceutical composition comprises nanocapsules, said nanocapsules comprising individual nanocapsules containing said encapsulated cannabinoid compound.

[0015] In some embodiments, the nanocapsules increase stem cell growth. In some embodiments, the nanocapsules are administered after stem cell therapy.

[0016] In some embodiments, the nanocapsules are administered to the subject by inhalation. In some embodiments, the nanocapsules are vaporized. In some embodiments, the nanocapsules are nebulized. In some embodiments, the nanocapsules are administered orally. In some embodiments, the nanocapsules are incorporated into a food or beverage. In some embodiments, the nanocapsules are administered topically.

[0017] In some embodiments, the nanocapsules are water-soluble.

[0018] In some embodiments, the at least one terpene compound is derived from Quillaja saponaria. In some embodiments, the cannabinoid compound comprises cannabidiol (CBD). In some embodiments, the cannabinoid compound comprises 0.3% or less tetrahydrocannabinol (THC). In some embodiments, the nanocapsules are water-soluble.

[0019] In some embodiments, the subject has or is suspected of having a disease or injury, and after (b), the subject is monitored for the progression of the disease or injury in response to administering the pharmaceutical composition to the subject.

[0020] In some embodiments, the subject has or is suspected of having the disease, and after (b), the subject is monitored for progression or regression of the disease in response to administering the pharmaceutical composition to the subject.

[0021] In another aspect, the disclosure provides a kit comprising a composition comprising an effective amount of an encapsulated cannabinoid compound; and instructions for administering a therapeutically effective amount of the food composition to a subject undergoing stem cell therapy.

[0022] In some embodiments, the composition is a food composition. In some embodiments, the composition is a pharmaceutical composition. In some embodiments, the composition comprises nanocapsules, the nanocapsules comprising individual nanocapsules containing the encapsulated cannabinoid compound. In some embodiments, the nanocapsule delivery device is an atomizer. In some embodiments, the nanocapsule delivery device is a vaporizer.

[0023] In some embodiments, the nanocapsules comprise a terpene compound, hi some embodiments, the terpene compound is derived from Quillaja saponaria.

[0024] In certain embodiments, for example, the following items are provided: (Item 1) 1. A method for enhancing stem cell function in a subject, comprising: (a) administering the stem cells to the subject; (b) administering to said subject a pharmaceutical composition comprising an encapsulated cannabinoid compound. wherein (b) is performed before, simultaneously with, or after step (a). (Item 2) Item 10. The method of claim 1, wherein step (b) further comprises at least one terpene compound. (Item 3) 10. The method of claim 1, wherein treatment with step (b) reduces the side effects normally associated with step (a). (Item 4) 2. The method of item 1, wherein the subject is suffering from or suspected of suffering from a disease selected from the group consisting of acute leukemia, chronic leukemia, and lymphoma, inherited platelet disorders, plasma cell disorders, autoimmune diseases, myeloproliferative disorders, lymphoproliferative disorders, phagocytic disorders, myelodysplastic syndromes, histiocytic disorders, congenital immune system disorders, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, and multiple sclerosis, stroke, diabetes, infertility, vision loss or other eye diseases, lysosomal storage diseases, peripheral arterial disease, ischemic limb injury, diabetes, heart disease, liver disease, bone disease, muscular dystrophy, dental disease, and cancer. (Item 5) Item 10. The method of item 1, wherein the subject has an injury selected from the group consisting of spinal column and spinal cord injury, wound, thermal or chemical burn, sports injury, occupational injury, or brain injury. (Item 6) 2. The method of claim 1, wherein the stem cells are derived from stem cells that are induced pluripotent stem cells, embryonic stem cells, fetal stem cells, or adult stem cells. (Item 7) The stem cells are selected from the group consisting of AA4, AA4.1, P-gp (CD243), ABCB5, ABCG2 (CDw338), ALDH, alkaline phosphatase, alpha6-integrin, WNT2B, antithrombin III (AT), asialoGM1, Bcl-2, beta1-integrin, bromodeoxyuridine, c-kit (CD117), c-Met, C1qR(p), END (CD105), PROM1 (CD133), ALCAM (CD166), I TGB1 (CD29), TNFRSF8 (CD30), PECAM-1 (CD31), Siglec-3 (CD33), CD34, CD44, NCAM (CD56), CD73, CD9, CD90, CDCP1, circulating anticoagulant protein C (PC), CK19, CLV3, cyclic CMP, ECMA-7, EDR1, EEC, FGF-4, Flk-2, Flk1(+), Flt3 / Flk2, FMS (CD115), FORSE-1, G alpha 16, GDF3, GFPM, Gli2, Gli3, glial fibrillary acidic protein, glycoprotein IB, GSTA1, HAS2 gene expression, Her5, hMYADM, HSA, hsp25, Id2, IL-3R alpha, integrin, interleukin-3 receptor alpha chain, iron oxide nanoparticles, KDR, keratin 15 (also known as CK15, cytokeratin 15), keratin 19 (also known as CK19, cytokeratin 19, K19), Kit, L-selectin (CD62L ), lamin A / C, Lewis X antigen (Le(X)), LeX, Lgr5, Lrp4, MCM2, MCSP, metallothionein (MT) crypt-restricted immunopositive index (MTCRII), monosomy 7, mouse ortholog of ARX, MRP4, Msi-1, Musashi, Musashi-1, mutant BCRP, nestin, neurofilament-microtubule-associated protein 2, neuron-glial antigen 2 (NG2), Notch 1, nrp-1, nucleostemin, OC.3, Oct-4, OST-PTP, P-gp / MDR1, p21, p63, p75, PCLP, PCNA, PECAM, PgP-1, phosphorylated-p38, podocalyxin, procalcitonin (PCT), PSC, pSV2gpt, PTPRC, purified LRC, rat liver fatty acid binding protein / human growth hormone transgene (Fabpl / hGH), RC1 antigen, Rex-1, Sca-1, SCF, sialyl-lactotetra, side population (SP), SOX10, SO 2. The method of claim 1, wherein the cell expresses at least one of X2, SOX9, SP phenotype, SSEA-1, SSEA-3, SSEA-4, Stat3, Stat5, Stella, Stra8, Stro-1, tartrate-resistant acid phosphatase (TRAcP), TdT, telomerase reverse transcriptase, hemoglobin electrophoresis pattern, thrombomucin, Thy-1, Tra-1-60, TWIST1, VEGFR-2, vimentin, X-smoothened, XKrk1, or Zac1. (Item 8) 2. The method according to item 1, wherein the stem cells are derived from stem cells exhibiting totipotency, pluripotency, bipotency, or unipotency. (Item 9) The stem cells may be selected from the group consisting of fibroblasts, keratinocytes, melanocytes, cold-sensitive primary sensory neurons, auditory inner hair cells or organs of Corti, Merkel cells, photoreceptor cells, taste bud cells, cholinergic neurons, adrenergic neurons, peptidergic neurons, hepatocytes, adipocytes, hepatic adipocytes, kidney glomerular podocytes, pancreatic duct cells, gallbladder epithelial cells, pericytes, corneal fibroblasts, skeletal muscle cells, cardiac myocytes, Purkinje fibrocytes, erythrocytes, megakaryocytes, monocytes, Langerhans cells, osteoclasts, osteoblasts, dendritic cells, microglial cells, neutrophil granulocytes, hybridoma cells, mast cells, helper T cells, suppressor T cells, cytotoxic T cells, natural killer T cells, B cells, oocytes, sperm cells, follicle cells, Schwann cells, satellite 2. The method according to item 1, wherein the cells are derived from stem cells that give rise to glial cells, enteric glial cells, astrocytes, neuronal cells, oligodendrocytes, anterior lens epithelial cells, crystallin-containing lens fiber cells, growth hormone-producing cells, adrenocorticotropic hormone-producing cells, melanocyte-stimulating hormone-producing cells, thyroid cells, or dental cells. (Item 10) 2. The method of claim 1, wherein the stem cells are derived from stem cells delivered via intravenous infusion, intradermal, transplanted microvascular bed of bone marrow, subcutaneous, oral (e.g., ingested or inhaled), transdermal (topical), transmucosal, rectal administration, engineered monolayer tissue transplant, intraarterial, intramuscular, intratracheal, intraperitoneal, intravitreal, or direct injection into the target site. (Item 11) Item 10. The method of item 1, wherein steps (a) and (b) have a synergistic effect on the process in the subject. (Item 12) 10. The method of claim 1, wherein the pharmaceutical composition comprises nanocapsules, the nanocapsules comprising individual nanocapsules containing the encapsulated cannabinoid compound. (Item 13) 13. The method of claim 12, wherein the nanocapsules increase stem cell growth. (Item 14) 13. The method of claim 12, wherein the nanocapsules are administered after stem cell therapy. (Item 15) 13. The method of claim 12, wherein the nanocapsules are administered to the subject by inhalation. (Item 16) Item 13. The method of item 12, wherein the nanocapsules are vaporized. (Item 17) 13. The method of claim 12, wherein the nanocapsules are sprayed. (Item 18) 13. The method of claim 12, wherein the nanocapsules are administered orally. (Item 19) 13. The method according to item 12, wherein the nanocapsules are incorporated into a food or beverage. (Item 20) 13. The method of claim 12, wherein the nanocapsules are administered topically. (Item 21) Item 13. The method of item 12, wherein the nanocapsules are water-soluble. (Item 22) 3. The method according to claim 2, wherein the at least one terpene compound is derived from Quillaja saponaria. (Item 23) Item 1. The method of item 1, wherein the cannabinoid compound comprises cannabidiol (CBD). (Item 24) 2. The method of claim 1, wherein the cannabinoid compound contains 0.3% or less tetrahydrocannabinol (THC). (Item 25) 2. The method of claim 1, wherein the subject has or is suspected of having a disease or injury, and after (b), the subject is monitored for progression of the disease or injury in response to administering the pharmaceutical composition to the subject. (Item 26) 26. The method of claim 25, wherein the subject is suffering from or suspected of suffering from the disease, and after (b), the subject is monitored for progression or regression of the disease in response to administering the pharmaceutical composition to the subject. (Item 27) (a) a composition comprising an effective amount of an encapsulated cannabinoid compound; and (b) A kit comprising instructions for administering a therapeutically effective amount of the food composition to a subject undergoing stem cell therapy. (Item 28) 28. The kit according to item 27, wherein the composition is a food composition. (Item 29) 28. The kit according to item 27, wherein the composition is a pharmaceutical composition. (Item 30) 28. The kit of claim 27, wherein the composition comprises nanocapsules, the nanocapsules comprising individual nanocapsules containing the encapsulated cannabinoid compound. (Item 31) 31. The kit of item 30, wherein the nanocapsule delivery device is a nebulizer. (Item 32) 31. The kit of item 30, wherein the nanocapsule delivery device is a vaporizer. (Item 33) 31. The kit of item 30, wherein the nanocapsules comprise a terpene compound. (Item 34) Item 34. The kit according to item 33, wherein the terpene compound is derived from Quillaja saponaria. Other objects and advantages of the present invention will be further appreciated and understood when considered in conjunction with the following description and accompanying drawings. While the following description may contain specific details describing particular embodiments of the present invention, this should not be construed as limiting the scope of the invention, but rather as an illustration of preferred embodiments. Many variations known to those skilled in the art are possible with respect to each aspect of the present invention as presented herein. Various changes and modifications can be made within the scope of the present invention without departing from the spirit thereof.

[0025] Incorporation by Reference All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. DETAILED DESCRIPTION OF THE INVENTION

[0026] (Detailed explanation) While various embodiments of the present invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. The following claims define the scope of the invention, and it is intended that methods and structures within the scope of these claims and their equivalents be covered thereby.

[0027] As used herein, the term "about" or "approximately" refers to within + / - 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% of the specified amount.

[0028] As used herein, the terms "treatment," "treat," "alleviate," and "ameliorate" are used interchangeably. These terms refer to an approach to obtaining beneficial or desired results, including, but not limited to, therapeutic benefit and / or preventative benefit. Therapeutic benefit refers to the eradication or amelioration of the underlying disorder being treated. Therapeutic benefit is also achieved by the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disorder, such that improvement is observed in the patient, although the patient may still be afflicted by the underlying disorder.

[0029] As used herein, the term "migratory capacity" may refer to the migratory capacity of therapeutic cells to migrate to a lesion site. The term "migratory capacity" may refer to the migratory capacity of stem cells under culture conditions.

[0030] The present disclosure provides a method for enhancing stem cell function in a subject, comprising: (a) administering to the subject stem cells; and (b) administering to the subject a pharmaceutical composition comprising an encapsulated cannabinoid compound, wherein (b) occurs before, simultaneously with, or after step (a).

[0031] stem cells The stem cells used in the present disclosure may be induced pluripotent stem cells, embryonic stem cells, fetal stem cells, or adult stem cells. Fetal stem cells may be either fetal-specific stem cells derived from the fetus itself or extraembryonic fetal stem cells.

[0032] The stem cells used in the present disclosure can be induced pluripotent stem cells (iPSCs), which are artificially induced stem cells from non-pluripotent cells, typically adult somatic cells, by inducing the expression of one or more stem cell-specific genes. Such stem cell-specific genes include, but are not limited to, the octameric transcription factor family, i.e., Oct-3, Oct-4; the Sox gene family, i.e., Sox1, Sox2, Sox3, Sox15 and Sox18; the Klf gene family, i.e., Klf1, Klf2, Klf4 and Klf5; the Myc gene family, i.e., c-myc and L-myc; the Nanog gene family, i.e., OCT4, NANOG and REX1; or LIN28. Examples of iPSCs are described in Takahashi K. et al. (2014). 07) Cell 131:861-72; Takahashi K. and Yamanaka S. (200 (2006) Cell 126:663-76; Okita K. et al. (2007) Nature 448:260-262; Yu, J. et al. (2007) Science 318:1917-20; and Nakagawa, M. et al. (2008) Nat. Biotechnol. 26:101-106.

[0033] The stem cells used in the compositions and methods disclosed herein can be derived in various ways.For example, stem cells can be isolated from the tissue they are used in treatment or from other tissues.In some examples, stem cells are isolated from blood, brain, bone marrow, blood vessel, skeletal muscle, skin, teeth, heart, intestine or liver tissue.Stem cells can be isolated from the subject, from the subject's relatives, from donors, from tissue banks or from stem cell banks.

