THATTHE TOUT UNTUK TAUS ON20170348276A1 MI LOVAU IT ALIANA (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2017/ 0348276 A1 Bryson et al. (43 ) Pub . Date : Dec . 7 , 2017

( 54 ) NASAL CANNABIDIOL COMPOSITIONS A61K 47 /26 (2006 .01 ) A61K 47/ 02 (2006 .01 ) (71 ) Applicant: Acerus Pharmaceutical Corporation , A61K 36 / 185 ( 2006 .01 ) Mississauga (CA ) A61K 31 /05 ( 2006 .01 ) A61K 9 / 06 ( 2006 . 01 ) (72 ) Inventors : Nathan Bryson , Toronto (CA ) ; A61K 47/ 44 ( 2006 . 01) Avinash Chander Sharma, Brampton A61K 9 /00 (2006 . 01) (CA ) (52 ) U . S . CI. CPC ...... A61K 31/ 352 (2013 . 01 ); A61K 47 /44 (21 ) Appl . No. : 15 /613 , 116 (2013 .01 ); A61K 47/ 38 ( 2013 .01 ); A61K 47/ 26 (2013 .01 ) ; A61K 9 / 0043 ( 2013 .01 ) ; A61K ( 22 ) Filed : Jun . 2 , 2017 36 / 185 ( 2013 .01 ) ; A61K 31 /05 ( 2013 . 01 ) ; Related U .S . Application Data A61K 9 /06 (2013 . 01 ) ; A61K 47/ 02 (2013 . 01) (60 ) Provisional application No . 62 /426 ,403 , filed on Nov. (57 ) ABSTRACT 25 , 2016 , provisional application No. 62 /344 ,486 , A nasally administered cannabinoid semi- solid or viscous filed on Jun . 2 , 2016 . liquid composition ; nasal methods for administering the nasal pharmaceutical compositions ; methods for manufac Publication Classification turing the nasal pharmaceutical compositions ; and nasal ( 51 ) Int. Cl. methods of treating diseases treatable by the nasal pharma A61K 31/ 352 ( 2006 .01 ) ceutical compositions formulated with a cannabinoid or A61K 4738 (2006 .01 ) mixtures thereof.

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NASAL CANNABIDIOL COMPOSITIONS rons. The CB , receptor is also expressed in many other organs and tissues including adipocytes, leukocytes , spleen , RELATED APPLICATIONS heart , lung, the gastrointestinal tract ( liver , pancreas , stom [0001 ] This application for U . S patent claims the benefit ach , and the small and large intestine ) , kidney , bladder , of and priority to U . S . Provisional Application Ser . No . reproductive organs, skeletalmuscle , bone, joints , and skin . 62/ 426 , 403 , filed Nov. 25 , 2016 and entitled “ Cannabidiol CB , receptor expression appears to be relatively sparse in Nasal Formulations” , and U .S . Provisional Application Ser. the brainstem region . CB2 receptors are most highly con No . 62 /344 ,486 , filed Jun . 2 , 2016 and entitled “ Cannabidiol centrated in the tissues and cells of the immune system such Nasal Formulations ” . Each of the foregoing U .S . Provisional as the leukocytes and the spleen , but can also be found in Applications and their content are incorporated herein by bone and to a lesser degree in liver and in nerve cells reference in their entireties . including astrocytes , oligodendrocytes and microglia , and even some neuronal sub - populations. FIELD OF THE INVENTION [ 0006 ] Dysregulation of the endocannabinoid system [0002 ] The present invention is directed to cannabinoid appears to be connected to a number of pathological con pharmaceutical compositions for topical application into the ditions , with the changes in the functioning of the system nasal cavity of a subject, nasal methods of use thereof and being either protective or maladaptive. Modulation of the methods of manufacture . In accordance with the present endocannabinoid system either through the targeted inhibi invention , the nasal cannabinoid compositions of the present tion of specific metabolic pathways, and /or directed agonism invention can be used as medical cannabis to treat disorders or antagonism of its receptors may hold therapeutic promise . or disease states or alleviate or mitigate symptoms thereof However , a major and consistent therapeutic challenge con where it is useful to administer cannabinoid , such as schizo fronting the routine use of psychoactive cannabinoids (e . g . phrenia , epilepsy, pain , anxiety, spasticity and migraine . The THC ) in the clinic has remained that of achieving selective nasal cannabinoid compositions of the present invention are targeting of the site of disease and the sparing of other bodily semi- solid or viscous liquid pharmaceutical compositions , regions such as the mood and cognitive centers of the brain . namely, creams, gels and emulsions, preferably thixotropic creams, gels and emulsions, that are formulated with thera [0007 ] Cannabis peutically effective amounts of cannabinoid and are nasally [ 0008 ] Marihuana (Marijuana ) is the common name for administered to treat disorders or disease states or alleviate Cannabis sativa ( i. e . cannabis ), a hemp plant that grows or mitigate symptoms thereof that are treatable with can throughout temperate and tropical climates . The leaves and nabinoid . flowering tops of Cannabis plants contain at least 489 distinct compounds distributed among 18 different chemical BACKGROUND classes , and harbor more than 70 different phytocannabi [ 0003] Endocannabinoid System noids. The principal cannabinoids appear to be delta - 9 [ 0004 ] The endocannabinoid system is an ancient, evolu tetrahydrocannabinol (i .e . 19- THC , THC ) , cannabinol tionarily conserved , and ubiquitous lipid signaling system ( CBN ) , and cannabidiol (CBD ) , although the relative abun found in all vertebrates , and which appears to have impor dance of these and other cannabinoids can vary depending tant regulatory functions throughout the human body . The on a number of factors such as the Cannabis strain , the soil endocannabinoid system has been implicated in a very broad and climate conditions , and the cultivation techniques . Other number of physiological as well as pathophysiological pro cannabinoids found in cannabis include cannabigerol cesses including neural development, immune function , (CBG ) , cannabichromene (CBC ) , tetrahydrocannabivarin inflammation , appetite , metabolism and energy homeostasis , ( THCV ) and many others . In the living plant, these phyto cardiovascular function , digestion , bone development and cannabinoids exist as both inactive monocarboxylic acids bone density , synaptic plasticity and learning , pain , repro ( e . g . THCA ) and as active decarboxylated forms ( e . g . THC ) ; duction , psychiatric disease , psychomotor behaviour, however , heating (at temperatures above 120° C .) promotes memory , wake /sleep cycles , and the regulation of stress and decarboxylation ( e . g . THCA to THC ) and results in biologi emotional state . The system consists of the cannabinoid 1 cal activation . Furthermore , pyrolysis transforms each of the and 2 (CB1 and CB2 ) receptors, the CB receptor ligands hundreds of compounds in cannabis into a number of other N - arachidonoylethanolamine ( i . e . anandamide or AEA ) and compounds, many of which remain to be characterized both 2 -arachidonoylglycerol (2 - AG ) as well as the endocannabi chemically and pharmacologically . Therefore , marihuana noid -synthesizing and degrading enzymes fatty acid amide ( cannabis ) can be considered a very crude drug containing a hydrolase (FAAH ) and monoacylglycerol lipase (MAGL ) . very large number of chemical and pharmacological con [ 0005 ] Most tissues contain a functional endocannabinoid stituents , the properties of which are only slowly being system with the CB , and CB , receptors having distinct understood . patterns of tissue expression . The CB , receptor is one of the [0009 ] Among all the chemical constituents of cannabis , most abundant G - protein coupled receptors in the central and particularly among the cannabinoids, A9 - THC is by far and peripheral nervous systems. It has been detected in the the best studied and is responsible for many, if not most , of cerebral cortex , hippocampus, amygdala , basal ganglia , sub the physical and psychotropic effects of cannabis . Other stantia nigra pars reticulata , internal and external segments cannabinoids ( such as CBD , CBC , CBG ) are present in of the globus pallidus and cerebellum (molecular layer) , and lesser amounts in the plant and have little , if any, psycho at central and peripheral levels of the pain pathways includ tropic properties . It is reasonable to consider about 10 % ing the periaqueductal gray matter , rostral ventrolateral (range 1 - 30 % ) as an average for A9 - THC content in canna medulla , the dorsal primary afferent spinal cord regions bis found on the illicit market . The dried marihuana cur including the peripheral nociceptors , and the spinal interneu rently provided by Health Canada is composed of themature US 2017 /0348276 A1 Dec . 7 , 2017

flowering heads of female plants and contains 12 .5 + 2 % total be caused by inhibition of THC metabolism in the liver , THC (A9 - THC and A9 - THCA ), and less than 0 . 5 % CBD resulting in higher plasma levels of THC . CBG , CBN , and CBC . [0016 ] Cannabidiol [0010 ] Much of the pharmacodynamic information on [0017 ] Cannabidiol ( CBD ) is one of 85 phytocannabinoids cannabis refers to the effects of the major constituent found in the cannabis plant (Iseger 2015 ). While there is a Aº - THC which acts as a partial agonist at both CB receptors , rich history of cannabis use for medicinal purposes , a focus has activity at non - CB receptors and other targets , and is on CBD has not arisen until recently , as it became known as responsible for the psychoactive effects of cannabis through the main non - psychoactive cannabinoids found within Can its actions at the CB , receptor . Aº - THC (an isomer of nabis sativa (Iseger 2015 ) . CBD also has a close relation to ^ ° - THC ) is found in smaller amounts in the plant, but like the other major component of such cannabis plants , 49 - tet A - THC , it is a partial agonist at both CB receptors and rahydrocannabinol ( THC ) . While CBD is typically admin shares relatively similar efficacy and potency with Aº - THC istered orally , the oral bioavailability is believed to be < 5 % in in vitro assays . An in vivo animal study and one clinical due to extensive first pass hepatic metabolism . Cannabidiol study suggest A8 - THC to be a more potent anti - emetic than has the following formula : 1° - THC . [0011 ] Cannabinol (CBN ) is a product of A - THC oxida tion and has 10 % of the activity of A9 - THC . Its effects are Formula I not well studied but it appeared to have some possible immunosuppressive properties in a small number of in vitro studies . Cannabigerol (CBG ) is a partial CB1/2 receptor agonist and a small number of in vitro studies suggest it may have some anti - inflammatory and analgesic properties. It watH OH may also block 5 -HT 14 receptors and act as an a2- adreno ceptor agonist. [0012 ] Cannabidiol ( CBD ) lacks detectable psychoactiv ity and does not appear to bind to either CB , or CB , HO receptors at physiologically meaningful concentrations, but CANNABIDIOL it affects the activity of a significant number of other targets including ion channels , receptors, and enzymes. Results from pre - clinical studies suggest CBD has anti - inflamma [ 0018 ] Medicinal preparations from the flowers and resin tory , analgesic , anti- nausea , anti -emetic , anti -psychotic , of C . sativa have been used in China since ~ 2700 BCE to anti- ischemic , anxiolytic , and anti -epileptiform effects . treat menstrual disorders , gout, rheumatism , malaria , con [ 0013 ] Tetrahydrocannabivarin ( THCV ) acts as a CB , stipation , and absent- mindedness . In medieval times , receptor antagonist and CB2 receptor partial agonist in vitro Islamic physicians used cannabis to treat nausea and vom and in vivo , and pre - clinical studies suggest it may have iting , epilepsy , inflammation , pain , and fever . Western medi anti - epileptiform / anti- convulsant properties . cine used cannabis widely in the 1800s; before aspirin , it [ 00141 p Much of what is known about the beneficial was a common analgesic drug . More recently , cannabis has properties of cannabinoids ( e . g . CBD , THCV ) is derived been used to treat glaucoma, pain , nausea and vomiting , from in vitro and animal studies and few , if any, clinical muscle spasms, insomnia , anxiety, and epilepsy. Evidence studies of these substances exist . However, the results from for efficacy varies substantially for different indications , these in vitro and animal studies point to potential thera with the best data in painful HIV - associated sensory neu peutic indications such as psychosis , epilepsy , anxiety , sleep ropathy, chronic pain , chemotherapy - induced nausea and disturbances , neurodegeneration , cerebral and myocardial vomiting , and spasms in patients with multiple sclerosis . ischemia , inflammation , pain and immune responses, Other medicinal uses for cannabis have been proposed , but emesis , food intake , type- 1 diabetes , liver disease, osteo none has been examined in well -controlled clinical trials . genesis , and cancer. [0019 ] CBD and Schizophrenia [0015 ] In general, there appear to be two types of mecha [0020 ] Schizophrenia is a chronic mental disorder that nisms which could govern possible interactions between typically presents in early adulthood or late adolescence . CBD and A9- THC : those of a pharmacokinetic origin , and Although the incidence of schizophrenia is relatively low those of a pharmacodynamic origin . Despite the limited and ( 10 - 22 per 100 000 ) , its prevalence is relatively high (0 . 3 - 0 . 7 complex nature of the available information , it generally per 100 ) due to the chronic nature of the illness (McGrath et appears that pre -administration of CBD may potentiate some al. , 2008 ). Schizophrenia is characterized by a wide range of of the effects of THC ( through a pharmacokinetic mecha symptoms, including disturbances of thought, perception , nism ) , whereas simultaneous co -administration of CBD and volition , and cognition ( see for reviews Tandon et al. , 2009 ; THC may result in the attenuation of some of the effects of van Os and Kapur , 2009 ). Because of the pervasiveness of THC (through a pharmacodynamic mechanism ) . Further associated impairments and frequently life - long course , it is more , the ratio between the two phytocannabinoids also among the top ten leading causes of disease - related disabil appears to play a role in determining whether the overall ity in the world . Although extensive research has been effect will be of a potentiating or antagonistic nature. CBD performed , its etiology and pathophysiology remain rela mediated attenuation of THC - induced effects may be tively unclear, and available treatments are only modestly observed when the ratio of CBD to THC is at least 8 : 1 effective and cause serious metabolic and neurological ( + 11 . 1 ) , whereas CBD appears to potentiate some of the adverse effects ( Tandon et al. , 2008 ) . effects associated with THC when the CBD to THC ratio is [0021 ] There is current belief that the endocannabinoid around 2 : 1 ( 1 .4 ) . Potentiation of THC effects by CBD may system may have a role in the pathophysiology of schizo US 2017 /0348276 A1 Dec . 7 , 2017 phrenia ( Leweke and Koethe, 2008 ; Bossong and Niesink , and MES - induced seizures , but one study has showed no 2010 ) . For example , epidemiological studies indicate that effect on PTZ - or MES - induced seizures the use of cannabis increases the risk for developing schizo [ 0027 ] CBD combined with THCV has been proposed as phrenia ( Arseneault et al . , 2004 ; Moore et al . , 2007 ) and a means of treating epilepsy . See , e . g . , U .S . patent applica lowers the age of onset of the illness ( Veen et al. , 2004 ). In tion , Ser . No. 13 / 380, 305 , entitled " Use of One or a Com patients , cannabis use has been related to higher relapse bination of Phyto - Cannabinoids in the Treatment of Epi rates, poor treatment outcome, and increased severity of lepsy ” , filed on 9 Jun . 2010 and published as U . S . Patent symptoms (Linszen et al ., 1994 ; D 'Souza et al. , 2005 ; Foti Publication No . 20120165402 on 28 Jun . 2012 , which is et al. , 2010 ) , as well as accelerated loss of grey matter incorporated herein by reference in its entirety . See , also , volume (Rais et al. , 2008 ). In addition , schizophrenia U . S . patent application , Ser. No . 15 / 183 , 947 , entitled " Use patients show increased levels of endogenous cannabinoids of Cannabinoids in the Treatment of Epilepsy ” , filed on 16 in cerebrospinal fluid (Leweke et al. , 1999 ; Giuffrida et al. , Jun . 2016 and published as U .S . Patent Publication No . 2004) . Autoradiography studies with post- mortem brain 2017 / 0007551 on 12 Jan . 2017 ; U . S . patent application , Ser . tissue show enhanced CB1 receptor densities in schizophre No . 14 /881 , 969 , entitled “ Use of Cannabinoids in the Treat nia patients , with significant increases demonstrated in the ment of Epilepsy ” , filed on 13 Oct . 2015 and published as dorsolateral prefrontal cortex (Dean et al. , 2001; Dalton et U . S . Patent Publication No. 2016 /0166515 on 16 Jun . 2016 ; al. , 2011 ; Jenko et al. , 2012 ) , anterior cingulate cortex U . S . patent application , Ser. No . 14 /881 , 954 , entitled " Use ( Zavitsanou et al. , 2004 ) and posterior cingulate cortex of Cannabinoids in the Treatment of Epilepsy ” , filed on 13 (Newell et al. , 2006 ). Neuroimaging studies measuring in Oct. 2015 and published as U . S . Patent Publication No . vivo CB1 receptor availability in schizophrenia patients 2016 /0166514 on 16 Jun . 2016 ; U . S . patent application , Ser. report a widespread increase in levels of CB1 receptors , No . 14 /741 , 829 , entitled “ Use of Cannabinoids in the Treat including the nucleus accumbens, insula , cingulate cortex , ment of Epilepsy ” , filed on 17 Jun . 2015 and published as inferior frontal cortex , parietal cortex , mediotemporal lobe U . S . Patent Publication No. 2015 /0359756 on 17 Dec. 2015 ; and pons ( Wong et al ., 2010 ; Ceccarini et al ., 2013 ). U . S . patent application , Ser . No. 14 / 579, 061, entitled “ Use [0022 ] Cannabidiol (CBD ) , a major non -psychotomimetic of One or a Combination of Phyto -Cannabinoids in the cannabinoid compound extracted from Cannabis sativa , Treatment of Epilepsy ” , filed on 22 Dec . 2014 and published may present potential therapeutic effects in the treatment of as U . S . Patent Publication No . 2015 /0335590on 26 Nov . schizophrenia . CBD is a phytocannabinoid , accounting for 2015 ; U . S . patent application , Ser. No . 14 / 741, 783 , entitled up to 40 % of the plant' s extract . Several pre - clinical studies “ Use of Cannabinoids in the Treatment of Epilepsy ” , filed on have suggested that this drug induces antipsychotic - like 17 Jun . 2015 and published as U . S . Patent Publication No . effects ( for review see Campos et al. , 2012 ) . These CBD 2015 /0359755 on 17 Dec. 2015 ; U . S . patent application , Ser . effects have also been described in open - label clinical stud No . 13 / 977 , 766 , entitled “ Use of the Phytocannabinoid ies ( Zuardi et al. , 1995 , 2006 ) and in a recent controlled , Cannabidiol (Cód ) in Combination with a Standard Anti randomized , double -blind clinical trial ( Leweke et al. , Epileptic Drug ( Saed ) in the Treatment of Epilepsy ” , filed on 2012 ) . The mechanism of these effects is still unknown 3 Jan . 2012 and published as U . S . Patent Publication No . (Campos et al. , 2012 ) . CBD is believed to have anxiolytic 2014 /0155456 on 5 Jun . 2014 ; and U . S . patent application , and antipsychotic properties while being devoid of any Ser. No . 13 / 977 , 766 , entitled “ Use of the Phytocannabinoid psychotropic effects (Zuardi et al. , 2012 ; Schubart et al. , Cannabidiol ( Cbd ) in Combination with a Standard Anti 2014 ) . Although the mode of action of CBD is not fully Epileptic Drug ( Saed ) in the Treatment of Epilepsy ” , filed on understood , there is belief that CBD acts as a cannabinoid 3 Jan . 2012 and published as U . S . Patent Publication No. CB1/ CB2 receptor inverse agonist (Pertwee , 2008 ), and that 2013/ 0296398 on 7 Nov. 2013 ; each of which is incorpo CBD inhibits the uptake and metabolism of anandamide, rated herein by reference in its entirety . thereby enhancing levels of endogenous cannabinoids (Bi [ 0028 ] CBD Compositions sogno et al. , 2001; de Petrocellis et al. , 2011 ; Leweke et al . , [0029 ] CBD can be administered orally , yet the oral bio 2012 ) . availability is believed to be < 5 % due to extensive first pass 0023 ] Besides its antipsychotic properties, CBD is also hepatic metabolism (Karschner et al ., 2011 , Clin . Chem . believed to possibly induce anti - inflammatory and neuro 57 :66 - 75 ) . CBD has been delivered orally in an oil - based protective effects A considerable number of preclinical stud capsule in some human trials , but low water solubility and ies have suggested that CBD attenuates or increases glial absorption from the gastrointestinal system lead to erratic reactivity associated to pathological conditions (Mecha et and variable pharmacokinetics. Bioavailability from oil al. , 2013 ; Perez et al. , 2013 ; Schiavon et al. , 2014 ). based oral delivery has been estimated at 6 % due to signifi [0024 ] CBD and Epilepsy cant first- pass metabolism in the liver. Oral- mucosal / sublin [0025 ] Epilepsy is a chronic neurological disorder present gual delivery through sprays/ lozenges has similar ing a wide spectrum of diseases that affects approximately bioavailability to the oral route but is reported as less 50 million people worldwide ( Sander, 2003 ) . Advances in variability , up to 12 % (Mannila et. Al. 2005 Eur. J . Pharm . the understanding of the body ' s internal ' endocannabinoid ' Sci. , 26 , 71 ) . Smoking typically delivers cannabinoids at an system have led to the suggestion that some cannabis - based average bioavailability rate of 30 % (Huestis , 2007 , Chem . medicines may have the potential to treat this disorder of Biodivers. 4 : 1770 - 1804 ; McGilveray 2005 , Pain Res . hyperexcitability in the central nervous system (Mackie , Manag . 10 Suppl. A : 15A - 22A ) . 2006 , Wingerchuk , 2004 , Alger , 2006 ) . [ 0030 ] Oral -mucosal delivery comes from studies of [0026 ] It is believed that CBD is the only non - A9 - THC Sativex® oral spray, which is a mixture of ~ 1 : 1 THC and phytocannabinoid to have been assessed in preclinical and CBD . Specifically , the studies were of serum CBD levels in clinical studies for anticonvulsant effects . It has been healthy volunteers after a single dose of Sativex containing reported that oral CBD may be effective against both PTZ - a 1 : 1 ratio of CBD and THC . 10 . 8 mg CBD is believed to US 2017 /0348276 A1 Dec . 7 , 2017 produce a Cmax of 2 . 5 to 3 . 0 + 3 . 1 pg / L and Tmax of 2 . 8 1 . 3 cally effective amounts of cannabinoid to treat subjects who hrs. See , e . g ., E . L . Karschner et al .: Plasma Cannabinoid suffer from and /or have been diagnosed with anti -psychosis , Pharmacokinetics following Controlled Oral A9 - Tetrahydro epilepsy , schizophrenia , anxiety, sleep disturbances , neuro cannabinol and Oromucosal Cannabis Extract Administra degeneration , cerebral and myocardial ischemia , inflamma tion . Clin Chem . 2011 January ; 57 ( 1 ) : 66 -75 ; see also Public tion , pain including chronic pain , immune responses , Information Report on Sativex® Oromucosal Spray avail emesis , food intake, such as appetite stimulation in HIV / able at http :/ /www .mhra . gov. uk / home/ groups/ par/ docu AIDS , type -1 diabetes, liver disease , osteogenesis , glau ments /websiteresource / con2033379 . pdf; both of which are coma, cancer , conditions relating to certain types of cancer, incorporated herein in their entireties. Oral- mucosal forms including nausea and vomiting , a movement disorder , are believed to have undesireable side effects including bad depression , a mood disorder or a psychological disorder and taste and dry mouth / sores possibly due to the alcohol Tourette syndrome. content. [ 0040 ] The present invention relates to a system for dis [ 0031 ) Other Cannabinoid Compositions pensing intranasally a precise dosage amount of such nasal [0032 ] Cannabinoids , such as THC and CBD are largely pharmaceutical compositions at an optimal anatomical loca consumed by smoking or vaporizing of dried cannabis plant tion within each nostril of the subject, so that an effective material (leafs , stems, flower ) . The active components of amount of the cannabinoid is deposited within each nostril cannabis can be extracted with alcohols and applied in the at the optimal anatomical location , i . e . , the nasal vestibule , oral cavity . The active components can be extracted into oils to use the nasal pharmaceutical compositions as medical for use in oral administration ( as an additive to food or baked cannabis to effectively treat subjects to treat disease states or goods ) . Pharmaceutical preparations in oils may come in the alleviate or mitigate symptoms thereof treatable with can form of, e . g . , gelatin capsules for oral administration (Mari nabis . nol® ) . [0041 ] The term “ a therapeutically effective amount” [0033 ] Smoked or vaporized cannabis releases a distinct means an amount of cannabinoid containing THC and /or odor that may be unpleasant and clearly identifies the user . CBD sufficient to induce a therapeutic or prophylactic effect Oral administration has variable absorption due to the highly in treating or to alleviating or mitigating symptoms associ lipophilic nature of most cannabinoids, THC and CBD in ated with anti - psychosis , epilepsy, schizophrenia , arthritis , particular. The oral- mucosal spray can cause drying of asthma, antipsychosis, anxiety, sleep disturbances, neurode mucosal tissues and a burning sensation , particularly if there generation , psychosis , depression , glaucoma, neurodegen are any open sores or during upon repeat chronic usage . eration , cerebral and myocardial ischemia , inflammation , [0034 ] Transdermal approaches to CBD delivery have also immune response , emesis , food intake , such as appetite been investigated , but due to CBD ' s high lipophilicity, stimulation in HIV /AIDS , diabetes ), liver disease , osteogen special ethosomal delivery systems are needed to prevent esis, cancer conditions relating to certain types of cancer drug accumulation in the skin , which are believed to be including nausea and vomiting , a movement disorder , a impractical and costly at this time. mood disorder ) , a psychological disorder and Tourette syn [0035 ] CBD can also be obtained for treatment by smok drome. ing CBD -enriched marijuana , however, particularly in the (0042 ] Thus , generally speaking , the present invention case of treatment of psychotic patients this is a discouraged provides for new and improved , substantially less - irritating , route of administration as it may lead to further abuse of cannabinoid semi- solid or viscous liquid nasal pharmaceu THC and further relapses in psychosis . tical compositions formulated with cannabinoid in amounts [0036 ] Thus, there is a need for alternative means of ranging from between about 0 . 1 % to about 25 % or more by administration of the drug that does not require smoking or weight , for nasal administration to deliver a therapeutically oral- mucosal administration ; preferably , the alternative effective amount of cannabinoid to effectively treat disorders forms of administration should be convenient to the user , or disease states treatable with cannabinoid or to alleviate or discreet , increase bioavailbility over known forms of admin mitigate symptoms associated therewith . The present inven istration , and at least as safe as other known methods . tion is also directed to novel methods for pernasal admin [0037 ] Nasal Administration istration of the nasal cannabinoid pharmaceutical composi [0038 ] Methods of nasal administration of hormone -based tions. Generally speaking , the novel methods involve drugs are known , for example , an oil based vehicle for depositing the nasal cannabinoid pharmaceutical composi testosterone is described in U . S . patent application , Ser. No. tions topically into the nasal cavity of each nostril to deliver 13 / 194 , 928 and PCAT Application No . PCT / IB2012 / a therapeutically effective amount of cannabinoid , e . g . , from 001127 , which are incorporated herein by reference in their about 0 .5 mg/ nostril to about 37. 5 mg/ nostril per application entireties . delivered in a dose amount ranging from about 50 ul/ per nostril to about 150 ul/ nostril or from about 0 . 1 % /50 ul per SUMMARY OF THE INVENTION nostril per application to about 25 % / 150 ul per nostril per [0039 ] The present invention overcomes the limitations application , over dose life for providing constant effective and disadvantages associated with the treatment of medical cannabinoid brain and / or blood levels for use in cannabinoid cannabis therapies available today through the discovery of therapy . novel nasal pharmaceutical compositions for topical appli [ 0043 ] In accordance with the novel methods of the pres cation into the nasal cavity of a subject, namely humans. ent invention , the intranasal cannabinoid nasal pharmaceu Particularly , the present invention overcomes the limitations tical compositions are topically deposited on the outer and disadvantages of currently available options for admin external walls (opposite the nasal septum ) inside the naval istration of cannabis through the discovery of novel and cavity of each nostril, preferably at about the middle to about improved nasal pharmaceutical composition , specifically the upper section of the outer external wall ( opposite the designed for intranasal administration to deliver therapeuti nasal septum ) just under the cartilage section of the outer US 2017 /0348276 A1 Dec . 7 , 2017 external wall inside the naval cavity of each nostril. Once cannabinoid to a level of at least about 0 .5 ng/ ml within nasal pharmaceutical composition deposition is complete about 15 minutes immediately after nasal administration of within each nostril of the nose , the outer nose is then gently the nasal cannabinoid pharmaceutical compositions of the and carefully squeezed and / or rubbed by the subject, so that present invention ); ( 2 ) a sustained increase in the plasma the deposited nasal pharmaceutical composition remains in cannabinoid plasma level ( e .g ., an increase in the plasma contact with the mucosal membranes within the nasal cavity cannabinoid level that is maintained in a subject for at least for sustained release of the cannabinoid over dose life . about 8 hours following nasal administration of the nasal Typical cannabinoid nasal pharmaceutical composition dos cannabinoid pharmaceutical compositions of the present age amounts deposited pernasal application is between about invention ) ; and (3 ) a higher maximum level of plasma 50 to about 150 microliters per nostril, and preferably about cannabinoid as compared to the maximum level of plasma 100 microliters per nostril . cannabinoid following topical skin administration . [ 0044 ] In carrying out the methods of the present inven [0049 ] In accordance with the present invention , the nasal tion , approximately between 50 microliters and about 150 cannabinoid pharmaceutical compositions for nasal admin microliters of a nasal cannabinoid pharmaceutical compo istration of the invention may further comprise any phar sition of the present invention is applied to each nostril of a maceutically acceptable vehicle , excipient and /or other subject once , twice , three times , four times , five times , six active ingredient . times , seven times , eight times of more daily , e . g ., for one , 10050 ] In addition , the present invention contemplates two, three , four or more consecutive weeks , or for two, cannabinoid compositions for nasal administration that are three , four, five or six consecutive months or more , or pharmaceutically equivalent, therapeutically equivalent, intermittently such as every other day or once , twice or three bioequivalent and /or interchangeable , regardless of the times weekly, or on demand , to the cannabinoid treatable method selected to demonstrate equivalents or bioequiva disorders . lence , such as pharmacokinetic methodologies , microdialy [ 0045 ] While the present invention has identified what it sis , in vitro and in vivo methods and /or clinical endpoints believes to be preferred concentrations of intranasal can described herein . nabinoid compositions , numbers of applications per day , [ 0051 ] Thus , the present invention contemplates nasal durations of therapy, pernasalmethods and pre - filled , multi cannabinoid pharmaceutical compositions for topical dose applicator systems, it should be understood by those administration into the nasal cavity of a subject that are versed in this art that any effective dosage concentration of bioequivalent, pharmaceutically equivalent and / or therapeu a cannabinoid or mixtures thereof, e . g ., between about 0 . 1 % tically equivalent. Thus, the present invention contemplates : and about 25 % % by weight, in an intranasal composition ( a ) pharmaceutically equivalent nasal cannabinoid pharma that delivers an effective amount of cannabinoid or mixtures ceutical compositions for nasal administration which con thereof and any numbers of applications per day , week , tain the same amount of cannabinoid in the same dosage month or year, as described herein , that can effectively treat form ; (b ) bioequivalent nasal cannabinoid pharmaceutical cannabinoid treatable disordes without causing unwanted compositions for nasal administration which are chemically cannabinoid treatment limiting reactions or related adverse equivalent and which , when administered to the same indi events is contemplated by the present invention . viduals in the same dosage regimens , result in comparable [ 0046 The present invention therefore provides for a new bioavailabilities ; ( c ) therapeutic equivalent nasal cannabi and improved treatment for cannabinoid treatable disorders , noid pharmaceutical compositions for nasal administration wherein nasal administration of a nasal cannabinoid phar which , when administered to the same individuals in the maceutical composition of the present invention provides same dosage regimens , provide essentially the same efficacy for : ( 1 ) rapid delivery of cannabinoid due to the highly and /or toxicity ; and ( d ) interchangeable nasal cannabinoid permeable nasal tissue both systemically and across the pharmaceutical compositions for nasal administration of the blood -brain barrier into the brain ; (2 ) fast onset of action ; ( 3 ) present invention which are pharmaceutically equivalent, avoidance of hepatic first -pass metabolism ; ( 4 ) ease of bioequivalent and therapeutically equivalent. administration ; ( 5 ) avoidance of irritation from transdermal [0052 ] While the intranasalnasal cannabinoid pharmaceu administration and no local irritability from topical patch tical compositions of the present invention are preferred products ; and (6 ) a more pleasant mode of administration , as pharmaceutical preparations when practicing the novel compared to inhalation , topical skin applications and buccal methods of the present invention , it should be understood or sublingual tablets . that the novel topical intranasal cannabinoid pharmaceutical [0047 ] In other words, the present invention provides for compositions and methods of the present invention also a new and improved cannabinoid treatment that ( a ) is easy contemplate the pernasal administration of any suitable and convenient to use either according to a prescribed active ingredient, either alone or in combination with can treatment regimen or on - demand , ( b ) rapidly delivers thera nabinoid , mixtures of cannabinoids or other active ingredi peutically effective amounts of cannabinoid or mixtures ents , in any suitable semi- solid or viscous liquid nasal thereof, ( c ) provides for simple use , ( d ) has reduced side pharmaceutical preparation , such as a cream , a gel or an effects associated with prior inhalation and exogenous sys emulsion . temic cannabinoid therapies , ( e ) avoids local irritability [0053 ] In accordance with the present invention , the vis associated with prior topical cannabinoid compositions, and cosity of the novel nasal pharmaceutical compositions ofthe ( f ) eliminates the need for embarrassing inhalation therapies . present invention is at least about 500 cps and may from [ 0048 ] The present invention , in one embodiment , pro range from between about 500 cps to about 100 ,000 cps vides numerous surprising advantages over currently avail prior to administration given associated thixotropic proper able cannabinoid therapies . For example , the present inven ties with some of the novel nasal pharmaceutical composi tion provides for ( 1 ) a rapid increase in the plasma tions. Preferably , the viscosity may ranges from between cannabinoid plasma level ( e .g ., an increase in the plasma about 1000 cps and about 75, 000 cps, more preferably US 2017 /0348276 A1 Dec . 7 , 2017 between about 2500 cps and about 50 , 000 cps, and most myocardial ischemia , inflammation , immune responses , dia preferably between about 5 ,000 cps and about 25 , 000 cps betes , liver disease , osteogenesis , a movement disorder , a prior to administration or pump actuation , in view of thixo mood disorder, a psychological disorder and Tourette syn tropic properties associated with some of the novel nasal drome or alleviating or reducing pain symptoms associated pharmaceutical compositions . therewith or caused thereby , the cannabinoid utilized to [ 0054 In accordance with the present invention , in certain formulate the novel nasal pharmaceutical compositions of formulations the content of THC in the cannabinoid in the the present invention has a CBD purity of preferably about novel nasal pharmaceutical compositions of the present 50 % , more preferably a BCD purity of about 60 % , more invention when treating indications such as pain , including preferably a BCD purity of about 70 % , more preferably a pain caused by chronic pain , neuropathic pain , cancer and BCD purity of about 80 % , even more preferably a BCD fibromyalgia , glaucoma, emesis , food intake , diabetes , liver purity of about 90 % , about 95 % , and about 98 % , and about disease , osteogenesis and cancer conditions relating to cer 99 % , and even more preferably a CBD purity of about 99 % , tain types of cancer including nausea and vomiting and the and most preferably a CBD purity of about 100 % THC or like or alleviating or reducing the symptoms associated otherwise pure CBD . therewith or caused thereby is at least about 0 . 1 mg of THC . [0058 ] The present invention is also directed to packaged Preferably , the THC content ranges from between about 0 . 1 pharmaceuticals comprising the novel and improved nasal mg and about 37 . 5 mg, more preferably between about 1 mg cannabinoid pharmaceutical compositions for topical to about 20 mg, more preferably the THC content ranges administration into the nasal cavity of a subject . For between about 2 mg and about 10 mg, and most preferably example , the present invention contemplates pre - filled , the THC content ranges between about 0 . 5 mg and about 2 . 5 single or multi- dose applicator systems for pernasal admin mg. istration to strategically and uniquely deposit the nasal [0055 ] As to THC purity when for example treating indi cannabinoid pharmaceutical compositions at the preferred cations such as pain , including pain caused by chronic pain , locations within the nasal cavity for practicing the novel neuropathic pain , cancer and fibromyalgia , glaucoma, methods and teachings of the present invention . emesis , food intake, diabetes , liver disease , osteogenesis and [ 0059 ] Generally , speaking the applicator systems of the cancer conditions relating to certain types of cancer includ present invention are , e. g ., airless fluid , dip -tube fluid dis ing nausea and vomiting and the like or alleviating or pensing systems or pumps or any other system suitable for reducing the symptoms associated therewith or caused practicing the methods of the present invention . The appli thereby, the cannabinoid utilized to formulate the novel cator systems or pumps include , for example , a chamber , nasal pharmaceutical compositions of the present invention pre - filled with multiple doses of an intranasal testosterone has a THC purity of preferably about 90 % , more preferably gel of the present invention , that is closed by an actuator a THC purity of about 95 % , even more preferably a THC nozzle . The actuator nozzle may comprise an outlet channel purity of about 98 % , and even more preferably a THC purity and tip , wherein the actuator nozzle is shaped to conform to of about 99 % , and most preferably a THC purity of about the interior surface of a user ' s nostril for ( a ) consistent 100 % THC , otherwise pure THC . Thus , it should be under delivery of uniform dose amounts of an intranasal testos stood that while the present invention contemplates a THC terone gel of the present invention during pernasal applica purity range when treating pain or alleviating or reducing tion within the nasal cavity , and ( b ) deposition at the pain symptoms caused by pain of from about 50 % to about instructed location within each nostril of a patient as con 100 % , the most preferable THC purity range is between templated by the novel methods and teachings of the present about 90 % and about 100 % and the most preferable THC invention . Preferably , when inserted into a nasal cavity , the purity range is about 100 % THC . pump design is configured to help ensure that the nasal tip [0056 ] In accordance with the present invention , in certain is properly positioned within the nasal cavity so that, when formulations the content of CBD in the cannabinoid in the the gel is dispensed , the gel is dispensed within the appro novel nasal pharmaceutical compositions of the present priate location within the nasal cavity . See Steps 3 and 8 in invention , when treating indications such as epilepsy , FIG . 7A . See also FIG . 7B . Additionally , the nozzles to the schizophrenia , antipsychosis , anxiety , sleep disturbances , pumps are preferably designed to dispense the gels from the neurodegeneration , psychosis , depression , glaucoma, neu side in a swirl direction , i. e ., the tips of the nozzles are rodegeneration , cerebral and myocardial ischemia , inflam designed to dispense in a side distribution direction , as mation , immune responses , diabetes , liver disease , osteo opposed to a direct distribution direction , onto the nasal genesis , a movement disorder , a mood disorder, a mucosa, as shown in steps 4 and 9 of FIG . 7A . See also FIG . psychological disorder and Tourette syndrome or alleviating 7B . It is believed that the swirl action allows for better gel or reducing pain symptoms associated therewith or caused adhesion and side distribution from the nozzle tip avoids the thereby , is at least about 0 . 1 mg of CBD . Preferably , the dispensed gel from splashing back onto the tip . Finally, it is CBD content ranges from between about 0 .1 mg to about preferred to design the nozzle and tip to allow for any 37 . 5 mg, more preferably between about 1 mg and about 35 residual gel on the nozzle / tip to be wiped off as the tip is mg, more preferably the CBD content ranges between about removed from the nasal cavity . See, e . g ., FIGS. 7A and 7B . 2 mg to about 30 mg, and most preferably the CBD content 10060 ] Examples of pre - filled , multi - dose applicator sys ranges between about 5 mg and about 25 mg. Dosage tems include , e . g ., ( a ) the COMOD system available from amount particularly contemplated by the present invention Ursatec, Verpackung -GmbH , Schillerstr . 4 , 66606 St. Wen include 20 mg and 37 .5 mg of CBD . del, Germany, ( b ) the Albion or Digital airless applicator [0057 ] As to CBD purity when , for example , when treat systemsavailable from Airlessystems, RD 149 27380 Char ing indications such as epilepsy, schizophrenia , antipsycho leval, France or 250 North Route 303 Congers, N . Y . 10950 , sis , anxiety , sleep disturbances , neurodegeneration , psycho as shown in FIGS. 1 - 6 , ( c ) the nasal applicators from sis , depression , glaucoma, neurodegeneration , cerebral and Neopac, The Tube, Hoffmann Neopac AG , Burgdorfstrasse US 2017 /0348276 A1 Dec . 7 , 2017

