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JP-7856584-B2 - Treatment of autism spectrum disorder with cannabidiol

JP7856584B2JP 7856584 B2JP7856584 B2JP 7856584B2JP-7856584-B2

Inventors

  • セブリー，テリ
  • ガターマン，ドナ
  • オニール，キャロル
  • パルンボ，ジョーセフ

Assignees

  • ハーモニー・バイオサイエンシズ・マネージメント・インコーポレイテッド

Dates

Publication Date
20260511
Application Date
20210525
Priority Date
20200526

Claims (19)

  1. The use of cannabidiol (CBD) in the manufacture of a pharmaceutical product for treating one or more behavioral symptoms of moderate to severe autism spectrum disorder in a subject , The CBD is 2-[3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediol or a pharmaceutically acceptable salt thereof. The CBD is in the form of a pharmaceutically acceptable formulation that does not contain tetrahydrocannabinol .
  2. The use according to claim 1, wherein one or more behavioral symptoms include generalized anxiety, clinical anxiety, irritability, inappropriate speech, stereotypic behavior, social withdrawal, repetitive behavior, and hyperactivity.
  3. The use according to claim 1 or 2, wherein the cannabidiol is administered as an add-on therapy.
  4. The use according to claim 3, wherein the cannabidiol is used together with one or more psychotropic agents.
  5. The use according to claim 4, wherein the one or more psychotropic agents include at least one agent selected from the group consisting of antidepressants, anxiolytics, psychostimulants, antipsychotics, and combinations thereof.
  6. The use according to claim 4 or 5, wherein the one or more psychotropic agents include an antipsychotic agent.
  7. The use according to claim 6, wherein the antipsychotic drug is selected from the group consisting of risperidone, haloperidol, olanzapine, and quetiapine fumarate.
  8. The use according to claim 4 or 5, wherein the one or more psychotropic agents include psychostimulants.
  9. The use according to claim 8, wherein the psychostimulant is selected from the group consisting of clonidine, guanfacine, methylphenidate hydrochloride, atomoxetine hydrochloride, dexamfetamine, and lisdexamfetamine mesylate.
  10. The use according to any one of claims 1 to 9, wherein the subject experiences a significant improvement in stereotypic behavior, repetitive behavior, or both.
  11. The use according to any one of claims 1 to 10, wherein the subject experiences a significant improvement in irritability, communication deficit, or both.
  12. The use according to any one of claims 1 to 11, wherein the cannabidiol is administered transdermally.
  13. The use according to any one of claims 1 to 12, wherein all treatment-related adverse events are mild and transient.
  14. The use according to any one of claims 1 to 13, wherein the amount of cannabidiol used to treat one or more symptoms of moderate to severe autism spectrum disorder in the subject is 250 mg in total per day.
  15. The use according to any one of claims 1 to 13, wherein the amount of cannabidiol used to treat one or more symptoms of moderate to severe autism spectrum disorder in the subject is 500 mg in total per day.
  16. The use according to any one of claims 1 to 13, wherein the amount of cannabidiol used to treat one or more symptoms of moderate to severe autism spectrum disorder in the subject is 750 mg in total per day.
  17. The use according to any one of claims 1 to 13, wherein the amount of cannabidiol used to treat one or more symptoms of moderate to severe autism spectrum disorder in the subject is 250 mg or 500 mg in total per day.
  18. The use according to any one of claims 1 to 17, wherein cannabidiol, used to treat one or more symptoms of moderate to severe autism spectrum disorder in the subject, is administered in two divided doses per day.
  19. The use according to any one of claims 1 to 18 , wherein the cannabidiol is a synthetic cannabidiol.