[0034] The stem cells used in the present disclosure can be isolated from blood (i.e., hematopoietic tissue).Possible sources of human hematopoietic tissue include, but are not limited to, embryonic hematopoietic tissue, fetal hematopoietic tissue, and postnatal hematopoietic tissue.Embryonic hematopoietic tissue can be yolk sac or embryonic liver.Fetal hematopoietic system can be selected from fetal liver, fetal bone marrow, and fetal peripheral blood.Postnatal hematopoietic system can be umbilical cord blood, bone marrow, normal peripheral blood, mobilized peripheral blood, liver hematopoietic tissue, or spleen hematopoietic tissue.

[0035] The stem cells used may express any stem cell marker. Many stem cell markers are known in the art, and some examples of stem cell markers that may be expressed include those in which the stem cells express AA4, AA4.1, P-gp (CD243), ABCB5, ABCG2 (CDw338), ALDH, alkaline phosphatase, alpha6-integrin, WNT2B, antithrombin III (AT), asialoGM1, Bcl-2, beta1-integrin, bromodeoxyuridine, c-kit (CD117), c-Met, C1qR(p), E ND (CD105), PROM1 (CD133), ALCAM (CD166), ITGB1 (CD29), TNFRSF8 (CD30), PECAM-1 (CD31), Siglec-3 (CD33), CD34, CD44, NCAM (CD56), CD73, CD9, CD90, CDCP1, circulating anticoagulant protein C (PC), CK19, CLV3, cyclic CMP, ECMA-7, EDR1, EEC, FGF-4, Flk-2, Flk1(+), Flt3 / Flk2, FMS (CD115), FORSE-1, G alpha 16, GDF3, GFPM, Gli2, Gli3, glial fibrillary acidic protein, glycoprotein IB, GSTA1, HAS2 gene expression, Her5, hMYADM, HSA, hsp25, Id2, IL-3R alpha, integrin, interleukin-3 receptor alpha chain, iron oxide nanoparticles, KDR, keratin 15 (also known as CK15, cytokeratin 15), keratin 19 (also known as CK19, cytokeratin 19, K19), Kit, L -selectin (CD62L), lamin A / C, Lewis X antigen (Le(X)), LeX, Lgr5, Lrp4, MCM2, MCSP, metallothionein (MT) crypt-restricted immunopositive index (MTCRII), monosomy 7, mouse ortholog of ARX, MRP4, Msi-1, Musashi, Musashi-1, mutant BCRP, nestin, neurofilament-microtubule-associated protein 2, neuron-glial antigen 2 (NG2), Notch 1, nrp-1, nucleostemin, and OC.3, Oct-4, OST-PTP, P-gp / MDR1, p21, p63, p75, PCLP, PCNA, PECAM, PgP-1, phosphorylated-p38, podocalyxin, procalcitonin (PCT), PSC, pSV2gpt, PTPRC, purified LRC, rat liver fatty acid binding protein / human growth hormone transgene (Fabpl / hGH), RC1 antigen, Rex-1, Sca-1, SCF, sialyl-lactotetra, side population (SP), SOX These include, but are not limited to, SOX2, SOX9, SP phenotype, SSEA-1, SSEA-3, SSEA-4, Stat3, Stat5, Stella, Stra8, Stro-1, tartrate-resistant acid phosphatase (TRAcP), TdT, telomerase reverse transcriptase, hemoglobin electrophoretic pattern, thrombomucin, Thy-1, Tra-1-60, TWIST1, VEGFR-2, vimentin, X-smoothened, XKrk1, and Zac1.

[0036] Stem cells can express any single stem cell marker. Alternatively, stem cells can express several stem cell markers. In some cases, stem cells can express at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, or more stem cell markers.

[0037] In some instances, the stem cells may express cannabinoid receptors or putative cannabinoid receptors. The stem cells may express cannabinoid receptor type 1, cannabinoid receptor type 2, or another cannabinoid receptor. Examples of other cannabinoid receptors include GPR18, GPR55, and GPR119.

[0038] The stem cells used in the present disclosure can be maintained in culture before being administered to a subject by any method known in the art.Stem cells can be maintained in serum-containing or serum-free medium with or without a feeder layer.Stem cells can be maintained in conditioned medium.

[0039] Stem cells can be partially differentiated before being administered to a subject.Many methods for differentiating stem cells into either mixed cell populations or specific cell lineages are known in the art.For example, embryonic stem cells or iPSCs can be cultured under conditions that allow the formation of embryoid bodies, thus inducing differentiation.In another example, embryonic stem cells or iPSCs can be differentiated on a layer of stromal cells.In another example, embryonic stem cells or iPSCs can be differentiated on extracellular matrix proteins.

[0040] The presence of growth factors, serum, or small molecules in the culture medium can affect the differentiation of embryonic stem cells or iPSCs.These growth factors include, but are not limited to, bone morphogenetic proteins, colony-stimulating factors, epidermal growth factors, ephrins, fibroblast growth factors, fetal bovine growth hormone, GDNF ligand family, hepatocyte growth factors, insulin-like growth factors, interleukins, keratinocyte growth factors, migration-stimulating factors, macrophage-stimulating proteins, myostatin, neuregulins, neurotrophins, placental growth factors, platelet-derived growth factors, transforming growth factors, tumor necrosis factor alpha, vascular endothelial growth factors, and Wnt signaling pathway proteins.

[0041] For example, mouse embryonic stem cells can be cultured in the presence of VEGF, activin, BMP4, StemPro34, glutamine, ascorbic acid, bFGF, and FGF10 to induce cardiomyocyte differentiation (Kokkinopoulos, Ioannis, et al., "Cardiomyocyte differentiation from mouse embryonic stem cells using a simple and defined protocol." Developmental Dynamics, Vol. 245, No. 2 (2016): pp. 157-165). In another example, human iPSCs can be grown with SCF, TPO, FLT3L, VEGF, IL-3, IL-6, and EPO to induce erythroid differentiation (Dorn, Isabel, et al., "Erythroid differentiation of human induced pluripotent stem cells is independent of donor cell type of origin." Haematologica, Vol. 100, No. 1 (2015): pp. 32-41).

[0042] The stem cells used in the disclosures described herein can be capable of differentiating into any number of cell types. For example, the stem cells used can be totipotent, pluripotent, bipotent, or unipotent. In some preferred applications, the stem cells used are pluripotent or bipotent.

[0043] The stem cells used in the present disclosure may be capable of differentiating into one or more cells of the ectodermal, mesodermal, or endodermal lineage. Examples of cells that differentiate from the ectodermal lineage include, but are not limited to, epidermal cells, neurogenic cells, and gliogenic cells. Examples of cells that differentiate from the mesodermal lineage or give rise to specific mesodermal cells include, but are not limited to, adipogenic, smooth muscle-forming, chondrogenic, cardiogenic, dermal, hematopoietic, angiogenic, myogenic, nephrogenic, urogenital, osteogenic, pericardiogenic, or interstitial cells. Examples of cells that differentiate from the endodermal lineage include, but are not limited to, pleuropoietic cells, hepatogenic cells, cells that give rise to the lining of the intestine, and cells that give rise to pancreatic and visceral cells.

[0044] Stem cells used in the present disclosure may be capable of differentiating into any type of mature cell or precursor. Selected examples of cell types include autonomic nerve cells, blood and immune system cells, central nervous system neurons and glial cells, contractile cells, exocrine secretory epithelial cells, extracellular matrix cells, germ cells, cardiac muscle cells, hormone-secreting cells, integumentary system, interstitial cells, keratinizing epithelial cells, lens cells, metabolic and storage cells, nervous system, nurse cells, sensory organ and peripheral neuron supporting cells, sensory transducer cells, skeletal muscle cells, and moist stratified barrier epithelial cells.

[0045] The stem cells used in the present disclosure may be capable of differentiating into any mature cell or precursor. Selected examples of cells include salivary gland mucous cells (secreting polysaccharides), salivary gland number 1 cells (secreting glycoprotein enzymes), von Ebner's gland cells in the tongue (cleansing taste buds), mammary gland cells (secreting milk), lacrimal gland cells (secreting tears), ear canal gland cells (secreting earwax), eccrine sweat gland dark cells (secreting glycoproteins), eccrine sweat gland clear cells (secreting small molecules), apocrine sweat gland cells (secreting odor, sex hormone sensitive), moll glands in the eyelids (specialized sweat glands), sebaceous gland cells (secreting lipid-rich sebum), and Bowman's gland cells in the nose (supra-olfactory). cleansing the skin), Brunner's gland cells in the duodenum (secretes enzymes and alkaline mucus), seminal vesicle cells (secretes seminal fluid components including fructose in swimming sperm), prostate cells (secretes seminal fluid components), bulbourethral gland cells (secretes mucus), Bartholin's gland cells (secretes vaginal lubrication), Little cell glands (secretes mucus), endometrial cells (secretes carbohydrates), goblet cells in the respiratory and digestive tracts (secretes mucus), mucous cells in the stomach lining (secretes mucus), gastric gland zymogen cells (secretes pepsinogen), gastric gland acid-secreting cells (secretes hydrochloric acid), pancreatic acinar cells (secretes bicarbonate and digestive enzymes), Pancreatic thyroid cells (lysozyme-secreting), type II pneumocytes of the lung (surfactant-secreting), Clara cells of the lung, growth hormone-producing cells, prolactin-producing cells, thyrotropic cells, gonadotropic cells, corticotropic cells, intermediate pituitary cells, magnocellular neurosecretory cells, intestinal and respiratory tract cells, thyroid cells, thyroid epithelial cells, parafollicular cells, parathyroid cells, chief parathyroid cells, eosinophilic cells, adrenal cells, chromaffin cells, Leydig cells of the testes that secrete testosterone, theca cells of the ovarian follicles that secrete estrogen, progesterone-producing cells, and theca cells of the ovarian follicles that secrete progesterone. Luteal cells of ruptured follicles secreting steroids, granulosa luteal cells, theca luteal cells, juxtaglomerular cells (renin secretion), macula densa cells of the kidney, circumpolar cells of the kidney, mesangial cells of the kidney, epidermal keratinocytes (differentiated epidermal cells), epidermal basal cells (stem cells), fingernail and toenail keratinocytes, nail bed basal cells (stem cells), melanocytes, medullary hair stem cells, cortical hair stem cells, cuticle hair stem cells, cuticle root sheath cells, root sheath cells of Huxley's layer, root sheath cells of Henle's layer, outer root sheath cells, hair matrix cells (stem cells), cornea, tongue, oral cavity, esophagus, anal canal,Surface epithelial cells of the stratified squamous epithelium of the distal urethra and vagina, basal cells (stem cells) of the epithelium of the cornea, tongue, oral cavity, esophagus, anal canal, distal urethra and vagina, urothelial cells (lining the bladder and ureters), auditory inner hair cells of the organ of Corti, auditory outer hair cells of the organ of Corti, basal cells of the olfactory epithelium (stem cells of olfactory neurons), cold-sensitive primary sensory neurons, heat-sensitive primary sensory neurons, Merkel cells (touch sensors) of the epidermis, olfactory receptor neurons, pain-sensitive primary sensory neurons (various types), photoreceptor cells of the retina of the eye, photoreceptor rod cells, photoreceptor blue-sensitive cone cells of the eye alveoli, photoreceptors green-sensitive cone cells of the eye, photoreceptors red-sensitive cone cells of the eye, proprioceptive primary sensory neurons (various types), tactile primary sensory neurons (various types), type I carotid somatic cells (blood pH sensor), type II carotid somatic cells (blood pH sensor), type I hair cells of the vestibular system of the ear (acceleration and gravity), type II hair cells of the vestibular system of the ear (acceleration and gravity), type I taste bud cells, cholinergic neurons (various types), adrenergic neurons (various types), peptidergic neurons (various types), inner column cells of the organ of Corti, organ of Corti outer column cells of the organ of Corti, inner phalangeal cells of the organ of Corti, outer phalangeal cells of the organ of Corti, border cells of the organ of Corti, Hensen's cells of the organ of Corti, vestibular supporting cells, taste bud supporting cells, olfactory epithelial supporting cells, Schwann cells, satellite glial cells (encapsulated peripheral nerve cell bodies), enteric glial cells, astrocytes (various types), neuronal cells (various types, still poorly classified), oligodendrocytes, spindle neurons, anterior lens epithelial cells, crystallin-containing lens fiber cells, hepatocytes (liver cells), adipocytes (white and brown adipocytes), liver adipocytes, kidney parietal cells, kidney glomeruli Podocytes, renal proximal tubule brush border cells, thin segment cells of Henle's loop, renal distal tubule cells, renal collecting duct cells, chief cells, interstitial cells, type I pneumocytes (lining the inner surface of the air spaces in pneumocytes), pancreatic duct cells (central acinar cells), non-striated duct cells (of sweat glands, salivary glands, mammary glands, etc.), chief cells, interstitial cells, duct cells (of seminal vesicles, prostate, etc.), intestinal brush border cells (containing microvilli), exocrine gland striated duct cells, gallbladder epithelial cells, non-ciliated cells of testicular efferent ducts, epididymal chief cells, epididymal basal cells, ameloblast epithelial cells (secreting tooth enamel), semilunar epithelial cells of the vestibular system of the ear (secreting proteoglycans),Interdental epithelial cells of the organ of Corti (secreting the tectorial membrane that covers the hair cells), loose connective tissue fibroblasts, corneal fibroblasts (keratocytes), tendon fibroblasts, bone marrow reticular tissue fibroblasts, other non-epithelial fibroblasts, pericytes, nucleus pulposus cells of the intervertebral disc, cementoblasts / cementocytes (secreting root bone-like Ewan cells), odontoblasts / odontocytes (secreting tooth dentin), hyaline chondrocytes, fibrochondrocytes, elastocytes Chondrocytes, osteoblasts / osteocytes, osteoprogenitor cells (stem cells of osteoblasts), vitreous cells of the vitreous body of the eye, stellate cells of the perilymphatic space of the ear, hepatic stellate cells (Ito cells), pancreatic stellate cells, red skeletal muscle cells (slow twitch), white skeletal muscle cells (fast twitch), intermediate skeletal muscle cells, nuclear bag cells of muscle spindles, nuclear chain cells of muscle spindles, satellite cells (stem cells), ordinary cardiomyocytes, nodular cardiomyocytes, Purkinje fiber cells, smooth muscle cells (various types), iris These include, but are not limited to, myoepithelial cells, exocrine gland myoepithelial cells, erythrocytes (red blood cells), megakaryocytes (platelet precursors), monocytes (white blood cells), connective tissue macrophages (various types), epidermal Langerhans cells, osteoclasts (in bone), dendritic cells (in lymphoid tissue), microglial cells (in the central nervous system), neutrophil granulocytes, eosinophil granulocytes, basophil granulocytes, hybridoma cells, mast cells, helper T cells, suppressor T cells, cytotoxic T cells, natural killer T cells, B cells, natural killer cells, reticulocytes, stem cells and related precursors (various types) for the blood and immune systems, oogonia / oocytes, spermatids, spermatocytes, spermatogonia (stem cells for spermatocytes), sperm, follicle cells, Sertoli cells (in testis), thymic epithelial cells, and interstitial kidney cells.