22 , Postfach , 3672 Oberdiessbach , Switzerland , or (d ) the [0069 ] In certain embodiments , the cannabinoid therapeu syringes for nasal delivery of the cannabinoid pharmaceu tic active is derived synthetically . tical compositions . 10070 ] In certain embodiments, the cannabinoid therapeu [0061 ] Preferably , the intranasal cannabinoid pharmaceu tic active or mixture of actives is obtained by extraction from tical compositions are filled into a preservative - free , airless a natural source such as a pure strain or blend of strains of multi - dose device able to accurately deliver doses of the cannabis sativa . above cannabinoid pharmaceutical composition , also at [0071 ] According to certain embodiments, the a wetting higher viscosities . agent or mixture of wetting agents and / or a pharmaceutically [ 0062 ] According to one aspect of the invention is pro acceptable surfactant or mixture of surfactants is selected vided a pharmaceutical composition of cannabinoid for from the group consisting of: a polysorbate , a polyoxyeth nasal administration . ylene hydrogenated vegetable oil , a polyoxyethylene veg [0063 ] According to certain embodiments, the composi etable oil ; a polyoxyethylene sorbitan fatty acid ester ; a tion comprises: ( 1 ) a cannabinoid therapeutic active ; ( 2 ) an polyoxyethylene - polyoxypropylene block copolymer ; a oily vehicle ; and ( 3 ) a wetting agent or mixture of wetting polyglycerol fatty acid ester; a polyoxyethylene glyceride ; a agents and / or a pharmaceutically acceptable surfactant or polyoxyethylene sterol, or a derivative or analogue thereof; a reaction mixture ofpolyols and at least one member of the mixture of surfactants . group consisting of fatty acids, glycerides, vegetable oils , [0064 ] According to certain embodiments , the oily vehicle hydrogenated vegetable oils , fractionated oils and sterols; a is one or more pharmaceutically acceptable Generally Rec tocopheryl polyethylene glycol succinate ; a sugar ester; a ognized as Safe lipid . sugar ether ; a sucroglyceride ; an alkylglucoside; an alkyl [0065 ] According to certain embodiments, the oily vehicle maltoside ; an alkylthioglucosides; a lauryl macrogolglycer is selected from the group consisting of: a pharmaceutically ide ; a polyoxyethylene alkyl ether; a polyoxyethylene alky acceptable vegetable oil, a monoglyceride , a diglyceride , Iphenol; a polyethylene glycol fatty acid ester ; a Sucrose acetate isobutyrate (SAIB ), a synthetic triglyceride, polyethylene glycol glycerol fatty acid ester ; a polyoxyeth and a combination thereof. ylene sorbitan fatty acid ester ; a polyoxyethylene - polyoxy [ 0066 ] According to certain embodiments , the pharmaceu propylene block copolymer such as poloxamer - 108 , 188 , tically acceptable vegetable oil is selected from the group 217 , 238 , 288 , 338, 407 , 124 , 182 , 183 , 212 , 331, or 335 , or consisting of: Almond Oil Sweet ( Prunus dulcis ), Almond combinations thereof; an ionic hydrophilic surfactant such Oil Virgin (Prunus amygdalus ), Aloe Vera Oil (Aloe bar as sodium dodecyl sulphate or docusate sodium ; a bile acid ; badensis ) , Apricot Kernel Oil ( Prunus armeniaca ) , Argan a cholic acid ; a deoxycholic acid ; a chenodeoxycholic acid ; Oil ( Argania spinosa ) , Avocada Oil ( Persea americana ), salts thereof, and mixtures thereof . Apricot Oil (Prunus armeniaca ) , Amla Oil ( Emblica offici [ 0072 ] According to certain embodiments , the composi nalis ), Borage Oil (Borago officinalis ) , Black Seed Oil tion further comprises a rheology modifying agent, for (Nigella sativa ) , Carrot Oil (Daucus carota ) , Coconut Oil example , colloidal silica , silicates , alumina , a high molecu (Cocus nucifera ) , Corn Oil, Cucumber Oil (Cucumis sativa ), lar weight polymer or a solid / waxy substance , bee wax , Chaulmogra Oil (Hydnocarpus wightianus) , Emu Oil ( Dro alumina, silica , silicates and high melting waxes, and /or maius novae - Hollandiae ) , Evening Primrose Oil (Oeno cetostearyl alcohol. thera biennis ), Flaxseed Oil (Linum usitatissimum ) , Grape [0073 ] According to certain embodiments , the composi seed Oil ( Vitus vinifera ) , Hazel Nut Oil ( Avekkana ) , Jojoba tion further comprises a mineral , an osmotic complement, a Oil Refined (Simmondsia chinensis ), Moringa Oil (Moringa thickener, and / or a hydrophilic polymer. oliefera ) , Marula Oils ( Sclerocarya birrea ), Wheatgerm Oil , 10074 ) According to certain embodiments , the hydrophilic Triticum vulgare , Macadamia Oil, (Macadamia ternifolia ), polymer is selected from the group consisting of: HPMC , Musk Melon Oil ( Cuvumis melon ), Musk Oil ( Abelmoschus HPC , Sodium CMC , Sodium CMC and MCC , natural gums moschatus ) , Mustered Oil , Neem Oil ( Azadirachta indica ) , like Xanthan gum , Guar gum , gum acacia , gum tragacanth , Olive Oil (Olea europaea ), Peach Kernel Oil ( Prunus per starches like maize starch , potato starch , and pregelatinized sica ), Peanut Oil (Arachis hypogeae ), Pomegranate Oil , starch . Punica granatum , Psoralea Oil ( Psoralea corylifolia ), Prim [0075 ] According to certain embodiments , the surfactant rose Oil ( Oenothera bienni) , Papaya Seed Oil ( Carica is selected from the group consisting of: Glycol Distearate , papaya ), Rosehip Seed Oil ( Rosa rubiginosa ) , Safflower Sorbitan Trioleate , Propylene Glycol Isostearate, Glycol Oil, Seasame Seed (Refined ) ( Sesamum indicum ), Sea Buck Stearate, Sorbitan Sesquioleate , Lecithin , Sorbitan Oleate , thorn Oil (Hippophae rhamnoides) , Soya Bean Oil ( Soja Sorbitan Monostearate NF, Sorbitan Stearate , Sorbitan hispida ) , Sunflower Oil ( Helianthus annus ), Sweet Almond Isostearate , Steareth - 2 , Oleth - 2 , Glyceryl Laurate , Ceteth - 2 , Oil ( Prunus amygdalus Var. Dulcus) , Sweet Cherry Kernel PEG - 30 Dipolyhydroxystearate , Glyceryl Stearate SE , Sor Oil ( Prunus avium ), Walnut Oil (Juglans regia ), Water bitan Stearate ( and ) Sucrose Cocoate, PEG - 4 Dilaurate , Melon Oil (Citrullus vulgaris ) . Methyl Glucose Sesquistearate , Lecithin HLB ( variable ) 10067 ] According to certain preferred embodiments, the PEG - 8 Dioleate , Sorbitan Laurate, Sorbitan Laurate , PEG oily vehicle comprises Castor Oil and / or sesame oil and / or 40 Sorbitan Peroleate , a polyoxyl glyceride, such as Labra SAIB . fil® M1944CS , Laureth - 4 , PEG - 7 Glyceryl Cocoate , PEG [ 0068 ] According to certain embodiments , the cannabi 20 Almond Glycerides, PEG - 25 Hydrogenated Castor Oil. noid therapeutic active, or mixture of actives, is selected Stearamide MEA , Glyceryl Stearate ( and ) PEG - 100 Stear from one or more of the group consisting of: tetrahydrocan ate , Polysorbate 85 , PEG - 7 Olivate , Cetearyl Glucoside, nabinol ( THC ) , cannabidiol (CBD ) or a mixture thereof, a Stearamide MEA , PEG - 8 Oleate , Polyglyceryl - 3 Methyg prodrug of THC or CBD , a derivative of THC or CBD , and lucose Distearate , Oleth - 10 , Oleth - 10 /Polyoxyl 10 Oleyl an analog of THC or CBD . Ether NF, Ceteth - 10 , PEG - 8 Laurate , Cocamide MEA , Poly US 2017 /0348276 A1 Dec . 7 , 2017 sorbate 60 NF, Polysorbate 60 , Polysorbate 80 , Isosteareth - oil is about 73. 4 % w /w , the Oleoyl Polyoxylglycerides are 20 , PEG -60 Almond Glycerides , PEG - 20 Methyl Glucose about 3 . 3 % w / w , and the Silicon Dioxide is about 3 . 3 % w / w Sesquistearate , Ceteareth - 20 , Oleth -20 , Steareth - 20 , of the composition . Steareth - 20 , Steareth - 21 , Steareth -21 , Ceteth - 20 , and [0086 ] In certain embodiments , the cannabinoid therapeu Steareth - 100 . tic active is cannabinoid therapeutic active or mixture of [0076 ] According to certain preferred embodiments , the actives , the oily vehicle is sesame oil and olive oil, the cannabinoid therapeutic active is CBD , the oily vehicle is wetting agent is Oleoyl Polyoxylglycerides , and the rehol Castor Oil, and the wetting agent is Oleoyl Polyoxylglyc ogy modifying agent is Hydroxypropylcellulose . erides. 10087 ) In certain embodiments , the cannabinoid therapeu tic active or mixture of actives is about 12 % w / w , the sesame [0077 ] According to certain preferred embodiments , the oil is about 20 % w / w , the olive oil is about 20 % w / w , the cannabinoid therapeutic active is THC , the oily vehicle is Oleoyl Polyoxylglycerides are about 4 % w / w , the Hydroxy Castor Oil, and the wetting agent is Oleoyl Polyoxylglyc propylcellulose is about 4 % w / w , further comprising about erides . 40 % w /w water . [0078 ] According to certain preferred embodiments , the [0088 ] In certain embodiments , the composition com cannabinoid therapeutic active is a mixture comprising THC prises cannabinoid therapeutic active or mixture of actives and CBD , the oily vehicle is Castor Oil , and the wetting and SAIB . For example , the composition may consist essen agent is Oleoyl Polyoxylglycerides. tially of cannabinoid therapeutic active or mixture of actives [0079 ] According to certain embodiments , the cannabi and SAIB . noid therapeutic active is a mixture comprising THC and [0089 ] In certain embodiments , the composition com CBD , wherein the ratio of THC :CBD is between about prises about 10 % w / w cannabinoid therapeutic active or 0 .1 : 99. 9 and about 99 .9 : 0 .1 , preferably between 95 :5 and mixture of actives . about 75 : 25 ( THC rich ) , between 60 :40 and 40 :60 ( approx . 10090 ] In certain embodiments , the cannabinoid therapeu 1 : 1 ) and between 1 : 99 and 25 :75 (CBD - rich ) . Thus , when tic active is cannabinoid therapeutic active or mixture of using CBD - rich in combination with THC , the ratio con actives , the oily vehicle is SAIB and medium chain triglyc templated in accordance with the present invention is 0 - 100 : erides, and the wetting agent is Polyoxyl 35 Hydrogenated 25 - 75 . The use of pure synthetic CBD or THC as contem Castor Oil . plated by the present invention includes greater than about [0091 ] In certain embodiments , the cannabinoid therapeu 95 % , greater than about 98 % or even 100 % . Thus , the tic active or mixture of actives is about 10 % w / w , the SAIB present invention contemplates use of both , herbal extract is about 50 % w / w , the medium chain triglycerides are about mixtures (with their corresponding terpenes ) or synthetically 35 % w / w , and the Polyoxyl 35 Hydrogenated Castor Oil is pure compounds. Cannababinoid products are regulated by about 5 % w / w . Medical Marijuana legislation , while pure synthetics follow [0092 ] In certain embodiments , the cannabinoid therapeu the traditional FDA -Health Canada clinical development tic active is cannabinoid therapeutic active or mixture of pathway . actives, the oily vehicle is SAIB and medium chain triglyc [0080 ] According to certain embodiments , the cannabi erides, and the wetting agent is Oleoyl Polyoxylglycerides . noid therapeutic active or mixture of actives is about 10 % [0093 ] In certain embodiments , the cannabinoid therapeu w / w , the Castor Oil is about 82 % w / w , and the Oleoyl tic active or mixture of actives is about 20 % w / w , the SAIB Polyoxylglycerides are about 4 % w / w of the composition . In is about 44. 5 % w / w , the medium chain triglycerides are certain preferred embodiments , the composition further about 31 % w /w , and the Oleoyl Polyoxylglycerides are comprises Silicon Dioxide. about 4 . 5 % w / w . [0081 ] In certain embodiments , the cannabinoid therapeu [0094 ] According to a further aspect of the invention is tic active or mixture of actives is about 10 % w / w , the provided a composition capable of achieving a serum can Sesame Oil is about 86 % w / w , the Oleoyl Polyoxylglycer nabinoid therapeutic active or mixture of actives concentra ides are about 2 % w / w of the composition , and the Silicon tion of from at least about 0 . 5 ng /ml before about 8 hours Dioxide is about 2 % w / w of the composition . after a single administration , such as from at least about 0 . 5 [0082 ] In certain embodiments , the cannabinoid therapeu ng /ml to about 40 ng /ml within 8 h after a single adminis tic active or mixture of actives is about 20 % w / w , the Castor tration in one or both nasal vestibules of the nostrils of a Oil is about 73. 4 % w / w , the Oleoyl Polyoxylglycerides are fasted subject. about 3 . 3 % w / w , and the Silicon Dioxide is about 3 . 3 % w / w [0095 ] According to a further aspect of the invention is of the composition . provided a composition capable of achieving a serum can nabinoid therapeutic active or mixture of actives concentra [0083 ] In certain embodiments , the cannabinoid therapeu tion of > 40 ng /ml within 8 h after a single administration in tic active is cannabinoid therapeutic active or mixture of one or both nasal vetsibules of the nostrils of a fasted subject actives, the oily vehicle is sesame oil , the wetting agent is a fasted subject . Oleoyl Polyoxylglycerides, and the rheology modifying [0096 ] According to a further aspect of the invention is agent is Silicon Dioxide . provided a composition capable of achieving a serum can [0084 ] In certain embodiments , the cannabinoid therapeu nabinoid therapeutic active or mixture of actives concentra tic active or mixture of actives is about 10 % w / w , the Castor tion of > 30 ng /ml within 8 h after a single administration in oil is about 86 % w /w , the Oleoyl Polyoxylglycerides are one or both nasal vetsibules of the nostrils of a fasted subject about 2 % w /w , and the Silicon Dioxide is about 2 % w / w of a fasted subject. the composition . [ 0097 ] According to a further aspect of the invention is [0085 ] In certain embodiments , the cannabinoid therapeu provided a composition capable of achieving a serum can tic active or mixture of actives is about 20 % w /w , the sesame nabinoid therapeutic active or mixture of actives concentra US 2017 /0348276 A1 Dec . 7 , 2017 tion of > 25 ng/ ml within 8 h after a single administration in therapeutic active or mixture of actives comprised in a gel one or both nasal vetsibules of the nostrils of a fasted subject composition to the nasal vestibule of patients to patients in a fasted subject. need thereof . 10098 ) According to a further aspect of the invention is [0109 ] According to a further aspect of the present inven provided a composition capable of achieving a serum can tion is the use of an airless metered - dose dispenser to nabinoid therapeutic active or mixture of actives concentra administer from about 0 . 1 to about 75 mg of cannabinoid tion of > 20 ng/ ml within 8 h after a single administration in therapeutic active or mixture of actives dissolved in a gel one or both nasal vetsibules of the nostrils of a fasted subject composition , as herein described to the nasal vestibule of a fasted subject. patients to patients in need thereof. [0099 ] According to a further aspect of the invention is [0110 ] According to a further aspect of the present inven provided a composition capable of achieving a serum can tion is provided the use of an airless metered -dose dispenser nabinoid therapeutic active or mixture of actives concentra to administer a dose per nostril in an amount of between tion of > 10 ng/ ml within 8 h after a single administration in about 50 and about 150 uL of a cannabinoid therapeutic one or both nasal vetsibules of the nostrils of a fasted subject active or mixture of actives gel composition , wherein each a fasted subject nasal dose contains from between about 0 . 1 and about 37 . 5 mg of cannabinoid therapeutic active or mixture of actives , [ 0100 ) According to a further aspect of the invention is as herein described to the nasal vestibule of patients to provided a composition capable of achieving a serum can patients in need thereof. In other words, about 0 . 1 % for a 50 nabinoid therapeutic active or mixture of actives concentra ul dose = 0 . 5 mg ( lowest dose volume) to about 25 % for a 150 tion of > 1 ng /ml within 8 h after a single administration in uL dose = 37 . 5 mg (highest dose volume) , when applied the one or both nasal vetsibules or nostrils of a fasted subject a dose is applied to one nostril as a single dose . However, fasted subject. when the dose is applied to each nostril , the total dose [0101 ] According to a further aspect of the invention is amount administered doubles and will range from about 0 .2 provided a composition capable of achieving a serum can mg to about 75 mg (or from about 0 . 1 mg /per each nostril nabinoid therapeutic active or mixture of actives concentra to about 37 . 5 mg/ per each nostril) . tion of at least about 0 .5ng /ml within 8 h after a single nasal [0111 ] According to a further aspect of the present inven administration in one or both nasal vetsibules or nostrils of tion is provided a nasal administration of a cannabinoid a fasted subject a fasted subject. therapeutic active or mixture of actives composition as [0102 ] According to a further aspect of the invention is herein described for the treatment of antipsychosis, epilepsy, provided a composition capable of achieving a serum can anxiety , sleep disturbances , neurodegeneration , psychosis , nabinoid therapeutic active or mixture of actives concentra depression , glaucoma, neurodegeneration , cerebral and tion of > 0 . 1ng /ml within 8 h after nasal administration in one myocardial ischemia , inflammation , pain including chronic or both nasal vetsibules or nostrils of a fasted subject a fasted pain , immune responses , emesis , food intake , such as appe subject. tite stimulation in HIV / AIDS , type - 1 diabetes , liver disease , [0103 ] According to a further aspect of the present inven osteogenesis , cancer, conditions relating to certain types of tion is provided the use of a dispenser to administer can cancer including nausea and vomiting , a movement disorder , nabinoid therapeutic active or mixture of actives composi a mood disorder, a psychological disorder and Tourette tions as herein described to the nasal vestibule or nostril of syndrome. patients in need thereof. [0112 ] According to a further aspect of the present inven [0104 ] According to a further aspect of the present inven tion is provided a nasal administration of a cannabinoid tion is provided the use of an airless dispenser to administer therapeutic active or mixture of actives composition as cannabinoid therapeutic active or mixture of actives com herein described for the treatment of schizophrenia , pain , positions as herein described to the nasal vestibule of including chronic pain , migraine , spasticity , epilepsy or patients to patients in need thereof. anxiety . [0113 ] According to a further aspect of the present inven [0105 ] According to a further embodiment of the present tion are provided nasal semi-solid or viscous liquid phar invention is provided the use of an airless metered - dose maceutical compositions, namely , creams, gels and emul dispenser to administer cannabinoid therapeutic active or sions , preferably thixotropic creams, gels and emulsions, of mixture of actives compositions as herein described to the which each is formulated with a therapeutically effective nasal vestibule of patients to patients in need thereof. amount of cannabinoid for topical administration into one or [0106 ] According to a further aspect of the present inven more nasal vestibules or nostrils of a subject to treat a tion is provided a use of an airless metered - dose dispenser subject for a disease state, or to alleviate or mitigate symp to administer cannabinoid therapeutic active or mixture of toms thereof, that is treatable with cannabinoid . actives compositions as herein described to the nasal vesti 101141. In certain embodiments contemplated by the pres bule of patients to patients in need thereof. ent invention , the nasal cannabinoid composition is a nasal [0107 ] According to a further aspect of the present inven gel composition , preferably a thixotropic nasal gel compo tion is provided the use of an airless metered -dose dispenser sition , formulated with a therapeutically effective amount of to administer a dose per nostril in an amount of between cannabinoid for topical application into one or both nasal about 50 and about 150 uL of a cannabinoid therapeutic vestibules of the nostrils of a subject. active or mixture of actives gel composition as herein [0115 ] It should be understood by those versed in this art described to a nasal vestibule of a patient in need thereof . that the amount of cannabinoid , including mixtures thereof , [0108 ] According to a further aspect of the present inven in a nasal cannabinoid pharmaceutical composition of the tion is provided the use of an airless metered - dose dispenser present invention that will be therapeutically effective in a to administer from about 0 . 1 to about 75 mg of cannabinoid specific situation will depend upon such things as the type of US 2017 /0348276 A1 Dec . 7 , 2017 cannabinoid utilized , the dosing regimen selected , the appli - " and /or ” refers to and encompasses any and all possible cation site , the particular composition , dose longevity and combinations of one or more of the listed items, as well as the cannabinoid condition being treated . As such , it is the lack of combinations when interpreted in the alternative generally not practical to identify specific administration (“ or” ) . amounts herein ; however , it is believed that those skilled in [0128 ] As used herein , " at least one” is intended to mean the art will be able to determine appropriate therapeutically " one or more ” of the listed elements . effective amounts based on the guidance provided herein , [0129 ] Singular word forms are intended to include plural information available in the art pertaining to cannabinoid word forms and are likewise used herein interchangeably therapy , and routine testing . where appropriate and fall within each meaning , unless [0116 ] It should be further understood that the above expressly stated otherwise . summary of the present invention is not intended to describe [0130 ] Except where noted otherwise , capitalized and each disclosed embodiment or every implementation of the non - capitalized forms of all terms fall within each meaning . present invention . The description further exemplifies illus [0131 ] Unless otherwise indicated , it is to be understood trative embodiments. In several places throughout the speci that all numbers expressing quantities , ratios, and numerical fication , guidance is provided through examples , which properties of ingredients , reaction conditions , and so forth examples can be used in various combinations . In each used in the specification and claims are contemplated to be instance , the examples serve only as representative groups able to be modified in all instances by the term “ about” . and should not be interpreted as exclusive examples . 10132 ] All parts, percentages , ratios, etc . herein are by weight unless indicated otherwise . BRIEF DESCRIPTION OF THE DRAWINGS [0133 ] As used herein , “ bioequivalence ” or “ bioequiva [ 0117 ] The foregoing and other objects , advantages and lent” , refers to nasally administered nasal cannabinoid phar features of the present invention , and the manner in which maceutical compositions or drug products which are phar the same are accomplished , will become more readily appar maceutically equivalent and their bioavailabilities ( rate and ent upon consideration of the following detailed description extent of absorption ) after administration in the same molar of the invention taken in conjunction with the accompanying dosage or amount are similar to such a degree that their figures and examples , which illustrate embodiments , therapeutic effects , as to safety and efficacy, are essentially wherein : the same. In other words , bioequivalence or bioequivalent [ 0118 ] FIG . 1 is a side view of a first embodiment of a means the absence of a significant difference in the rate and distributor pump of the invention ; extent to which cannabinoid becomes available from such [0119 ] FIG . 2 is a cross - sectional side view of the dis compositions at the site of cannabinoid action when admin tributor pump of the first embodiment of the invention ; istered at the samemolar dose under similar conditions, e . g . , [0120 ] FIG . 3 is a side view of a second embodiment of a the rate at which cannabinoid can leave such a composition distributor pump of the invention ; and the rate at which cannabinoid can be absorbed and / or [0121 ] FIG . 4 is a cross- sectional side view of the dis become available at the site of action to affect the disorder. tributor pump of the second embodiment of the invention ; In other words , there is a high degree of similarity in the 0122] FIG . 5 is a side view of a second embodiment of a bioavailabilities of two cannabinoid gel composition phar distributor pump of the invention concerning an airless maceutical products for nasal administration ( of the same bottle assembly of the invention ; galenic form ) from the same molar dose , that are unlikely to [0123 ] FIG . 6 is a side view of a second embodiment of a produce clinically relevant differences in therapeutic effects , distributor pump of the invention concerning digital actuator or adverse reactions , or both . The terms “ bioequivalence ” , as and rounded cap ; well as " pharmaceutical equivalence ” and “ therapeutic [0124 ] FIGS . 7A and 7B illustrate use of a multiple dose equivalence” are also used herein as defined and / or used by dispenser in accordance with the present invention ; ( a ) the FDA , ( b ) the Code of Federal Regulations (“ C . F . R . " ) , 10125 ) FIG . 8 depicts a pharmacokinetic analysis of Com Title 21, ( c ) Health Canada , ( d ) European Medicines Agency position Examples 9A ( 20 % CBD gel, N = 2 , Subj # 1 and # 2 ) (EMEA ) , and / or ( e ) the Japanese Ministry of Health and and 9B ( 10 % CBD gel, N = 2 Subj # 3 and # 4 ) after admin Welfare . Thus, it should be understood that the present istration to healthy volunteer subjects . (See Example 22 . invention contemplates cannabinoid nasal compositions for nasal administration or drug products thatmay be bioequiva DESCRIPTION OF THE INVENTION lent to other cannabinoid nasal compositions for nasal administration or drug products of the present invention . By [0126 ] By way of illustrating and providing a more com way of example , a first cannabinoid nasal composition for plete appreciation of the present invention and many of the nasal administration or drug product is bioequivalent to a attendant advantages thereof, the following detailed descrip second cannabinoid nasal composition for nasal administra tion and examples are given concerning the novel lower tion or drug product , in accordance with the present inven dosage strength intranasalnasal cannabinoid pharmaceutical tion , when the measurement of at least one pharmacokinetic compositions, application devices and methods of the pres parameter ( s ) , such as a Cmax , Tmax , AUC , etc . , of the first ent invention . cannabinoid nasal composition for nasal administration or drug product varies by no more than about # 25 % , when Definitions compared to the measurement of the same pharmacokinetic 0127 ]. As used in the description of the invention and the parameter for the second cannabinoid nasal composition for appended claims, the singular forms “ a ” , “ an ” and “ the” are nasal administration or drug product of the present inven used interchangeably and intended to include the plural tion . forms as well and fall within each meaning , unless the [0134 ] As used herein , “ bioavailability ” or “ bioavailable" , context clearly indicates otherwise . Also , as used herein , means generally the rate and extent of absorption of can US 2017 /0348276 A1 Dec . 7 , 2017 nabinoid into the systemic circulation and , more specifically , including, but not limited to , Caucasian , African - American , the rate or measurements intended to reflect the rate and African , Asian , Hispanic , Indian , etc . Subject as used herein extent to which cannabinoid becomes available at the site of may also include an animal, particularly a mammal such as action or is absorbed from a drug product and becomes a canine , feline , bovine , caprine , equine , ovine , porcine , available at the site of action . In other words , and by way of rodent ( e . g . , a rat and mouse ) , a lagomorph , a primate example, the extent and rate of cannabinoid absorption from ( including non -human primate ), etc . , that may be treated in a nasal pharmaceutical composition for nasal administration accordance with the methods of the present invention or of the present invention as reflected by a time- concentration screened for veterinary medicine or pharmaceutical drug curve of cannabinoid in systemic circulation . development purposes . A subject according to some embodi [0135 ] As used herein , the terms “ pharmaceutical equiva ments of the present invention include a patient, human or lence " or " pharmaceutically equivalent” , refer to cannabi otherwise , in need of therapeutic treatment for a disorder noid nasal compositions for nasal administration or drug treatable with cannabinoid . products of the present invention that contain the same 10141 ] “ Treatment, ” as used herein , includes any drug , amount of cannabinoid , in the same dosage forms, but not drug product, method , procedure, lifestyle change , or other necessarily containing the same inactive ingredients , for the adjustment introduced in attempt to effect a change in a same route of administration and meeting the same or particular aspect of a subject ' s health (i . e ., directed to a comparable compendial or other applicable standards of particular disease , disorder , or condition ) or alleviate or identity, strength , quality , and purity , including potency and , mitigate symptoms of a particular diseasw , disorder or where applicable , content uniformity and /or stability. Thus , condition . it should be understood that the present invention contem [0142 ] “ Drug ” or “ drug substance, " as used herein , refers plates cannabinoid nasal compositions for nasal administra to an active ingredient, such as a chemical entity or biologi tion or drug products that may be pharmaceutically equiva cal entity , or combinations of chemical entities and /or bio lent to other cannabinoid nasal compositions for nasal logical entities , suitable to be administered to a subject to ( a ) administration or drug products used in accordance with the treat anorgasmia and /or (b ) treat HSDD . In accordance with present invention . the present invention , the drug or drug substance is cannabi [0136 ] As used herein , “ therapeutic equivalence ” or noid , such as therapeutic CBD or THC or mixtures thereof . “ therapeutically equivalent" , means those cannabinoid nasal [0143 ] The term “ drug product, ” as used herein , is syn compositions for nasal administration or drug products onymous with the terms “ medicine, ” “ medicament, ” “ thera which ( a ) will produce the same clinical effect and safety peutic intervention , " " pharmaceutical product or " pharma profile when utilizing cannabinoid drug product to treat a ceutical composition .” Most preferably, a drug product is cannabinoid treatable disorder in accordance with the pres - approved by a government agency for use in accordance ent invention and ( b ) are pharmaceutical equivalents , e . g . , with the methods of the present invention . A drug product, they contain cannabinoid in the same dosage form , they have in accordance with the present invention , is an intranasal the same route of administration ; and they have the same pharmaceutical composition or composition formulated with cannabinoid strength . In other words, therapeutic equiva a drug substance , i . e . , a cannanbinoid , such as CBD and lence means that a chemical equivalent of a cannabinoid THC and mixtures thereof. nasal composition of the present invention ( i . e . , containing 101441 “ Disease ," " disorder , " and " condition ” are com the same amount of cannabinoid in the same dosage form monly recognized in the art and designate the presence of when administered to the same individuals in the same signs and / or symptoms in an individual or patient that are dosage regimen ) will provide essentially the same efficacy generally recognized as abnormal and / or undesirable . Dis and toxicity . eases or conditions may be diagnosed and categorized based [ 0137 ) As used herein , " plasma cannabinoid level” means on pathological changes . The disease or condition may be the level of cannabinoid in the plasma of a subject . The selected from the types of diseases listed in standard texts , plasma cannabinoid level is determined by methods known such as Harrison 's Principles of Internal Medicine, 1997 , or in the art. Robbins Pathologic Basis of Disease , 1998 . [ 0138 ] “ Diagnosis ” or “ prognosis , " as used herein , refers [ 0145 ] As used herein , “ diagnosing ” or “ identifying a to the use of information ( e . g ., biological or chemical patient or subject having a disorder treatable with a can information from biological samples, signs and symptoms, nabinoid ” refers to a process of determining if an individual physical exam findings, psychological exam findings, etc . ) is afflicted with a disorder treatable with a cannabinoid . to anticipate the most likely outcomes , timeframes , and/ or 10146 ] The present invention provides a non - oral, non responses to a particular treatment for a given disease , injectable form of cannabinoids, for example , THC , CBD disorder, or condition , based on comparisons with a plurality and mixtures, which is convenient and can be self -admin of individuals sharing symptoms, signs , family histories , or istered . The composition can be administered by a care - giver other data relevant to consideration of a patient ' s health if needed , is relatively stable , is readily absorbed after status , or the confirmation of a subject' s affliction . administration comparatively to other available forms, has [0139 ] A “ subject ” according to some embodiments is an good bioavailability , is believed to avoid or at least have individual whose signs and symptoms, physical exams find reduced first pass metabolism , and is able to achieve desired ings and / or psychological exam findings are to be deter levels of cannabinoids in the bloodstream . The therapeutic is mined and recorded in conjunction with the individual 's formulated for nasal delivery , by administration to , and condition (i . e ., disease or disorder status) and / or response to absorption through , the mucosa of the nasal cavity . a candidate drug or treatment. [0147 ] Until the present, it is believed that semi- solid or [0140 ] “ Subject, ” as used herein , is preferably , but not viscous liquid pharmaceutical compositions of cannabi necessarily limited to , a human subject. The subject may be noids , namely , cannabinoid gels , creams or emuslison , for male or female , and and may be of any race or ethnicity , topical application into the nasal cavity of humans have been US 2017 /0348276 A1 Dec . 7 , 2017 unknown. Cannabinoids are substances with a high octanol Aloe Vera Oil ( Aloe barbadensis ), Apricot Kernel Oil water partition coefficient ( logP > 5 ) , that will dissolve in (Prunus armeniaca ) , Argan Oil (Argania spinosa ) , Avocada organic solvents , such as toluene , dichloromethane acetone, Oil (Persea americana ) , Apricot Oil (Prunus armeniaca ) , ethanol, etc . , in natural vegetable oils , such as sesame oil , Amla Oil (Emblica officinalis ) , Borage Oil (Borago offici Castor Oil, olive oil and similar, and in synthetic resins and nalis ) , Black Seed Oil (Nigella sativa ) , Carrot Oil (Daucus waxy materials , such as sucrose acetate isobutyrate . carota ) , Coconut Oil (Cocus nucifera ) , Corn Oil , Cucumber [0148 ] In accordance with the present invention , and gen Oil (Cucumis sativa ), Chaulmogra Oil (Hydnocarpus wight erally speaking a therapeutically effective , nasally adminis ianus ), Emu Oil (Dromaius novae -Hollandiae ), Evening tered semi- solid or viscous liquid composition of cannabi Primrose Oil (Oenothera biennis ) , Flaxseed Oil ( Linum noids, such a a gel, a cream or an emulsion , prefa = erably a usitatissimum ), Grapeseed Oil ( Vitus vinifera ), Hazel Nut thixotropic gel, cream or an emulsion , can be formulated Oil (Avekkana ), Jojoba Oil Refined (Simmondsia chinensis ), comprising cannabinoid therapeutic active or mixture of Moringa Oil (Moringa oliefera ), Marula Oils (Sclerocarya actives and a pharmaceutically acceptable vehicle . birrea ), Wheatgerm Oil , Triticum vulgare , Macadamia Oil, [ 0149 In one aspect of the present invention , a therapeu Macadamia( ternifolia ) , Musk Melon Oil (Cuvumis melon ) , tically effective , nasally administered gel composition of Musk Oil ( Abelmoschus moschatus ) , Mustered Oil , Neem cannabinoids can be formulated comprising the following Oil ( Azadirachta indica ) , Olive Oil (Olea europaea ) , Peach three ingredients : Kernel Oil (Prunus persica ), Peanut Oil ( Arachis hypogeae ) , [0150 ) ( 1 ) The cannabinoid therapeutic active or mix Pomegranate Oil , Punica granatum , Psoralea Oil (Psoralea ture of actives; corylifolia ), Primrose Oil (Oenothera bienni) , Papaya Seed [0151 ] ( 2 ) An oily vehicle selected from any one or Oil (Carica papaya ), Rosehip Seed Oil (Rosa rubiginosa ), mixture of lipids . Preferably , lipids Generally Recog Safflower Oil , Seasame Seed (Refined ) ( Sesamum indicum ) , nized as Safe (GRAS ) are used . More preferably , the Sea Buckthorn Oil ( Hippophae rhamnoides) , Soya Bean Oil lipids are common , natural, GRAS lipids . Preferably, ( Soja hispida ) , Sunflower Oil (Helianthus annus ), Sweet the lipids should also be pharmaceutically acceptable . Almond Oil (Prunus amygdalus Var. Dulcus) , Sweet Cherry 10152 ]. ( 3 ) Awetting agent or mixture of wetting agents , Kernel Oil ( Prunus avium ), Walnut Oil ( Juglans regia ) , and / or a pharmaceutically acceptable surfactant or mix Water Melon Oil (Citrullus vulgaris ) . Sucrose acetate isobu ture of surfactants . tyrate (SAIB ) was also found to be an acceptable vehicle , as [0153 ] Optionally , a rheology modifying agent can were mixtures of oils or mixtures of oils with SAIB . additionally be used in the composition . [0158 ] In preferable embodiments , the oily or emulsified [ 0154 ] Optionally , the oily composition may be emulsified vehicle comprises about 3 % - 99 % , by weight, of the total into an aqueous phase to form an emulsion or cream . composition . [0155 ] The therapeutic active is preferably THC or CBD , (0159 ] The wetting agent or mixture of wetting agents , butmay also be prodrugs , derivatives , or analogs of THC or and /or a pharmaceutically acceptable surfactant or mixture CBD , or a combination of these . In accordance with the of surfactants may be, for example , a polysorbate , a poly present invention , when THC and CBD are used in combi oxyethylene hydrogenated vegetable oil , a polyoxyethylene nation , the ratio of THC : CBD contemplated is between vegetable oil ; a polyoxyethylene sorbitan fatty acid ester; a about 0 . 1 : 99 . 9 and about 99 . 9 : 0 . 1 , preferably polyoxyethylene -polyoxypropylene block copolymer, a [0156 ] preferably between 95 : 5 and about 75 :25 , more polyglycerol fatty acid ester; a polyoxyethylene glyceride ; a prefereably between 1: 1, and most preferably between 60 :40 polyoxyethylene sterol, or a derivative or analogue thereof; and 40 :60 . When using CBD - rich in combination with THC , a reaction mixture of polyols and at least one member of the the ratio contemplated in accordance with the present inven group consisting of fatty acids, glycerides, vegetable oils , tion is 0 - 100 : 25 - 75 . The use of pure synthetic CBD or THC hydrogenated vegetable oils , fractionated oils and sterols ; a as contemplated by the present invention includes greater tocopheryl polyethylene glycol succinate ; a sugar ester ; a than about 95 % , greater than about 98 % or even 100 % . sugar ether ; a sucroglyceride ; an alkylglucoside ; an alkyl Thus , the present invention contemplates use of herbal maltoside; an alkylthioglucosides ; a lauryl macrogolglycer extract mixtures (with their corresponding terpenes ) derived ide ; a polyoxyethylene alkyl ether ; a polyoxyethylene alky from plant sources , may or may not contain traces of other lphenol; a polyethylene glycol fatty acid ester ; a cannabinoids or natural products , or they may be derived polyethylene glycol glycerol fatty acid ester ; a polyoxyeth after at least 1 synthetic chemistry step . It would be under ylene sorbitan fatty acid ester ; a polyoxyethylene -polyoxy stood to a person of skill in the art that other cannabinoids propylene block copolymer such as poloxamer - 108 , 188 , may also be used to form the composition , though they may 217 , 238 , 288 , 338 , 407 , 124 , 182 , 183 , 212 , 331 , or 335 , or have therapeutic properties different from those of the combinations thereof, an ionic hydrophilic surfactant such CBD - based compositions , and that cannababinoid products as sodium dodecyl sulphate or docusate sodium ; a bile acid ; are regulated by Medical Marijuana legislation , while pure a cholic acid ; a deoxycholic acid ; a chenodeoxycholic acid ; synthetics follow the traditional FDA -Health Canada clini salts thereof, and mixtures thereof . cal development pathway . In preferable embodiments , the [0160 ] In preferable embodiments , the wetting agent com therapeutic active comprises about 0 . 1- 40 % by weight of the prises about 0 .1 % -10 % , by weight, of the total composition . total composition , preferably about 5 - 30 % by weight of the f0161 ] The rheology modifying agent, for example , a total composition ,most preferably about 15 -30 % by weight thickener, may be, for example, colloidal silica , silicates, of the total composition . alumina , or a high molecular weight polymer or a solid / [ 0157 ] The oily vehicle may be, for example , any phar waxy substance , which may be added to obtain the desired maceutically acceptable vegetable oil, monoglycerides , rheology . Examples of thickeners include any one or mixture diglycerides, synthetic triglycerides , Almond Oil Sweet of the following substances : bee wax , alumina , silica , sili (Prunus dulcis ), Almond Oil Virgin (Prunus amygdalus ), cates and high melting waxes and surfactants like cetostearyl US 2017 /0348276 A1 Dec . 7 , 2017

alcohol. Ranges for incorporation into the composition those well as methods already described , depending on the con that increase the viscosity to a preferable minimum of about sistency of the composition . The container from which gel is 500 cPs, a preferable maximum of about 30 ,000 cPs, and applied may be a tube , a jar, an applicator, etc. , and the preferably into a range of 1000 - 10 ,000 cPs for rapid and container may be single -dose or may be a multidose device . convenient administration . Too fluid and the liquid will drain The single dose container and applicator may be in the form from the nose , and too viscous and the product cannot be of ampule made from soft gelatine . The delivery device may administered easily with a small metered dose pump . The be disposable or reusable . optimal viscosity for oily gels for use in devices such as [0166 ] A metered dose pump delivery device can be used Aptar Albion 15 manually actuated pump device is in the to deliver exact quantities of the drug substance to the range of 1000 - 5000 cPs. patient. For example , a multi -dose device that allows deliv [0162 ] When used , typically , the rheology modifying ery of precise dosage amounts to the external wall of one or agent comprises no more than about 10 % , by weight, of the both nostrils of the middle -upper nasal cavity ( under carti total composition . lage) may be used for depositing the dosage thereon . Once [0163 ] Optionally , the composition can be dispersed or the drug substance is administered onto the external wall of emulsified in an aqueous phase wherein the lipid and aque the nasal cavity of a nostril, the outer nose is preferably ous phases are mixed until homogeneous to form a cream gently massaged with fingers to evenly distribute the drug ( c /w or w /o creams) or emulgel or multiple emulsions substance throughout the nasal cavity with minimal or no ( o / w / o or w / o / w ) type product like topical mixture . The dosage loss into the throat or outside the nose . Examples of aqueous phase in such compositions can make up 10 - 90 % multi- dose devices for pernasal deposition at the preferred (by weight) of the total composition , the remaining being a location within the nose in accordance with the present lipid vehicle composition as described above. The aqueous invention include the COMOD system available from phase optionally may contain minerals , osmotic comple Ursatec, Verpackung -GmbH , Schillerstr. 4 , 66606 St. Wen ments and thickeners . Hydrophilic polymers can be used to del, Germany , or the Albion or Digital airless applicator gel the aqueous phase if required . The non - limiting systems available from Airless systems, RD 149 27380 examples of these include HPMC , HPC , Sodium CMC , Varleval, France or 250 North Route 303 Congers , N . Y . Sodium CMC and MCC , natural gums like Xanthan gum , 10950 . Such nasal multi- dose dispenser devices may be Guar gum , gum acacia , gum tragacanth , starches like maize further adapted for an airless fluid dispensing system , or for starch , potato starch , pregelatinized starch etc . The viscosity a dip tube fluid dispensing system . of aqueous based product can be higher compared to oily f0167 ] Preferably , the dose administered is in the range of gels . between about 0 . 1 mg and about 75 mg of cannabinoid [0164 ] For emulsification of oil into water or vice versa ( total) or up to about 37 .5 mg per single application per any single or combination of surfactants can be used . nostril . Examples of surfactants include any one or mixture of [ 0168 ] The delivery device or container is single -use or surfactants. The surfactants may belong to non - ionic , multi - use and is devised to avoid contact of the product with anionic or cationic surfactants : Glycol Distearate , Sorbitan air during storage and use . Trioleate , Propylene Glycol Isostearate , Glycol Stearate , [0169 ] The oily gel, emulsion or cream can be applied in Sorbitan Sesquioleate , Lecithin , Sorbitan Oleate , Sorbitan the nose approximately 1 inch inside the opening (nostril ) Monostearate NF, Sorbitan Stearate , Sorbitan Isostearate , using a dispenser tip appropriately designed and safe to Steareth - 2 , Oleth - 2 , Glyceryl Laurate , Ceteth - 2 , PEG - 30 reach up into the nose and attached to a container. The tip Dipolyhydroxystearate , Glyceryl Stearate SE , Sorbitan preferably has rounded edges to avoid injury . The nose is Stearate ( and ) Sucrose Cocoate , PEG - 4 Dilaurate , Methyl then massaged to spread the composition to a thin film inside Glucose Sesquistearate , Lecithin HLB (variable ) PEG - 8 the nostril which will assist in absorption of the active Dioleate , Sorbitan Laurate , Sorbitan Laurate , PEG -40 Sor ingredient into the mucosal tissues . bitan Peroleate , a polyoxyl glyceride, such as Labrafil® [0170 ] Oily gel emulsion and cream compositions may be M1944CS , Laureth - 4 , PEG -7 Glyceryl Cocoate , PEG - 20 abuse deterrent or have low abuse liability . Almond Glycerides, PEG - 25 Hydrogenated Castor Oil , [0171 ] Food effects are often observed when a fat soluble Stearamide MEA , Glyceryl Stearate ( and) PEG - 100 Stear drug is administered orally . Food effects may also be ate , Polysorbate 85 , PEG - 7 Olivate , Cetearyl Glucoside , observed when there is a high concentration of lipids in the Stearamide MEA , PEG - 8 Oleate , Polyglyceryl- 3 Methyg bloodstream (LDL , HDL etc ). lucose Distearate , Oleth - 10 , Oleth - 10 / Polyoxyl 10 Oleyl f0172 ] The compositions according to the present inven Ether NF . Ceteth - 10 , PEG - 8 Laurate , Cocamide MEA , Poly tion can be used as medical cannabis to treat a number of sorbate 60 NF, Polysorbate 60 , Polysorbate 80 , Isosteareth conditions. The following list is representative of conditions 20 , PEG - 60 Almond Glycerides , PEG - 20 Methyl Glucose treatable by either one or another of the cannabinoids and is Sesquistearate , Ceteareth - 20 , Oleth - 20 , Steareth -20 , not meant to be exclusive or exhaustive : antipsychosis , Steareth - 20 , Steareth - 21 , Steareth - 21 , Ceteth - 20 , Steareth epilepsy , anxiety , sleep disturbances, neurodegeneration , 100 . Ranges for incorporation into the composition are those psychosis , depression , glaucoma, neurodegeneration , cere that allow for the spreading of the gel upon the nasal mucosa bral and myocardial ischemia , inflammation , pain including and that allow absorption of the medication through the chronic pain , immune responses , emesis , food intake , such nasal tissues and into the bloodstream , 0 . 001 - 20 % , prefer as appetite stimulation in HIV /AIDS , type - 1 diabetes, liver ably 1 - 10 % or 1 - 5 % (by weight) . disease , osteogenesis , cancer, conditions relating to certain [0165 ] Viscous oily , emulsions or creams compositions of types of cancer including nausea and vomiting, a movement the invention can be administered by finger, syringe, single disorder, a mood disorder , a psychological disorder and use blow - fill -seal devices, airless pump devices and other Tourette syndrome. See , e . g . : Whiting P . F . et al. : Cannabi alternatives . Emulsions may also be delivered via sprays , as noids for Medical Use: A Systematic Review and Meta US 2017 /0348276 A1 Dec . 7 , 2017 14

