WO2019064031A1 – April 4, 2019 – USE OF CANNABIDIOL IN COMBINATION WITH 5-HT2B RECEPTOR AGONISTS OR AMPHETAMINS IN THE TREATMENT OF EPILEPSY

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Inventors :

WHALLEY, Benjamin - GW Pharma Limited, Sovereign House, Vision Park, Chivers Way, Histon, Cambridge Cambridgeshire CB24 9BZ; GUY, Geoffrey - GW Pharma Limited, Sovereign House, Vision Park, Chivers Way, Histon, Cambridge Cambridgeshire CB24 9BZ; KNAPPERTZ, Volker - GW Pharma Limited, Sovereign House, Vision Park, Chivers Way, Histon, Cambridge Cambridgeshire CB24 9BZ; GRAY, Royston - GW Pharma Limited, Sovereign House, Vision Park, Chivers Way, Histon, Cambridge Cambridgeshire CB24 9BZ; RANA, Rohini - GW Pharma Limited, Sovereign House, Vision Park, Chivers Way, Histon, Cambridge Cambridgeshire CB24 9BZ

Owner :

GW RESEARCH LIMITED

Application Number :

WOGB18052805

Document Number :

WO2019064031A1

Priority Date :

January 1, 1970

Filing Date :

October 1, 2018

Date of Grant/ Publication :

April 4, 2019

Class :

; A61K45 / 06; A61K31 / 137; A61K31 / 352; A61P25 / 08; A61K31 / 165

Abstract

The present invention relates to the use of cannabidiol (CBD) in combination with an agonist of 5-HT2B receptors. Such a combination provides protection against the adverse effects caused by agonists of 5-HT2B receptors. The invention further relates to the use of CBD in combination5 with an amphetamine or amphetamine derivative in the treatment of epilepsy. In one embodiment the CBD is used in combination with the amphetamine derivative fenfluramine to produce a significant reduction in seizures. Preferably the CBD used is in the form of a highly purified extract of cannabis such that the CBD is present at greater than 98% of the total extract (w/w) and the other components of the extract are characterised. In particular the cannabinoid10 tetrahydrocannabinol (THC) has been substantially removed, to a level of not more than 0.15% (w/w) and the propyl analogue of CBD, cannabidivarin, (CBDV) is present in amounts of up to 1%. Alternatively, the CBD may be a synthetically produced CBD. In use the CBD in combination with an agonist of 5-HT2B receptors, amphetamine or amphetamine derivative may be formulated for administration separately, sequentially or simultaneously with the15 amphetamine or amphetamine derivative or the combination may be provided in a single dosage form. Where the CBD is formulated for administration separately, sequentially or simultaneously it may be provided as a kit or together with instructions to administer the one or more components in the manner indicated.

Claim(s)