[0046] The stem cells used can be a single type of stem cell, a mixed population of stem cells, or two or more separate stem cell populations.The stem cells used can be derived from a single source or multiple sources.Stem cells can differentiate into a single cell type or into several different cell types.

[0047] The stem cells used in the present disclosure may be genetically modified.For example, iPSCs generated from autologous cells can be modified to correct defects or mutations.Modification methods can include CRISPR, zinc finger nucleases, Talen, homologous recombination, transfection or transduction.This modification can be used to shut down genes, replace defective genes, or increase the expression of gene products.

[0048] The stem cells of the present disclosure can be delivered by any method known in the art. Methods known in the art include parenteral, for example, intravenous infusion, intradermal, transplanted bone marrow microvascular bed, subcutaneous, oral (e.g., ingestion or inhalation), transdermal (topical), transmucosal, rectal administration, or engineered monolayer tissue transplantation. In certain aspects, the population of modified cells is administered by a route selected from the group consisting of intra-arterial, intramuscular, subcutaneous, transdermal, intratracheal, intraperitoneal, intravitreal, and intranasal, and is administered by direct injection into the target site, for example, into the bone compartment, into the heart, or into the spinal fluid. In certain aspects, the population of modified cells is administered at or near the site of injury. In some embodiments, the cells can be administered by multiple routes and sites simultaneously or sequentially.

[0049] The delivery route of stem cells depends on the application. For example, stem cells can be delivered topically to treat skin. Stem cells can be delivered intravenously to treat blood disorders. Stem cells can be delivered intramuscularly to treat muscle disorders. Stem cells can be delivered into the brain via intranasal delivery to treat brain disorders. Stem cells can be delivered to the heart via intramyocardial injection to treat heart disorders. Stem cells can also be delivered intravenously to treat some non-blood-related diseases and disorders.

[0050] In some embodiments, stem cells can be administered with a scaffold support. Scaffold supports that can be used include bioactive glass, hydrogels, photopolymerizable poly(ethene) glycol hydrogels, collagen gels, Matrigel (Corning), or decellularized tissues such as cartilage or connective tissue. Stem cells can be added to the scaffold after it is formed, or the scaffold can be formed around the stem cells.

[0051] The stem cells disclosed herein can be used to treat diseases. Examples of the types of diseases that can be treated include blood diseases, cancer, immune diseases, cardiovascular diseases, muscle diseases, metabolic diseases, neurological diseases, connective tissue diseases, and eye diseases. Stem cells can be used to replace cells lost and / or damaged by disease. Stem cells can be used to replace cells with harmful mutations.

[0052] Some examples of blood diseases that can be treated with stem cell therapy include, but are not limited to, acute leukemia, chronic leukemia, lymphoma, inherited platelet disorders, plasma cell disorders, autoimmune diseases such as lupus, myeloproliferative disorders, lymphoproliferative disorders, phagocytic disorders, myelodysplastic syndromes, histiocytic disorders, or congenital immune system disorders.For example, leukemia can be treated by using cytotoxic drugs and / or radiation therapy to kill cancerous and non-cancerous blood stem cells, and then replacing the stem cells with donor bone marrow.The stem cells from the donor bone marrow repopulate the hematopoietic system.Stem cell treatment for autoimmune diseases can involve killing mature autoreactive immune cells with cytotoxic drugs and / or radiation, and then repopulating the hematopoietic system with previously isolated autologous blood stem cells.

[0053] The examples of neurological diseases that can be treated by the method of the present disclosure include, but are not limited to, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis and stroke.These diseases are associated with the loss of neuron and / or glial cells, and stem cell therapy may be able to replace these cells.

[0054] Treatment of cardiovascular and muscle diseases involves using stem cells to replace lost or damaged muscle fibers. Cardiomyocytes derived from human embryonic stem cells have been shown to successfully integrate into the hearts of guinea pigs (Shiba, Yuji et al., "Human ES-cell-derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts." Nature 489, No. 7415 (2012): 322-325).

[0055] Other examples of diseases that can be treated with the methods of the present disclosure include, but are not limited to, diabetes, infertility, lysosomal storage diseases, peripheral arterial disease, diabetes, heart disease, liver disease, bone disease, muscular dystrophy, dental disease, or cancer.

[0056] Stem cell therapy has been successfully used to regenerate teeth in mice (Ohazama, A. et al. "Stem-cell-based tissue engineering of murine teeth." Journal of Dental Research, Vol. 83, No. 7 (2004): pp. 518-522. Stem cell therapy combined with gene editing has been used to restore hearing in deaf chickens (Izumikawa, Masahiko et al., "Auditory hair cell replacement and hearing loss"). improvement by Atoh1 gene therapy in deaf mammals.”Nature medicine 11, No. 3 (2005): 271-276). Delivery of retinal stem cells to the eye can treat blindness caused by macular degeneration. Embryonic stem cells can differentiate into insulin-producing beta cells that can be delivered to the pancreas to treat diabetes.

[0057] The disclosed methods described herein can also be used to treat injuries. Injuries that can potentially be treated with stem cells include spinal column injuries and spinal cord injuries, wounds, thermal or chemical burns, sports injuries, occupational injuries, or brain injuries. In adults, wounds often heal through the formation of scar tissue, and placing stem cells into the wound can allow tissue regeneration and promote healing without the formation of scar tissue. Stem cells can be used in spinal cord injuries to promote healing and motor recovery (Cummings, Brian J. et al., "Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice." Proceedings of the National Academy of Sciences, pp. 111-114, 2014). of Sciences of the United States of America, Vol. 102, No. 39 (2005): 14069-14074).

[0058] The function of stem cell therapy can be measured by any method known in the art.Stem cell function can be measured in vitro by any method known in the art, including but not limited to, gene expression analysis, stem cell marker expression, cell morphology, cell migration, cell growth, stem cell proliferation rate and stability, spontaneous differentiation, induced differentiation, response to growth factor or lineage marker expression.Cell surface antigens and biochemical markers can be evaluated by immunocytochemistry, immunofluorescence, fluorescence-activated cell sorting, ELISA, Western blotting, qPCR, RNA sequencing or microarray.

[0059] Stem cell function can be measured in vivo. For example, stem cell function can be measured by biopsy of the target tissue and analysis of tissue derived from transplanted stem cells. PCR amplification of variable number tandem repeat (VNTR) loci can be used to identify donor and recipient cells. Furthermore, these cells can be characterized for morphology, cell surface antigens, biochemical markers, gene expression, karyotyping, and biological activity. Cell surface antigens and biochemical markers can be assessed by immunocytochemistry, immunofluorescence, fluorescence-activated cell sorting, ELISA, Western blotting, qPCR, RNA sequencing, or microarrays. The efficacy of treatment can be assayed by measuring the expression of markers for desired and undesired cell types. The efficacy of treatment can be assayed by measuring the function of the target tissue or cell type. For example, the efficacy of cardiac stem cell treatment can be examined by measuring an increase in ejection fraction (EF); the percentage of blood ejected from the left ventricle with each heartbeat; electrocardiograms; echocardiograms; exercise / intranuclear stress tests; Holter monitoring; or the expression of cardiac or non-cardiac markers, such as neural markers. In another example, the effectiveness of treatment with neural stem cells can be measured by testing for changes in neural function, such as spatial memory, working memory, motor coordination, MRI, PET scan, and quality of life outcomes.In another example, the effectiveness of treatment with hepatocyte stem cells can be measured by liver enzyme tests, which are commonly used clinically and measure the presence of liver enzymes such as ALT and AST in blood.In one aspect of the present invention, it can improve the migration ability of stem cells.In some examples, enhancing the function of stem cells in a subject can refer to improving any aspect of stem cell therapy.Some non-limiting examples include increased survival of stem cells in a subject, increased self-renewal of stem cells in a subject, increased replication of transit amplifying cells derived from stem cells, increased engraftment of stem cells into desired niches in a subject, increased migratory capacity of stem cells, increased homing of stem cells to desired tissues or organs, increased differentiation of stem cells into desired cell type or cell types, decreased engraftment of stem cells into undesired niches in a subject, decreased differentiation of stem cells into undesired cell type or cell types, reduced side effects associated with treatment, improved functional recovery resulting from stem cell treatment, reduced required doses of immunosuppressive drugs, or extended lifespan of stem cells in a subject.

[0060] Subjects who receive a pharmaceutical composition containing encapsulated cannabinoid compounds before, during, or after stem cell therapy may show improved outcomes compared to subjects who do not receive the pharmaceutical composition.For example, subjects who receive the pharmaceutical composition may experience fewer side effects, milder side effects, or shorter side effects.Compared to subjects who do not receive the pharmaceutical composition, subjects may show more rapid recovery, stronger recovery, maintain a longer recovery state, or improve the function of the treated organ or organ system.Examples of side effects that can be reduced include nausea, vomiting, fatigue, temporary hair loss, infection, bleeding, anemia, graft-versus-host disease, venous occlusive disease, digestive problems, skin problems, pain, parotid inflammation, engraftment syndrome, lung problems, kidney problems, nerve and muscle problems, transplant failure, transplant rejection, heart problems, eye problems, thyroid problems, developmental problems, bladder problems, central nervous system problems, fertility problems, and cancer.

[0061] Stem cell treatment and cannabinoid composition can be co-administered.The terms "co-administration," "administered in combination with," and their grammatical equivalents include the administration of two or more drugs to an animal, so that both drugs and / or their metabolites are present in the animal at the same time.Co-administration includes simultaneous administration in separate compositions, administration at different times in separate compositions, or administration in a composition in which both drugs are present.Co-administered drugs can be in the same formulation.Co-administered drugs can also be in different formulations.

[0062] Subjects of the present disclosure can include humans as well as other animals, such as pets (e.g., dogs, cats, birds, small animals, snakes) and livestock or agricultural animals (e.g., cows, pigs, horses, sheep, chickens). The compositions of the present disclosure can be useful in veterinary applications. In some embodiments, the subject of the disclosure described herein is a human.

[0063] The subject may have reached adulthood. In some embodiments, the subject has not reached adulthood. In some embodiments, the subject is a fetus.

[0064] The subject can be a human or animal with a disease that is suitable for stem cell treatment.The example of the disease that can be treated with stem cell has been discussed above.The subject can also be a human or animal with a lesion that is suitable for stem cell treatment.The example of the lesion that can be treated with stem cell has been discussed above.

[0065] Cannabinoid Composition The compositions administered to a subject to enhance stem cell function include encapsulated cannabinoid compounds. Cannabinoids utilized in the compositions disclosed herein include cannabigerol (CBG), cannabigerolic acid (CBGA), cannabigerolic acid monomethyl ether (CBGAM), cannabigerol monomethyl ether (CBGM), cannabichromene (CBC), cannabichromanone (CBCN), cannabichromenic acid (CBCA), cannabichromevarin (CBCV), cannabichromevaric acid (CBCVA), cannabidiol (CBD), tetrahydrocannabinol (THC), iso-tetrahydrocannabinol (iso-THC), cannabinol (CBN), cannabinol acid (CBNA), cannabinol methyl ether (CBNM), cannabinol-C4 (CBN-C4), cannabinol-C2 (CBN-C2), cannabiolchol (CBN-C1), cannabinol-C1, cannabinol-C2, cannabinol-C1, cannabinol-C4, cannabinol-C2, cannabinol-C1 ... Cannabinoids may include, but are not limited to, cannabinodiol (CBND), cannabielsoin-type (CBE), cannabielsonic acid A (CBEA-A), cannabielsonic acid B (CBEA-B), cannabicyclol-type (CBL), cannabicyclol acid (CBLA), cannabicyclovaline (CBLV), cannabicitran-type (CBT), cannabidiol, cannabidiolvaline (CBTV), ethoxy-cannabidiolvaline (CBTVE), cannabivarin-type (CBV), cannabinodivaline (CBVD), tetrahydrocannabivarin-type (THCV), cannabidivarin-type (CBDV), cannabigerovarin-type (CBGV), cannabigerovaric acid (CBGVA), cannabifuran (CBF), dehydrocannabifuran (DCBF), and cannabilipsol (CBR) cannabinoids.

[0066] Cannabinoids used in the compositions and methods of the present disclosure can be derived from a variety of sources, including, but not limited to, cannabis (e.g., cannabis stalk, cannabis stem, cannabis seed), cannabis (e.g., cannabis flower, cannabis leaf, cannabis stalk, cannabis stem, cannabis seed), Echinacea purpurea, Echinacea angustifolia, Echinacea pallida, Acmella oleracea, Helichrysum umbraculigerum, Radula marginata, kava, black truffle, Syzygium aromaticum (clove), Rosmarinus oficinalis, basil, oregano, black pepper, lavender, true cinnamon, malabarum, cananga odorata, copaifera spp., and hops.

[0067] The encapsulated cannabinoid may be included in an amount of at least about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 micrograms per capsule. The encapsulated cannabinoid may be included in an amount of up to about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 micrograms per capsule. The encapsulated cannabinoid may be present in an amount of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 micrograms per capsule. The encapsulated cannabinoid may be present in an amount of about 1 to about 10 micrograms per capsule. The encapsulated cannabinoid may be present in an amount of at least about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by weight of the capsule. The encapsulated cannabinoid may comprise up to about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by weight of the capsule.The encapsulated cannabinoid may be present in an amount of about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45% or 50% by weight of the capsule.