analysis . JAMA. 2015 Jun . 23 -30 ; 313 (24 ): 2456 -73 . doi: (0179 ] The distributor pump has a body 142 provided with 10 . 1001/ jama . 2015 .6358 ; Grotenhermen , F . et al. : The a bottom intake having an inlet valve 160 with a ball 162 as Therapeutic Potential of Cannabis and Cannabinoids. Dtsch its valve member. The ball 162 is held in place by a cage 164 Arztebl Int. 2012 July ; 109 ( 29 - 30 ) : 495 -501 , Published and by a return spring 170. online 2012 Jul. 23 . doi: 10 . 3238 /arzteb1 . 2012 .0495 ; Bertha [0180 ] At its bottom end , the stem 144 carries a spring cap K . Madras : Update of Cannabis and its medical use. 37th 172 . A piston 174 is located above the spring cap 172 . The ECDD (2015 ) Agenda item 6 .2 available at http :/ / www .who . stem 144 passes through an axial orifice of the piston base int/ medicines /access / controlled -substances / 6 _ 2 _ cannabis _ _ 176 . update .pdf ; Drug Facts , Marijuana as Medicine . National 10181 ] The side walls of the piston 174 seals against the Institutes of Drug Abuse, Revised April , 2017 , available at distributor pump body 142 via lips . The sleeve 128 tightly https : / /www . drugabuse . gov / publications /drugfacts / mari pinches a stem gasket 152 against the stem collar 146 , juana -medicine and https: // d14rmgtrwzf5a .cloudfront . net / distributor pump body 142 and top of the piston 174 . sites/ default / files/ df _ mj_ medicine _ april2017 .pdf ; and 10 [0182 ] A precompression spring 178 placed between the Cannabinoids and Their Medicinal Properties . Cannabis piston base 176 and the stem collar 146 . The precompression Career Institute ( Oct. 30 , 2014 ), available at https : // canna spring 178 biases the actuator nozzle 130 via the stem 144 biscareerinstitute .com / 10 - cannabinoids - and - their -medici to the closed position . nal- properties / ; each of which is incorporated herein by [0183 ] The return spring 170 , which returns the piston 174 reference in their entireties . back upwards, is compressed between two opposed seats on [0173 ] A nasal multi -dose dispenser device according to the cage 164 and the spring cap 172 . embodiments of the present invention , such as the Albion or [0184 ] The distributor pump 140 has a dosing chamber Digital airless applicator systems available from Airlessys 180 formed between the cage 164 and piston 174 . When the tems, is comprised of a fluid container and a distributor user pushes the actuator nozzle downwards to the open pump for delivery of multiple doses of a gel or other topical position , fluid in the dosing chamber is withdrawn by the formulation . In one embodiment of the present invention , distributor pump 140 and dispensed from the tip of the the nasal multi -dose dispenser device is adapted for an actuator nozzle 130 . airless fluid dispensing system . In another embodiment of 10185 ]. When the user releases the actuator nozzle 130 the present invention , the nasal multi- dose dispenser device upwards to the closed is adapted for a dip tube fluid dispensing system . [ 0186 ] position , a fluid in the container body 122 is [0174 ] An example of an airless system that is contem withdrawn into the dosing chamber 180 by the distributor plated by the present invention is one that will deliver a pump 140 . Thus, a dose of fluid is ready for the next liquid , including gel , without the need for a pressured gas or actuation of the actuator nozzle by the user. air pump to be in contact with the liquid (or gel ) . In general , (0187 ] In another embodiment of the present invention , an airless system of the present invention comprises a the dispenser 200 of flexible pouch containing the liquid , a solid cylindrical [0188 ] FIG . 3 is provided with a fluid container 220 , a container a moving piston , an aspirating pump , a dosing distributor pump 240 and a cap 202 . valve and a delivery nozzle , as depicted , for example , in 10189 ] The fluid container 220 comprises a container body FIGS . 1 - 4 . 222 , a base 224 and a neck 226 . The distributor pump 240 [0175 ] In accordance with the present invention , the multi is fastened to the neck by a sleeve 228 . The top end of the dose dispenser 100 of FIG . 1 is provided with a fluid container body 222 is closed by the distributor pump 240 . container 120 , a distributor pump 140 and a cap 102 . Fluid The sleeve 228 tightly pinches a neck gasket 250 against the container 120 comprises a container body 122 , a base 124 top end of the container body 222 . The container body 222 and a neck 126 . The distributor pump 140 is fastened to the houses the fluid to be dispensed . neck by a sleeve 128 . The top end of the container body 122 [0190 ] The distributor pump 240 is closed by its actuator is closed by the distributor pump 140 . The sleeve 128 tightly nozzle 230 , which pinches a neck gasket 150 against the top end of the [0191 ] retains the stem 244 at the stem head . The actuator container body 122 . The container body 122 forms a vacuum nozzle 230 comprises an outlet channel 232 and tip 234 . The and houses the fluid to be dispensed . actuator nozzle 230 is shaped to conform with the interior surface of a user ' s nostril . The actuator nozzle 230 is [0176 ] The distributor pump 140 is closed by its actuator moveable between a downward open position and upward nozzle 130 , which retains the stem 144 at the stem head . The closed position . The user removes the cap 202 and inserts the actuator nozzle 130 comprises an outlet channel 132 and tip actuator nozzle 230 in the user ' s nostril . When the user 134 . pushes the actuator nozzle 230 downwards to the open [0177 ] The actuator nozzle 130 is shaped to conform with position , fluid in the dosing chamber 280 is withdrawn by the interior surface of a user ' s nostril . The actuator nozzle the distributor pump 240 and exits at the tip 234 via the 130 is moveable between a downward open position and outlet channel 232 of the actuator nozzle 230 . upward closed position . The user removes the cap 102 and [0192 ] FIG . 4 shows a cross - sectional view of the dis inserts the actuator nozzle 130 in the user ' s nostril . When the tributor pump 240 . user pushes the actuator nozzle 130 downwards to the open [0193 ] The distributor pump has a body 242 provided with position , fluid in the dosing chamber 180 is withdrawn by a bottom intake having an inlet valve 260 with a ball 262 as the distributor pump 140 and exits at the tip 134 via the its valve member . The ball 262 is held in place by a cage 264 outlet channel 132 of the actuator nozzle 130 . and by a return spring 270 . Optionally , a dip tube 290 can [0178 ] FIG . 2 shows a cross - sectional view of the dis extend downward from the inlet valve 260 and is immersed tributor pump 140 . in the liquid contained in the container body . US 2017 /0348276 A1 Dec . 7 , 2017

[0194 ] At its bottom end , the stem 244 carries a spring cap TABLE 1 272 . A piston 274 [0195 ] is located above the spring cap 272 . The stem 244 Ingredients Function % w / w passes through an axial orifice of the piston base 276 . Tetrahydrocannabinol Active 0 .02 Cannabidiol Active 15 . 48 [0196 ] The side walls of the piston 274 seals against the Castor Oil Oily Vehicle 76 . 50 distributor pump body 242 via lips . The sleeve 228 tightly Colloidal Silicon Dioxide Thickening agent 4 . 00 pinches a stem gasket 252 against the stem collar 246 , Oleoyl Polyoxylglycerides Surfactant/ Wetting Agent 4 . 00 distributor pump body 242 and top of the piston 274 . [0197 ] A precompression spring 278 placed between the Total 100 piston base 276 and the stem collar 246 . The precompression spring 278 biases the actuator nozzle 230 via the stem 244 to the closed position . Example 2 [0198 ] The return spring 270 , which returns the piston 274 15 .5 % Cannabinoids in Castor OilBased back upwards, is compressed between two opposed seats on Composition the cage 264 and the spring cap 272 . [0205 ] Heat Castor Oil to about 50° C . Dissolve THC and [0199 ] The distributor pump 240 has a dosing chamber CBD in this heated Castor Oil under inert atmosphere . Apply 280 formed between the cage 264 and piston 274 . When the vacuum with continuous mixing to remove any entrapped user pushes the actuator nozzle downwards to the open air . Add Oleoyl Polyoxylglycerides and continue mixing position , air enters the dosing chamber 280 , which forces the under vacuum . Release the vacuum with Nitrogen and cool fluid in the dosing chamber to be withdrawn by the distribu the product to below about 30° C . with slow mixing . tor pump 240 and dispensed from the tip of the actuator Ingredients are mixed in the proportions listed in Table 2 , nozzle 230 . below . [0200 ] When the user releases the actuator nozzle 230 upwards to the closed position , the air contained in the TABLE 2 dosing chamber 280 forces the fluid in the container body 222 to be withdrawn into the dosing chamber 280 . Thus, a Ingredients Function % w / w dose of fluid is ready for the next actuation of the actuator Tetrahydrocannabinol Active 15 . 48 nozzle by the user . Cannabidiol Active 0 . 02 Castor Oil Oily Vehicle 80 . 50 [ 0201] The amount of fluid withdrawn by the distributor Oleoyl Polyoxylglycerides Surfactant/ Wetting Agent 4 . 00 pump into the dosing chamber may be a fixed volume. The distributor pumps may be of a variety of sizes to accom Total 100 . 00 modate a range of delivery volumes . For example , a dis tributor pump may have a delivery volume of up to about 150 ul. See FIGS . 1 - 6 . Example 3 [ 0202 ] The dispensers of the present invention may dis pense topical intranasal cannabinoid pharmaceutical com Sucrose Acetate Isobutyrate Based Composition positions, preferably pernasally , such as in the form of a with 15 . 5 % Cannabinoids cream , gel or viscous emulsion and , in particular a thixo [0206 ] Heat Sucrose Acetate Isobutyrate to about 50° C . tropic cream , gel and viscous emulsion . Add and mix Medium Chain Triglycerides, Polyoxyl 35 [0203 ] Examples of various embodiments of the present Hydrogenated Castor Oil and Oleoyl Polyoxylglycerides invention will now be further illustrated with reference to under inert atmosphere . Add and dissolve THC and CBD to the following examples. Thus, the following examples are make a clear solution . Ingredients are mixed in the propor provided to illustrate the invention , but are not intended to tions listed in Table 3 , below . be limiting thereof. Parts and percentages are by weight unless otherwise specified . TABLE 3 Ingredients Function % EXAMPLES Function w / w Tetrahydrocannabinol Active 0 .02 Cannabidiol Active 15 . 48 Example 1 Sucrose Acetate Isobutyrate Oily Vehicle 50 .00 Medium Chain Triglycerides Emollient 30 . 50 Polyoxyl 35 Hydrogenated Castor Oil Surfactant /Wetting 2 .00 15 . 5 % Cannabinoids in a Castor Oil Based Agent Composition Oleoyl Polyoxylglycerides Surfactant/ Wetting 2 .00 Agent [0204 ] Heat Castor Oil to about 50° C . Dissolve THC and CBD in this heated Castor Oil under inert atmosphere . Add Total 100 . 00 Colloidal Silicon Dioxide and homogenize to break any lumps . Apply vacuum with continuous mixing to remove any entrapped air . Add Oleoyl Polyoxylglycerides and con Example 4 tinue mixing under vacuum . Release the vacuum with Nitro gen and cool the product to below about 30° C . with slow 16 % Cannabinoid in Castor Oil mixing . Ingredients are mixed in the proportions listed in [0207 ] Heat Sucrose Acetate Isobutyrate to about 50° C . Table 1, below . Add and mix medium chain triglycerides, Polyoxyl 35 US 2017 /0348276 A1 Dec . 7 , 2017

Hydrogenated Castor Oil and Oleoyl Polyoxylglycerides [0211 ] Add Hydroxypropylcellulose in water that is under inert atmosphere . Add and dissolve THC and CBD to heated to about 55° C . and mix to form uniform suspension . make a clear solution . Ingredients are mixed in the propor Then add Dextrose and mix to dissolve using a homogenizer . tions listed in Table 4 , below . Add oily phase to this aqueous phase and continue mixing and homogenizing to form a uniform emulsion . TABLE 4 [0212 ] All processing should be performed under inert atmosphere. Ingredients are mixed in the proportions listed Ingredients Function % w / w in Table 6 , below . Tetrahydrocannabinol Active 8 . 00 Cannabidiol Active 8 . 00 TABLE 6 Sucrose Acetate Isobutyrate Oily Vehicle 50 . 00 Medium Chain Triglycerides Oily Vehicle 30 .00 Ingredients Function % w / w Polyoxyl 35 Hydrogenated Castor Oil Surfactant /Wetting 2 .00 Agent Tetrahydrocannabinol Active 2 .44 Oleoyl Polyoxylglycerides Surfactant/ Wetting 2 .00 Cannabidiol Active 0 .06 Agent Sesame Oil Oily Vehicle 10 .00 Olive Oil Oily Vehicle 4 . 00 Total 100 .00 Oleoyl Polyoxylglycerides Surfactant/ Wetting 4 .00 Agent Polyoxyl 35 Hydrogenated Castor Oil Emulsifier 2 .00 Methylparaben Preservative 0 . 10 Example 5 Propylparaben Preservative 0 .05 Dextrose Tonicity adjuster 3 .60 Hydroxypropylcellulose Thickener 3 .00 Oil in Water Based Emulsion containing about 2 % Purified Water 70 . 75 Cannabinoids Solvent [ 0208 ] Heat Seasame Oil and Castor Oil to about 55 -60° Total 100 . 00 C . Add Polyoxyl 35 Hydrogenated Castor Oil and Oleoyl Polyoxylglycerides, Methylparaben and Propylparaben and Example 7 continue mixing to make a clear solution . Add and dissolve THC and CBD with continuous mixing and homogeniza 5 % Cannabinoids in SAIB Based Gel tion . [ 0209 ] Add Dextrose in water that is heated to about 55° [0213 ] Heat Sucrose Acetate Isobutyrate to about 50° C . C . and mix to dissolve . Then disperse Carbopol using a under inert atmosphere . Add and mix Coconut oil , Glycer homogenizer . Add oily phase to this aqueous phase and ylmonostearate and Oleoyl Polyoxylglycerides. Add and continue mixing and homogenizing to form a uniform dissolve THC and CBD to make a clear solution . Ingredients emulsion . Adjust the pH of the gel to about 7 . 4 using about are mixed in the proportions listed in Table 7 , below . IN NaOH with continuous mixing . Cool the product to below about 30° C . while mixing . Ingredients are mixed in TABLE 7 the proportions listed in Table 5, below . Ingredients FunctionFunction % w / w Tetrahydrocannabinol Active 3 . 75 TABLE 5 Cannabidiol Active 1 . 25 Sucrose Acetate Isobutyrate Oily Vehicle 50 . 00 Ingredients Function % w / w Coconut Oil Emollient 41 . 00 Tetrahydrocannabinol Active 1 .00 Glycerylmonostearate Surfactant/ Wetting Agent 2 .00 Cannabidiol Active 1 . 00 Oleoyl Polyoxylglycerides Surfactant/ Wetting Agent 2 .00 Sesame Oil Oily Vehicle 10 . 00 Castor Oil Oily Vehicle 4 . 00 Total 100 . 00 Oleoyl Polyoxylglycerides Surfactant/ Wetting 4 . 00 Agent Polyoxyl 35 Hydrogenated Castor Oil 2 . 00 Example 8 Methylparaben Preservative 0 . 10 Propylparaben Preservative 0 .05 Dextrose Tonicity adjuster 3 .60 10 % Cannabinoid in Castor Oil Gel Carbomer 934P Thickening agent 0 . 35 [ 0214 ] Castor Oil and Oleoyl Polyoxylglycerides are Sodium Hydroxide pH adjustment 0 .00 heated and then mixed . Silicon Dioxide is then added and Purified Water Solvent 73 . 90 further mixing is performed . Apply vacuum to remove any Total 100 .00 entrapped air in the gel . CBD is added and is dissolved upon mixing and with gently heating ( to about 40° C . ) under inert atmosphere . The gel is loaded into bottles for storage and syringes for administration . Ingredients are mixed in the Example 6 proportions listed in Table 8 , below . 2 . 5 % Cannabinoid in Emulsion TABLE 8 [0210 ] Heat Sesame Oil and Olive Oil to about 55 -60° C . Add Polyoxyl 35 Hydrogenated Castor Oil, Oleoyl Polyox Ingredients Function % w / w yglycerides , Methylparaben and Propylparaben and con Tetrahydrocannabinol Active 2 .00 tinue mixing to make a clear solution . Add and dissolve THC Cannabidiol Active 8 .00 and CBD with continuous mixing and homogenization . US 2017 /0348276 A1 Dec . 7 , 2017

TABLE 8 -continued TABLE 9 Ingredients Function % w / w Ingredients Function % w / w Castor Oil Oily Vehicle 82 . 00 Tetrahydrocannabinol Active 0 . 10 Colloidal Silicon Dioxide Thickening agent 4 . 00 Cannabidiol Active 19 . 90 Oleoyl Polyoxylglycerides Surfactant/ Wetting Agent 4 . 00 Castor Oil Oily vehicle AND wetting agent 80 . 00 Total 100 . 00 Total 100 .00

Example 9 Example 10 20 % Cannabinoid in Castor Oil — Gel 0 .4 % Cannabinoids in Castor Oil [ 0219 ] Heat Castor Oil to about 50° C . under inert atmo [0215 ] Combine about 120 g gel composition that is sphere . Add THC and CBD and dissolve to make a clear oily composed of 88 parts castor oil , 4 parts colloidal silica and solution . Ingredients are mixed in the proportions listed in 4 parts Labrafil , with 14 g CBD and heat to about 50° C . with Table 10 , below . mixing until transparent and CBD is dissolved ( visual inspection ) in Table 9 ). Remove from heat and using a cold TABLE 10 water bath , cool the mixture while stirring . Put gel into syringes for use in PK study. Remaining gel is put into a Ingredients Function % w / w bottle for storage and analysis . Tetrahydrocannabinol Active 0 . 20 Cannabidiol Active 0 . 20 TABLE 9 Castor Oil Oily vehicle AND wetting agent 99 . 60 Ingredients Function % w / w Total 100 .00 Cannabidiol Active 14 g Castor Oil based gel composition Solvent 120 g Example 11 Total 134 .00 4 % Cannabinoids in Water in Oil (W / O ) Emulsion . [0220 ] Heat Coconut oil to about 55 -60° C . under inert Example 9B atmosphere . Add Glycerylmonostearate , Beeswax , Oleoyl Polyoxylglycerides, Methylparaben and Propylparaben and continue mixing to make a clear solution . Add and dissolve 20 % CBD in Castor Oil Gel Composition THC and CBD with continuous mixing and homogeniza (0216 ) Combined about 95 g gel composition that is tion . composed of 88 parts castor oil , 4 parts colloidal silica and [0221 ] Add Purified Water, heat to about 55° C ., to this 4 parts Labrafil® , with 23 . 8 g CBD and heat to about 40° C . oily phase and continued mixing and homogenizing to form with mixing until transparent and CBD is dissolved (visual a uniform emulsion . Cool to below about 30° C . while inspection ) in Table 9 ) . Removed from heat and using a mixing. Ingredients are mixed in the proportions listed in cold water bath , cool the mixture while stirring . Fill syringes Table 11, below . with gel for use in PK study. Store remaining gel in a bottle for analysis . TABLE 11 Example 9C Ingredients Function % w / w Tetrahydrocannabinol Active 2 .00 Cannabidiol Active 2 .00 16 % CBD in Castor Oil Gel Composition Beeswax Thickening agent 5 . 00 Coconut Oil Oily vehicle 50 . 00 Glycerylmonostearate Surfactant/ Wetting Agent 3 . 00 [0217 ] Combined about 90 g gel composition from Oleoyl Polyoxylglycerides Surfactant/ Wetting Agent 2 . 00 example 9B and 22 . 5 g ( inactive ) gel composition that is Methylparaben Preservative 0 . 10 composed of 88 parts castor oil , 4 parts colloidal silica and Propylparaben Preservative 0 . 05 4 parts Labrafil BD and heat to about 40° C . with mixing Purified Water Solvent 35 . 85 until transparent and CBD is dissolved ( visual inspection ) ( in Table 9 ). Remove from heat and using a cold water bath , Total 100 .00 cool the mixture while stirring. Fill syringes with gel for use in PK study . Store remaining gel in a bottle for analysis . [ 0218 ] Though castor oil is traditionally thought of as an Example 12 oily vehicle , it is found that castor oil has sufficient wetting agent properties to be a dual - use compound . Heat Castor Oil 10 % CBD in a Castor -Oil Based Composition to about 50° C . under inert atmosphere . Add THC and CBD [0222 ] Castor oil and oleoyl polyoxylglycerides are mixed and dissolve to make a clear oily solution . Ingredients are together thoroughly . CBD is added and is dissolved upon mixed in the proportions listed in Table 9, below . mixing to form a clear gel or a viscous solution . The gel is US 2017 /0348276 A1 Dec . 7 , 2017 18 deaerated under vacuum and is loaded into tubes for storage Example 15 and administration . Ingredients are mixed in the proportions listed in Table 12 , below . 20 % CBD in Sesame Oil TABLE 12 [0225 ] Castor Oil and Oleoyl polyoxylglycerides are mixed and silicone dioxide is then added and furthermixing Ingredient Function % w /w is performed . CBD is added and is dissolved upon mixing CBD Active ingredient and with gently heating ( to about 40° C .) . The resultant gel Castor Oil Oily Vehicle is deaerated under vacuum and is then loaded into tubes for Oleoyl Polyoxylglycerides Surfactant/Wetting Agent storage or syringes for administration . Ingredients are mixed Total in the proportions listed in Table 4 , below . 88 TABLE 16 Example 13 Ingredient Function % w / w CBD Active ingredient 20 10 % CBD in Sesame Oil Based Composition Sesame Oil Oily Vehicle 73 . 4 [ 0223] Sesame oil and oleoyl polyoxylglycerides are Oleoyl Polyoxylglycerides Wetting Agent 3. 3 mixed together thoroughly . Silicon dioxide is then added and Silicon Dioxide Thickener 3 . 3 further mixing is performed . CBD is then added and is Total 100 dissolved upon mixing with gentle heating ( to about about 40° C .) . The resultant gel is deaerated under vacuum and is loaded into tubes for storage or syringes for administration . Ingredients are mixed in the proportions listed in Table 2 , Example 16 below . 10 % CBD in SAIB Mixture TABLE 14 [0226 ] Though SAIB is traditionally thought of as a Ingredient % w / w vehicle , it also has sufficient wetting agent properties to be Function a dual- use compound . SAIB is heated to about 40C and is CBD Active ingredient then poured into a beaker. CBD is added and is dissolved Sesame Oil Oily Vehicle 90 upon mixing with gently heating ( at about 40C ) . The gel is Oleoyl Polyoxylglycerides Surfactant/Wetting Agent loaded into vials for storage . The resulting product is a very Silicon Dioxide Thickener viscous liquid . Ingredients are mixed in the proportions Total % listed in Table 5 , below . TABLE 17 Example 14 Ingredient Function % w / w Emulsified Composition of 12 % CBD in Mixture CBD Active ingredient 10 of Oils SAIB Oily vehicle AND wetting agent 90 [0224 ] Sesame oil , olive oil, oleoyl polyoxylglycerides Total 100 and polyoxyl 40 hydrogenated castor oil are mixed together thoroughly . CBD is added and is dissolved with mixing (Oil Phase) . In a separate vessel, hydroxypropyl cellulose is added to water, and is mixed to form a viscous liquid Example 17 ( Aqueous Phase ) . The Aqueous Phase is added to the Oil Phase and homogenized to create a cream , which is then 10 % CBD in SAIB Mixture deaerated using vacuum and is then loaded into tubes for [0227 ] SAIB is heated to about 40 C and then poured into storage and administration . Ingredients are mixed in the a beaker. The medium chain triglycerides and Cremophore proportions listed in Table 3 , below . EL are added and are mixed until homogeneous . This is followed by the addition of CBD which is dissolved upon TABLE 15 mixing with gently heating (at about 40° C . ) . The resultant Ingredient Function % w / w gel/ viscous solution is deaerated under vacuum and is then loaded into vials for storage or syringes for administration . CBD Active ingredient 12 Sesame Oil Oily Vehicle Ingredients are mixed in the proportions listed in Table 6 , Olive Oil Oily Vehicle below . Oleoyl Polyoxylglycerides Wetting Agent OON Polyoxyl 40 Hydrogenated Castor Oil Surfactant TABLE 18 Hydroxypropyl Cellulose Thickener Water Solvent Ingredient Function % w / w Total 100 CBD Active ingredient SAIB Oily Vehicle so US 2017 /0348276 A1 Dec . 7 , 2017

