Cannabidiol preparations and its uses

Abstract

Cannabidiol (CBD) is a cannabinoid designated chemically as 2-[(1R,6R)-3-Methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediol. Its empirical formula is C21H30O2 and its molecular weight is 314.46. CBD is a cannabinoid that naturally occurs in the Cannabis sativa L. plant. CBD is a white to pale yellow crystalline solid which is insoluble in water and soluble in organic solvents. The present invention encompasses the surprising recognition that certain CBD preparations which are prepared from a botanical origin are more effective in treating diseases or disorders than preparations of CBD which are synthetic or purified to the extent no other impurities in the form of other cannabinoids are present. Prior CBD compositions have been prepared such that no psychoactive components, e.g., tetrahydrocannabinol (THC), remain in the final CBD preparation. Surprisingly, the absence of such minor impurities reduces the efficacy of CBD treatment. Such CBD preparations are characterized by chemical components and/or functional properties that distinguish them from prior CBD compositions. One or more components of the preparations described herein provide an unexpectedly synergistic effect when utilized in combination.

1 . A cannabidiol (CBD) preparation characterized in that it comprises greater than or equal to 98% (w/w) CBD and less than or equal to 2% (w/w) other cannabinoids, wherein the less than or equal to 2% (w/w) other cannabinoids comprise the cannabinoids tetrahydrocannabinol (THC); cannabidiol-C1 (CBD-C1); cannabidivarin (CBDV); and cannabidiol-C4 (CBD-C4), and wherein the THC is present as a mixture of trans-THC and cis-THC. 
     
     
         2 . A cannabidiol (CBD) preparation characterized in that it comprises greater than or equal to 98% (w/w) CBD and less than or equal to 2% (w/w) other cannabinoids, wherein the less than or equal to 2% (w/w) other cannabinoids comprise the cannabinoids tetrahydrocannabinol (THC); cannabidiol-C1 (CBD-C1); cannabidivarin (CBDV); and cannabidiol-C4 (CBD-C4), and wherein the THC is present as a mixture of trans-THC and cis-THC for use as a medicament. 
     
     
         3 . A cannabidiol (CBD) preparation characterized in that it comprises greater than or equal to 98% (w/w) CBD and less than or equal to 2% (w/w) other cannabinoids, wherein the less than or equal to 2% (w/w) other cannabinoids comprise the cannabinoids tetrahydrocannabinol (THC); cannabidiol-C1 (CBD-C1); cannabidivarin (CBDV); and cannabidiol-C4 (CBD-C4), and wherein the THC is present as a mixture of trans-THC and cis-THC for use in the treatment of neurodevelopmental diseases and conditions. 
     
     
         4 . A cannabidiol (CBD) preparation characterized in that it comprises greater than or equal to 98% (w/w) CBD and less than or equal to 2% (w/w) other cannabinoids, wherein the less than or equal to 2% (w/w) other cannabinoids comprise the cannabinoids tetrahydrocannabinol (THC); cannabidiol-C1 (CBD-C1); cannabidivarin (CBDV); and cannabidiol-C4 (CBD-C4), and wherein the THC is present as a mixture of trans-THC and cis-THC for use in the treatment of epilepsy. 
     
     
         5 . A cannabidiol (CBD) preparation characterized in that it comprises greater than or equal to 98% (w/w) CBD and less than or equal to 2% (w/w) other cannabinoids, wherein the less than or equal to 2% (w/w) other cannabinoids comprise the cannabinoids tetrahydrocannabinol (THC); cannabidiol-C1 (CBD-C1); cannabidivarin (CBDV); and cannabidiol-C4 (CBD-C4), and wherein the THC is present as a mixture of trans-THC and cis-THC for use in the treatment of schizophrenia. 
     
     
         6 . A cannabidiol (CBD) preparation as claimed in any of the preceding claims, wherein the preparation comprises not more than 1.5% (w/w) THC based on total amount of cannabinoid in the preparation. 
     
     
         7 . A cannabidiol (CBD) preparation as claimed in  claim 6 , wherein the preparation comprises about 0.01% to about 0.1% (w/w) THC based on total amount of cannabinoid in the preparation. 
     
     
         8 . A cannabidiol (CBD) preparation as claimed in  claim 6 , wherein the preparation comprises about 0.02% to about 0.05% (w/w) THC based on total amount of cannabinoid in the preparation. 
     
     
         9 . A cannabidiol (CBD) preparation as claimed in any of the preceding claims, wherein the mixture of trans-THC and cis-THC is present at a ratio of about 3.6:1 trans-THC:cis-THC. 
     
     
         10 . A cannabidiol (CBD) preparation as claimed in any of the preceding claims, wherein the mixture of trans-THC and cis-THC is present at a ratio of about 0.8:1 trans-THC:cis-THC. 
     