[0068] The cannabinoid may be incorporated into a product, e.g., a food product, in an amount of at least about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, or 500 milligrams (mg). The cannabinoid may be incorporated into a product, e.g., a food product, in an amount of up to about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, or 500 milligrams (mg). The cannabinoid may be incorporated into a product, e.g., a food product, in an amount of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, or 500 milligrams (mg). The cannabinoid may be incorporated into a product, e.g., a food product, in an amount of about 50 to about 150 mg. The cannabinoids may be present in an amount of at least about 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1% or 2% by weight of the product. %, 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, 10 wt%, 11 wt%, 12 wt%, 13 wt%, 14 wt%, 15 wt%, 16 wt%, 17 wt%, 18 wt%, 19 wt%, 20 wt%, 25 wt%, 30 wt%, 35 wt%, 40 wt%, 45 wt%, or 50 wt% may be incorporated into a product, for example, a food product.Cannabinoids may be present in a maximum of approximately 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2% by weight of the product. , 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, 10 wt%, 11 wt%, 12 wt%, 13 wt%, 14 wt%, 15 wt%, 16 wt%, 17 wt%, 18 wt%, 19 wt%, 20 wt%, 25 wt%, 30 wt%, 35 wt%, 40 wt%, 45 wt%, or 50 wt% may be incorporated into a product, e.g., a food product. Cannabinoids may be present in the product at approximately 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3% and 4% by weight. It may be incorporated into a product, for example, a food product, in an amount of 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by weight.

[0069] The cannabinoids of the encapsulated cannabinoid compounds utilized in the methods disclosed herein can include compounds of the cannabidiol class, including, but not limited to, cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidiol monomethyl ether (CBDM), cannabidiol-C4 (CBD-C4), cannabidivarin (CBDV), cannabidivarinic acid (CBDVA), cannabidiolcol (CBD-C1), and combinations thereof. CBD can include delta-1-cannabidiol, delta-2-cannabidiol, delta-3-cannabidiol, delta-3,7-cannabidiol, delta-4-cannabidiol, delta-5-cannabidiol, delta-6-cannabidiol, and combinations thereof.

[0070] The encapsulated cannabidiol compound may be included in an amount of at least about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 micrograms per capsule. The encapsulated cannabidiol compound may be included in an amount of up to about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 micrograms per capsule. The encapsulated cannabidiol compound may be included in an amount of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 micrograms per capsule. The encapsulated cannabidiol compound may be included in an amount of about 1 to about 10 micrograms per capsule. The encapsulated cannabidiol compound may be comprised in an amount of at least about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by weight of the capsule.The encapsulated cannabidiol compound may comprise up to about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by weight of the capsule. The encapsulated cannabidiol compound may be included in an amount of about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by weight of the capsule.

[0071] Compositions containing encapsulated cannabinoid compounds may be water-soluble. Compositions containing encapsulated cannabinoid compounds may be water-soluble even when the gravity of the atmosphere is lower than sea level. The encapsulated cannabinoid compounds may be soluble at temperatures ranging from about 6°C to about 55°C. The encapsulated cannabinoid compounds may be soluble at pressures ranging from about 1 atmosphere to about 5 atmospheres. The encapsulated cannabinoid compounds may be soluble under ambient conditions. Ambient conditions may be from about 15°C to about 30°C and from about 1 atmosphere to about 3 atmospheres. For example, about 2.5 milligrams of the composition may be soluble in 25 milliliters of water.

[0072] The cannabidiol compound may be included in a product, e.g., a food product, in an amount of at least about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, or 500 milligrams (mg). The cannabidiol compound may be included in a product, e.g., a food product, in an amount of up to about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, or 500 milligrams (mg). The cannabidiol compound may be included in a product, e.g., a food product, in an amount of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, or 500 milligrams (mg). The cannabidiol compound may be included in a product, e.g., a food product, in an amount of about 50 to about 150 milligrams. The cannabidiol compound may comprise at least about 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1% or 2% by weight of the product. %, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by weight of the product, e.g., food product.Cannabidiol compounds may be present in a maximum of about 0.01% by weight, 0.02% by weight, 0.03% by weight, 0.04% by weight, 0.05% by weight, 0.06% by weight, 0.07% by weight, 0.08% by weight, 0.09% by weight, 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1% by weight, 2% by weight, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 21% by weight, 22% by weight, 23% by weight, 24% by weight, 25% by weight, 26% by weight, 27% by weight, 28% by weight, 29% by weight, 30% by weight, 31% by weight, 32% by weight, 33% by weight, 34% by weight, 35% by weight, 36% by weight, 37% by weight, 38% by weight, 39% by weight, 40% by weight, 41% by weight, 42% by weight, 43% by weight, 44% by weight, 45% by weight, 46% by weight, 47% by weight, 48% by weight, 49% by weight, 49% by weight, 50 The product may be included in a product, e.g., a food product, in an amount of 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by weight. The cannabidiol compound may be present in an amount of approximately 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1% and 2% by weight of the product. %, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by weight of the product, e.g., food product.

[0073] The compositions and methods of the present disclosure can include tetrahydrocannabinol (THC) as one type of cannabinoid. THC can include delta-9-THC, delta-8-THC, and combinations thereof. THC can include delta-6a,7-tetrahydrocannabinol, delta-7-tetrahydrocannabinol, delta-8-tetrahydrocannabinol, delta-9,11-tetrahydrocannabinol, delta-9-tetrahydrocannabinol, delta-10-tetrahydrocannabinol, delta-6a,10a-tetrahydrocannabinol, and combinations thereof. Delta-9-tetrahydrocannabinol can include stereoisomers including (6aR,10aR)-delta-9-tetrahydrocannabinol, (6aS,10aR)-delta-9-tetrahydrocannabinol, (6aS,10aS)-delta-9-tetrahydrocannabinol, (6aR,10aS)-delta-9-tetrahydrocannabinol, and combinations thereof.

[0074] In some embodiments, the capsules may contain THC. The THC compound may be included in an amount of at least about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 micrograms per capsule. The encapsulated THC compound may be included in an amount of up to about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 micrograms per capsule. The encapsulated THC compound may be included in an amount of about 1 to about 10 micrograms per capsule. The encapsulated THC compound may be included in an amount of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 micrograms per capsule. The encapsulated THC compound may be included in an amount of at least about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by weight of the capsule.The encapsulated THC compound may comprise up to about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by weight of the capsule. The encapsulated THC compound may be included in an amount of about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by weight of the capsule.

[0075] The THC compound may be included in a product, e.g., a food product, in an amount of at least about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, or 500 milligrams (mg). The THC compound may be included in a product, e.g., a food product, in an amount of up to about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, or 500 milligrams (mg). The THC compound may be included in a product, e.g., a food product, in an amount of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, or 500 milligrams (mg). The THC compound may be included in a product, e.g., a food product, in an amount of about 50 to about 150 mg. The THC compound may comprise at least about 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1% or 2% by weight of the product. %, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by weight of the product, e.g., food product.THC compounds may be present in a maximum of approximately 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2% by weight of the product. , 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight. THC compounds may be present in the product at approximately 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3% by weight. %, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by weight of the product, e.g., food product.

[0076] In some cases, the compositions of the present disclosure do not contain psychoactive amounts of THC. For example, the cannabinoids in the compositions of the present disclosure may contain less than 100%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%, 5%, 1%, 0.7%, 0.5%, 0.3%, or 0.1% THC relative to the total amount of cannabinoid compounds. In some cases, the ratio of non-THC cannabinoids (e.g., cannabidiol) to THC in the compositions of the present disclosure is greater than or equal to about 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 25:1, 30:1, 35:1, 40:1, 45:1, 50:1, or 100:1. In some cases, the compositions of the present disclosure contain less than 0.3% THC.

[0077] In some embodiments, the compositions of the present disclosure may contain an antioxidant. Antioxidants can inhibit oxidation by reactive species. Antioxidants can refer to compounds that inhibit or slow the oxidation of other molecules by inhibiting the initiation or propagation of oxidative chain reactions. Antioxidants can be compounds that neutralize reactive oxygen species, which can cause oxidative stress. Antioxidants can be compounds that act as oxygen scavengers or chelators. Antioxidants can neutralize free radicals by donating one of their electrons. Antioxidants can be enzymatic or non-enzymatic molecules. Enzymatic antioxidants include enzymes that metabolize oxidative toxic intermediates, such as reactive oxygen species. Enzymatic molecules include enzymes such as superoxide dismutase, glutathione peroxidase, glutathione reductase, catalase, and ascorbate oxidase. Non-enzymatic molecules can include glutathione, vitamin C, uric acid, albumin, bilirubin, vitamin E (α-tocopherol), carotenoids (eg, β-carotene), and flavonoids.

[0078] The composition of the present disclosure can include one or more terpene compounds, including but not limited to terpenoids such as monoterpenoids, sesquiterpenoids, diterpenoids, and triterpenoids.Terpenes can be acyclic, monocyclic, or polycyclic.Terpenes include myrcene, limonene, linalool, trans-ocimene, cis-ocimene, alpha-pinene, beta-pinene, alpha-humulene (alpha-caryophyllene), beta-caryophyllene, delta-3-carene, trans-gamma-bisabolene, cis-gamma-bisabolene, trans-alpha-farnesene, cis-beta-farnesene, beta-fenchol, beta-phellandrene, guayol, alpha-gualene, alpha-eudesmol, beta-eudesmol, gamma-eudesmol, These may include, but are not limited to, terpinolene, alpha-selinene, beta-selinene, alpha-terpineol, fenchone, camphene, cis-sabinene hydrate, alpha-trans-bergamotene, alpha-cis-bergamotene, borneol, gamma-curcumene, alpha-thujene, epi-alpha-bisabolol, ipsdienol, alpha-iluangene, beta-elemene, gamma-muurolene, alpha-cadinene, alpha-longipinene, caryophyllene oxide, and combinations thereof.

[0079] The encapsulated terpene may be included in an amount of at least about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 micrograms per microcapsule. The encapsulated terpenes may be present in an amount of up to about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 micrograms per capsule. The encapsulated terpenes may be present in an amount of up to about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 micrograms per capsule. The encapsulated terpene compound may be present in an amount of about 1 to about 10 micrograms per capsule, and may be present in an amount of at least about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by weight of the capsule. The encapsulated terpene may comprise up to about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by weight of the capsule.The encapsulated terpene may be included in an amount of about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by weight of the capsule.

[0080] The terpene compounds may be included in a product, e.g., a food product, in an amount of at least about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, or 500 milligrams (mg). The terpene compounds may be included in a product, e.g., a food product, in an amount of up to about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, or 500 milligrams (mg). The terpene compounds may be included in a product, e.g., a food product, in an amount of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, or 500 milligrams (mg). The terpene compounds may be included in a product, e.g., a food product, in an amount of about 50 to about 150 milligrams. The terpene compounds may be present in an amount of at least about 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1% or 2% by weight of the product. %, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by weight of the product, e.g., food product.Terpene compounds may be present in a maximum of approximately 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, and 2% of the product by weight. , 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight. Terpene compounds account for approximately 0.01 wt%, 0.02 wt%, 0.03 wt%, 0.04 wt%, 0.05 wt%, 0.06 wt%, 0.07 wt%, 0.08 wt%, 0.09 wt%, 0.1 wt%, 0.2 wt%, 0.3 wt%, 0.4 wt%, 0.5 wt%, 0.6 wt%, 0.7 wt%, 0.8 wt%, 0.9 wt%, 1 wt%, 2 wt%, and 3 wt% of the product. It may be included in a product, e.g., a food product, in an amount of 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by weight.

[0081] The composition of the present disclosure can be enriched with cannabinoids compared to hemp oil.For example, the composition can include hemp oil and cannabinoids from plant sources, such as extracts (e.g., hemp extracts) and essential oils.The composition can include about 0%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900% or 1000% higher cannabinoid concentrations compared to hemp oil.

[0082] The composition of the present disclosure can be enriched with cannabidiol compounds compared with hemp oil.For example, the composition can comprise hemp oil and cannabidiol compounds from plant sources such as extracts (e.g., hemp extracts) and essential oils.Compared to hemp oil, the composition can comprise about 0%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900% or 1000% higher cannabidiol compound concentration.

[0083] The composition of the present disclosure can be enriched with THC compounds compared to hemp oil.For example, the composition can include hemp oil and THC compounds from plant sources such as extracts (e.g., hemp extracts) and essential oils.Compared to hemp oil, the composition can include about 0%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900% or 1000% higher concentrations of THC compounds.

[0084] The composition of the present disclosure can be enriched with terpenes compared to hemp oil.For example, the composition can include hemp oil and terpenes from plant sources such as extracts (e.g., hemp extracts) and essential oils.Compared to hemp oil, the composition can include about 0%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900% or 1000% higher terpene concentration.

[0085] The encapsulated cannabinoid compounds contained in the compositions of the present disclosure can be derived from various sources. The source of the compounds can be natural products, such as plant extracts or essential oils. The compounds in the compositions of the present disclosure can be derived from hemp oil, which contains cannabinoid compounds, THC compounds, and terpene compounds. The compounds in the compositions of the present disclosure can be derived from essential oils, including but not limited to the essential oils discussed further in this disclosure. These compounds can include cannabinoid compounds and terpene compounds. In some cases, all compounds or ingredients in the composition are natural or naturally derived. In some cases, all compounds or ingredients in the composition are vegetarian. In some cases, all compounds or ingredients in the composition are vegan.

[0086] The terpenes and / or essential oils in the compositions of the present disclosure can be selected to benefit specific conditions or subjects.Terpenes and / or essential oils can be used in combination with each other and in combination with cannabinoids, for example, to reduce cellular oxidative stress, and in some cases, to alleviate one or more health conditions.For example, terpinolene, terpineol and linalool, or lavender, valerian and jasmine essential oils can be combined with cannabinoids or cannabis extract to act as sleep aids or treat sleep disorders.

[0087] Alpha-pinene can be used as an anti-inflammatory, anti-angiogenic, anti-ulcer, and bronchodilator.

[0088] Linalool reduces anxiety and reduces inflammation (e.g., inflammation in the lungs), and can therefore be used as a sedative, analgesic, antimicrobial, antibacterial, and antiepileptic agent to ameliorate Alzheimer's disease or its symptoms.

[0089] Myrcene can be used as an antibacterial agent, a neuroprotective agent, an antinociceptive agent, an analgesic, and to relieve neuropathic pain, peptic ulcer disease, and inflammation. Depending on the concentration, myrcene can be used as a sedative (e.g., greater than 0.5% myrcene) or to exert an energizing effect (e.g., less than 0.5% myrcene).

[0090] Limonene can be used to reduce anxiety and depression, dissolve cholesterol-containing gallstones, neutralize stomach acid, support normal peristalsis, relieve heartburn and gastroesophageal reflux, improve immune function, and as a chemopreventive agent against cancer.

[0091] Ocimene can be used as an antifungal, antitumor, and cytotoxic agent.

[0092] Terpinolene can be used for its antioxidant, mood-regulating, central nervous system (CNS)-regulating, anti-inflammatory, antidiarrheal, antifilarial, antifungal, antimalarial, antiamoebic, antibacterial, cytotoxic, and anticancer effects.

[0093] Terpineol can be used to relax a subject, aid digestion, improve gastrointestinal disorders, and relieve flu, bronchitis, coughs, nasal congestion, and sinusitis.

[0094] Beta-caryophyllene can be used as an anti-inflammatory, anti-tumor, and analgesic agent.

[0095] Geraniol can be used to reduce or prevent neuropathy, as an antidepressant, to inhibit angiogenesis, to improve the efficacy of anticancer drugs, to inhibit the growth of cancer cells (e.g., lung cancer), as a chemopreventive agent against cancer, to reduce inflammation and apoptosis (e.g., in liver cells), to reduce oxidative stress, as an antioxidant, and as an antimicrobial.

[0096] Alpha-humulene can be used as an appetite suppressant, anti-inflammatory, insect repellent, antibacterial, antioxidant, and allelopathic agent.

[0097] Phellandrene can be used as an antidepressant and antihyperalgesic.

[0098] Carene can be used as an antioxidant, antiproliferative, antimicrobial, and to reduce excess body fluid production such as tears, mucus, or sweat.

[0099] Terpinene can be used as an antioxidant, anti-inflammatory, antimicrobial, and anti-proliferative agent to reduce oxidative stress and to manage diabetes.

[0100] Fenchol can be used as an antibacterial, antimycobacterial, antimicrobial, and antioxidant agent.

[0101] Borneol can be used as a TRPA1 inhibitor, anti-inflammatory agent, and antinociceptive agent to reduce hyperalgesia.

[0102] Bisabolol can be used as an anti-cancer agent, such as inducing apoptosis in leukemia, an anti-tumor agent (eg, pancreatic cancer), and an anti-genotoxic agent.

[0103] Phytol can be used to relax a subject, such as by inhibiting the breakdown of GABA, as an anxiolytic agent, to counter menadione-induced oxidative stress, and as an antimicrobial agent.

[0104] Camphene can be used for pain relief, as an antioxidant, to induce apoptosis in cancer cells (eg, melanoma), as an antitumor agent, and as an antibacterial agent.

[0105] Sabinene can be used as an antioxidant, antimicrobial, anti-cancer agent (e.g., for oral, liver, lung, colon, melanoma, and leukemic cancers), to support liver function, aid digestion, relieve arthritis, and alleviate skin conditions.

[0106] Camphor can be used as a local anesthetic, muscle relaxant, anti-pathogenic, and anti-microbial agent to improve skin healing (eg, reconstructed human epithelium).

[0107] Isoborneol can be used as an antioxidant, cytotoxic agent, DNA protecting agent, to inhibit herpes simplex virus type 1, and to inhibit HIV.

[0108] Menthol can be used as an analgesic, to desensitize α3β4 nicotinic acetylcholine receptors, as an antinociceptive agent, and as an anti-inflammatory agent.

[0109] Nerolidol can be used as an antifungal, antimicrobial, antioxidant, and antimalarial agent.

[0110] Guaiol can be used as an antimicrobial, antifungal, and antibiotic agent.

[0111] Isopulegol can be used as a gastroprotectant, an anti-inflammatory agent, to increase the permeability of transdermal administered compounds, and to reduce the severity of attacks.

[0112] Geranyl acetate can be used as an antimicrobial, antibacterial, and antioxidant agent.

[0113] Cymene can be used as an anti-inflammatory, anti-hyperalgesic, antioxidant, anti-diabetic agent, to aid in weight loss, to help with immune disorders, and to prevent acute lung injury.

[0114] Eucalyptol can be used as an antifungal agent, to reduce inflammation (eg, inflammation of the lungs), as an antioxidant, and as an anti-cancer agent.

[0115] Pulegone can be used to enhance skin penetration, as an insecticide, and as an antioxidant.

[0116] The compositions of the present disclosure may include one or more essential oils or essential oil compounds. Essential oils include, but are not limited to, linalool; B-caryophyllene; B-myrcene; D-limonene; humulene; a-pinene; ylang-ylang (Cananga odorata); yarrow (Achillea millefolium); violet (Viola odorata); vetiver (Vetiveria zizanoides); vanilla (Vanilla plantifolia); tuberose (Polianthes tuberosa); thyme (Thymus vulgaris L.); tea tree (Melaleuca alternifolia); tangerine (Citrus reticulata); black spruce (Picea mariana); spruce (Tsuga Canadensis); jack-in-the-box (Nardostachys jatamansi); spearmint (Mentha spicata); sandalwood (Santalum spicatum); rosewood (Aniba rosaeodora); rosemary verbenone (Rosmarinus officinalis; rosemary (Rosmarinus officinalis); rose (Rosa damascena); pelargonium (Pelargonium roseum); Ravensara (Ravensara aromatica); pine (Zingiber cassumunar); pinecone (Pinus sylvestris L.); petitgrain (Citrus aurantium); peppermint (Mentha piperita); black pepper (Piper nigrum L.);Patchouli (Pogostemon cablin);Palo Santo (Bursera graveolens);Palmarosa (Cymbopogon martini);Osmanthus (Osmanthus fragrans);Oregano (Origanum vulgare);Sweet orange (Citrus sinensis);Oakmoss (Evernia prunastri);Nutmeg (Myristica fragrans);Niaouli (Melaleuca viridifloria);Neroli (also known as orange blossom) (Citrus aurantium);Myrtle (Myrtus communis);Myrrh (Commiphora. myrrha; mimosa (Acacia decurrens); melissa (Melissa officinalis L.); sweet marjoram (Origanum majorana); manuka (Leptospermum scoparium); red mandarin (Citrus deliciosa); mandarin (Citrus deliciosa); white lotus (Nelumbo nucifera); pink lotus (Nelumbo nucifera); blue lotus (Nelumbo nucifera); lime (Citrus aurantifolia); lily (Lilum aurantum; lemongrass (Cymbopogon citratus); lemon (Citrus limonum); lavender (Lavandula angustifolium); lavandin (Lavandula hybrida grosso); kanuka (Kunzea ericoides); juniper berry (Juniperus cummunis); jasmine (Jasminum officinale); jasmine Abs (Jasminum sambac); strawberry (Helichrysum italicum); white grapefruit (Citrus x paradisi); pink grapefruit (Citrus paradisi); ginger (Zingiber officinalis); geranium (Pelargonium graveolens); Bourbon geranium (Pelargonium graveolens, 'Herit'); Gardenia (Gardenia jasminoides); Galbanum (Ferula galbaniflua); Frankincense (Boswellia carterii); Frangipani (Plumeria alba); White fir needle (Abies alba); Siberian fir needle (Abies siberica); Canadian fir needle (Abies balsamea); Sweet fennel (Foeniculum vulgare); Eucalyptus Smithii, Eucalyptus Radiata, Eucalyptus Globulus, Eucalyptus Citriodora, Eucalyptus Blue Mallee (Eucalyptus polybractea); Elemi (Canarium luzonicum); Dill (Anethum graveolens); Cypress (Cupressus sempervirens); Cumin (Cuminum cyminum); Coriander (Coriandum sativum; cocoa (Theobroma cacao); cloves (Eugenia caryophylatta); clary sage (Salvia sclarea); cistus (also known as Labdanum) (Cistus ladaniferus L.); cinnamon (Cinnamomum zeylanicum); Roman chamomile (Anthemis nobilis); blue chamomile (Matricaria chamomilla); celery seed (Apium graveolins); western red cedar (Thuja plicata); cedarwood, blood (Juniperus virginiana); Atlas cedarwood (Cedrus atlantica); carrot seed (Daucus carota); cardamom (Elettaria cardamomum); caraway seed (Carum carvi); cajuput (Melaleuca cajuputi); cade (Juniperus oxycedrus); American birch (Betula alba); American water chestnut (Betula lenta); bergamot (Citrus bergamia); bay laurel (Laurus nobilis); basil (Ocimum basilicum); sacred basil (Ocimum sanctum); basil (Ocimum basilicum); balsam poplar (Populus balsamifera); balsam Peru (Myroxylon balsamum); angelica (Angelica archangelica L.); and combinations thereof.

[0117] The compositions of the present disclosure may include one or more additional ingredients, including, but not limited to, mushrooms or mushroom-derived products (e.g., Reishi, Chaga, Maitake, Pleurotus ostreatus, Cordyceps ulmoides), maca (Lepidium meyenii), Polygonum multiflorum (also known as he show wu or shou wu chih), superfoods or superfood-derived products (e.g., blueberries, acai berries, Inca berries, goji berries, camu camu, coconut, lucuma, kale, cacao (e.g., cocoa powder, cocoa butter), sacha inchi, chia, flax, hemp, amaranth, quinoa, Moringa oleifera), and combinations thereof.

[0118] The compounds used in the compositions of the present disclosure can be extracted by a variety of methods, for example, extraction can be performed by maceration, infusion, decoction, percolation, Soxhlet extraction, pressurized solvent extraction, countercurrent extraction, sonication, or supercritical fluid (e.g., carbon dioxide) extraction.

[0119] In some cases, the compounds used in the compositions of the present disclosure are extracted via supercritical fluid (e.g., carbon dioxide) extraction. For example, cannabinoid compounds can be extracted from cannabis (e.g., cannabis stalks and stems) using supercritical carbon dioxide extraction.

[0120] The compositions of the present disclosure can include pregnenolone, including its derivatives. Pregnenolone can help protect subjects from cannabis intoxication, such as THC. Pregnenolone or its derivatives can be formulated to be water-soluble. The compositions of the present disclosure can include between about 1 and 50 milligrams (mg) of pregnenolone or its derivatives. For example, a unit dosage of the present disclosure can include between about 1 and 50 milligrams (mg) of pregnenolone. The compositions (e.g., unit dosages) of the present disclosure can include about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, or 50 mg of pregnenolone. Compositions (e.g., unit dosages) of the present disclosure can contain at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, or 50 mg of pregnenolone. Compositions (e.g., unit dosages) of the present disclosure can contain up to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, or 50 mg of pregnenolone. Compositions containing pregnenolone can be used in combination with any other compound, ingredient, or formulation described herein, including esters, cyclodextrin complexes, capsules (e.g., sodium alginate capsules), immediate-release formulations, delayed- or extended-release agents, buccal formulations, and sublingual formulations.

[0121] The compositions of the present disclosure include encapsulated cannabinoid compounds. The capsules can include components discussed in this disclosure, such as cannabinoid compounds. In some embodiments, compositions including terpene compounds, cannabidiol, THC, and / or others can also be encapsulated. In some cases, the compositions can be encapsulated without the use of liposomes. In some cases, the compositions can be encapsulated without the use of micelles. In some cases, the compositions can be encapsulated without the use of liposomes or micelles. The compounds of the compositions can be present and encapsulated in forms including, but not limited to, liquids, gels, semi-solids, and solids. The encapsulated compositions disclosed herein can be further processed into forms including, but not limited to, solids, powders, liquids, suspensions, gels, tablets, foods, lotions, cosmetics, and other forms discussed in this disclosure.

[0122] Encapsulation can be performed in an encapsulation device, including a microfluidic droplet generation or encapsulation device. Exemplary microencapsulation devices are described, for example, in U.S. Pat. No. 7,482,152, the entire contents of which are incorporated herein by reference. Microfluidic droplets or emulsions can be generated by flowing an encapsulated fluid with an immiscible carrier fluid. For example, an oil fluid to be encapsulated can be flowed with an aqueous carrier fluid, or an aqueous fluid to be encapsulated can be flowed with an oil carrier fluid. Air can also be used as a fluid. Microfluidic droplet generators useful for microencapsulation include those using co-flow, cross-flow (e.g., flow at a T-junction), focusing of the flow, flow through a perforated plate, and flow through a nozzle. Droplet size can be controlled by parameters including the device geometry, the relative flow rates of the fluid streams, and the operating pressure.

[0123] Examples of encapsulated compositions, including encapsulated cannabinoid compositions, are provided in WO2016 / 094810, which is incorporated by reference in its entirety.

