Improved use of cannabinoids in the treatment of epilepsy

Abstract

A method of treating epilepsy in a subject, whereby the subject in need thereof is administered, via the oral mucosa, a rapidly infusing composition that includes (a) a pharmaceutically acceptable binder and/or excipient system containing gelatin and a sugar alcohol, and (b) a therapeutically effective amount of cannabidiol (CBD) or a derivative/analog thereof.

1 . A method of treating epilepsy in a subject, comprising:
 administering to the subject in need thereof, via the oral mucosa, a rapidly infusing composition comprising (a) a pharmaceutically acceptable binder and/or excipient system comprising gelatin and a sugar alcohol, and (b) a therapeutically effective amount of cannabidiol (CBD) or a derivative/analog thereof.   
     
     
         2 . The method of  claim 1 , wherein the rapidly infusing composition is lyophilized. 
     
     
         3 . The method of  claim 1 , wherein the rapidly infusing composition has a disintegration time of approximately 1 to 30 seconds in deionized water maintained at 37° C.±2° C. 
     
     
         4 . The method of  claim 1 , wherein the rapidly infusing composition has a disintegration time of approximately 1 to 5 seconds in deionized water maintained at 37° C.±2° C. 
     
     
         5 . The method of  claim 1 , wherein the gelatin is present in the rapidly infusing composition in an amount of 10 to 35 wt. %, based on a total weight of the rapidly infusing composition on a dry basis. 
     
     
         6 . The method of  claim 1 , wherein the gelatin is bovine gelatin. 
     
     
         7 . The method of  claim 1 , wherein the sugar alcohol is present in the rapidly infusing composition in an amount of 5 to 35 wt. %, based on a total weight of the rapidly infusing composition on a dry basis. 
     
     
         8 . The method of  claim 1 , wherein the sugar alcohol comprises mannitol. 
     
     
         9 . The method of  claim 1 , wherein the CBD or derivative/analog thereof is present in the rapidly infusing composition in an amount of 20 to 70 wt. %, based on a total weight of the rapidly infusing composition on a dry basis. 
     
     
         10 . The method of  claim 1 , wherein the rapidly infusing composition is formulated with a solid form of the CBD. 
     
     
         11 . The method of  claim 1 , wherein the rapidly infusing composition is formulated with a solid form of the CBD having a purity between 95 and 99.9 wt. %. 
     
     
         12 . The method of  claim 1 , wherein the rapidly infusing composition is formulated with a solid form of the CBD that has been micronized to have a D50 diameter between 1 and 50 μm. 
     
     
         13 . The method of  claim 1 , wherein the rapidly infusing composition is formulated with a CBD derivative/analog. 
     
     
         14 . The method of  claim 13 , wherein the CBD derivative/analog is cannabidiolic acid methyl ester. 
     
     
         15 . The method of  claim 1 , wherein the rapidly infusing composition further comprises at least one selected from the group consisting of a sweetener, a flavorant, and a colorant. 
     
     
         16 . The method of  claim 15 , wherein the rapidly infusing composition comprises the flavorant, and the flavorant comprises lemon-lime flavor. 
     
     
         17 . The method of  claim 15 , wherein the rapidly infusing composition comprises the colorant, and the colorant comprises FD&C Yellow #5. 
     
     
         18 . The method of  claim 15 , wherein the rapidly infusing composition comprises the sweetener, and the sweetener comprises a mixture of sucralose and acesulfame-K. 
     
     
         19 . The method of  claim 1 , wherein the rapidly infusing composition is administered to the subject via the buccal mucosa. 
     
     
         20 . The method of  claim 1 , wherein the therapeutically effective amount of CBD or derivative/analog thereof is from 0.1 mg/kg/day to less than 5 mg/kg/day. 
     
     
         21 . The method of  claim 1 , wherein the rapidly infusing composition is administered to the subject 1 to 3 times per day. 
     
     
         22 . The method of  claim 1 , wherein the subject presents with focal onset seizures. 
     
     
         23 . The method of  claim 1 , wherein the subject presents with generalized onset seizures. 
     
     
         24 . The method of  claim 1 , wherein the subject presents with both generalized onset and focal onset seizures. 
     
     
         25 . The method of  claim 1 , wherein the epilepsy is childhood epilepsy. 
     
     
         26 . The method of  claim 25 , wherein the subject has Dravet Syndrome, myoclonic-absence epilepsy, Lennox-Gastaut syndrome, generalized epilepsy of unknown origin, CDKL5 deficiency disease, PCDH19-epilepsy, continuous spikes and waves during sleep (CSWS), electrical status epilepticus during slow-wave sleep (ESES) epilepsy, Aicardi syndrome, Ohtahara syndrome, bilateral polymicrogyria, Dup15q syndrome, SNAP25-associated epilepsy, febrile infection related epilepsy syndrome (FIRES), benign rolandic epilepsy, juvenile myoclonic epilepsy, Doose syndrome, infantile spasm (West syndrome), or Landau-Kleffner syndrome. 
     
     
         27 . The method of  claim 1 , wherein the epilepsy is drug resistant epilepsy. 
     
     
         28 . The method of  claim 27 , wherein the subject has Dravet syndrome, Lennox-Gastaut syndrome, myoclonic absence seizures, febrile infection related epilepsy syndrome (FIRES), treatment-resistant adult focal epilepsy (TRAFE), or PCDH19-epilepsy. 
     
     
         29 . The method of  claim 1 , wherein the subject presents with atonic seizures. 
     
     
         30 . The method of  claim 29 , wherein the subject has Lennox-Gastaut syndrome, tuberous sclerosis complex, Dravet syndrome, Doose syndrome, Aicardi syndrome, CDKL5 deficiency, or Dup15q syndrome. 
     
     
         31 . The method of  claim 1 , wherein the subject has Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex. 
     
     
         32 . The method of  claim 1 , wherein a total convulsive frequency of the subject is reduced by at least 50%, relative to the total convulsive frequency observed prior to administration of the rapidly infusing composition. 
     
     
         33 . The method of  claim 1 , wherein a total convulsive frequency of the subject is reduced by at least 70%, relative to the total convulsive frequency observed prior to administration of the rapidly infusing composition. 
     
     
         34 . The method of  claim 1 , wherein the rapidly infusing composition is administered in combination with an antiepileptic drug. 
     
     
         35 . The method of  claim 34 , wherein the antiepileptic drug is at least one selected from the group consisting of phenobarbital, eslicarbazepine, ethosuximide, everolimus, tiagabine, acetazolamide, brivaracetam, cenobamate, clorazepate, lorazepam, methsuximide, primidone, diazepam, divalproex, felbamate, fenfluramine, carbamazepine, oxcarbazepine, lacosamide, vigabatrin, gabapentin, lamotrigine, pregabalin, baclofen, phenytoin, valproic acid or its salts such as sodium valproate, topiramate, zonisamide, levetiracetam, clonazepam, rufinamide, stiripentol, perampanel, and fosphenytoin.