Use of cannabinoids in the treatment of epilepsy

Abstract

The present disclosure relates to the use of cannabidiol (CBD) for the reduction of total convulsive seizure frequency in the treatment of “treatment-resistant epilepsy” (TRE). In particular, the disclosure relates to the use of CBD of treating TRE when the TRE is Dravet syndrome; myoclonic absence seizures or febrile infection related epilepsy syndrome (FIRES). The disclosure further relates to the use of CBD in combination with one or more anti-epileptic drugs (AEDs).

1 . A method of treating seizures in Lennox-Gastaut or Dravet Syndrome comprising administering to a patient in need thereof a highly pure botanical drug substance (BDS), comprising at least 98% w/w cannabidiol (CBD), and one or more of cannabidiolic acid (CBDA), cannabidivarin (CBDV), delta-9 tetrahydrocannabinol (Δ 9 THC), or cannabidiol-C4 (CBD-C4). 
     
     
         2 . A highly pure botanical drug substance (BDS), comprising at least 98% w/w cannabidiol (CBD), and one or more of cannabidiolic acid (CBDA), cannabidivarin (CBDV), delta-9 tetrahydrocannabinol (Δ 9 THC), or cannabidiol-C4 (CBD-C4), prepared by a process comprising the steps of:
 (a) harvesting  Cannabis saliva  L. plants to form botanical raw material (BRM); 
 (b) decarboxylating CBDA in the BRM to form CBD; 
 (c) extracting CBD, and at least one of CBDA, CBDV, Δ 9 THC, or CBD-C4, from the BRM, to form a crude botanical drug substance (BDS); 
 (d) winterizing the crude BDS in to yield an intermediate BDS; 
 (e) crystallizing the intermediate BDS with a C 5 -C 12  straight or branched alkane to yield a highly pure BDS. 
 
     
     
         3 . The BDS of  claim 2 , comprising CBD and two or more of CBDA, Δ 9 THC, and CBD-C4. 
     
     
         4 . The BDS of  claim 2 , comprising CBD, CBDA, Δ 9 THC, and CBD-C4. 
     
     
         5 . The BDS of  claim 2 , comprising not more than 0.15% w/w CBDA. 
     
     
         6 . The BDS of  claim 2 , comprising not more than 0.15 % w/w Δ 9 THC. 
     
     
         7 . The BDS of  claim 2 , comprising not more than 0.5% w/w CBD-C4. 
     
     
         8 . The BDS of  claim 4 , comprising not more than 0.15% w/w CBDA. 
     
     
         9 . The BDS of  claim 4 , comprising not more than 0.15% w/w Δ9THC. 
     
     
         10 . The BDS of  claim 4 , comprising not more than 0.5% w/w CBD-C4. 
     
     
         11 . The BDS of  claim 4 , comprising not more than 0.15% w/w CBDA; not more than 0.15% w/w Δ 9 THC; and not more than 0.5% w/w CBD-C4. 
     
     
         12 . The BDS of  claim 2 , wherein the BDS is formulated in a pharmaceutically acceptable oral solution. 
     
     
         13 . The BDS of  claim 12 , wherein the pharmaceutical composition comprises sesame oil. 
     
     
         14 . The BDS of  claim 4 , wherein the BDS is formulated in a pharmaceutically acceptable oral solution. 
     
     
         15 . The BDS of  claim 14 , wherein the pharmaceutical composition comprises sesame oil. 
     
     
         16 . The BDS of  claim 2 , wherein the decarboxylating in step (b;) is performed by heating the BRM to a temperature ranging from about 105° C. to about 150° C. 
     
     
         17 . The BDS of  claim 2 , wherein the extracting in step (c) is performed using liquid CO 2 . 
     
     
         18 . The BDS of  claim 2 , wherein the winterizing in step (d) is performed using ethanol. 
     
     
         19 . The BDS of  claim 2 , wherein the crystalizing in step (e) comprises a first crystallization step using C 5 -C 12  straight or branched alkane, then filtering the BDS, followed by second crystallization step using C 5 -C 12  straight or branched alkane to yield the highly pure BDS. 
     
     
         20 . The BDS of  claim 2 , further comprising step (f), preparing the highly pure BDS as an oral solution.