[0124] Encapsulation can be performed over a range of operating parameters, such as different flow rates or pressures. Encapsulation can be performed at pressures of at least about 10 pounds per square inch (psi), 20 psi, 30 psi, 40 psi, 50 psi, 60 psi, 70 psi, 80 psi, 90 psi, 100 psi, 200 psi, 300 psi, 400 psi, 500 psi, 600 psi, 700 psi, 800 psi, 900 psi, 1000 psi, 2000 psi, 3000 psi, 4000 psi, 5000 psi, 6000 psi, 7000 psi, 8000 psi, 9000 psi, 10000 psi, 15000 psi, 20000 psi, 25000 psi, 30000 psi, 35000 psi, 40000 psi, 45000 psi, 50000 psi, or more. Encapsulation can be performed at pressures of up to about 10 pounds per square inch (psi), 20 psi, 30 psi, 40 psi, 50 psi, 60 psi, 70 psi, 80 psi, 90 psi, 100 psi, 200 psi, 300 psi, 400 psi, 500 psi, 600 psi, 700 psi, 800 psi, 900 psi, 1000 psi, 2000 psi, 3000 psi, 4000 psi, 5000 psi, 6000 psi, 7000 psi, 8000 psi, 9000 psi, 10000 psi, 15000 psi, 20000 psi, 25000 psi, 30000 psi, 35000 psi, 40000 psi, 45000 psi, or 50000 psi. Microencapsulation can be carried out at pressures of about 10 pounds per square inch (psi), 20 psi, 30 psi, 40 psi, 50 psi, 60 psi, 70 psi, 80 psi, 90 psi, 100 psi, 200 psi, 300 psi, 400 psi, 500 psi, 600 psi, 700 psi, 800 psi, 900 psi, 1000 psi, 2000 psi, 3000 psi, 4000 psi, 5000 psi, 6000 psi, 7000 psi, 8000 psi, 9000 psi, 10000 psi, 15000 psi, 20000 psi, 25000 psi, 30000 psi, 35000 psi, 40000 psi, 45000 psi, 50000 psi or greater.Encapsulation may occur at a rate of at least about 1 milliliter per minute (mL / min), 2 mL / min, 3 mL / min, 4 mL / min, 5 mL / min, 6 mL / min, 7 mL / min, 8 mL / min, 9 mL / min, 10 mL / min, 20 mL / min, 30 mL / min, 40 mL / min, 50 mL / min, 60 mL / min, 70 mL / min, 80 mL / min, 90 mL / min, 100 mL / min, 110 mL / min, 120 mL / min, 130 mL / min, 140 mL / min, 150 mL / min, 160 mL / min, 170 mL / min, 180 mL / min, 190 mL / min, 200 mL / min, 210 mL / min, 220 mL / min, 230 mL / min, 240 mL / min, 250 mL / min, 260 mL / min, 270 mL / min, 280 mL / min, 290 mL / min, 300 mL / min, 310 mL / min, 320 mL / min, 330 mL / min, 340 mL / min, 350 mL / min, 360 mL / min, 370 mL / min, 380 mL / min, 390 mL / min, 400 mL / min, 410 mL / min, 420 mL / min, 430 mL / min, 440 mL / min, 450 mL / min, 460 mL / min, 470 mL / min, 480 mL / min, 490 mL / min, 500 mL / min, 510 mL / min, 520 mL / min, 530 mL / min, 540 mL / min, 550 mL / min, 560 mL / min, The flow rates can be 230 mL / min, 240 mL / min, 250 mL / min, 260 mL / min, 270 mL / min, 280 mL / min, 290 mL / min, 300 mL / min, 310 mL / min, 320 mL / min, 330 mL / min, 340 mL / min, 350 mL / min, 360 mL / min, 370 mL / min, 380 mL / min, 390 mL / min, 400 mL / min, 410 mL / min, 420 mL / min, 430 mL / min, 440 mL / min, 450 mL / min, 460 mL / min, 470 mL / min, 480 mL / min, 490 mL / min, 500 mL / min or more.Encapsulation is possible up to approximately 1 milliliter per minute (mL / min), 2mL / min, 3mL / min, 4mL / min, 5mL / min, 6mL / min, 7mL / min, 8mL / min, 9mL / min, 10mL / min, 20mL / min, 30mL / min, 40mL / min, 50mL / min, 60mL / min, 70 mL / min, 80mL / min, 90mL / min, 100mL / min, 110mL / min, 120mL / min, 130mL / min, 140mL / min, 150mL / min, 160mL / min, 170mL / min, 180mL / min, 190mL / min, 200mL / min, 210mL / min, 220mL Flow rates of 230 mL / min, 240 mL / min, 250 mL / min, 260 mL / min, 270 mL / min, 280 mL / min, 290 mL / min, 300 mL / min, 310 mL / min, 320 mL / min, 330 mL / min, 340 mL / min, 350 mL / min, 360 mL / min, 370 mL / min, 380 mL / min, 390 mL / min, 400 mL / min, 410 mL / min, 420 mL / min, 430 mL / min, 440 mL / min, 450 mL / min, 460 mL / min, 470 mL / min, 480 mL / min, 490 mL / min, or 500 mL / min can be used.Encapsulation is approximately 1 milliliter per minute (mL / min), 2mL / min, 3mL / min, 4mL / min, 5mL / min, 6mL / min, 7mL / min, 8mL / min, 9mL / min, 10mL / min, 20mL / min, 30mL / min, 40mL / min, 50mL / min, 60mL / min, 70mL / m in, 80mL / min, 90mL / min, 100mL / min, 110mL / min, 120mL / min, 130mL / min, 140mL / min, 150mL / min, 160mL / min, 170mL / min, 180mL / min, 190mL / min, 200mL / min, 210mL / min, 220mL / min , 230 mL / min, 240 mL / min, 250 mL / min, 260 mL / min, 270 mL / min, 280 mL / min, 290 mL / min, 300 mL / min, 310 mL / min, 320 mL / min, 330 mL / min, 340 mL / min, 350 mL / min, 360 mL / min, 370 mL / min, 380 mL / min, 390 mL / min, 400 mL / min, 410 mL / min, 420 mL / min, 430 mL / min, 440 mL / min, 450 mL / min, 460 mL / min, 470 mL / min, 480 mL / min, 490 mL / min, 500 mL / min, or more.

[0125] A droplet generator can use multiple parallel droplet generation operations in parallel. For example, a droplet generator (e.g., a plate, a device with channels) can use at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, or more droplet generation features (e.g., holes, channels, nozzles). A droplet generator can use up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 droplet generation features. The droplet generator can use about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100 or more droplet generation features.

[0126] Encapsulation can be carried out via an emulsification process. For example, the composition can be emulsified in a mixer, such as a stirrer, impeller, centrifugal mixer, or high-shear mixer. High-shear mixers can include batch high-shear mixers and in-line high-shear mixers (e.g., rotor-stator mixers). Emulsification can also be carried out without a mixer by combining fluids that are thermodynamically favored to form an emulsion, optionally with the aid of one or more emulsifiers or surfactants.

[0127] The encapsulation process can be carried out with the aid of one or more emulsifiers or surfactants, which can include, but are not limited to, saponins (e.g., quillaja tree extracts, such as Q-NATURALE®, yucca extracts), lecithin, soy lecithin, mustard seed husk extract, sodium stearoyl lactylate, polysorbate 20, and combinations thereof.

[0128] The encapsulated cannabinoid compound may contain one or more stabilizers or gelling agents that can be used to stabilize the capsule or emulsion.Stabilizing or gelling agents can include, but are not limited to, alginate (also known as algin or alginic acid) and agar.Alginate can be used in various forms, including, but not limited to, inorganic salts such as sodium alginate, potassium alginate, calcium alginate, and combinations thereof.Alginate can be derived from sources such as seaweed (e.g., Macrocystis pyrifera, Ascophyllum nodosum, Laminaria spp.) or bacteria (e.g., Pseudomonas spp., Azotobacter spp.).A cross-linking agent or solution, such as calcium chloride, can be used to stabilize or gel the capsule.

[0129] The encapsulated cannabinoid compound can be characterized by size (e.g., diameter). The size of the capsule (e.g., droplet) can be about 0.154 micrometers. The size of the capsule can be less than or equal to about 0.154 micrometers. The size of the capsule can be greater than or equal to about 0.154 micrometers. The capsule sizes are approximately 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0. It can be 8, 0.85, 0.9, 0.95, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300, 350, 400, 450, or 500 micrometers. The capsule sizes are approximately 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9 It may be less than or equal to 0.9, 0.95, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300, 350, 400, 450, or 500 micrometers.The capsule sizes are approximately 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9 , 0.95, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300, 350, 400, 450, or 500 micrometers. The capsule size can be about 0.1 to about 0.2 micrometers. The capsule size can be about 0.05 to about 0.25 micrometers. The capsule size can be about 0.05 to about 0.55 micrometers. The capsule size can be about 0.05 to about 1 micrometer. The size distribution in the population of capsules can be homogeneous or substantially homogeneous. For example, the population of capsules can be about 20, 19, 18, 17, 16, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4.9, 4.8, 4.7, 4.6, 4.5, 4.4, 4.3, 4.2, 4.1, 4.0, 3.9, 3.8, 3.7, 3.6, 3.5, 3.4, 3.3, 3.2, 3.1, 3.0, 2.9, 2.8, 2.7, 2.6, 2.5, 2.4, 2.3, 2.2, 2. and may be characterized by a dispersity or polydispersity index (PDI) of less than or equal to 1, 2.0, 1.9, 1.8, 1.7, 1.6, 1.5, 1.45, 1.40, 1.35, 1.30, 1.25, 1.20, 1.15, 1.14, 1.13, 1.12, 1.11, 1.10, 1.09, 1.08, 1.07, 1.06, 1.05, 1.04, 1.03, 1.02, 1.01, or 1.00.

[0130] A composition containing an effective amount of an encapsulated cannabinoid compound is administered to a subject. The term "effective amount" or "therapeutically effective amount" refers to an amount of the encapsulated cannabinoid compound described herein sufficient to achieve the intended application, including, but not limited to, enhancing stem cell function and / or treating a disease in a subject. The therapeutically effective amount may vary depending on the subject and condition being treated, such as the subject's weight and age, the severity of the disease state, the method of administration, etc., and can be easily determined by one skilled in the art. The term also applies to a dose that induces a specific response in target cells, such as a change in the expression of stem cell markers. The specific dose will vary depending on the specific formulation of the encapsulated cannabinoid compound, the administration regimen followed, whether it is administered in combination with other compounds, the timing of administration, the tissue to which it is administered, the route of administration, and the bodily delivery system through which it is delivered.

[0131] Any of the subject compositions can be provided as unit dosage form.A unit dosage is the amount of compound, such as cannabinoid compound, delivered alone or in combination with other components, that is administered to subject at one time or approximately one time.Other components that can be included with unit dosage include, but are not limited to, cosmetics, food carriers, food bars, baked goods, dairy products, oils, beverages, solid dosages (e.g., tablets), or liquid dosages. The unit dosage of the cannabinoid compound can be about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000 or more milligrams (mg). The unit dosage amount of the cannabinoid compound can be at least about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000 or more milligrams (mg). The unit dosage of cannabinoid compound can be up to about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000 or more milligrams (mg).The unit dosage can be an hourly dosage.The unit dosage can be a daily dosage. A unit dosage may provide about 1 / 24, 1 / 12, 1 / 8, 1 / 6, 1 / 4, 1 / 3, 1 / 2, or all of the daily dosage of one or more cannabinoids for a subject. The unit dosage may be in the form of a tablet, gel, liquid, food, food bar, container of a defined volume of liquid, or other form as described herein, packaged for single consumption or administration.

[0132] The amount of the composition of the present invention administered will depend on the subject being treated, the severity of the disorder or condition, the rate of administration, and the nature of the composition and encapsulated cannabinoid compound. The amount of the composition administered will also depend on the type and amount of stem cells administered. Effective dosages range from about 0.1 mg to about 2000 mg per kg of body weight per day. For example, for a 70 kg human, this may amount to about 7 mg / day to about 1.75 g / day. In some instances, dosage levels below the lower end of the above range may be more than sufficient, while in other cases, larger doses may be used without causing any adverse side effects, for example, by dividing such larger doses into several smaller doses for administration throughout the day. Dosages may be administered over a period of several hours, days, weeks, or months. Compositions containing encapsulated cannabinoid compounds can be administered to a subject in any of several ways to result in enhanced stem cell function. The compositions can be administered, for example, orally or transdermally. Other delivery routes include, but are not limited to, intranasal, sublingual, transmucosal, or intradermal. An effective amount of the composition may be in a dosage unit formulation containing conventional non-toxic physiologically acceptable carriers, adjuvants, and vehicles, as needed.

[0133] Oral administration can be achieved by using oral dosage forms.Oral dosage forms can be solid (for example, tablets or bulk powder) or liquid (for example, suspension or slurry).Tablets can include tablets, caplets, capsules including soft gelatin capsules, and lozenges.Tablets can further comprise suitable binders, lubricants, diluents, disintegrants, colorants, flavoring agents, flow inducers, and melting agents.

[0134] A composition containing an encapsulated cannabinoid compound formulated for oral administration can be incorporated into a food composition. The food composition can be a beverage, a solid food, or a semi-solid food. The food composition can include an encapsulated cannabinoid compound and a food carrier. The food carrier can be virtually any food. Examples of food carriers include, but are not limited to, food bars (such as granola bars, protein bars, and candy bars), cereal products (such as oatmeal, breakfast cereals, and granola), bakery products (such as bread, donuts, crackers, bagels, pastries, and cakes), beverages (milk-based beverages, sports drinks, fruit juices, alcoholic beverages, and mineral water), pasta, grains (such as rice, corn, oats, rye, wheat, and flour), egg products, snacks (such as candy, chips, gum, and chocolate), meat, fruits, and vegetables.

[0135] Compositions containing encapsulated cannabinoid compounds can be administered transdermally, for example, via a patch. Compositions of the present disclosure can be administered intravenously. Compositions of the present disclosure can be administered topically. Compositions of the present disclosure can be administered by topical exposure to an aqueous solution, such as by immersing a subject in a float tank. Compositions of the present disclosure can be formulated as bath salts or liquid bath products that can be dissolved or dispersed in water (e.g., a bathtub) for skin exposure, for example, by immersion of the subject. Compositions containing encapsulated cannabinoid compounds for topical or transdermal application can be provided as cosmetics or personal care products, such as soaps (e.g., solid, bar, liquid, or foam), hand sanitizers, lotions, massage oil masks, makeup, moisturizers, sunscreens, toothpastes, mouthwashes, or throat sprays.

[0136] To enhance the function of stem cells, compositions containing encapsulated cannabinoid compounds can be administered by a variety of different mechanisms.The composition can be nebulized and delivered from a pressurized pack or aerosolized from a dry powder inhaler in aerosol spray preparations.Suitable propellants that can be used in nebulizers include, for example, dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane and carbon dioxide.In the case of pressurized aerosols, dosage can be determined by providing a valve to deliver a controlled amount of compound.

