Cannabinoids for Behavioral Problems in Children With ASD
Condition: Autistic Disorder
MeSH terms: Autistic Disorder; Problem Behavior
Study type: Interventional
Phase: Phase 2

Summary: 
      This study aims to assess the safety, tolerability and efficacy of cannabinoids mix
      [cannabidiol (CBD), Δ9-tetrahydrocannabinol (THC) in a 20:1 ratio, BOL Pharma, Israel] for
      behavioral problems in children and youth with ASD.
    

Detailed description: 
      Disruptive behaviors are very common in children and youth with autism spectrum disorder
      (ASD). Behavioral problems increase social impairment in children with ASD, make
      interventions more difficult and place considerable strain on families and caregivers.
      Current treatment is based on behavioral interventions combined with atypical antipsychotics
      which often have low tolerability and questionable efficacy.

      Cannabis exerts profound effects on human social behavior. Research using animal models of
      ASD indicate a possible dysregulation of the endocannabinoid system, and stress that it may
      be a novel target for pharmacological interventions. Anecdotal evidence suggest efficacy of
      various phytocannabinoids in resistant behavioral problems. However controlled human studies
      are lacking.

      Objective: To assess the safety, tolerability and efficacy of cannabinoids mix [cannabidiol
      (CBD), Δ9-tetrahydrocannabinol (THC) in a 20:1 ratio, BOL Pharma, Israel] for behavioral
      problems in children and youth with ASD.

      Setting: A double blind randomized placebo-controlled trial with crossover.

      Methods: One hundred and fifty participants, ages 5-21 years, with ASD and moderate to severe
      refractory behavioral problems will be randomized to receive 1 out of 3 treatments for
      12-weeks and cross-over to another treatment in a second 12 weeks period. Treatment options
      are: (1) oral placebo (2) cannabis extract, contains cannabidiol and Δ9-tetrahydrocannabinol
      in a 20:1 ratio, at a cannabidiol dose of 10 mg/kg/d and (3) pure cannabidiol and
      Δ9-tetrahydrocannabinol in the same ratio and dose.

      Outcomes and measures: Two co-primary endpoints will compare the whole plant extract
      treatment to the placebo treatment on a within subject design. 1) The change from baseline
      Home Situations Questionnaire-ASD score after 3 months of treatment (HSQ-ASD; a parent rated
      assessment of disruptive behavior). 2) The Clinical Global Impression- improvement (CGI-I; a
      clinician rated assessment of improvement in disruptive behavior following treatment)

      Secondary efficacy outcomes include:

        -  Within subject differences between the placebo condition and the pure cannabinoids
           condition and between the whole plant extract condition and the pure cannabinoids
           condition in the change from baseline HSQ-ASD score after 3 months of treatment and in
           the CGI-I.

        -  Within subject differences between each pair of the 3 conditions in the Clinical Global
           Impression- drug effect (CGI-D).

        -  Within subject differences between each pair of the 3 conditions in the change from
           baseline after 3 months of treatment in: Social Responsiveness Scale (SRS) parent and
           teacher rated, Child Behavior Checklist (CBCL) and autism parenting stress index (APSI).

      Safety endpoints will include the proportion of patients with adverse events measured by the
      investigators and the Liverpool Adverse Events Profile (modified).

      Exploratory measures are: markers of the endocannabinoid system in the patients' blood and
      possible correlation to phytocannabinoids bioavailability and treatment response, change from
      baseline at the end of treatment in BMI and Children's Sleep Habits Questionnaire (CSHQ)
      score and quality of parent- child interaction during the study (Emotional Availability- EA).

      Long term safety, tolerability and efficacy of cannabidiol-rich medical cannabis will be
      assessed after 12 and 24 months of open treatment, in a subgroup of patients who will apply
      for medical license to use cannabis after completing the study.
    

Intervention name(s): Cannabinoids - 99% pure cannabinoids mix; Placebo; Cannabinoids - whole plant extract
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 99% pure cannabidiol (CBD) and 99% pure Δ9-tetrahydrocannabinol (THC) in a 20:1 ratio (B.O.L Pharma, Israel), in a 160/8.0 mg per mL (CBD/THC) olive oil-based solution.; Olive oil and flavors solution.; Whole plant extract enriched with cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) to achieve 20:1 ratio (B.O.L Pharma, Israel), in a 160/8.0 mg per mL (CBD/THC) olive oil-based solution.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment