International forskning

Mediators of Placebo Response to Cannabinoid Treatment in Children with Autism Spectrum Disorder

Adi Aran 1 2, Moria Harel 1, Aminadav Ovadia 3, Shulamit Shalgy 3, Dalit Cayam-Rand 1

  • 1Neuropediatric Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel.
  • 2Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
  • 3Psychology Department, Yezreel Valley College, Yezreel Valley 1930600, Israel.


The placebo response has a substantial impact on treatment outcome. However, data regarding mediators of the placebo response in children with autism spectrum disorder (ASD) are sparse. This retrospective study investigated possible mediators of the placebo response among participants of a placebo-controlled trial of cannabinoid treatment for behavioral problems in children with ASD (CBA trial, age 5-21 years). We used a specifically designed questionnaire to explore possible mediators of the placebo response in 88 participants of the CBA trial who received a placebo and had valid outcome scores. The parents of 67 participants completed the questionnaire. The placebo response was positively associated with the child’s comprehension of the treatment purpose (p = 0.037). There was also a trend for participants who had a relative aggravation of symptoms before treatment onset to improve following placebo treatment (p = 0.053). No other domains, including parental expectations, previous positive experience with similar treatments (behavioral conditioning), parental locus of control, quality of the patient-physician relationships, and adherence to study medications were associated with placebo-response. This finding suggests that efforts to explain the treatment purpose to children with disabilities may enhance treatment efficacy in clinical practice and decrease differences in the placebo response between study arms. Contrary to our hypothesis, parental expectations regarding cannabinoid treatment were not associated with the placebo response.