[0137] The composition can be administered to a subject in various forms to enhance stem cell function. The composition can be administered as a dry powder. For example, an oil-based composition (e.g., hemp oil) can be combined with a drying or powdering agent such as cyclodextrin. In some cases, the powder composition can be provided on its own. In other cases, the powder composition can be provided in another product or composition, such as a food or composition, a cosmetic, or other product, and in the composition as disclosed herein.

[0138] Compositions comprising encapsulated cannabinoid compounds can be administered in any suitable form, including, but not limited to, liquid, gel, semi-liquid (e.g., a liquid such as a viscous liquid containing some solids), semi-solid (a solid containing some liquid), or solid form. The compositions can be provided, for example, in tablet, capsule, food, chewable, non-chewable, buccal, sublingual, slow release, non-slow release, sustained release, or non-sustained release form.

[0139] Compositions containing encapsulated cannabinoid compounds for inhalation or insufflation include solutions and suspensions in pharmaceutically acceptable aqueous or organic solvents, or mixtures thereof, as well as powders. Liquid or solid compositions may contain suitable excipients as described above. Preferably, the compositions of the present invention are administered orally, intranasally, or via the respiratory route for local or systemic effect. Compositions in acceptable solvents may be nebulized by the use of inert gases. Nebulized solutions may be inhaled directly from the nebulizing device, or the nebulizing device may be attached to a face mask, tent, or intermittent positive pressure breathing machine. Solution, suspension, or powder compositions may be administered orally or intranasally from a device that delivers the formulation in an appropriate manner.

[0140] The compositions of the present disclosure can contain one or more additional active or passive agents. Examples of such agents include sweeteners, flavoring agents, coloring agents, fillers, binders, lubricants, excipients, preservatives, or manufacturing agents. Additional pharmaceutically acceptable excipients (in the case of pharmaceuticals) or other additives (in the case of non-pharmaceutical applications) can be added to the compositions. For example, if desired, any generally acceptable soluble or insoluble inert pharmaceutical filler (diluent) material can be included in the final product (e.g., solid dosage form). Such inert pharmaceutical fillers can include monosaccharides, disaccharides, polyhydric alcohols, inorganic phosphates, sulfates, or carbonates, and combinations thereof. Examples of suitable inert pharmaceutical fillers include sucrose, dextrose, lactose, xylitol, fructose, sorbitol, calcium phosphate, calcium sulfate, calcium carbonate, microcrystalline cellulose, and combinations thereof. An effective amount of any generally acceptable pharmaceutical lubricant, such as calcium or magnesium soap, can be added.

[0141] In a related but separate aspect, the present disclosure provides a food composition comprising an encapsulated cannabinoid in an amount effective to enhance stem cell function, and a food carrier. Any type, amount, or form of composition comprising the encapsulated cannabinoids disclosed herein is applicable to preparing the food compositions disclosed herein.

[0142] The food composition or food product may include food bars, including but not limited to granola bars, protein bars, candy bars, and energy bars. The food composition or food product may include grain products, including but not limited to oatmeal, flours (e.g., wheat flour, rice flour, corn flour, barley flour), breakfast cereals, granola, bread, pasta, rice cakes, and popcorn. The food composition or food product may include bakery products, including but not limited to bread, pastries, brownies, cakes, pies, donuts, crackers, and muffins. The food composition or food product may include dairy products, including but not limited to milk, cultured milk, curd, whey, yogurt, cream, cheese, butter, clarified butter, ghee, and ice cream. The food composition or food product may include nut butter or seed butter, including but not limited to peanut butter, almond butter, cashew butter, hazelnut butter, macadamia nut butter, pecan butter, pistachio butter, walnut butter, pumpkin seed butter, sesame seed butter, soybean butter, and sunflower seed butter. The food composition or food product can include oils (e.g., cooking oils), including, but not limited to, olive oil, coconut oil, vegetable oil, canola oil, corn oil, peanut oil, sunflower seed oil, almond oil, avocado oil, rice bran oil, cottonseed oil, flax oil, linseed oil, grape seed oil, hemp oil, mustard oil, macadamia oil, palm oil, tea oil, walnut oil, margarine, lard, butter, clarified butter, ghee, or tallow. The food composition or food product can include sports foods, such as energy gels, sports drinks, energy powders, energy bars, energy shots, protein powders, and protein drinks (e.g., protein shakes).The food composition or food product can comprise beverages, including, but not limited to, water, electrolyte drinks, soda, coconut water, tea (e.g., Jun tea, black tea, green tea, white tea, herbal tea), coffee, soft drinks, alcoholic beverages (e.g., cocktails, liquor, spirits, beer, wine, malt drinks), water, juice (e.g., apple juice, orange juice, tomato juice, vegetable juice, cranberry juice), sports drinks, electrolyte-enriched water, vitamin-enriched water, hangover drinks, milk (e.g., dairy-based milk, coconut milk, almond milk, soy milk, hemp milk, rice milk, oat milk, cashew milk, hazelnut milk), and yogurt. The food composition or food product may comprise a fungal or fermented food or beverage, including, but not limited to, kifir, jung, amasi, amazake, appa, ayran, doog, bagoong, bulum, cheonggukjang, chicha, kombucha, fermented bean curd, kimchi, lassi, miso, poi, Yakult, and yogurt.

[0143] Compositions of the present disclosure can include products for pets or other animals, such as animal foods (e.g., dog food, cat food), treats, and nutritional supplements (e.g., liquids, sprays, or powders applied to food or water). These compositions can be formulated for or administered to domestic or pet animals (e.g., dogs, cats, small animals, birds), livestock and other agricultural animals (e.g., cows, pigs, horses, sheep, goats), zoo animals, or any other vertebrate. Compositions for administration to animals can be formulated with encapsulated or unencapsulated cannabinoid-rich oils, alone or in combination with essential oils, terpenes, and other components described herein. Compositions for administration to animals can be mixed with feed or water, prepared for spray application (e.g., mixed with glycerin), for intravenous administration (e.g., in a syringe or IV bag), as ointments, vitamins, liquid vitamin pumps, treats, or other forms.

[0144] Packaging for food compositions containing encapsulated cannabinoids can take several configurations. Packaging can be configured for single serving. Packaging can be disposable. By way of non-limiting example, the packaging can be a pouch, can, flexible container, or sealed tube. Food packaging can be made of any of a variety of materials, including Mylar®, Aclar®, polyethylene, foil, and aluminum. Food compositions can be packaged in retort pouches or flexible bowls with lids, food condiment pouches, or full-panel drawer cans. Food composition packaging may incorporate utensils such as forks, spoons, knives, or scissors. The packaging can be configured to allow a portion to be removed for ease of consumption. For example, the package can remain sealed during rehydration or reheating; a portion of the package can be removed for consumption. The packaging can be configured for rehydration of dehydrated food composition powders. For example, food and beverage packaging can further include a septum adapter to allow for rehydration of dehydrated foods. The sealed container containing the food composition may be configured to be secured to a tray. Dry, powdered, or otherwise disintegrating foods may be coated with gelatin to reduce disintegration. Oxygen may be removed from the package and replaced with nitrogen gas and an oxygen scavenger. Nitrogen gas may be flushed through the package before sealing. The package may be sealed with a vacuum seal. The package may be sealed at a vacuum of about 15 to about 35 inches of Hg.

[0145] The kit may include a food composition comprising an effective amount of an encapsulated cannabinoid compound. The kit may be configured to be consumed by a subject under a variety of conditions.

[0146] In addition to enhancing stem cell function, administering the composition of the present disclosure to a subject can produce one or more additional beneficial effects.These beneficial effects can include but are not limited to: pain relief, reduced bacterial growth, reduced blood glucose level, improved blood lipid and cholesterol profile, increased fat burning, reduced appetite, stimulated appetite, reduced vomiting or nausea, reduced seizures or convulsions, antifungal effect, reduced inflammation, reduced arthritis (for example, rheumatoid arthritis), reduced insomnia or improved sleep, reduced arterial blockage, inhibited cancer cell growth, improved psoriasis, calming effect, anticonvulsant effect, reduced anxiety, promoted bone growth, reduced intestinal contraction, and nervous system protection.

[0147] The compositions described herein can provide several advantages, including, but not limited to, increased storage stability, increased bioavailability, increased bioactivity, and delayed release. The compositions described herein can have a variety of release profiles, half-lives, and metabolic characteristics when administered to a subject. The subject compositions may include a plurality of capsules, each individual capsule of the plurality being characterized by exhibiting at least one of: (a) a sigmoid release profile of the at least one cannabinoid compound; (b) a plasma half-life of the at least one cannabinoid compound that is more than twice as long as the at least one cannabinoid compound in non-encapsulated form; (c) a first-pass metabolism of the at least one cannabinoid compound that is reduced by at least 50% compared to the at least one cannabinoid compound in non-encapsulated form; d) an excretion rate of the at least one cannabinoid compound from the body of the subject that is reduced by at least 20% compared to the at least one cannabinoid compound in non-encapsulated form; or (e) a decomposition rate of the at least one cannabinoid compound at an ambient temperature of at least 20°C that is less than about 50% of the decomposition rate of the at least one cannabinoid compound in non-encapsulated form.

[0148] The compositions described herein can have a storage half-life of at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 240, 270, 300, 330, or 360 days. In some cases, the compositions described herein can have a storage half-life of at least about 1, 2, 3, 4, or 5 years. The composition in encapsulated form may be characterized by a cannabinoid decomposition rate at an ambient temperature of at least 20°C that is at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% less than the decomposition rate of the non-encapsulated cannabinoid composition.

[0149] The encapsulated cannabinoid composition may be characterized by a plasma half-life in a subject that is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.5, 4.0, 4.5, or 5.0 times that of a non-encapsulated cannabinoid composition. The plasma half-life of a composition can be determined experimentally by administering the composition to a subject, collecting plasma samples from the subject at multiple time points, and measuring the concentration of one or more compounds of interest in these plasma samples. The concentration of one or more compounds of interest will reach a peak value in the plasma and then decline as the one or more compounds are metabolized, decomposed, or removed from the bloodstream. The plasma half-life is the time it takes for the plasma concentration value to decrease by half.

[0150] The cannabinoid release profile can be sigmoidal (e.g., having an "S" curve, such as a logistic function). The cannabinoid release profile can be non-sigmoidal. The cannabinoid release profile can be linear. The cannabinoid release profile can be non-linear. The cannabinoid release profile can be instantaneous release. The cannabinoid release profile can be non-instantaneous release. The cannabinoid release profile can be delayed release. The cannabinoid release profile can be constant or sustained release. The cannabinoid release profile can be variable or non-sustained release.

[0151] Tablets can be formulated into sustained release format.The method of making sustained release tablets is known in the art; for example, refer to US Patent Application Publication No. 2006 / 0051416 and US Patent Application Publication No. 2007 / 0065512.Progressive release tablets are known in the art; for example, an example of such tablets is described in US Patent No. 3,456,049.Slow or sustained release form can delay the disintegration or absorption of composition or one or more of its components.

[0152] In some cases, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or less of the cannabinoid compound is released from the capsule within 1 hour of administration to a subject. In some cases, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or less of the cannabinoid compound is released from the capsule within 2 hours of administration to a subject. In some cases, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or less of the cannabinoid compound is released from the capsule within 3 hours of administration to a subject. In some cases, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or less of the cannabinoid compound is released from the capsule within 4 hours of administration to a subject. In some cases, no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% of the cannabinoid compound is released from the capsule within 5 hours of administration to a subject. In some cases, no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% of the cannabinoid compound is released from the capsule within 6 hours of administration to a subject.In some cases, no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% of the cannabinoid compound is released from the capsule within 7 hours of administration to a subject. In some cases, no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% of the cannabinoid compound is released from the capsule within 8 hours of administration to a subject.

[0153] Release profile is the relationship between time and the amount of compound released into subject or the concentration of compound in subject (for example, in plasma).Release profile can be measured in a manner similar to plasma half-life.Composition can be administered to subject, and samples (for example, plasma samples or blood samples) can be taken from subject at multiple time points.The concentration of one or more compounds of interest can be measured in such samples, and release profile can be plotted.

[0154] Compounds ingested by a subject through the gastrointestinal system can be transported to the liver and then enter the systemic circulation. Compounds that are susceptible to metabolic degradation in the liver can have their activity substantially reduced by first-pass metabolism through the liver. Encapsulation of compounds (e.g., microencapsulation) can reduce the first-pass metabolism of compounds in the liver. Encapsulated compositions can be characterized by at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% less first-pass metabolism in subjects than non-encapsulated cannabinoid compositions. The composition in encapsulated form may be characterized by a cannabinoid excretion rate from a subject that is at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% less than a non-encapsulated cannabinoid composition.

[0155] The compositions described herein can have improved bioavailability, bioactivity, or both when administered to a subject. Bioavailability is the percentage of an administered dose of unchanged compound that reaches the systemic circulation. Encapsulated cannabinoid compositions can be characterized by a bioavailability in a subject that is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, or 10.0 times greater than that of non-encapsulated cannabinoid compositions. The cannabinoid composition in encapsulated form may be characterized by a bioavailability in a subject of at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%. Bioactivity, or biological activity, is the activity provided by one or more active ingredients in the composition. The cannabinoid composition in microencapsulated form may be characterized by a bioavailability in a subject that is at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, or 10.0 times that of the non-encapsulated cannabinoid composition.

[0156] The compositions described herein can be used to treat a subject having a disease, including, but not limited to, the conditions described in paragraph 64. The compositions described herein can be used to treat a subject having an injury, including, but not limited to, the conditions described in paragraph 64.

[0157] As used herein, treating a disease encompasses therapeutic benefit and / or prophylactic benefit. A prophylactic effect includes delaying or eliminating the appearance of a disease or condition, delaying or eliminating the onset of symptoms of a disease or condition, slowing, halting, or reversing the progression of a disease or condition, or any combination thereof.

[0158] The methods disclosed herein can produce synergistic effects. Using cannabinoid compositions with stem cells can synergistically enhance stem cell function. In some examples, stem cell treatments and cannabinoid compositions can be administered in subtherapeutic amounts. In some embodiments, subtherapeutic amounts of stem cells and / or cannabinoid compositions can be used. A subtherapeutic amount of a drug or treatment is an amount that is less than the effective amount of that drug or treatment, but when combined with an effective or subtherapeutic amount of another drug or treatment, can produce results that are desirable to a physician, for example, due to a synergistic effect in the resulting effective effect or reduced side effects.