     
         11 . A cannabidiol (CBD) preparation as claimed in any of the preceding claims, wherein the preparation comprises about 0.1% to about 0.15% (w/w) CBD-C1 based on total amount of cannabinoid in the preparation. 
     
     
         12 . A cannabidiol (CBD) preparation as claimed in any of the preceding claims, wherein the preparation comprises about 0.2% to about 0.8% (w/w) CBDV based on total amount of cannabinoid in the preparation. 
     
     
         13 . A cannabidiol (CBD) preparation as claimed in any of the preceding claims, wherein the preparation comprises about 0.3% to about 0.4% (w/w) CBD-C4 based on total amount of cannabinoid in the preparation. 
     
     
         14 . A cannabidiol (CBD) preparation as claimed in any of the preceding claims, wherein at least a portion of at least one of the cannabinoids present in the CBD preparation is isolated from  Cannabis  plant material. 
     
     
         15 . A cannabidiol (CBD) preparation as claimed in  claim 14 , wherein at least a portion of the CBD present in the CBD preparation is isolated from  Cannabis  plant material. 
     
     
         16 . A cannabidiol (CBD) preparation as claimed in  claim 14 , wherein at least a portion of the THC present in the CBD preparation is isolated from  Cannabis  plant material. 
     
     
         17 . A cannabidiol (CBD) preparation as claimed in  claim 14 , wherein at least a portion of the CBD-C1 present in the CBD preparation is isolated from  Cannabis  plant material. 
     
     
         18 . A cannabidiol (CBD) preparation as claimed in  claim 14 , wherein at least a portion of the CBDV present in the CBD preparation is isolated from  Cannabis  plant material. 
     
     
         19 . A cannabidiol (CBD) preparation as claimed in  claim 14 , wherein at least a portion of the CBD-C4 present in the CBD preparation is isolated from  Cannabis  plant material. 
     
     
         20 . A cannabidiol (CBD) preparation as claimed in any of the preceding claims, wherein substantially all of at least one of the cannabinoids present in the CBD preparation is isolated from  Cannabis  plant material. 
     
     
         21 . A cannabidiol (CBD) preparation as claimed in  claim 20 , wherein substantially all of the CBD present in the CBD preparation is isolated from  Cannabis  plant material. 
     
     
         22 . A cannabidiol (CBD) preparation as claimed in  claim 20 , wherein substantially all of the THC present in the CBD preparation is isolated from  Cannabis  plant material. 
     
     
         23 . A cannabidiol (CBD) preparation as claimed in  claim 20 , wherein substantially all of the CBD-C1 present in the CBD preparation is isolated from  Cannabis  plant material. 
     
     
         24 . A cannabidiol (CBD) preparation as claimed in  claim 20 , wherein substantially all of the CBDV present in the CBD preparation is isolated from  Cannabis  plant material. 
     
     
         25 . A cannabidiol (CBD) preparation as claimed in  claim 20 , wherein substantially all of the CBD-C4 present in the CBD preparation is isolated from  Cannabis  plant material. 
     
     
         26 . A cannabidiol (CBD) preparation as claimed in any of the preceding claims, wherein substantially all of the cannabinoids present in the CBD preparation are isolated from  Cannabis  plant material. 
     
     
         27 . A cannabidiol (CBD) preparation as claimed in any of  claims 14  to  26 , wherein the  Cannabis  plant material is from a  Cannabis sativa, Cannabis indica,  or  Cannabis ruderalis  plant. 
     
     
         28 . A cannabidiol (CBD) preparation as claimed in any of  claims 14  to  26 , wherein the  Cannabis  plant is a high-CBD containing  Cannabis  chemotype. 
     
     
         29 . A cannabidiol (CBD) preparation as claimed in any of  claims 1  to  13 , wherein at least a portion of at least one of the cannabinoids present in the CBD preparation is prepared synthetically. 
     
     
         30 . A cannabidiol (CBD) preparation as claimed in  claim 29 , wherein at least a portion of the CBD present in the CBD preparation is prepared synthetically. 
     
     
         31 . A cannabidiol (CBD) preparation as claimed in  claim 29 , wherein at least a portion of the THC present in the CBD preparation is prepared synthetically. 
     
     
         32 . A cannabidiol (CBD) preparation as claimed in  claim 29 , wherein at least a portion of the CBD-C1 present in the CBD preparation is prepared synthetically. 
     
     
         33 . A cannabidiol (CBD) preparation as claimed in  claim 29 , wherein at least a portion of the CBDV present in the CBD preparation is prepared synthetically. 
     
     
         34 . A cannabidiol (CBD) preparation as claimed in  claim 29 , wherein at least a portion of the CBD-C4 present in the CBD preparation is prepared synthetically. 
     
     
         35 . A cannabidiol (CBD) preparation as claimed in any of  claims 1  to  13 , wherein substantially all of at least one of the cannabinoids present in the CBD preparation is prepared synthetically. 
     
     
         36 . A cannabidiol (CBD) preparation as claimed  claim 35 , wherein substantially all the CBD present in the CBD preparation is prepared synthetically. 
     
     
         37 . A cannabidiol (CBD) preparation as claimed  claim 35 , wherein substantially all the THC present in the CBD preparation is prepared synthetically. 
     
     
         38 . A cannabidiol (CBD) preparation as claimed  claim 35 , wherein substantially all the CBD-C1 present in the CBD preparation is prepared synthetically. 
     
     
         39 . A cannabidiol (CBD) preparation as claimed  claim 35 , wherein substantially all the CBDV present in the CBD preparation is prepared synthetically. 
     
     
         40 . A cannabidiol (CBD) preparation as claimed  claim 35 , wherein substantially all the CBD-C4 present in the CBD preparation is prepared synthetically. 
     
     
         41 . A cannabidiol (CBD) preparation as claimed  claim 35 , wherein substantially all of the cannabinoids present in the CBD preparation are prepared synthetically. 
     
     
         42 . A cannabidiol (CBD) preparation as claimed in  claim 3 , wherein the neurodegenerative disease or disorder is Alzheimer's disease; Parkinson's disease; essential tremor; amyotrophic lateral sclerosis (ALS); Huntington's disease; Friedreich's ataxia; multiple sclerosis; frontotemporal dementia; prion disease; Lewy body dementia; progressive supranuclear palsy; vascular dementia; normal pressure hydrocephalus; traumatic spinal cord injury; HIV dementia; alcohol induced neurotoxicity; Down's syndrome; movement disorders of the central and/or peripheral nervous system; motor neurone diseases (MND); spinal muscular atrophy; or any other related neurological or psychiatric neurodegenerative disease; brain damage; brain injury; brain dysfunction; dysgraphia; dysarthria; apraxia; agnosia; amnesia; dizziness; vertigo; coma; stroke; spinal cord damage; spinal cord injury; spinal cord disorders; central neuropathy; peripheral neuropathy; cranial nerve disorder; trigeminal neuralgia; tumors of the nervous system; infections of the brain or spinal cord; encephalitis; meningitis; prion disease; complex regional pain syndrome; an autonomic nervous system disorder; autonomic neuropathy; dysautonomia; postural orthostatic tachycardia syndrome (POTS); neurocardiogenic syncope (NCS); multiple system atrophy (MSA); hereditary sensory and autonomic neuropathy (HSAN); Holmes-Adie syndrome (HAS); a sleep disorder; narcolepsy; pain; migraine; cluster headache; tension headache; back pain; lower back pain; neck pain; neuropathic pain; cancer pain; allodynia; arthritic pain; inflammatory pain; a neuropsychiatric disorder; attention deficit hyperactivity disorder; autism; Tourette's Syndrome; obsessive compulsive disorder; an autism spectrum disorder; Rett syndrome; Fragile X syndrome; Angelman syndrome; hyperkinetic disorder; mitochondrial disease; dystonia; a cancer; brain cancer; glioma; breast cancer; liver cancer; lung cancer; pancreatic cancer; melanoma; ovarian cancer; gastric cancer; renal cancer; bladder cancer; addiction; nicotine addiction; smoking; alcohol addiction; drug addiction;  Cannabis  use disorder; a mental disorder; post-traumatic stress disorder; anxiety; early psychosis; schizophrenia; a cognitive disorder; stroke; cardiac ischemia; coronary artery disease; thromboembolism; myocardial infarction; ischemic related disease; a gastrointestinal disorder; inflammatory bowel disease; Crohn's disease; ulcerative colitis; nausea; vomiting; emesis; motion sickness; chemotherapy induced nausea; chemotherapy induced nausea vomiting; inflammation; arthritis; rheumatoid arthritis; osteoarthritis; diabetes; high blood pressure; poor insulin control; appetite suppression; anorexia; neonatal hypoxic-ischemic encephalopathy (NHIE); a degenerative skeletal muscle disease; or Duchenne muscular dystrophy (DMD). 
     
     
         43 . A cannabidiol (CBD) preparation as claimed in  claim 4 , wherein the epilepsy is Dravet syndrome, Lennox Gastaut syndrome, febrile infection related epilepsy syndrome (FIRES), Doose syndrome, Sturge Weber syndrome, CDKL5 mutation; Aicardi syndrome; bilateral polymicrogyria; Dup15q; SNAP25; benign rolandic epilepsy; juvenile myoclonic epilepsy; infantile spasm (West syndrome); and Landau-Kleffner syndrome, refractory epilepsy, juvenile spasms, West syndrome, infantile spasms, refractory infantile spasms, tuberous sclerosis complex (TSC); neurogenetic storage disorder, neuronal ceroid lipofuscinoses (NCL), Batten disease, brain abnormality, atonic, idiopathic, absence seizure, partial seizure, simple partial seizure, or complex partial seizure.