TABLE 18 -continued TABLE 21 Ingredient Function % w / w Ingredient Function % w / w Medium Chain Triglycerides Oily Vehicle 35 CBD Active ingredient 20 Cremophore EL Wetting agent Tu Castor Oil Oily Vehicle 73 . 4 Oleoyl Polyoxylglycerides Surfactant /Wetting Agent 3 . 3 Total 100 Silicon Dioxide Thickener 3. 3 Total 100 Example 18 20 % CBD in SAIB Example 21 [ 0228 ] SAIB is heated to about 40° C . and is then poured Pharmaceutical Product with Cannabinoids into a beaker . The medium chain triglycerides and Cremo [0231 ] About 5 grams of a Composition according to the phore EL are added and are mixed until homogeneous. This previous 18 examples are each loaded into a collapsible tube is followed by the addition of CBD which is dissolved upon shaped multidose dispenser equipped with a metered -dose mixing with gently heating ( at about 40° C . ). The resultant pump dispensing about 70 UL per actuation . The dispenser gel / viscous solution is deaerated under vacuum and is then contains an elongated nozzle end which allows the compo loaded into vials for storage or syringes for administration . sition to be applied in the nasal vestibule of a nostril . The Ingredients are mixed in the proportions listed in Table 7 , pump is manually primed by actuating the pump . The pump below . is used to nasally administer a cannabinoid or a cannabinoid TABLE 19 mixture to a patient in need thereof. Ingredient Function %% w / w Example 22 CBD Active ingredient 20 SAIB Oily Vehicle 44 . 5 Pharmacokinetics of Cannabinoid Administration Medium Chain Triglycerides Fluidifying agent/ Oily vehicle 31 [0232 ] Pharmacokinetics of CBD gel from Example 9A Oleoyl Polyoxylglycerides Wetting agent 4 . 5 and 9B is performed in 4 healthy volunteers. Two subjects Total 100 receive an approximate 25 mg dose of CBD contained in ca . 125 mg of the gel composition in Example 9B (20 % CBD in Castor Oil ; Subj # 1 and # 2 ) into a single nostril via syringe. Two other subjects received an approximate 25 mg Example 19 dose of CBD contained in ca . 250 mgof the Composition in Example 9A ( 10 % CBD in sesame oil ; Subj # 3 and # 4 ) , 125 10 % CBD in Castor Oil mg per nostril , via syringe . Blood samples are taken at: [0229 ] Castor oil and oleoyl polyoxylglycerides are mixed predose , about 15 min , 30 min , 45 min , 1 h , 2 h , 3 h , 4 h , 5 and then silicone dioxide is added and further mixing is h and 24 h directly into tubes containing EDTA . Blood performed . CBD is added and is dissolved upon mixing and samples are centrifuged and serum is analyzed by LCMS for with gently heating ( to about 40° C .) . The gel is loaded into CBD . The following PK parameters are determined using a bottles for storage and syringes for administration . Ingredi noncompartmental PK mode ( Table 22a and FIG . 8 ) . ents are mixed in the proportions listed in Table 8 , below . TABLE 22 TABLE 20 Composition Weight of Ingredient Function % w / w Subj ( example ) dose Cmax , Tmax , AUC applied administered Fasted ? ng /ml h ng /ml h CBD Active ingredient Castor Oil Oily Vehicle 86 9B 132 mg Y 2 . 45 4 . 47 . 3 Oleoyl Polyoxylglycerides Surfactant/ Wetting Agent 9B 126 mg 1. 98 3 34 . 0 Silicon Dioxide Thickener INM 9A 260 mg N 24 . 8 4 . 371 . 2 8No 9A 273 mg Y 3 . 58 5 55 . 8 Total Example 23 Example 20 Cannabis Oil Composition for Nasal Application 20 % CBD in Castor Oil - Gel [0233 ] About 250 g of dried cannabis is extracted with 2L [0230 ] Castor oil and Oleoyl polyoxylglycerides are ethanol. After filtration , the ethanol is evaporated to leave a mixed and then silicone dioxide is added and further mixing resinous material containing cannabinoids ( 10 -60 g ; > 70 % is performed . CBD is added and is dissolved upon mixing cannabinoids) . About 90 g Grape seed oil is added to the and with gently heating ( to about 40° C . ) . The resultant gel resin . Vacuum , stirring and heat is applied until a homog is loaded into bottles for storage and syringes for adminis enous mixture is obtained . About 6 g colloidal silica is added tration . Ingredients are mixed in the proportions listed in and dispersed using a high shear mixer while under vacuum Table 9 , below . over a period of about 1 h . About 4 g Labrafil® is added and US 2017 /0348276 A1 Dec . 7 , 2017 20 is mixed under vacuum until homogeneous . The vessel is Example 28 allowed to come to atmospheric pressure with input of nitrogen gas . The resulting product is removed from the Indications vessel and placed in 5 ml and 15 ml dispensers . [0238 ] Pain . Example 24 [0239 ] Types of Pain and doses of THC ( it is believed that CBD can reduce the high associated with THC ) . Cannabis Oil Composition for Nasal Application [0240 ] i. Acute pain : There is not general agreement that THC works here . Positive results have been [0234 ] About 250 g of dried cannabis is extracted using observed with 65 mg THC from smoked cannabis liquid CO2. After filtration , the CO2 is allowed to evaporate [0241 ] ii . Chronic pain ( including neuropathic pain ): to leave a resinous material containing cannabinoids ( about Typically 2 . 5 -50 mg smoked THC per dose, with 10 -60 g ; about > 70 % cannabinoids ). About 90 g Sesame oil repeat dosing per day up to 100 mg/ day is added to the resin . Vacuum , stirring and heat is applied until a homogenous mixture is obtained . About 5 g Labra [0242 ] iii. Cancer pain : typically 5 -20 mg oral dose , fil® is added and is mixed under vacuum until homoge with repeat dosing per day. neous. About 5 g colloidal silica is added and is dispersed [0243 ] iv . Fibromyalgia : typically 5 -15 mg oral dose , using a high shear mixer while under vacuum over a period up to 15 mg per day of about 1 h . The vessel is allowed to come to atmospheric [ 0244 ] v . Can be used in conjunction with codeine or pressure with input of nitrogen gas. The resulting product is opiods as adjuncts and as a means to reduce doses of analyzed for cannabinoid content and diluted with additional opioid sesame oil to achieve a concentration of about 3 % . It is then [0245 ] THC (pure synthetic ) or THC - rich cannabis removed from the vessel and is placed in 5 ml and 15 ml extract, may optionally contain CBD in ratios up to dispensers for use . 50 % 10246 ] 3 % THC is a specific legal limit in current Example 25 Canadian cannabis regulations . The CBD content is not regulated and can vary depending on the strain . THC in Cannabis Oil in an Emulsion cannabis for pain is typically at least 50 % to 99 % of the mixture of cannabinoids in cannabis extract and be [0235 ] About 50 g of a concentrated cannabis oil (6 % > 97 % to > 99 % if considering pure synthetic THC . cannabinoids in grapeseed oil ) is dispersed into a mixture of 0247 ] i. Dose : 1 mg- 20 mg THC cannabinoids con about 3 g ethoxylated - castor oil and about 47 g water and the tained in volume of 70 - 150 uL of a nasal cannabinoid resulting spray emulsion is filled into 5 ml and 15 ml pharmaceutical composition of the present invention dispensers for use . ( ca . 0 .6 % to 30 % THC ) which is applied in a nostril ; [0248 ] ii. Dose : preferably 1 - 10 mg THC cannabi Example 26 noids contained in volume of 70 - 150 uL of the composition ( ca. 0 .6 % to 7 % THC ) which is applied Cannabis Oil in a Cream in a nostril [0236 ] About 50 g of a concentrated cannabis oil ( 6 % [0249 ] iii. preferably cannabinoids comprising 3 % of cannabinoids in grapeseed oil) is dispersed into a mixture of the composition and supply a dose of 2 . 1 mg to 4 . 5 about 3 g ethoxylated - castor oil , about 47 g water and about mg of THC cannabinoids contained in volume within 0 .35 g Carbomer 934P . The resulting cream is filled into 5 the range of 70 - 150 uL , prefer a volume of 70 - 125 ml and 15 ml dispensers for use . ul , pref 100 - 125 uL , specifically 70 UL , 100 uL or 125 uL Example 27 [0250 ] iv . Dose volume (70 - 150 L ) is applied inside the nasal vestibule, preferably to the ( soft) tissues opposite the nasal septum just below the boney Rheology Assessment bridge section of the nose [0237 ] A composition according to example 9A was ana [ 0251 ] V . Dose ( 1 - 20 mg, for example ) can be applied lyzed using a Brookfield model HB cone -plate rheometer per nostril , to one or both nostrils ( total dose is 1 - 40 ( spindle CP41) with varying shear. Shear was cycled from mg, for example ) low ( 0 / sec ) at start to high ( 128 / sec ) shear and then back to [0252 ] Composition low shear over a period of 200 sec at 25C . The viscosity initially recorded at 2900 cPs at low shear decreased to 370 [0253 ] i. Composition comprised of THC cannabi cPs at highest shear and returned to 5750 CPs at the end of noids in an oily vehicle or SAIB (sucrose acectate the cycle . Using the same apparatus and program , but with isobutyrate ) spindle CP52 , the viscosity of the same sample could only [ 0254 ] ii. Composition comprised of THC cannabi be measured at low shear and showed a viscosity > 30 ,000 noids in an oily vehicle to which is added a sufficient cPs . Using a Brookfield model RV06 viscometer and # 6 wetting agent to allow spreading in the nose on the spindle , and turning for 5 min prior to capturing a measure , nasal mucosa the viscosity is measured as 5000 cPs for the same compo [0255 ] iii. Wetting agentmay be a mixture of wetting sition . This highlights the difficulty in stating precise vis agents / surfactants cosity values when referencing a pseduplastic material [0256 ] iv . List of wetting agents ( surfactants ) is pro according to certain composition examples . vided in specification US 2017 /0348276 A1 Dec . 7 , 2017

10257 ] v . Concentration of wetting agent or mixture [0276 ] i. Dose: 15 mg -75 mg CBD cannabinoids of wetting agents comprises 1 - 10 % by weight of the contained in volume of 70 - 150 uL of the composition composition , preferably 1- 5 % , more preferably (ca . 10 % to 50 % CBD ) which is applied in the nose 2 - 4 % [0277 ] ii. Dose: preferably 20 -50 mg CBD cannabi [ 0258 ] vi . Composition comprised of THC cannabi noids contained in volume of 70 - 150 uL of the noids in an oily vehicle to which is added a wetting composition ( ca . 13 % to 50 % CBD ) which is applied agent and a rheology agent in the nose . [ 0259 ] Rheology modifying agent increases viscosity [0278 ] Schizophrenia and provides reversible or partially , reversible pseudo [0279 ] CBD (pure synthetic ) , as it contains no THC . plastic or thixotropic , behavior such that the viscosity Can be herbal extract but preferred to avoid THC which is lower ( < 1000 cPs) when dispensed and upon stand has negative consequences (AEs ) in schizophrenia ing in the nose increases (> 5000 cPs ). Quantity of [0280 ] Dose : about 50 mg to 250 mg CBD per day , rheology modifying agents is adjusted to achieve a taken as multiple doses of viscosity range of 5000 -50 ,000 cPs ), preferably , based [0281 ) i. Dose : 15 mg - 75 mg CBD cannabinoids on a specific method of measurement. Viscosity values contained in volume of 70 - 150 uL of the composition are method dependent because with thixotropic / pseu ( ca . 10 % to 50 % CBD ) which is applied in the nose doplastic materials , the viscosity is a function of energy [ 0282 ] ii. Dose: preferably 20 -50 mg CBD cannabi ( shear forces ) applied when measuring . noids contained in volume of 70 - 150 uL of the [0260 ] i . List of rheology modifying agents (surfac composition ( ca . 13 % to 50 % CBD ) which is applied tants ) is provided in claims already in the nose . 50261 ] ii . Some rheology modifying agents are added [0283 ] Unless otherwise defined , all technical and scien to emulsion type compositions tific terms used herein have the same meaning as commonly [0262 ] iii. Some other rheology modifying agents can understood by one of ordinary skill in the art to which this be added to the oil -based compositions , quantities invention belongs . Although methods and materials similar may not be the same, but are typically < 10 % , < 5 % , or equivalent to those described herein can be used in the > 0 . 5 % practice or testing of the present invention , suitable methods and materials are described below . All publications, patent [0263 ] Dispensers applications , patents , abstracts , articles , websites , and other [ 0264 ] i . Unit dose able to deliver 70 - 150 uL to the referencesmentioned herein are incorporated by reference in nasal vestibule as described their entirety . [0265 ] ii. Airless device [0284 ] In case of conflict, the present specification , includ [0266 ] iii. Manually actuated , 5 ml multidose dis ing definitions, will control. penser with a nasal applicator comprises at least 60 [0285 ] In addition , the materials , methods, and examples individual metered doses of 70 UL pump are illustrative only and not intended to be limiting. Various (0267 ) iv . Manually actuated , 15 ml multidose dis modifications and alterations to this invention will become penser with a nasal applicator comprises at least 90 apparent to those skilled in the art without departing from individual metered doses of 125 uL pump the scope and spirit of this invention . Illustrative embodi [0268 ] v. Manually actuated , multidose dispenser ments and examples are provided as examples only and are with a nasal applicator comprises a metered dose 125 not intended to limit the scope of the present invention . uL pump and has a nominal volume of 15 ml or 30 Having described our invention , we claim : mlIn 1. A nasal pharmaceutical composition for topical appli [0269 ] vi. Manually actuated , multidose dispenser cation in the nasal cavity of a subject, said nasal pharma with a nasal applicator comprises a metered dose 70 ceutical composition comprising : uL pump and has a nominal volume of 5 ml ( a ) a therapeutically effective amount of a cannabinoid ; [0270 ] vii . 100 L volume is also preferred on 5 , 15 and or 30 ml dispenser ( b ) a pharmaceutically acceptable excipient, wherein the [0271 ] viii. Nasal applicator through which is dis nasal pharmaceutical composition is a semi- solid or pensed the composition such that the tip can reach viscous liquid nasal pharmaceutical composition . into the nasal vestibule just up to ( but below ) the 2 . The nasal pharmaceutical composition of claim 1 boney bridge of the nose when held in one hand comprising : ( 1 ) a cannabinoid therapeutic active ; ( 2 ) an oily (with finger on the pump ) and when actuated places vehicle ; and ( 3 ) a wetting agent or mixture of wetting agents a 70 - 150 uL volume of the composition at that and /or a pharmaceutically acceptable surfactant or mixture position . The composition is spread through an of surfactants . action of pinching the nose across the bridge and 3 . The nasal pharmaceutical composition of claim 2 , lightly massaging ( image available ) wherein the oily vehicle is one or more pharmaceutically [0272 ] ix . A 30 ml multidose dispenser that com acceptable Generally Recognized as Safe lipid . prises at least 224 individual metered doses of 100 4 . The nasal pharmaceutical composition of claim 3 , UL - 150 uL wherein the oily vehicle is selected from the group consist [ 0273 ] Epilepsy or Seizures ing of: a pharmaceutically acceptable vegetable oil , a mono [0274 ] CBD ( pure synthetic ) or CBD - rich cannabis glyceride, a diglyceride , Sucrose acetate isobutyrate (SAIB ) , extract , may optionally contain THC in low ratios a synthetic triglyceride , and a combination thereof. ( < 20 % , preferably < 10 % , < 5 % ) 5 . The nasal pharmaceutical composition of claim 4 , [0275 ] Dose for nasal delivery is about 50 mg to 250 mg wherein the pharmaceutically acceptable vegetable oil is CBD per day , taken as multiple doses of selected from the group consisting of: Almond Oil Sweet US 2017 /0348276 A1 Dec . 7 , 2017

( Prunus dulcis ), Almond Oil Virgin ( Prunus amygdalus ), polyoxyethylene sorbitan fatty acid ester , a polyoxyethyl Aloe Vera Oil ( Aloe barbadensis ), Apricot Kernel Oil ene -polyoxypropylene block copolymer such as poloxamer (Prunus armeniaca ), Argan Oil ( Argania spinosa ) , Avocada 108 , 188 , 217 , 238 , 288 , 338 , 407 , 124 , 182 , 183 , 212 , 331 , Oil ( Persea americana ) , Apricot Oil (Prunus armeniaca ) , or 335 , or combinations thereof; an ionic hydrophilic sur Amla Oil (Emblica officinalis ) , Borage Oil (Borago offici factant such as sodium dodecyl sulphate or docusate sodium ; nalis ) , Black Seed Oil (Nigella sativa ) , Carrot Oil (Daucus a bile acid ; a cholic acid ; a deoxycholic acid ; a chenode carota ) , Coconut Oil ( Cocus nucifera ) , Corn Oil , Cucumber oxycholic acid ; salts thereof, and mixtures thereof. Oil ( Cucumis sativa ) , Chaulmogra Oil (Hydnocarpus wight 13. The nasal pharmaceutical composition of claim 2 , said ianus ), Emu Oil (Dromaius novae -Hollandiae ) , Evening nasal composition further comprising a rheology modifying Primrose Oil ( Oenothera biennis ) , Flaxseed Oil ( Linum agent. usitatissimum ) , Grapeseed Oil ( Vitus vinifera ) , Hazel Nut 14 . The nasal pharmaceutical composition of claim 11 , Oil ( Avekkana ), Jojoba Oil Refined ( Simmondsia chinensis ), wherein the rheology modifying agent is selected from the Moringa Oil (Moringa oliefera ) , Marula Oils ( Sclerocarya group consisting of : colloidal silica , silicates , alumina , a birrea ) , Wheatgerm Oil, Triticum vulgare , Macadamia Oil , high molecular weight polymer or a solid /waxy substance , (Macadamia ternifolia ), Musk Melon Oil ( Cuvumis melon ), bee wax , alumina , silica , silicates and high melting waxes , Musk Oil ( Abelmoschus moschatus ) , Mustered Oil, Neem and cetostearyl alcohol. Oil ( Azadirachta indica ) , Olive Oil (Olea europaea ), Peach Kernel Oil (Prunus persica ), Peanut Oil ( Arachis hypogeae ) , 15 . The nasal pharmaceutical composition of claim 2 , said Pomegranate Oil, Punica granatum , Psoralea Oil (Psoralea nasal pharmaceutical composition further comprising a min corylifolia ) , Primrose Oil ( Oenothera bienni) , Papaya Seed eral, an osmotic complement, a thickener , and / or a hydro Oil ( Carica papaya ), Rosehip Seed Oil (Rosa rubiginosa ) , philic polymer. Safflower Oil , Seasame Seed (Refined ) ( Sesamum indicum ), 16 . The nasal pharmaceutical composition of claim 13 , Sea Buckthorn Oil (Hippophae rhamnoides ), Soya Bean Oil wherein the hydrophilic polymer is selected from the group ( Soja hispida ) , Sunflower Oil (Helianthus annus ) , Sweet consisting of: HPMC , HPC , Sodium CMC , Sodium CMC Almond Oil ( Prunus amygdalus Var. Dulcus ) , Sweet Cherry and MCC , natural gums like Xanthan gum , Guar gum , gum Kernel Oil (Prunus avium ), Walnut Oil ( Juglans regia ), acacia , gum tragacanth , starches like maize starch , potato Water Melon Oil ( Citrullus vulgaris ). starch , and pregelatinized starch . 6 . The nasal pharmaceutical composition of claim 4 , 17 . The nasal pharmaceutical composition of claim 2 , wherein the oily vehicle comprises Castor Oil. wherein the surfactant is selected from the group consisting 7 . The nasal pharmaceutical composition of claim 4 , of: Glycol Distearate , Sorbitan Trioleate , Propylene Glycol wherein the oily vehicle comprises sesame oil . Isostearate , Glycol Stearate , Sorbitan Sesquioleate, Lecithin , 8 . The nasal pharmaceutical composition of claim 4 , Sorbitan Oleate , Sorbitan Monostearate NF , Sorbitan Stear ate , Sorbitan Isostearate , Steareth - 2 , Oleth - 2 , Glyceryl Lau wherein the oily vehicle comprises SAIB . rate , Ceteth - 2 , PEG - 30 Dipolyhydroxystearate , Glyceryl 9 . The nasal pharmaceutical composition of claim 2 Stearate SE , Sorbitan Stearate ( and ) Sucrose Cocoate , wherein the cannabinoid is a therapeutic active cannabinoid , PEG - 4 Dilaurate , Methyl Glucose Sesquistearate, Lecithin or a mixture of cannabinoid actives , that is selected from the HLB ( variable ) PEG - 8 Dioleate , Sorbitan Laurate , Sorbitan group consisting of tetrahydrocannabinol ( THC ), canna Laurate, PEG -40 Sorbitan Peroleate , a polyoxyl glyceride , bidiol (CBD ) or a mixture thereof, a prodrug of THC or such as Labrafil® M1944CS , Laureth - 4 , PEG - 7 Glyceryl CBD , a derivative of THC or CBD , and an analog of THC , Cocoate , PEG -20 Almond Glycerides , PEG - 25 Hydroge CBD or mixtures thereof . nated Castor Oil , Stearamide MEA , Glyceryl Stearate (and ) 10 . The nasal pharmaceutical composition of claim 9 , PEG - 100 Stearate , Polysorbate 85 , PEG - 7 Olivate, Cetearyl wherein the cannabinoid is derived synthetically . Glucoside , Stearamide MEA , PEG - 8 Oleate , Polyglyceryl- 3 11. The nasal pharmaceutical composition of claim 9 , Methyglucose Distearate, Oleth - 10 , Oleth - 10 /Polyoxyl 10 wherein the cannabinoid is obtained by extraction from a Oleyl Ether NF, Ceteth - 10 , PEG - 8 Laurate , Cocamide MEA , natural source such as a pure strain or blend of strains of Polysorbate 60 NF, Polysorbate 60 , Polysorbate 80 , Isoste cannabis sativa . areth - 20 , PEG -60 Almond Glycerides, PEG - 20 Methyl Glu 12 . The nasal pharmaceutical composition of claim 2 , cose Sesquistearate , Ceteareth - 20 , Oleth -20 , Steareth - 20 , wherein the a wetting agent or mixture of wetting agents Steareth -20 , Steareth - 21 , Steareth - 21, Ceteth - 20 , and and /or a pharmaceutically acceptable surfactant or mixture Steareth - 100 . of surfactants is selected from the group consisting of: a polysorbate , a polyoxyethylene hydrogenated vegetable oil, 18 . The nasal pharmaceutical composition of claim 2 , a polyoxyethylene vegetable oil ; a polyoxyethylene sorbitan wherein the cannabinoid is CBD , the oily vehicle is Castor fatty acid ester ; a polyoxyethylene -polyoxypropylene block Oil, and the wetting agent is Oleoyl Polyoxylglycerides . copolymer ; a polyglycerol fatty acid ester; a polyoxyethyl 19 . The nasal pharmaceutical composition of claim 2 , ene glyceride ; a polyoxyethylene sterol, or a derivative or wherein the cannabinoid is THC , the oily vehicle is Castor analogue thereof; a reaction mixture of polyols and at least Oil, and the wetting agent is Oleoyl Polyoxylglycerides. one member of the group consisting of fatty acids , glycer 20 . The composition of claim 2 , wherein the cannabi ides , vegetable oils , hydrogenated vegetable oils , fraction noidis a mixture comprising THC and CBD , the oily vehicle ated oils and sterols ; a tocopheryl polyethylene glycol is Castor Oil, and the wetting agent is Oleoyl Polyoxylglyc succinate ; a sugar ester ; a sugar ether; a sucroglyceride ; an erides . alkylglucoside ; an alkylmaltoside ; an alkylthioglucosides ; a 21 . The nasal pharmaceutical composition of claim 2 , lauryl macrogolglyceride ; a polyoxyethylene alkyl ether ; a wherein the cannabinoid is a mixture comprising THC and polyoxyethylene alkylphenol; a polyethylene glycol fatty CBD , wherein the ratio of THC :CBD is between about acid ester; a polyethylene glycol glycerol fatty acid ester ; a 0 . 1 : 99 . 9 and about 99 . 9 : 0 . 1 . US 2017 /0348276 A1 Dec . 7 , 2017