[0159] A "synergistically effective therapeutic amount" or "synergistically effective amount" of a drug or treatment is an amount that, when combined with an effective or sub-therapeutic amount of another drug or treatment, produces a greater effect than either of the two drugs used alone. In some embodiments, a synergistically effective therapeutic amount of a drug or treatment produces an effect when used in combination that is greater than the additive effect of each of the two drugs or treatments when used alone. In certain preferred embodiments of the present disclosure, the stem cell therapy and cannabinoid composition exhibit synergistic effects.

[0160] In some cases, efficacy can be assessed by determining changes in overall survival, improvement in disease-related symptoms, disease-free survival, progression-free survival, and / or time to treatment failure. Efficacy can be determined by a variety of methods, including, but not limited to, monitoring changes in gene expression levels and biomarker expression levels. [Example]

[0161] Example 1 Microencapsulated cannabinoids improve stem cell engraftment A hemp oil composition containing cannabinoids, including cannabidiol, is produced. The composition is microencapsulated through a microfluidic nozzle device. The microcapsules are administered to a subject before the subject undergoes stem cell treatment. After the subject undergoes stem cell treatment, the subject shows increased stem cell engraftment compared to a control subject that did not receive the cannabinoid-containing microcapsules.

[0162] Example 2 Microencapsulated cannabinoids improve stem cell survival during transplantation A hemp oil composition containing cannabinoids, including cannabidiol, is produced. The composition is microencapsulated through a microfluidic nozzle device. The microcapsules are administered to a subject before the subject undergoes stem cell treatment. After the subject undergoes stem cell treatment, the subject has more viable stem cells than a control subject that does not receive the cannabinoid-containing microcapsules.

[0163] Example 3 Microencapsulated cannabinoids reduce immune activation against transplanted stem cells A hemp oil composition containing cannabinoids, including cannabidiol, is produced. The composition is microencapsulated through a microfluidic nozzle device. The microcapsules are administered to a subject at the same time the subject undergoes bone marrow transplantation. Thereafter, compared to control subjects who did not receive the cannabinoid-containing microcapsules, reduced graft rejection is observed. Graft rejection is determined by using PCR amplification of variable number tandem repeat (VNTR) loci to identify donor and recipient cells in bone marrow.

[0164] Example 4 Cannabinoids affect gene expression in mouse embryonic stem cells Mouse embryonic stem cells are cultured in a medium treated with either cannabidiol (1 μM, 5 μM, 10 μM, or 50 μM) or vehicle control. Samples are collected on days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10, and RNA is extracted for next-generation sequencing. Expression analysis is performed on the sequencing data to determine the genes that are differentially expressed in cannabidiol-treated cells. The differential expression of stem cell markers, differentiation markers, DNA replication, cell cycle, proliferation, apoptosis, and cannabinoid pathway genes may be of particular interest.

[0165] Example 5 Cannabinoids affect mouse embryonic stem cell sphere formation Mouse embryonic stem cells are cultured in medium treated with either cannabidiol (1 μM, 5 μM, 10 μM, or 50 μM) or vehicle control for 10 days. After 10 days of culture, the cells are transferred to a sphere-forming assay. Each treatment group is scored for the number of spheres formed, the size and shape of the spheres formed, the cell types found in each sphere, and the number of times the spheres can be passaged. Cannabidiol-treated stem cells can form spheres with higher efficiency, can form spheres with more neural cell types than spheres formed by vehicle-treated cells, or can form spheres with more or less different cell types than vehicle-treated cells.

[0166] Example 6 Cannabinoids increase engraftment of murine hematopoietic stem cells delivered by tail vein injection Mouse hematopoietic stem cells were isolated from the bone marrow of mice expressing GFP under the control of a constitutive promoter. Recipient mice were prepared by exposing congenic mice to sufficient radiation to deplete the hematopoietic stem cell population. The isolated hematopoietic stem cells were delivered to the recipient mice via tail vein injection. After injection, the mice were administered a control diet or a diet supplemented with a microencapsulated hemp oil composition containing cannabinoids, including cannabidiol. Blood samples were collected from both groups of mice at 4, 8, 12, 16, 20, 24, 28, and 32 weeks, and the number of donor-derived cells was determined by screening the cells for GFP expression.

[0167] Additional experiments will be performed using the above protocol to determine the efficacy of transplantation of hematopoietic stem cells from mice genetically engineered to lack cannabinoid receptors (CB null) into CB null recipient mice.

[0168] Example 7 Cannabinoids enhance stem cell processing after spinal cord injury Mouse neural stem cells expressing green fluorescent protein (GFP) under the control of a constitutive promoter were treated with either cannabidiol (1 μM, 5 μM, 10 μM, or 50 μM) or vehicle control for 10 days. The cells were then transplanted directly into the spinal cord of mice with spinal cord injuries. Mice were maintained on a control diet or a diet supplemented with a microencapsulated hemp oil composition containing cannabinoids, including cannabidiol, at concentrations similar to those used in the cell culture medium. Mice were monitored daily for signs of spinal cord recovery assessment of motor function based on the Basso Mouse Scale (BMS) score, a motor rating scale based on frequency analysis of seven movement categories, and rotarod treadmill testing. Two months after stem cell treatment, mice were sacrificed and their spinal cords were examined histologically. Mice receiving cannabinoid-treated stem cells and cannabinoid-supplemented diets showed more rapid and robust recovery.

[0169] While preferred embodiments of the present invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. It is not intended that the present invention be limited by the specific examples provided herein. While the present invention has been described with reference to the above specification, the descriptions and illustrations of the embodiments herein are not intended to be construed in a limiting sense. Numerous variations, changes, and substitutions will occur to those skilled in the art without departing from the invention. Furthermore, it is to be understood that all aspects of the present invention are not limited to the specific illustrations, configurations, or relative proportions set forth herein, which depend upon a wide variety of conditions and variables. It is to be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the present invention. It is therefore intended that the present invention encompass any such alternatives, modifications, variations, or equivalents. The following claims define the scope of the invention, and it is intended that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

1. 1. A combination for i) improving stem cell engraftment, ii) improving stem cell survival during transplantation, or iii) reducing immune activation against transplanted stem cells, the stem cells; and Pharmaceutical compositions containing encapsulated cannabinoid compounds wherein the encapsulated cannabinoid compound is characterized by at least one of: a) a sigmoidal release profile; b) a plasma half-life that is more than twice that of the cannabinoid compound in non-encapsulated form; c) a first-pass metabolism that is reduced by at least 50% compared to the cannabinoid compound in non-encapsulated form; d) a rate of elimination from the body of a subject that is reduced by at least 20% compared to the cannabinoid compound in non-encapsulated form; or e) a decomposition rate at an ambient temperature of at least 20°C that is less than 50% of the decomposition rate of the cannabinoid compound in non-encapsulated form. A combination wherein the pharmaceutical composition is administered before, simultaneously with, or after administration of the stem cells.

2. The combination of claim 1 , wherein the pharmaceutical composition further comprises at least one terpene compound.

3. The combination of claim 1 , wherein the pharmaceutical composition reduces side effects normally associated with the administration of the stem cells.

4. 2. The combination of claim 1, wherein the subject is suffering from or suspected of suffering from a disease selected from the group consisting of chronic leukemia and lymphoma, inherited platelet disorders, plasma cell disorders, autoimmune diseases, myeloproliferative disorders, lymphoproliferative disorders, phagocytic disorders, myelodysplastic syndromes, histiocytic disorders, congenital immune system disorders, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease and multiple sclerosis, stroke, diabetes, infertility, vision loss or other eye diseases, lysosomal storage diseases, peripheral arterial disease, ischemic limb injury, diabetes, heart disease, liver disease, bone disease, muscular dystrophy, dental disease, and cancer.

5. 2. The combination of claim 1, wherein the subject has suffered from an injury selected from the group consisting of spinal column and spinal cord injuries, wounds, thermal or chemical burns, sports injuries, occupational injuries, or brain injuries.

6. The combination of claim 1 , wherein the stem cells are derived from stem cells that are induced pluripotent stem cells, embryonic stem cells, fetal stem cells, or adult stem cells.

7. The stem cells contain AA4, AA4.1, P-gp (CD243), ABCB5, ABCG2 (CDw338), ALDH, alkaline phosphatase, alpha6-integrin, WNT2B, antithrombin III (AT), asialoGM1, Bcl-2, beta1-integrin, bromodeoxyuridine, c-kit (CD117), c-Met, C1qR(p), END (CD105), PROM1 (CD133), A LCAM (CD166), ITGB1 (CD29), TNFRSF8 (CD30), PECAM-1 (CD31), Siglec-3 (CD33), CD34, CD44, NCAM (CD56), CD73, CD9, CD90, CDCP1, circulating anticoagulant protein C (PC), CK19, CLV3, cyclic CMP, ECMA-7, EDR1, EEC, FGF-4, Flk-2, Flk1(+), Flt3 / Flk2, FM S (CD115), FORSE-1, G alpha 16, GDF3, GFPM, Gli2, Gli3, glial fibrillary acidic protein, glycoprotein IB, GSTA1, Her5, hMYADM, HSA, hsp25, Id2, IL-3R alpha, integrin, interleukin-3 receptor alpha chain, KDR, keratin 15 (also known as CK15, cytokeratin 15), keratin 19 (also known as CK19, cytokeratin 19, K19) ), Kit, L-selectin (CD62L), lamin A / C, Lewis X antigen (Le(X)), LeX, Lgr5, Lrp4, MCM2, MCSP, monosomy 7, mouse ortholog of ARX, MRP4, Msi-1, Musashi, Musashi-1, mutant BCRP, nestin, neurofilament-microtubule-associated protein 2, neuron-glial antigen 2 (NG2), Notch 1, nrp-1, nucleostemin, OC. 3, Oct-4, OST-PTP, P-gp / MDR1, p21, p63, p75, PCLP, PCNA, PECAM, PgP-1, phosphorylated-p38, podocalyxin, procalcitonin (PCT), PSC, pSV2gpt, PTPRC, rat liver fatty acid binding protein / human growth hormone transgene (Fabpl / hGH), RC1 antigen, Rex-1, Sca-1, SCF, sialyl-lactotetra, SOX10, SOX2, SOX9, SSEA-1, SSEA-3, SSEA-4, Stat3, Stat5,The combination according to claim 1, wherein the cells express at least one of Stella, Stra8, Stro-1, tartrate-resistant acid phosphatase (TRAcP), TdT, telomerase reverse transcriptase, thrombomucin, Thy-1, Tra-1-60, TWIST1, VEGFR-2, vimentin, X-smoothened, XKrk1, or Zac1.

8. The combination according to claim 1 , wherein the stem cells are derived from stem cells exhibiting totipotency, pluripotency, bipotency or unipotency.

9. The stem cells are selected from the group consisting of fibroblasts, keratinocytes, melanocytes, cold-sensitive primary sensory neurons, auditory inner hair cells or organs of Corti, Merkel cells, photoreceptor cells, taste bud cells, cholinergic neurons, adrenergic neurons, peptidergic neurons, hepatocytes, adipocytes, hepatic adipocytes, kidney glomerular podocytes, pancreatic duct cells, gallbladder epithelial cells, pericytes, corneal fibroblasts, skeletal muscle cells, cardiac myocytes, Purkinje fibrocytes, erythrocytes, megakaryocytes, monocytes, Langerhans cells, osteoclasts, osteoblasts, dendritic cells, microglial cells, neutrophils, and the like. The combination of claim 1, which is derived from stem cells that give rise to granulocytes, hybridoma cells, mast cells, helper T cells, suppressor T cells, cytotoxic T cells, natural killer T cells, B cells, oocytes, sperm cells, follicle cells, Schwann cells, satellite glial cells, enteric glial cells, astrocytes, neuronal cells, oligodendrocytes, anterior lens epithelial cells, crystallin-containing lens fiber cells, growth hormone-producing cells, adrenocorticotropic hormone-producing cells, melanocyte-stimulating hormone-producing cells, thyroid cells, or dental cells.

10. 10. The combination of claim 1, wherein the stem cells are delivered via intravenous infusion, intradermal, transplanted microvascular bed of bone marrow, subcutaneous, oral (e.g., ingested or inhaled), transdermal (topical), transmucosal, rectal administration, engineered monolayer tissue transplant, intraarterial, intramuscular, intratracheal, intraperitoneal, intravitreal, or direct injection into the target site.

11. The combination of claim 1 , wherein the stem cells and the pharmaceutical composition exhibit a synergistic effect on the process in the subject.

12. 2. The combination of claim 1, wherein the pharmaceutical composition comprises nanocapsules, the nanocapsules comprising individual nanocapsules containing the encapsulated cannabinoid compound.

13. The combination of claim 12, wherein the nanocapsules increase stem cell growth.

14. The combination of claim 12, wherein the nanocapsules are administered after stem cell therapy.

15. The combination of claim 12, wherein the nanocapsules are administered to the subject by inhalation.

16. The combination of claim 12, wherein the nanocapsules are vaporized.

17. The combination of claim 12, wherein the nanocapsules are sprayed.

18. The combination of claim 12, wherein the nanocapsules are administered orally.

19. The combination of claim 12, wherein the nanocapsules are incorporated into a food or beverage.

20. The combination of claim 12, wherein the nanocapsules are administered topically.

21. The combination of claim 12, wherein the nanocapsules are water-soluble.

22. 3. The combination of claim 2, wherein the at least one terpene compound is derived from Quillaja saponaria.

23. 2. The combination of claim 1, wherein the cannabinoid compound comprises cannabidiol (CBD).

24. 2. The combination of claim 1, wherein the cannabinoid compound contains 0.3% or less tetrahydrocannabinol (THC).

25. 10. The combination of claim 1, wherein the subject has or is suspected of having a disease or injury, and after said administration of said pharmaceutical composition, said subject is monitored for the progression of said disease or injury in response to administering said pharmaceutical composition to said subject.

26. 26. The combination of claim 25, wherein the subject is suffering from or suspected of suffering from the disease, and after said administration of said pharmaceutical composition, said subject is monitored for progression or regression of said disease in response to administering said pharmaceutical composition to said subject.