Description

This application claims the benefits and priority of U.S. Provisional Patent Application No. 63/029,899, filed on 26 May 2020, entitled “Treatment of Fragile X Syndrome and Autism Spectrum Disorder with Cannabidiol,” the contents of which are incorporated herein by reference in their entirety. This disclosure relates to a method for treating one or more behavioral symptoms of Fragile X syndrome in a subject by subject-administering an effective dose of cannabidiol (CBD) transdermally, and more specifically to a method for treating one or more behavioral symptoms of Fragile X syndrome in a subject. This disclosure also relates to a method for treating one or more behavioral symptoms of autism spectrum disorder (ASD) in a subject by subject-administering an effective dose of cannabidiol (CBD), and more specifically to a method for treating one or more behavioral symptoms of ASD in a subject. Cannabinoids are a group of compounds found in cannabis. The two main cannabinoids found in cannabis are cannabidiol, or CBD, and Δ9-tetrahydrocannabinol, or THC. CBD does not have the psychoactive effects of THC. Studies have shown that CBD can be used to treat conditions such as epilepsy, arthritis, and cancer. FXS is the most common genetic intellectual disability in males and a significant cause of intellectual disability in females. FXS is caused by a mutation in the Fragile X Mental Retardation 1 (FMR1) gene located on the X chromosome, resulting in dysregulation of the endocannabinoid system, including a decrease in endocannabinoids (2-AG and anandamide [AEA]). This disorder negatively impacts synaptic function, plasticity, and neuronal connectivity, leading to a continuum of intellectual disability, social anxiety, and memory problems. In the United States, there are approximately 71,000 people with FXS. "The most serious concerns reported by parents are often behavioral problems, and high levels of stress and depression, as well as low quality of life for parents, are usually associated with an increase in problematic behaviors in children." Wheeler A, Raspa M, Bann C, Bishop E, Hassl D, Sacco H, Bailey D. 2014. "Anxiety attention problems, hyperactivity, and the Aberrant Behavior Checklist in fragile X syndrome." Am J Med Genet Part A 164A:141-155, 141. "As a result, mitigating behavioral problems is the primary focus of ongoing clinical trials investigating the effectiveness of new drugs for FXS." Wheeler, pp. 141-142. The Anxiety, Depression, and Mood Scale (ADAMS) is a tool used by clinicians, physicians, and researchers to assess levels of anxiety, depression, and mood in patients with intellectual disabilities such as FXS. The ADAMS consists of questions grouped into five subscales: (i) generalized anxiety, (ii) social avoidance, (iii) obsessive-compulsive behavior, (iv) manic/hyperactive behavior, and (v) depressed mood. Clinicians/physicians respond to each question on a four-point scale ranging from 0 ("no problem") to 3 ("severe problem"). In addition to the subscale scores, the ADAMS generates an overall score. The original Behavioral Abnormalities Checklist (ABC) was "designed to assess behavioral problems in adults within institutional settings." (Wheeler, p. 142). Subsequently, the original ABC was revised for patients not institutionalized, specifically for FXS (ibid., same section). The Behavioral Abnormalities Checklist-FXS-Specific (ABC-FXS) scale is used by clinicians, physicians, and researchers to access specific behaviors in FXS patients. The ABC-FXS scale has six subscales, including (i) irritability, (ii) hyperactivity, (iii) social responsiveness/lethargy, (iv) social avoidance, (v) stereotypic behavior, and (vi) inappropriate speech. Like the ADAMS, the ABC-FXS scale is a four-point Likert scale ranging from 0 (no problem) to 3 (severe problem). Wheeler A, Raspa M, Bann C, Bishop E, Hassl D, Sacco H, Bailey DB. 2014. “Anxiety attention problems, hyperactivity, and the Aberrant Behavior Checklist in fragile X syndrome” Am J Med Genet Part A 164A: 141-155, 141 This disclosure relates to a method for treating one or more behavioral symptoms of Fragile X syndrome in a subject. The method comprises transdermal administration of an effective dose of cannabidiol (CBD) to the subject, thereby treating one or more behavioral symptoms of Fragile X syndrome in the subject. In some embodiments, the CBD is (-)-CBD. The effective dose of CBD may be approximately 50 mg to approximately 500 mg per day. In some embodiments, the effective dose of CBD is started at approximately 50 mg per day and gradually increased to approximately 500 mg per day. The effective dose of CBD can also be started at approximately 50 mg per day and gradually increased to approximately 250 mg per day. In some embodiments, the effective dose of CBD is started at 250 mg per day. The effective dose of CBD can be started at 500 mg per day. In some embodiments, a dose of 500 mg per day is administered to patients weighing more than