22 . The nasal pharmaceutical composition of claim 16 , about 50 % w / w , the medium chain triglycerides are about wherein the cannabinoid is about 10 % w / w , the Castor Oil 35 % w / w , and the Polyoxyl 35 Hydrogenated Castor Oil is is about 76 % w / w , and the Oleoyl Polyoxylglycerides are about 5 % w /w . about 4 % w / w of the composition . 36 . The nasal pharmaceutical composition of claim 2 , 23 . The nasal pharmaceutical composition of claim 16 , wherein the cannabinoid is a cannabinoid therapeutic active wherein said nasal pharmaceutical composition further com or mixture of actives , the oily vehicle is SAIB and medium prises a Silicon Dioxide . chain triglycerides, and the wetting agent is Oleoyl Polyox 24 . The nasal pharmaceutical composition of claim 18 , ylglycerides . wherein the cannabinoid is about 10 % w / w , the Castor Oil 37 . The nasal pharmaceutical composition of claim 31 , wherein the cannabinoid is about 20 % w / w , the SAIB is is about 86 % w /w , the Oleoyl Polyoxylglycerides are about about 44 . 5 % w / w , the medium chain triglycerides are about 2 % w / w of the composition , and the Silicon Dioxide is about 31 % w / w , and the Oleoyl Polyoxylglycerides are about 4 . 5 % 2 % w / w of the composition . w / w . 25 . The nasal pharmaceutical composition of claim 18 , 38 . The nasal pharmaceutical composition of claim 2 wherein the cannabinoid therapeutic active or mixture of capable of achieving a serum cannabinoid concentration of actives is about 20 % w / w , the Castor Oil is about 73 .3 % about > 40ng /ml within 8 h after a single administration to a w / w , the Oleoyl Polyoxylglycerides are about 3 . 3 % w / w , fasted subject. and the Silicon Dioxide is about 3. 3 % w /w of the compo 39 . The nasal pharmaceutical composition of claim 2 sition . capable of achieving a serum cannabinoid concentration of 26 . The nasal pharmaceutical composition of claim 11 , about > 1 ng/ ml within 8 h after a single administration to a wherein the cannabinoid therapeutic active is cannabinoid fasted subject . therapeutic active or mixture of actives , the oily vehicle is 40 . The nasal pharmaceutical composition of claim 2 sesame oil , the wetting agent is Oleoyl Polyoxylglycerides, capable of achieving a serum cannabinoid concentration of and the rheology modifying agent is Silicon Dioxide . about > 0 . 1ng /mlwithin 8 h after a single nasal administra 27. The nasal pharmaceutical composition of claim 21 , tion to a fasted subject. wherein the cannabinoid therapeutic active or mixture of 41. The nasal pharmaceutical composition of claim 2 actives is about 10 % w / w , the sesame oil is about 86 % w / w , capable of achieving a serum cannabinoid concentration of the Oleoyl Polyoxylglycerides are about 2 % w / w , and the at least about > 0 . 5ng /ml within 8 h after nasal administration Silicon Dioxide is about 2 % w /w of the composition . to a fasted subject. 28 . The nasal pharmaceutical composition of claim 21, 42 . Use of a dispenser to nasally administer the nasal wherein the cannabinoid therapeutic active or mixture of pharmaceutical composition of composition claim 1 to the actives is about 20 % w / w , the sesame oil is about 73 . 3 % nasal vestibule of a nostril of a subject in need thereof. w / w , the Oleoyl Polyoxylglycerides are about 3 . 3 % w / w , 43 . Use of an airless dispenser to nasally administer the and the Silicon Dioxide is about 3 . 3 % w / w of the compo nasal pharmaceutical composition of claim 1 to the nasal sition . vestibule of a nostril of a subject in need thereof. 29 . The nasal pharmaceutical composition of claim 2 , 44 . Use of an airless metered -dose dispenser to nasally wherein the cannabinoid therapeutic active is cannabinoid administer the nasal pharmaceutical composition of claim 1 therapeutic active or mixture of actives, the oily vehicle is to the nasal vestibule of a nostril of a patients to patients in sesame oil and olive oil , the wetting agent is Oleoyl Poly need thereof. oxylglycerides, and the rehology modifying agent is 45 . Use of an airless metered - dose dispenser to nasally Hydroxypropylcellulose . administer the nasal pharmaceutical composition of claim 1 30 . The nasal pharmaceutical composition of claim 24 to the nasal vestibule of a nostril of a patients to patients in wherein the cannabinoid therapeutic active or mixture of need thereof, wherein the therapeutically effective amount actives is about 12 % w / w , the sesame oil is about 20 % w / w , of a cannabinoid comprises a cannabinoid therapeutic active the olive oil is about 20 % w / w , the Oleoyl Polyoxylglycer or mixture of actives . ides are about 4 % w / w , the Hydroxypropylcellulose is about 46 . Use of an airless metered -dose dispenser to nasally 4 % w / w , further comprising about 40 % w / w water. administer about 50 to 150 uL of the nasal pharmaceutical 31 . The nasal pharmaceutical composition of claim 1 , composition of claim 1 to the nasal vestibule of a nostril of wherein the cannabinoid comprises a cannabinoid therapeu a patient in need thereof. 47. Use of an airless metered -dose dispenser to administer tic active or a mixture of actives and SAIB . from about 0 . 1 to 75 mg of cannabinoid therapeutic active 32 . The nasal pharmaceutical composition of claim 26 or mixture of actives comprised in a gel composition to the consisting essentially of a cannabinoid therapeutic active or nasal vestibule of a nostril of a subject in need thereof. mixture of actives and SAIB . 48 . Use of an airless metered - dose dispenser to administer 33 . The nasal pharmaceutical composition of claim 27 the nasal composition of claim 2 to the nasal vestibule of a comprising about 10 % w / w cannabinoid therapeutic active nostril of a subject in need thereof, wherein the therapeuti or mixture of actives. cally effective amount of the cannabinoid is from about 0 . 1 34 . The nasal pharmaceutical composition of claim 2 , to 75 mg, and the nasal pharmaceutical composition of claim wherein the cannabinoid is a cannabinoid therapeutic active 2 is a gel . or mixture of actives , the oily vehicle is SAIB and medium 49. Nasal administration of the nasal composition of chain triglycerides , and the wetting agent is Polyoxyl 35 claim 1 to the nasal vestibule of a nostril of a subject to treat Hydrogenated Castor Oil . the subject for antipsychosis , epilepsy, schizophrenia , anxi 35 . The nasal pharmaceutical composition of claim 29 , ety , sleep disturbances , neurodegeneration , psychosis , wherein the cannabinoid is about 10 % w /w , the SAIB is depression , glaucoma, neurodegeneration , cerebral and US 2017 /0348276 A1 Dec . 7 , 2017 24 myocardial ischemia , inflammation , pain including chronic 65 . The nasal pharmaceutical composition of claim 1 , pain , immune responses , emesis , food intake , such as appe - wherein the cannabinoid contains at least between about 0 . 1 tite stimulation in HIV / AIDS , type 1 diabetes , liver disease , mg to about 37 . 5 mg of THC . osteogenesis , cancer, conditions relating to certain types of 66 . The nasal pharmaceutical composition of claim 1 , cancer including nausea and vomiting , a movement disorder , wherein the cannabinoid contains at least between about 1 . 0 a mood disorder , a psychological disorder and Tourette mg to about 20 mg of THC . syndrome. 67 . The nasal pharmaceutical composition of claim 1, 50 . Nasal administration of the nasal composition of wherein the cannabinoid contains at least between about 2 . 0 claim 2 to the nasal vestibule of a nostril of a subject to treat mg to about 10 mg of THC . the subject for antipsychosis , epilepsy, schizophrenia , anxi 68 . The nasal pharmaceutical composition of claim 1 , ety , sleep disturbances , neurodegeneration , psychosis , wherein the cannabinoid is at least about 90 % THC . depression , glaucoma, neurodegeneration , cerebral and 69 . The nasal pharmaceutical composition of claim 1 , myocardial ischemia , inflammation , pain including chronic wherein the cannabinoid is at least about 95 % THC . pain , immune responses , emesis , food intake , such as appe 70 . The nasal pharmaceutical composition of claim 1 , tite stimulation in HIV / AIDS , type - 1 diabetes , liver disease , wherein the cannabinoid is at least about 98 % THC . osteogenesis , cancer , conditions relating to certain types of 71 . The nasal pharmaceutical composition of claim 1 , cancer including nausea and vomiting , a movement disorder , wherein the cannabinoid is at least about 99 % THC . a mood disorder , a psychological disorder and Tourette 72 . The nasal pharmaceutical composition of claim 1 , syndrome. wherein the cannabinoid is about 100 % THC . 51. Nasal administration of the nasal composition of 73 . The nasal pharmaceutical composition of claim 1 , claim 2 to the nasal vestibule of a nostril of a subject to treat wherein the nasal pharmaceutical formulation is free of the subject for schizophrenia , pain , migraine , spasticity , CBD . epilepsy or anxiety . 74 . The nasal pharmaceutical composition of claim 1, wherein the nasal pharmaceutical formulation is not a nasal 52. The nasal pharmaceutical composition of claim 1 , liquid spray. wherein the nasal pharmaceutical composition is a gel. 75 . The nasal pharmaceutical composition of claim , 53 . The nasal pharmaceutical composition of claim 52 , wherein the cannabinoid contains at least between about 5 wherein the gel is a thixotropic gel. mg to about 25 mg of CBD . 54 . The nasal pharmaceutical composition of claim 1 , 76 . The nasal pharmaceutical composition of claim 1 , wherein the nasal pharmaceutical composition is a cream . wherein the cannabinoid contains at least between about 0 . 1 55. The nasal pharmaceutical composition of claim 54 , mg to about 37. 5 mg of CBD . wherein the cream is a thixotropic cream . 77 . The nasal pharmaceutical composition of claim 1 , 56 . The nasal pharmaceutical composition of claim 1, wherein the cannabinoid contains at least between about 1 wherein the nasal pharmaceutical composition is a viscous mg to about 35 mg of THC . liquid . 78 . The nasal pharmaceutical composition of claim 1, 57 . The nasal pharmaceutical composition of claim 56 , wherein the cannabinoid contains at least between about 2 wherein the viscous liquid is a thixotropic viscous liquid . mg to about 30 mg of THC . 58 . The nasal pharmaceutical composition of claim 1 , 79 . The nasal pharmaceutical composition of claim 1 , wherein said nasal pharmaceutical composition has a for wherein the cannabinoid is at least about 50 % CBD . mulation selected from a group formulations consisting of 80 . The nasal pharmaceutical composition of claim1, the formulations set forth in Examples 1 - 21. wherein the cannabinoid is at least about 60 % CBD . 59 . The nasal pharmaceutical composition of claim 1 , 81 . The nasal pharmaceutical composition of claim 1 , wherein the semi- solid or viscous liquid nasal pharmaceu wherein the cannabinoid is at least about 70 % CBD . tical composition has a viscosity that ranges between 500 82 . The nasal pharmaceutical composition of claim 1 , cps and 1 ,000 cps. wherein the cannabinoid is at least about 80 % CBD . 60 . The nasal pharmaceutical composition of claim 1 , 83 . The nasal pharmaceutical composition of claim 1 , wherein the semi- solid or viscous liquid nasal pharmaceu wherein the cannabinoid is at least about 90 % CBD . tical composition has a viscosity that ranges between 1 , 000 84 . The nasal pharmaceutical composition of claim 1 , cps and 75 ,000 cps. wherein the cannabinoid is at least about 95 % CBD . 61 . The nasal pharmaceutical composition of claim 1 , 85 . The nasal pharmaceutical composition of claim 1 , wherein the semi- solid or viscous liquid nasal pharmaceu wherein the cannabinoid is at least about 98 % CBD . tical composition has a viscosity that ranges between 1 ,000 86 . The nasal pharmaceutical composition of claim 1 , cps and 75 ,000 cps. wherein the cannabinoid is at least about 99 % CBD . 62 . The nasal pharmaceutical composition of claim 1 , 87 . The nasal pharmaceutical composition of claim 1 , wherein the semi- solid or viscous liquid nasal pharmaceu wherein the cannabinoid is about 100 % CBD . tical composition has a viscosity that ranges between 2500 88 . The nasal pharmaceutical composition of claim 1 , cps and 50 , 000 cps. wherein the nasal pharmaceutical formulation is free of 63 . The nasal pharmaceutical composition of claim 1 , THC . wherein the semi- solid or viscous liquid nasal pharmaceu 89 . A nasal pharmaceutical composition for topical appli tical composition that ranges between 5 , 000 cps and 25, 000 cation in the nasal cavity of a subject to treat the subject for cps. pain who is in need of pain treatment, said nasal pharma 64 . The nasal pharmaceutical composition of claim 1 , ceutical composition comprising : wherein the cannabinoid contains at least between about 0 . 5 ( a ) a therapeutically effective amount of a cannabinoid ; mg to about 2 . 5 mg of THC . ( b ) a pharmaceutically acceptable excipient; US 2017 /0348276 A1 Dec . 7 , 2017 25

wherein , the nasal pharmaceutical composition is a semi 106 . The nasal pharmaceutical composition of claim 89 , solid or viscous liquid nasal pharmaceutical composi- wherein the nasal pharmaceutical formulation is free of tion ; CBD . wherein , the semi- solid or viscous liquid nasal pharma 107 . The nasal pharmaceutical composition of claim 89 , ceutical composition has a viscosity that ranges wherein the nasal pharmaceutical formulation is not a nasal between about 500 cps and about 100 , 000 cps; liquid spray . wherein , the semi- solid or viscous liquid nasal pharma 108 . A method of treating a subject for pain , who is in ceutical composition is selected from a group of a need of pain treatment , said method comprising : semi- solid or viscous liquid nasal pharmaceutical com nasally administering a nasal pharmaceutical composition positions consisting of a cream , a gel and a viscous into at least one nostril of the subject at least once per liquid ; and day in a dose amount effective to treat the subject ' s pain wherein , the therapeutically effective amount of the can or to alleviate or reduce the subject ' s pain symptoms nabinoid contains at least about 0 . 1 mg of THC , so that, caused by the pain ; upon nasal topical administration of the nasal pharma wherein the nasal pharmaceutical composition compris ceutical composition into at least one nostril of the ing: subject' s nasal cavity , the subject' s pain is treated or the ( a ) a therapeutically effective amount of a cannabinoid , subject' s symptoms caused by the pain are alleviated or ( b ) a pharmaceutically acceptable excipient; reduced wherein , the nasal pharmaceutical composition is a semi 90 . The nasal pharmaceutical composition of claim 89 , solid or viscous liquid nasal pharmaceutical composi tion ; wherein the semi- solid or viscous liquid nasal pharmaceu wherein , the semi- solid or viscous liquid nasal pharma tical composition has a viscosity that ranges between 1 ,000 ceutical composition has a viscosity that ranges cps and 75, 000 cps. between about 500 cps and about 100 ,000 cps; 91 . The nasal pharmaceutical composition of claim 89 , wherein , the semi- solid or viscous liquid nasal pharma wherein the semi- solid or viscous liquid nasal pharmaceu ceutical composition is selected from a group of a tical composition has a viscosity that ranges between 2500 semi- solid or viscous liquid nasal pharmaceutical com cps and 50 , 000 cps . positions consisting of a cream , a gel and a viscous 92 . The nasal pharmaceutical composition of claim 89 , liquid ; and wherein the semi- solid or viscous liquid nasal pharmaceu wherein , the dose amount ranges from between about 50 tical composition that ranges between 5 , 000 cps and 25, 000 ul and about 150 ul per nostril ; cps . wherein , the therapeutically effective amount of the can 93 . The nasal pharmaceutical composition of claim 89 , nabinoid ranges from about 0 . 1 mg to about 37 . 5 mg; wherein the pain is chronic pain . and 94 . The nasal pharmaceutical composition of claim 89 , wherein , the cannabinoid contains at least about 0 . 1 mg of wherein the pain is neuropathic pain THC . 95 . The nasal pharmaceutical composition of claim 89 , 109 . The method of claim 108 , wherein the pain is chronic wherein the subject is suffering from cancer and the pain is pain . ??caused by the cancer . 110 . The method of claim 108 , wherein the pain is 96 . The nasal pharmaceutical composition of claim 89 , neuropathic pain . wherein the subject is suffering from fibromyalgia and the 111. The method of claim 108 , wherein the subject is pain is fibromyalgia pain . suffering from cancer and the pain is caused by the cancer . 97 . The nasal pharmaceutical composition of claim 89 , 112 . The method of claim 108 , wherein the subject is wherein the cannabinoid contains at least between about 0 . 5 suffering from fibromyalgia and the pain is fibromyalgia mg to about 2 . 5 mg of THC . pain . 98 . The nasal pharmaceutical composition of claim 89 , 113 . The method of claim 108 , wherein the cannabinoid wherein the cannabinoid contains at least between about 0 . 1 contains at least between about 0 . 5 mg to about 2 . 5 mg of mg to about 37 . 5 mg of THC . THC . 114 . The method of claim 108 , wherein the cannabinoid 99 . The nasal pharmaceutical composition of claim 89 , contains at least between about 0 . 1 mg to about 37 . 5 mg of wherein the cannabinoid contains at least between about 1 . 0 THC . mg to about 20 mg of THC . 115 . The method of claim 108 , wherein the cannabinoid 100 . The nasal pharmaceutical composition of claim 89 , contains at least between about 1 mg to about 20 mg of THC . wherein the cannabinoid contains at least between about 2 . 0 116 . The method of claim 108 , wherein the cannabinoid mg to about 10 mg of THC . contains at leastbetween about 2 mg to about 10 mg of THC . 101 . The nasal pharmaceutical composition of claim 89 , 117 . The method of claim 108 , wherein the cannabinoid wherein the cannabinoid is at least about 90 % THC . is at least about 90 % THC . 102 . The nasal pharmaceutical composition of claim 89 , 118 . The method of claim 108 , wherein the cannabinoid wherein the cannabinoid is at least about 95 % THC . is at least about 95 % THC . 103 . The nasal pharmaceutical composition of claim 89 , 119 . The method of claim 108 , wherein the cannabinoid wherein the cannabinoid is at least about 98 % . is at least about 98 % THC . 104 . THC . The nasal pharmaceutical composition of claim 120 . The method of claim 108, wherein the cannabinoid 89 , wherein the cannabinoid is at least about 99 % THC . is at least about 99 % THC . 105 . The nasal pharmaceutical composition of claim 89 , 121. The method of claim 108 , wherein the cannabinoid wherein the cannabinoid is about 100 % THC . is about 100 % THC . US 2017 /0348276 A1 Dec . 7 , 2017 26

122 . The method of claim 108 , wherein said nasal admin 134 . The nasal pharmaceutical composition of claim 132 , istration step comprises : wherein the semi- solid or viscous liquid nasal pharmaceu nasally administering the nasal pharmaceutical composi tical composition has a viscosity that ranges between 2500 tion into at least one nostril of the subject at least twice cps and 50 ,000 cps . per day. 135 . The nasal pharmaceutical composition of claim 132 , 123 . The method of claim 108 , wherein said nasal admin wherein the semi- solid or viscous liquid nasal pharmaceu istration step comprises : tical composition that ranges between 5 ,000 cps and 25 ,000 nasally administering the nasal pharmaceutical composi cps . tion into at least one nostril of the subject at least three 136 . The nasal pharmaceutical composition of claim 132 , times per day . wherein the cannabinoid contains at least between about 0 . 1 122 . The method of claim 108 , wherein said nasal admin mg to about 37. 5 mg of CBD . istration step comprises : 137 . The nasal pharmaceutical composition of claim 132 , nasally administering the nasal pharmaceutical composi wherein the cannabinoid contains at least between about 0 . 5 tion into at least one nostril of the subject at least four mg to about 35 mg of CBD . times per day . 138 . The nasal pharmaceutical composition of claim 132 , 124 . Themethod of claim 108 , wherein said nasal admin wherein the cannabinoid contains at least between about 1 istration step comprises : mg to about 30 mg of THC . nasally administering the nasal pharmaceutical composi 139 . The nasal pharmaceutical composition of claim 132 , tion into at least one nostril of the subject up to at least wherein the cannabinoid contains at least between about 2 four times per day. mg to about 25 mg of THC . 125 . The method of claim 108 , wherein the semi- solid or 140 . The nasal pharmaceutical composition of claim 132 , viscous liquid nasal pharmaceutical composition has a vis wherein the cannabinoid contains at least between about 2 cosity that ranges between 500 cps and 100 , 000 cps. mg to about 25 mg of THC . 126 . The method of claim 108 , wherein the semi- solid or 141. The nasal pharmaceutical composition of claim 132 , viscous liquid nasal pharmaceutical composition has a vis wherein the cannabinoid contains at least between about 0 . 5 cosity that ranges between 1 , 000 cps and 75 , 000 cps . mg to about 2 . 5 mg of THC . 127 . The method of claim 108 , wherein the semi- solid or 142 . The nasal pharmaceutical composition of claim 132 , viscous liquid nasal pharmaceutical composition has a vis wherein the cannabinoid is at least about 50 % CBD . cosity that ranges between 2500 cps and 50 ,000 cps. 143. The nasal pharmaceutical composition of claim 132 , 128 . The method of claim 108 , wherein the semi- solid or wherein the cannabinoid is at least about 60 % CBD . viscous liquid nasal pharmaceutical composition that ranges 144 . The nasal pharmaceutical composition of claim 132 , between 5 ,000 cps and 25 , 000 cps. wherein the cannabinoid is at least about 70 % CBD . 129 . The method of claim 108 , wherein the nasal phar 145 . The nasal pharmaceutical composition of claim 132 , maceutical composition is a viscous liquid . wherein the cannabinoid is at least about 80 % CBD . 130 . The method of claim 108 , wherein the nasal phar - 146 . The nasal pharmaceutical composition of claim 132 , maceutical composition is a gel . wherein the cannabinoid is at least about 90 % CBD . 131 . The method of claim 108 , wherein the nasal phar 147. The nasal pharmaceutical composition of claim 132 , maceutical composition is a cream . wherein the cannabinoid is at least about 95 % CBD . 132 . A nasal pharmaceutical composition for topical 148 . The nasal pharmaceutical composition of claim 132 , application in the nasal cavity of a subject to treat the subject wherein the cannabinoid is at least about 98 % CBD . for epilepsy who is in need of epileptic treatment, said nasal 149 . The nasal pharmaceutical composition of claim 132 , pharmaceutical composition comprising : wherein the cannabinoid is at least about 99 % CBD . (a ) a therapeutically effective amount of a cannabinoid ; 150 . The nasal pharmaceutical composition of claim 132 , (b ) a pharmaceutically acceptable excipient; wherein the cannabinoid is about 100 % CBD . wherein , the nasal pharmaceutical composition is a semi 151. The nasal pharmaceutical composition of claim 132 , solid or viscous liquid nasal pharmaceutical composi wherein the nasal pharmaceutical formulation is free of tion ; THC . wherein , the semi- solid or viscous liquid nasal pharma 152. The nasal pharmaceutical composition of claim 132 , ceutical composition has a viscosity that ranges wherein the nasal pharmaceutical formulation is not a nasal between about 500 cps and about 100 ,000 cps ; liquid spray . wherein , the semi- solid or viscous liquid nasal pharma 153 . A method of treating a subject for epilepsy , who is in ceutical composition is selected from a group of a need of epileptic treatment, said method comprising : semi- solid or viscous liquid nasal pharmaceutical com nasally administering a nasal pharmaceutical composition positions consisting of a cream , a gel and a viscous into at least one nostril of the subject at least once per liquid ; and day in a dose amount effective to treat the subject for wherein , the cannabinoid is CBD - rich or pure CBD and epilepsy or to alleviate or reduce the subject' s epileptic contains at least about 0 . 1 mg of CBD , so that, upon symptoms caused by the epilepsy ; nasal topical administration of the nasal pharmaceutical wherein , the nasal pharmaceutical composition compris composition into at least one nostril of the subject' s ing : nasal cavity , the subject is treated for epilepsy . ( a ) a therapeutically effective amount of a cannabinoid , 133 . The nasal pharmaceutical composition of claim 132 , ( b ) a pharmaceutically acceptable excipient; wherein the semi- solid or viscous liquid nasal pharmaceu wherein , the nasal pharmaceutical composition is a semi tical composition has a viscosity that ranges between 1, 000 solid or viscous liquid nasal pharmaceutical composi cps and 75 ,000 cps. tion ; US 2017 /0348276 A1 Dec . 7 , 2017 27

wherein , the semi- solid or viscous liquid nasal pharma 171. The method of claim 153 , wherein the semi- solid or ceutical composition has a viscosity that ranges viscous liquid nasal pharmaceutical composition has a vis between about 500 cps and about 100 ,000 cps; cosity that ranges between 500 cps and 100 , 000 cps . wherein , the semi- solid or viscous liquid nasal pharma 172 . The method of claim 153, wherein the semi- solid or ceutical composition is selected from a group of a viscous liquid nasal pharmaceutical composition has a vis semi- solid or viscous liquid nasal pharmaceutical com cosity that ranges between 1 , 000 cps and 75 ,000 cps. positions consisting of a cream , a gel and a viscous 173 . The method of claim 153, wherein the semi- solid or liquid ; viscous liquid nasal pharmaceutical composition has a vis wherein , the cannabinoid is CBD - rich or pure CBD ; cosity that ranges between 2500 cps and 50 , 000 cps . 174 . The method of claim 153, wherein the semi- solid or wherein , the dose amount ranges from between about 50 viscous liquid nasal pharmaceutical composition that ranges ul and about 150 ul per nostril ; between 5 ,000 cps and 25 ,000 cps. wherein , the therapeutically effective amount of the can 175 . The method of claim 153, wherein the nasal phar nabinoid is at least about 0 . 1 mg ; and maceutical composition is a viscous liquid . wherein , the cannabinoid contains at least about 0 . 1 mg of 176 . The method of claim 153, wherein the nasal phar CBD . maceutical composition is a gel . 154 . The method of claim 153 , wherein the cannabinoid 177 . The method of claim 153 , wherein the nasal phar contains at least between about 0 . 1 mg to about 37 . 5 mg of maceutical composition is a cream . CBD . 178 . A nasal pharmaceutical composition for topical 155 . The method of claim 153 , wherein the cannabinoid application in the nasal cavity of a subject to treat the subject contains at least between about 1 mg to about 35 mg of for schizophrenia who is in need of schizophrenic treatment, CBD . said nasal pharmaceutical composition comprising : 156 . The method of claim 153 wherein the cannabinoid (a ) a therapeutically effective amount of a cannabinoid ; contains at least between about 2 . 5 mg to about 30 mg of ( b ) a pharmaceutically acceptable excipient; CBD . wherein , the nasal pharmaceutical composition is a semi 157 . The method of claim 153 , wherein the cannabinoid solid or viscous liquid nasal pharmaceutical composi contains at least between about 5 mg to about 25 mg of tion ; CBD . wherein , the semi- solid or viscous liquid nasal pharma 158 . The method of claim 153 , wherein the cannabinoid ceutical composition has a viscosity that ranges contains about 20 mg of CBD . between about 500 cps and about 100 , 000 cps; 159 . The method of claim 153 , wherein the cannabinoid wherein , the semi- solid or viscous liquid nasal pharma contains at least between about 37 .5 mg of CBD . ceutical composition is selected from a group of a 160 . The method of claim 153 , wherein the cannabinoid semi- solid or viscous liquid nasal pharmaceutical com is at least about 50 % CBD . positions consisting of a cream , a gel and a viscous 161 . The method of claim 153 , wherein the cannabinoid liquid ; and is at least about 60 % CBD . wherein , the cannabinoid is CBD - rich or pure CBD and 162 . The method of claim 153 , wherein the cannabinoid contains at least about 0 . 1 mg of CBD , so that, upon is at least about 70 % CBD . nasal topical administration of the nasal pharmaceutical 163 . The method of claim 153 , wherein the cannabinoid composition into at least one nostril of the subject' s nasal cavity , the subject is treated for schizophrenia . is at least about 80 % CBD . 179 . The nasal pharmaceutical composition of claim 178 , 164 . The method of claim 153 , wherein the cannabinoid wherein the semi- solid or viscous liquid nasal pharmaceu is at least about 95 % CBD . tical composition has a viscosity that ranges between 1 , 000 165 . The method of claim 153 , wherein the cannabinoid cps and 75 ,000 cps. is at least about 98 % CBD . 180 . The nasal pharmaceutical composition of claim 178 , 166 . The method of claim 153 , wherein the cannabinoid wherein the semi- solid or viscous liquid nasal pharmaceu is at least about 99 % CBD . tical composition has a viscosity that ranges between 2500 167 . The method of claim 153 , wherein the cannabinoid cps and 50 , 000 cps . is about 100 % CBD . 181 . The nasal pharmaceutical composition of claim 178 , 168 . The method of claim 153, wherein said nasal admin wherein the semi- solid or viscous liquid nasal pharmaceu istration step comprises: tical composition that ranges between 5 , 000 cps and 25 , 000 nasally administering the nasal pharmaceutical composi cps. tion into at least one nostril of the subject at least twice 182 . The nasal pharmaceutical composition of claim 178 , per day. wherein the cannabinoid contains at least between about 5 169 . The method of claim 153 , wherein said nasal admin mg to about 25 mg of CBD . istration step comprises: 183. The nasal pharmaceutical composition of claim 178, nasally administering the nasal pharmaceutical composi wherein the cannabinoid contains at least between about 0 . 1 tion into at least one nostril of the subject at least three mg to about 37 . 5 mg of CBD . times per day. 184 . The nasal pharmaceutical composition of claim 178 , 170 . The method of claim 153 , wherein said nasal admin wherein the cannabinoid contains at least between about 1 istration step comprises: mg to about 35 mg of CBD . nasally administering the nasal pharmaceutical composi 185 . The nasal pharmaceutical composition of claim 178 , tion into at least one nostril of the subject up to at least wherein the cannabinoid contains at least between about 2 three times per day. mg to about 30 mg of CBD . US 2017 /0348276 A1 Dec . 7 , 2017 28

186 . The nasal pharmaceutical composition of claim 178 , 201. The nasal pharmaceutical composition of claim 178 , wherein the cannabinoid is at least about 50 % CBD . wherein the cannabinoid contains at least between about 2 187 . The nasal pharmaceutical composition of claim 178 , mg to about 30 mg of CBD . wherein the cannabinoid is at least about 60 % CBD . 202 . The method of claim 197 , wherein the cannabinoid 188 . The nasal pharmaceutical composition of claim 178 , contains about 20 mg of CBD . wherein the cannabinoid is at least about 70 % CBD . 203. The method of claim 197 , wherein the cannabinoid 189 . The nasal pharmaceutical composition of claim 178 , contains at least between about 37 . 5 mg of CBD . wherein the cannabinoid is at least about 80 % CBD . 204 . The method of claim 197 , wherein the cannabinoid 190 . The nasal pharmaceutical composition of claim 178 , is at least about 50 % CBD . wherein the cannabinoid is at least about 90 % CBD . 205 . The method of claim 197 , wherein the cannabinoid 191 . The nasal pharmaceutical composition of claim 178 , is at least about 60 % CBD . wherein the cannabinoid is at least about 95 % CBD . 206 . The method of claim 197 , wherein the cannabinoid 192 . The nasal pharmaceutical composition of claim 178 , is at least about 70 % CBD . wherein the cannabinoid is at least about 98 % CBD . 207 . The method of claim 197 , wherein the cannabinoid 193 . The nasal pharmaceutical composition of claim 178 , is at least about 80 % CBD . wherein the cannabinoid is at least about 99 % CBD . 208 . The method of claim 197 , wherein the cannabinoid 194 . The nasal pharmaceutical composition of claim 178 , is at least about 95 % CBD . wherein the cannabinoid is about 100 % CBD . 195 . The nasal pharmaceutical composition of claim 178 , 209 . The method of claim 197, wherein the cannabinoid wherein the nasal pharmaceutical formulation is free of is at least about 98 % CBD . THC . 210 . The method of claim 197 , wherein the cannabinoid 196 . The nasal pharmaceutical composition of claim 178 , is at least about 99 % CBD . wherein the nasal pharmaceutical formulation is not a nasal 211 . The method of claim 197 , wherein the cannabinoid liquid spray . is about 100 % CBD . 197 . A method of treating a subject for schizophrenia , 212. The method of claim 197 , wherein said nasal admin who is in need of schizophrenia treatment, said method istration step comprises : comprising: nasally administering the nasal pharmaceutical composi nasally administering the nasal pharmaceutical composi tion into at least one nostril of the subject at least twice tion of claim 178 , into at least one nostril of the subject per day. at least once per day in a dose amount effective to treat 213 . The method of claim 197 , wherein said nasal admin the subject for schizophrenia or to alleviate or reduce istration step comprises : the subject' s schizophrenic symptoms caused by the nasally administering the nasal pharmaceutical composi schizophrenia ; tion into at least one nostril of the subject at least three wherein , the nasal pharmaceutical composition compris times per day . ing: 214 . The method of claim 197 , wherein said nasal admin ( a ) a therapeutically effective amount of a cannabinoid , istration step comprises ( b ) a pharmaceutically acceptable excipient , nasally administering the nasal pharmaceutical composi wherein , the nasal pharmaceutical composition is a semi tion of claim 197 , into at least one nostril of the subject solid or viscous liquid nasal pharmaceutical composi at least four times per day . tion , 215. The method of claim 197 , wherein said nasal admin wherein , the semi- solid or viscous liquid nasal pharma istration step comprises: ceutical composition has a viscosity that ranges nasally administering the nasal pharmaceutical composi between about 500 cps and about 100 , 000 cps, tion into at least one nostril of the subject up to at least wherein , the semi- solid or viscous liquid nasal pharma four times per day. ceutical composition is selected from a group of a 216 . The method of claim 197 , wherein the semi- solid or semi- solid or viscous liquid nasal pharmaceutical com viscous liquid nasal pharmaceutical composition has a vis positions consisting of a cream , a gel and a viscous cosity that ranges between 500 cps and 100 , 000 cps . liquid ; and 217 . The method of claim 197, wherein the semi- solid or wherein , the cannabinoid is CBD - rich or pure ; viscous liquid nasal pharmaceutical composition has a vis wherein , the dose amount ranges from between about 50 cosity that ranges between 1 , 000 cps and 75 , 000 cps . ul and about 150 ul per nostril ; 218 . The method of claim 197 , wherein the semi- solid or wherein , the therapeutically effective amount of the can viscous liquid nasal pharmaceutical composition has a vis nabinoid is about 0 . 1 mg; and cosity that ranges between 2500 cps and 50 ,000 cps . wherein , the cannabinoid contains at least about 0 . 1 mg of 219 . The method of claim 197 , wherein the semi- solid or CBD . viscous liquid nasal pharmaceutical composition that ranges 198 . The nasal pharmaceutical composition of claim 178 , between 5 ,000 cps and 25 ,000 cps . wherein the cannabinoid contains at least between about 5 220 . The method of claim 197 , wherein the nasal phar mg to about 25 mg of CBD . maceutical composition is a viscous liquid . 199 . The nasal pharmaceutical composition of claim 178 , 221 . The method of claim 197 , wherein the nasal phar wherein the cannabinoid contains at least between about 0 . 1 maceutical composition is a gel. mg to about 37 .5 mg of CBD . 222 . The method of claim 197 , wherein the nasal phar 200 . The nasal pharmaceutical composition of claim 178 , maceutical composition is a cream . wherein the cannabinoid contains at least between about 1 223 . A nasal pharmaceutical composition for topical mg to about 35 mg of CBD . application in the nasal cavity of a subject to treat the subject US 2017 /0348276 A1 Dec . 7 , 2017 29

for anxiety a disorder who is in need of disorder treatment, 240 . The nasal pharmaceutical composition of claim 223 , said nasal pharmaceutical composition comprising : wherein the nasal pharmaceutical formulation is free of ( a ) a therapeutically effective amount of a cannabinoid ; THC . (b ) a pharmaceutically acceptable excipient; 241 . The nasal pharmaceutical composition of claim 223 , wherein , the nasal pharmaceutical composition is a semi wherein the nasal pharmaceutical formulation is not a nasal solid or viscous liquid nasal pharmaceutical composi liquid spray. tion ; 242. The nasal pharmaceutical composition of claim 223 , wherein , the semi- solid or viscous liquid nasal pharma wherein the disorder is selected from a group of disorders ceutical composition has a viscosity that ranges consisting of anti -psychosis , epilepsy, schizophrenia , arthri between about 500 cps and about 100 ,000 cps ; tis , asthma, antipsychosis, anxiety , sleep disturbances , neu wherein , the semi- solid or viscous liquid nasal pharma rodegeneration , psychosis , depression , glaucoma , neurode ceutical composition is selected from a group of a generation , cerebral and myocardial ischemia , semi- solid or viscous liquid nasal pharmaceutical com inflammation , immune response , emesis, food intake , such positions consisting of a cream , a gel and a viscous as appetite stimulation in HIV /AIDS , diabetes ), liver dis liquid ; and ease , osteogenesis , cancer conditions relating to certain wherein , the cannabinoid is CBD - rich or pure CBD and types of cancer including nausea and vomiting , a movement contains at least about 0 . 1 mg of CBD and/ or about 0 . 1 disorder , a mood disorder ) , a psychological disorder and mg of THC , so that, upon nasal topical administration Tourette syndrome. of the nasal pharmaceutical composition into at least 243 . A method of treating a subject for a disorder , who is one nostril of the subject' s nasal cavity, the subject is in need of disorder treatment, said method comprising: treated for the disorder. nasally administering the nasal pharmaceutical composi 224 . The nasal pharmaceutical composition of claim 223 , tion of claim , into at least one nostril of the subject at wherein the semi- solid or viscous liquid nasal pharmaceu least once per day in a dose amount effective to treat the tical composition has a viscosity that ranges between 1 ,000 subject for the disorder or to alleviate or reduce the cps and 75 ,000 cps. subject' s symptoms caused by the disorder; 225 . The nasal pharmaceutical composition of claim 223 , wherein , the nasal pharmaceutical composition compris wherein the semi- solid or viscous liquid nasal pharmaceu ing : tical composition has a viscosity that ranges between 2500 ( a ) a therapeutically effective amount of a cannabinoid , cps and 50 , 000 cps. ( b ) a pharmaceutically acceptable excipient; 226 . The nasal pharmaceutical composition of claim 223 , wherein , the nasal pharmaceutical composition is a semi wherein the semi- solid or viscous liquid nasal pharmaceu solid or viscous liquid nasal pharmaceutical composi tical composition that ranges between 5 ,000 cps and 25 ,000 tion ; cps . wherein , the semi- solid or viscous liquid nasal pharma 227. The nasal pharmaceutical composition of claim 223 , ceutical composition has a viscosity that ranges wherein the cannabinoid contains at least between about 5 between about 500 cps and about 100 , 000 cps ; =mg to about 25 mg of CBD . wherein , the semi- solid or viscous liquid nasal pharma 228 . The nasal pharmaceutical composition of claim 223 , ceutical composition is selected from a group of a wherein the cannabinoid contains at least between about 0 . 1 semi- solid or viscous liquid nasal pharmaceutical com mg to about 37. 5 mg of CBD . positions consisting of a cream , a gel and a viscous 229. The nasal pharmaceutical composition of claim 223 , liquid ; wherein the cannabinoid contains at least between about 1 wherein , the cannabinoid is CBD - rich or pure CBD ; mg to about 35 mg of THC . wherein , the dose amount ranges from between about 50 230 . The nasal pharmaceutical composition of claim 223 , ul and about 150 ul per nostril; wherein the cannabinoid contains at least between about 2 wherein , the therapeutically effective amount of the can mg to about 30 mg of THC . nabinoid is at least about 0 . 1 mg; and 231 . The nasal pharmaceutical composition of claim 223 , wherein , the cannabinoid contains at least about 0 . 1 mg of wherein the cannabinoid is at least about 50 % CBD . CBD and / or THC . 232 . The nasal pharmaceutical composition of claim 223 , 244 . The method of claim 243 , wherein the cannabinoid wherein the cannabinoid is at least about 60 % CBD . contains at least between about 0 . 1 mg to about 37. 5 mg of 233 . The nasal pharmaceutical composition of claim 223 , CBD . wherein the cannabinoid is at least about 70 % CBD . 245 . The method of claim 243 , wherein the cannabinoid 234 . The nasal pharmaceutical composition of claim 223 , contains at least between about 1 mg to about 35 mg of =wherein the cannabinoid is at least about 80 % CBD . CBD . 235 . The nasal pharmaceutical composition of claim 223 , 246 . The method of claim 243 , wherein the cannabinoid wherein the cannabinoid is at least about 90 % CBD . contains at least between about 2 . 5 mg to about 30 mg of 236 . The nasal pharmaceutical composition of claim 223, CBD . wherein the cannabinoid is at least about 95 % CBD . 247 . The method of claim 243 , wherein the cannabinoid 237 . The nasal pharmaceutical composition of claim 223 , contains at least between about 5 mg to about 25 mg of wherein the cannabinoid is at least about 98 % CBD . CBD . 238 . The nasal pharmaceutical composition of claim 223 , 248 . The method of claim 243 , wherein the cannabinoid wherein the cannabinoid is at least about 99 % CBD . contains about 20 mg of CBD . 239 . The nasal pharmaceutical composition of claim 223 , 249 . The method of claim 243 wherein the cannabinoid wherein the cannabinoid is about 100 % CBD . contains at least between about 37 . 5 mg of CBD . US 2017 /0348276 A1 Dec . 7 , 2017 30

250 . The method of claim 243 , wherein the cannabinoid nasally administering the nasal pharmaceutical composi is at least about 50 % CBD . tion into at least one nostril of the subject up to at least 251. The method of claim 243, wherein the cannabinoid four times per day. is at least about 60 % CBD . 262 . The method of claim 243, wherein the semi- solid or 252 . The method of claim 243 , wherein the cannabinoid viscous liquid nasal pharmaceutical composition has a vis cosity that ranges between 500 cps and 100 ,000 cps . is at least about 70 % CBD . 263 . The method of claim 243 , wherein the semi- solid or 253 . The method of claim 243 , wherein the cannabinoid viscous liquid nasal pharmaceutical composition has a vis is at least about 80 % CBD . cosity that ranges between 1 ,000 cps and 75 ,000 cps. 254 . The method of claim 243 , wherein the cannabinoid 264 . The method of claim 243 , wherein the semi- solid or is at least about 95 % CBD . viscous liquid nasal pharmaceutical composition has a vis 255 . The method of claim 243 , wherein the cannabinoid cosity that ranges between 2500 cps and 50 ,000 cps . is at least about 98 % CBD . 265 . The method of claim 243 , wherein the semi- solid or 256 . The method of claim 243 , wherein the cannabinoid viscous liquid nasal pharmaceutical composition that ranges is at least about 99 % CBD . between 5 ,000 cps and 25 , 000 cps. 257 . The method of claim 243 , wherein the cannabinoid 266 . The method of claim 243 , wherein the nasal phar is about 100 % CBD . maceutical composition is a viscous liquid . 258 . The method of claim 243 , wherein said nasal admin 267 . The method of claim 243 , wherein the nasal phar istration step comprises : maceutical composition is a gel . nasally administering the nasal pharmaceutical into at 268 . The method of claim 243 , wherein the nasal phar least one nostril of the subject at least twice per day . maceutical composition is a cream . 259 . The method of claim 243 , wherein said nasal admin 269 . The method of claim 243 , wherein the disorder is istration step comprises: selected from a group of disorders consisting of anti - psy nasally administering the nasal pharmaceutical composi chosis , epilepsy, schizophrenia , arthritis , asthma, antipsy tion into at least one nostril of the subject at least three chosis, anxiety , sleep disturbances, neurodegeneration , psy times per day. chosis , depression , glaucoma, neurodegeneration , cerebral 260 . The method of claim 243 , wherein said nasal admin and myocardial ischemia , inflammation , immune response , istration step comprises : emesis , food intake , such as appetite stimulation in HIVI nasally administering the nasal pharmaceutical composi AIDS, diabetes ) , liver disease , osteogenesis , cancer condi tion into at least one nostril of the subject at least four tions relating to certain types of cancer including nausea and times per day. vomiting , a movement disorder, a mood disorder ), a psy 261. The method of claim 243 , wherein said nasal admin chological disorder and Tourette syndrome. istration step comprises: * * * * *