1. Cannabidiol (CBD) in combination with a 5-??2? receptor agonist, an amphetamine or an amphetamine derivative for use in the treatment of epilepsy.;
2. CBD in combination with a 5-??2? receptor agonist, an amphetamine or an amphetamine derivative for use according to claim 1 , wherein the combination is for use in the prevention or reduction of side effects associated with agonism of the 5-??2? receptor. 3. CBD in combination with a 5-??2? receptor agonist, an amphetamine or an amphetamine derivative for use according to claim 1 or claim 2, wherein the 5-??2? receptor agonist, amphetamine or amphetamine derivative is one or more of: guanfacine; 3,4- Methylenedioxymethamphetamine (MDMA); Methylenedioxyamphetamine (MDA); 2,5- Dimethoxy-4-ethoxyamphetamine (MEM); pergolide; cabergoline; norfenfluramine; fenfluramine; chlorphentermine; aminorex; meta-chlorophenylpiperazine (mCPP); bromo- dragonfly; ?,?-Dimethyltryptamine (DMT); 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT); lysergic acid diethylamide (LSD-25); psilocin; amphetamine; methamphetamine; ephedrine; cathinone; phentermine; mephentermine; bupropion; methoxyphenamine; selegiline; amfepramone; n-fenfluramine; pyrovalerone; MDMA (ecstasy) and DOM (STP). 4. CBD in combination with a 5-??2? receptor agonist, an amphetamine or an amphetamine derivative for use according to any of the preceding claims, wherein the 5-??2? receptor agonist, amphetamine or amphetamine derivative is norfenfluramine or fenfluramine. 5. Cannabidiol (CBD) in combination with a 5-??2? receptor agonist, an amphetamine or an amphetamine derivative for use according to claim 2, wherein the side effects that are prevented or reduced is heart valve disease.;
6. Cannabidiol (CBD) in combination with a 5-??2? receptor agonist, an amphetamine or an amphetamine derivative for use according to any of the preceding claims, wherein the CBD is in the form of a highly purified extract of cannabis which comprises at least 98% (w/w) CBD.;
7. Cannabidiol (CBD) in combination with a 5-??2? receptor agonist, an amphetamine or an amphetamine derivative for use according to claims 1 to 5, wherein the CBD is present as a synthetic compound.;
8. Cannabidiol (CBD) in combination with a 5-??2? receptor agonist, an amphetamine or an amphetamine derivative for use according to any of the preceding claims, wherein the epilepsy is treatment resistant epilepsy (TRE). 9. Cannabidiol (CBD) in combination with a 5-??2? receptor agonist, an amphetamine or an amphetamine derivative for use according to claim 8, wherein the treatment-resistant epilepsy is one of: Dravet Syndrome; Myoclonic-Absence Epilepsy; Lennox-Gastaut syndrome; Generalized Epilepsy of unknown origin; CDKL5 mutation; Aicardi syndrome; tuberous sclerosis complex; bilateral polymicrogyria; Dup15q; SNAP25; and febrile infection related epilepsy syndrome (FIRES); benign rolandic epilepsy; juvenile myoclonic epilepsy; infantile spasm (West syndrome); and Landau- Kleffner syndrome.;
10. Cannabidiol (CBD) in combination with a 5-??2? receptor agonist, an amphetamine or an amphetamine derivative for use according to claim 6, wherein the highly purified extract comprises less than 0.15% THC.;
11. Cannabidiol (CBD) in combination with a 5-??2? receptor agonist, an amphetamine or an amphetamine derivative for use according to claim 6, wherein the highly purified extract comprises up to 1 % CBDV.;
12. Cannabidiol (CBD) in combination with a 5-??2? receptor agonist, an amphetamine or an amphetamine derivative for use according to any of the preceding claims, wherein the ratio of CBD to 5-??2? receptor agonist, amphetamine or amphetamine derivative is between 20: 1 to 1 :20.;
13. Cannabidiol (CBD) in combination with a 5-??2? receptor agonist, an amphetamine or an amphetamine derivative for use according to any of the preceding claims, wherein the ratio of CBD to 5-??2? receptor agonist, amphetamine or amphetamine derivative is between 10: 1 to 1 : 10.;
14. Cannabidiol (CBD) in combination with a 5-??2? receptor agonist, an amphetamine or an amphetamine derivative for use according to any of the preceding claims, wherein the ratio of CBD to 5-??2? receptor agonist, amphetamine or amphetamine derivative is between 3: 1 to 1 :3.;
15. Cannabidiol (CBD) in combination with a 5-??2? receptor agonist, an amphetamine or an amphetamine derivative for use according to any of the preceding claims, wherein the ratio of CBD to 5-??2? receptor agonist, amphetamine or amphetamine derivative is between 2: 1 to 1 :2.;
16. Cannabidiol (CBD) in combination with a 5-??2? receptor agonist, an amphetamine or an amphetamine derivative for use according to any of the preceding claims, wherein the ratio of CBD to 5-HT2B receptor agonist, amphetamine or amphetamine derivative is approximately 1 : 1.;
17. Cannabidiol (CBD) in combination with a 5-??2? receptor agonist, an amphetamine or an amphetamine derivative for use according to any of the preceding claims, wherein the dose of CBD is between 5 and 50 mg/kg/day.;
18. Cannabidiol (CBD) in combination with a 5-??2? receptor agonist, an amphetamine or an amphetamine derivative for use according to any of the preceding claims, wherein the dose of a 5-??2? receptor agonist, amphetamine or amphetamine derivative is below 0.01 and 1 mg/kg/day.;
19. A method of treating epilepsy comprising administering cannabidiol (CBD) in combination with a 5-??2? receptor agonist, an amphetamine or an amphetamine derivative to a subject.

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