Use of cannabidivarin in the treatment of autism spectrum disorder, associated disorders and schizophrenia

Patent metadata

Field	Value
Publication number	US-11752111-B2
Application number	US-201716092374-A
Country	US
Kind code	B2
Filing date	Apr 11, 2017
Priority date	Apr 11, 2016
Publication date	Sep 12, 2023
Grant date	Sep 12, 2023

Abstract

The present invention relates to the use of cannabidivarin (CBDV) in the treatment of autism spectrum disorder (ASD) and ASD-associated disorders such as Fragile X syndrome (FXS); Rett syndrome (RS); or Angelman syndrome (AS). In a further embodiment the invention relates to the use of CBDV in the treatment of schizophrenia. CBDV has been shown to be particularly effective in improving cognitive dysfunction in rodent models of ASD, FXS, RS, AS and schizophrenia. The CBDV is preferably substantially pure. It may take the form of a highly purified extract of cannabis such that the CBDV is present at greater than 95% of the total extract (w/w) and the other components of the extract are characterised. Alternatively, the CBDV is synthetically produced.

First claim

The invention claimed is:

1. A method of treating one or more symptoms or disease characteristics associated with autistic spectrum disorder (ASD) or ASD-associated disorders, as defined by DSM-IV, in a subject in need thereof, the method comprising administering cannabidivarin to the subject, wherein the one or more symptoms or disease characteristics are one or more of: (i) qualitative impairment in social interaction; (ii) qualitative impairment in communication; and (iii) restricted repetitive and stereotyped patterns of behaviour interest and activities.

2. The method according to claim 1 , wherein the symptoms or disease characteristics of (i) qualitative impairment in social interaction include one or more of: (a) marked impairment in the use of multiple nonverbal behaviours; (b) failure to develop peer relationships appropriate to developmental level; (c) a lack of spontaneous seeking to share enjoyment, interests, or achievements with other people; and (d) lack of social or emotional reciprocity.

3. The method according to claim 1 , wherein the symptoms or disease characteristics of (ii) qualitative impairment in communication include one or more of: (a) delay in, or total lack of, the development of spoken language (not accompanied by an attempt to compensate through alternative modes of communication such as gesture or mime); (b) in individuals with adequate speech, marked impairment in the ability to initiate or sustain a conversation with others;
(c) stereotyped and repetitive use of language or idiosyncratic language; and (d) lack of varied, spontaneous make-believe play or social imitative play appropriate to developmental level.

4. The method according to claim 1 , wherein the symptoms or disease characteristics of (iii) restricted repetitive and stereotyped patterns of behaviour interest and activities include one or more of: (a) encompassing preoccupation with one or more stereotyped and restricted patterns of interest that is abnormal either in intensity or focus; (b) apparently inflexible adherence to specific, non-functional routines or rituals; (c) stereotyped and repetitive motor mannerisms; and (d) persistent preoccupation with parts of objects.

5. The method according to claim 1 , wherein the symptoms or disease characteristics associated with autistic spectrum disorder comprise two or more symptoms associated with (i) qualitative impairment in social interaction; one or more symptoms associated with (ii) qualitative impairment in communication, and one or more symptoms associated with (iii) restricted repetitive and stereotyped patterns of behavior interest and activities.

6. A method of treating one or more symptoms or disease characteristics associated with autistic spectrum disorder (ASD) or ASD-associated disorders, as defined by DSM-V, in a subject in need thereof, the method comprising administering cannabidivarin to the subject, wherein the one or more symptoms or disease characteristics are one or more of: (a) persistent deficits in social communication and social interaction across contexts, not accounted for by general developmental delays, and (b) restricted, repetitive patterns of behaviour, interests, or activities.

7. The method according to claim 6 , wherein the symptoms or disease characteristics of (a) persistent deficits in social communication and social interaction across contexts, not accounted for by general developmental delays include one or more of: (i) deficits in social-emotional reciprocity; (ii) deficits in nonverbal communicative behaviours used for social interaction; and (iii) deficits in developing and maintaining relationships.

8. The method according to claim 6 , wherein the symptoms or disease characteristics of (b) restricted, repetitive patterns of behaviour, interests, or activities include one or more of: (i) stereotyped or repetitive speech, motor movements, or use of objects; excessive adherence to routines, (ii) ritualized patterns of verbal or nonverbal behaviour, or excessive resistance to change; (iii) highly restricted, fixated interests that are abnormal in intensity or focus; and (iv) hyper-or hypo-reactivity to sensory input or unusual interest in sensory aspects of environment.

9. The method according to claim 6 wherein the symptoms or disease characteristics associated with autistic spectrum disorder comprise all three of (i) deficits in social-emotional reciprocity; (ii) deficits in nonverbal communicative behaviours used for social interaction; and (iii) deficits in developing and maintaining relationships together with two or more of (i) stereotyped or repetitive speech, motor movements, or use of objects; excessive adherence to routines, (ii) ritualized patterns of verbal or nonverbal behaviour, or excessive resistance to change; (iii) highly restricted, fixated interests that are abnormal in intensity or focus; and (iv) hyper-or hypo-reactivity to sensory input or unusual interest in sensory aspects of environment.

10. The method according to claim 1 , wherein the ASD-associated disorder is Fragile X syndrome.

11. The method according to claim 1 , wherein the ASD-associated disorder is Rett syndrome.

12. The method according to claim 1 , wherein the ASD-associated disorder is Angelman syndrome.

13. The method according to claim 6 , wherein the ASD-associated disorder is Fragile X syndrome.

14. The method according to claim 6 , wherein the ASD-associated disorder is Rett syndrome.

15. The method according to claim 6 , wherein the ASD-associated disorder is Angelman syndrome.

16. The method according to claim 2 , wherein the (a) marked impairment in the use of multiple nonverbal behaviours is one or more of eye-to-eye gaze, facial expression, body postures, and gestures to regulate social interaction.

17. The method according to claim 2 , wherein the (c) a lack of spontaneous seeking to share enjoyment, interests, or achievements with other people is a lack of showing, bringing, or pointing out objects of interest.

18. The method according to claim 4 , wherein the (c) stereotyped and repetitive motor mannerisms are one or more of hand or finger flapping or twisting or complex whole-body movements.

Assignees

• Gw Res Ltd

Inventors

• Guy Geoffrey
• Wright Stephen
• Brodie James
• Woolley-Roberts Marie
• Maldonado Rafael
• Parolaro Daniela
• Luongo Livio
• Neill Joanna

Classifications

• A61K36/3482

  Cannabis · CPC title

• A61K31/352

  condensed with carbocyclic rings, e.g. methantheline  {(cannabinoids A61K31/658)} · CPC title

• A61K31/658 Primary

  o-phenolic cannabinoids, e.g. cannabidiol, cannabigerolic acid, cannabichromene or tetrahydrocannabinol · CPC title

• A61K36/00 Primary

  Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines {(antigens from pollen A61K39/36)} · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title