- Change from baseline Home Situations Questionnaire-Autism Spectrum Disorder (HSQ-ASD) score, at three months [ Time Frame: At onset of each treatment period, at 1 month, 2 months and 3 months (end of treatment period) ] [ Designated as safety issue: No ]
This is a 24-item parent-rated measure of noncompliant behavior in children with ASD
- Change in Child Behavior Checklist (CBCL)- externalizing section score, at three months [ Time Frame: At onset of each treatment period, at 1 month, 2 months and 3 months (end of treatment period) ] [ Designated as safety issue: No ]
The CBCL generates 3 broad band results—an internalizing score (summing up anxious/depressed scale, somatic complaints scale and withdrawn scale) an externalizing score (summing up non-compliant scale and aggressive behavior scale) and a total score. For this study we will use the externalizing section only.
- Change in Autism Parenting Stress Index (APSI) score, at three months [ Time Frame: At onset of each treatment period, at 1 month, 2 months and 3 months (end of treatment period) ] [ Designated as safety issue: No ]
This is a 13-item parent rated measure designed to assess the effect of interventions to control disruptive behavior in children with ASD on parenting stress.
- Change in Clinical Global Impression scores (CGI, improvement and efficacy index items) at three months [ Time Frame: At onset of each treatment period and at 3 months (end of treatment period) ] [ Designated as safety issue: No ]
This is a 7-point scale designed to measure severity of illness (CGI-S), overall improvement from baseline (CGI-I) and the drug effects (both therapeutic effect and side effects, CGI-D).
- Change in Social Responsiveness Scale scores (SRS, parent and teacher rated) at three months [ Time Frame: At onset of each treatment period and at 3 months (end of treatment period) ] [ Designated as safety issue: No ]
This is a 69-71 item, caregiver (pSRS) or teacher (tSRS) questionnaire, used to determine the severity of social deficit exhibited by participants with ASD. The SRS contains five subscales: Social Awareness, Social Cognition, Social Communication, Social Motivation, and Autistic Mannerisms, which respectively measure the ability to recognize social cues, the ability to interpret social cues, the ability to use expressive verbal and nonverbal language skills, the ability to engage in social-interpersonal behaviors, and the tendency to display stereotypical behaviors and restricted interests characteristic of autism
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] for behavioral problems in children and youth with ASD.
Setting: A double blind randomized placebo-controlled trial with crossover. Methods: One hundred and twenty participants ages 6-30 years, with established ASD diagnosis and moderate to severe refractory behavioral problems will be treated with placebo and cannabinoids mix in a randomized cross-over trial. Each intervention period will be 12 weeks with additional 4 weeks for gradual dose decrease and wash-out. Baseline evaluations will include: Autism diagnostic observation schedule (ADOS-2), Social Communication Questionnaire (SCQ), Vineland II (interview based), Childhood Autism Rating Scale (CARS-2, observation based). Primary outcome measures: Home Situations Questionnaire-Autism Spectrum Disorder (HSQ-ASD), Child Behavior Checklist (CBCL, parent-rated), and Autism Parenting Stress Index (APSI) will be assessed every 4 weeks. Secondary outcome measures: Clinical Global Impression (CGI, improvement and efficacy index items, clinician-rated) and Social Responsiveness Scale (SRS, parent and teacher rated) will be assessed at baseline and termination of each treatment period. Adverse events will be taped every 4 weeks.