Gw Research Limited

Jazz Pharmaceuticals Research UK Limited

Royston Gray

Benjamin Whalley

Geoffrey W Guy

Volker Knappertz

Rohini Rajyalaxmi Rana

Marie Woolley-Roberts

James Brodie

Alan Sutton

Katarzyna Lach-Falcone

Claire Williams

Alan Silcock

Ines De Silva Serra

William Hind

Javier Fernandez-Ruiz

Irene Santos-Garcia

Alexander Cobb

Laura Garcia-Toscano

Carmen Rodriguez-Cueto

Eva De Lago

Laura Bryant

Karen Tse

Hannah Straker

Javier Fernández-ruiz

Michael Bazelot

Andrew Tee

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 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

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 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

Cannabidiol (CBD) is a cannabinoid designated chemically as 2-[(1R,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 funtional 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.

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Cambridge, United Kingdom

Royston Gray