Gw Research Limited

Jazz Pharmaceuticals Research UK Limited

Gw Pharma Limited

Otsuka Pharmaceutical Company, Limited

Benjamin Whalley

Geoffrey W Guy

Claire Williams

Volker Knappertz

Gary Stephens

Marie Woolley-Roberts

Royston Gray

Colin Stott

Thomas Hill

Rohini Rajyalaxmi Rana

James Brodie

Alan Sutton

Robin Williams

Nick Jones

Katarzyna Lach-Falcone

Stephen Wright

Tetsuro Kikuchi

Nicholas G Jones

Takashi Futamura

Alan Silcock

Nicholas Jones

Ines De Silva Serra

William Hind

Javier Fernandez-Ruiz

Rosario Moratalla Villalba

Irene Santos-Garcia

Laura Garcia-Toscano

Carmen Rodriguez-Cueto

Eva De Lago

Laura Bryant

Karen Tse

Hannah Straker

Alexander Cobb

Javier Fernández-ruiz

Michael Bazelot

Andrew Tee

Jacqueline Cilia

Amesha Patel

The present invention relates to a group of cannabinoid derivatives as pharmaceutically active compounds and methods of preparation thereof. The cannabinoid derivatives of the invention are analogues of cannabidiol (CBD). CBD is a non-psychoactive cannabinoid which has been used to treat various diseases and disorders. While such treatments hold promise, there remains a need in the art for more effective treatments and this has been brought about by way of the cannabinoid derivatives of the invention

Cannabinoid derivatives as pharmaceutically active compounds and methods of preparation thereof

The present invention relates to a cannabidiol (CBD) type cannabinoid compound for use as a medicament. The CBD-type cannabinoid, cannabidiol-C1 (CBD-C1), is a naturally occurring cannabinoid that can be found in minor quantities in theplant. Furthermore, the 5 cannabinoid can be produced by synthetic means and a method for the production of CBD-C1 is described herein. In addition, disclosed herein are data which demonstrate the efficacy of CBD-C1 in models of disease.

Cannabidiol-type cannabinoid compound

The present invention relates to a cannabidiol (CBD) type cannabinoid compound for use as a medicament. The CBD-type cannabinoid, 6-hydroxy cannabidiol (6-0 H CBD), is a metabolite of CBD. The cannabinoid can be produced by synthetic means and a method for the production of 6-0 H CBD is described herein. In addition, disclosed herein are data which demonstrate the efficacy of 6-0 H CBD in a model of disease.

The present invention relates to a cannabidiol (CBD) type cannabinoid compound for use as a medicament. The CBD-type cannabinoid, cannabidiol-C6 (CBD-C6), is a naturally occurring cannabinoid that can be found in minor quantities in the cannabis plant. Furthermore, the cannabinoid can be produced by synthetic means and a method for the production of CBD-C6 is described herein. In addition, disclosed herein are data which demonstrate the efficacy of CBD-C6 in models of disease.

The invention relates to the use of cannabidiol (CBD), at a dose of greater than 300 mg/day, in combination with a standard anti-epileptic drug (SAED) which acts via sodium or calcium channels, for use in the treatment of epilepsy. The SAED is preferably one which •modities low-threshold or transient neuronal calcium currents, or •reduces high-frequency neuronal firing and sodium-dependent action potentials and enhances GABA effects. Preferred SAEDs are ethosuximide and valproate.

Use of the phytocannabinoid cannabidiol (CBD) in combination with a standard anti-epileptic drug (SAED) in the treatment of epilepsy

The present disclosure relates to the use of cannabinoids in the treatment of dyskinesia associated with Parkinson's disease. In particular the cannabinoid is tetrahydrocannabivarin (THCV). Preferably the THCV used is in the form of a botanically derived purified THCV. Alternatively, a synthetically produced THCV is used.

Use of cannabinoids in the treatment of dyskinesia associated with parkinson's disease

The present invention relates to the use of cannabidiol (CBD) for the treatment of tumours associated with Tuberous Sclerosis Complex (TSC). In particular the CBD was able to decrease the number and size of marker cells, pS6, in a zebrafish model of TSC. This is suggestive of a disease modifying effect whereby treatment with CBD could result in the reduction or prevention of the benign tumours that occur in TSC patients. 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 cannabinoid 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 is given concomitantly with one or more other drugs used in the treatment of TSC. Such drugs may include rapamycin and/or everolimus.

