Cannabinoid-containing complex mixtures for the treatment of mast cell-associated or basophil-mediated inflammatory disorders

Abstract

Provided herein are cannabinoid-containing complex mixtures suitable for use as active pharmaceutical ingredients. The complex mixtures are comprised of the major cannabinoid, cannabidiol, a first minor cannabinoid, which is cannabigerol, at least a first selected terpene, and optionally a second minor cannabinoid. Also provided are methods of making the complex mixtures, pharmaceutical compositions comprising the complex mixture, and methods of using the pharmaceutical compositions for the treatment of mast cell-related immune disorders, including allergy and atopy (allergic asthma, eczema, rhinitis), mast cell activation syndrome (MCAS), physical and chemical urticarias, idiopathic urticaria, Crohn's disease, inflammatory bowel disorder, dermatitis and contact dermatitis, arthritis and rheumatoid arthritis, canine mastocytosis, and allergy and inflammation in cattle, swine, etc. The methods of the present invention further relate to the treatment of various basophil-mediated immune disorders.

1 - 93 . (canceled) 
     
     
         94 . A method of treating disorders of the immune system, the method comprising:
 administering to a subject with an immune disorder, an effective amount of the pharmaceutical composition comprising:   cannabidiol (CBD);   a first minor cannabinoid that is cannabigerol (CBG);   a second minor cannabinoid that is cannabichromene (CBC);   a third minor cannabinoid that is cannabidivarin (CBDV);   a first terpene that is limonene;   a second terpene that is linalool; and   a pharmaceutically acceptable carrier or diluent, wherein the pharmaceutical composition is free of delta-9 tetrahydrocannabinol (THC), wherein the immune disorder is a disease involving:
 (i) dysregulation of CB1 or CB2 receptor, or cAMP of mast cells, 
 (ii) hyper-activation of CB1 or CB2 receptor or suppression of cAMP of mast cells, 
 (iii) hyper-activation of mast cells, 
 (iv) dysregulation of one or more mast cell mediators or one or more basophil mediators, 
 (v) abnormal degranulation of mast cells or basophils, or 
 (vi) abnormal synthesis of bioactive lipid mediators. 
   
     
     
         95 . The method of  claim 94 , wherein the immune disorder is a disease involving dysregulation of CB1 or CB2 receptors. 
     
     
         96 . The method of  claim 94 , wherein the immune disorder is a disease involving dysregulation or suppression of cAMP of mast cells. 
     
     
         97 . The method of  claim 94 , wherein the immune disorder is a disease involving dysregulation of one or more mast cell mediators, wherein the mast cell mediators are preformed mediators, optionally selected from the group consisting of histamine, protease, serotonin, and heparin, or newly synthesized mediators optionally selected from the group consisting of bioactive lipids, prostaglandins, PAF, cytokines, growth factors, chemokines, free radicals, and Substance P. 
     
     
         98 . The method of  claim 94 , wherein the immune disorder is a disease involving hyper-activation of CB1 or CB2 receptors. 
     
     
         99 . The method of  claim 94 , wherein the immune disorder is a disease involving hyper-activation of mast cells or basophils, optionally wherein the hyper-activation of the mast cells is (i) by a receptor-binding agonist selected from the group consisting of IgE+Antigen, IgG, IgE, Ig light chain, Complement, Neuropeptides, Microbial products, Cytokines, and Chemokines, (ii) by mechanical perturbation, temperature or pressure, or (iii) by small molecules selected from the group consisting of secretagogue peptides and arachidonic acid metabolites. 
     
     
         100 . The method of  claim 94 , wherein the immune disorder is from allergy, atopy, dermatitis, contact dermatitis, physical urticarias, chemical urticarias, idiopathic urticarial, Crohn's Diseases, inflammatory bowel disease, arthritis, dermal response to a sting or anaphylactic or anaphylactoid stimulus, tissue response to a sting or anaphylactic or anaphylactoid stimulus, systemic response to a sting or anaphylactic or anaphylactoid stimulus, canine mastocytosis, or allergy and inflammation in a non-human animal. 
     
     
         101 . The method of  claim 100 , wherein the immune disorder is inflammatory bowel disease. 
     
     
         102 . The method of  claim 100 , wherein the immune disorder is dermatitis. 
     
     
         103 . The method of  claim 100 , wherein the immune disorder is Crohn's Disease. 
     
     
         103 . The method of  claim 94 , wherein the pharmaceutical composition is administered orally, by inhalation, by buccal administration, by sublingual administration, by injection, or by topical application. 
     
     
         104 . The method of  claim 94 , wherein the pharmaceutical composition is administered orally. 
     
     
         105 . The method of  claim 94 , wherein the pharmaceutical composition is administered by inhalation. 
     
     
         106 . The method of  claim 94 , wherein the pharmaceutical composition is administered by injection. 
     
     
         107 . The method of  claim 94 , wherein the pharmaceutical composition is administered once a day, 2-4 times a day, 2-4 times a week, once a week, or once every two weeks. 
     
     
         108 . The method of  claim 94 , wherein the cannabidiol (CBD) is administered in an amount of less than 1 gram per dose. 
     
     
         109 . The method of  claim 94 , wherein the cannabidiol (CBD) is administered in an amount of less than 500 milligrams per dose. 
     
     
         110 . The method of  claim 94 , wherein the cannabidiol (CBD) is administered in an amount of less than 100 milligrams per dose or less than 10 milligrams per dose. 
     
     
         112 . The method of  claim 94 , wherein the subject is human.