Use of cannabidiol in the treatment of tuberous sclerosis complex

This invention relates to a pharmaceutical composition comprising or consisting essentially of the phytocannabinoids cannabidivarin (CBDV) and cannabidiol (CBD). The composition is particularly safe and efficacious for use in the treatment of neurological conditions, characterized by hyper-excitability of the central nervous system, convulsions or seizures such as occur in epilepsy. Preferably the CBDV and the CBD are present with at least one non-cannabinoid component of cannabis such as one or more terpenes or a terpene fraction. More particularly the composition further comprises one or more cannabichromene type compounds. Particularly cannabichromene propyl variant (CBCV) and/or cannabichromene (CBC). More particularly still the composition is absent or substantially absent of other cannabinoids, including in particular tetrahydrocannabinol (THC) and tetrahydrocannabivarin (THCV), which would normally be present in significant amounts in cannabis chemotypes bred to contain a significant amount of CBDV and/or CBD.

Pharmaceutical composition comprising the phytocannabinoids cannabidivarin (CBDV) and cannabidiol (CBD)

The present invention relates to the use of cannabinoids in the treatment of a neurodegenerative disease or disorder. In particular the cannabinoids cannabidiolic acid (CBDA) and cannabidivarin (CBDV) were able to produce neuroprotective effects in a mouse model of neurodegenerative disease. In particular these effects were associated with the symptoms associated with amyotrophic lateral sclerosis (ALS). Furthermore, the combination of the cannabinoid tetrahydrocannabinol (THC) with the drug olexisome provided a synergistic disease modifying effect in a mouse model of neurodegenerative disease. In particular these effects were associated with the symptoms associated with ALS.

Use of cannabinoids in the treatment of a neurodegenerative disease or disorder

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

Cannabidiol preparations and its uses

The present invention relates to the use of 7-hydroxy-cannabidol (7-OH-CBD) and/or 7-hydroxy-cannabidivarin (7-OH-CBDV) in the treatment of epilepsy. Preferably the cannabinoid metabolites are isolated from plants to produce a highly purified extract or can be reproduced synthetically.

7-OH-cannabidiol (7-OH-CBD) and/or 7-OH-cannabidivarin (7-OH-CBDV) for use in the treatment of epilepsy

The present invention relates to the use of a therapeutically effective amount of cannabidiolic acid (CBDA) in the treatment of epilepsy. In one embodiment the CBDA is used in the treatment of generalised seizures, preferably tonic-clonic seizures. Preferably the CBDA used is in the form of a botanical drug substance in which the CBDA content is greater than 60%, and most preferably, it is a highly purified extract of cannabis such that the CBDA is present at greater than 95%, through 96% and 97% to most preferably, greater than 98% of the total extract (w/w) and the other components of the extract are characterised. In particular the cannabinoids tetrahydrocannabinol (THC) or tetrahydrocannabinol acid (THCA) have been substantially removed. Alternatively, the CBDA may be synthetically produced.

Use of cannabinoids in the treatment of epilepsy

The present invention relates to a cannabidiol (CBD) type cannabinoid compound for use as a medicament. The CBD-type cannabinoid, 6-hydroxy cannabidivarin (6-OH CBDV), is a metabolite of cannabidivarin (CBDV). The cannabinoid can be produced by synthetic means and a method for the production of 6-OH CBDV is described herein. In addition, disclosed herein are data which demonstrate the efficacy of 6-OH CBDV in a model of disease.

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.

Use of cannabidiol in combination with 5-HT2B receptor agonists or amphetamines in the treatment of epilepsy

This invention relates to a pharmaceutical composition comprising or consisting essentially of the phytocannabinoids cannabidivarin (CBDV) and cannabidiol (CBD). The composition is particularly safe and efficacious for use in the treatment of neurological conditions, characterized by hyper-excitability of the central nervous system, convulsions or seizures such as occur in epilepsy. Preferably the CBDV and the CBD are present with at least one non-cannabinoid component ofsuch as one or more terpenes or a terpene fraction. More particularly the composition further comprises one or more cannabichromene type compounds. Particularly cannabichromene propyl variant (CBCV) and/or cannabichromene (CBC). More particularly still the composition is absent or substantially absent of other cannabinoids, including in particular tetrahydrocannabinol (THC) and tetrahydrocannabivarin (THCV), which would normally be present in significant amounts inchemotypes bred to contain a significant amount of CBDV and/or CBD.

Growing community of inventors

Cambridge, United Kingdom

Benjamin Whalley