Aran 2021.

Study characteristics
Methods	12‐week cross‐over trial of cannabidiol versus placebo
Participants	Inclusion criteria: male or female outpatients aged 5–21 years old diagnosis of ASD according to DSM‐5 moderate or greater behavioral problems as measured by a CGI‐S score of ≥ 4 at screening involvement of a parent or caregiver able to consistently complete assessments throughout the study Exclusion criteria: lifetime history of psychotic disorder current or former treatment with cannabinoids a medical condition (such as heart, liver, renal or haematological disorder) that impacts the participant’s ability to participate in the study or makes them predisposed to severe adverse events changes in pharmacological, educational, or behavioiral treatments for 4 weeks prior to randomisation or planned changes in existing interventions for the duration of the trial Location/setting: Shaare Zedek Medical Center, Jerusalem, Israel Sample size: pure cannabis (44), placebo (44) Reasons for withdrawals/dropouts: pure cannabinoids: n = 6 (2 before treatment onset, 2 received license #, 1 had adverse events, 1 due to ineffectiveness) placebo: n = 6 (1 died (treatment unrelated), 2 received license #, 2 sheltered living decision, 1 had adverse events) Gender: 80% male, 20% female Mean age: 11.8 (SD4.1) years IQ: not reported Baseline ABC‐I or other BoC scale: Concomitant medications: any medication 72%; antipsychotics 54%; SSRIs 15%; antiepileptics 12%; stimulants 12%; benzodiazepines 7%; alpha‐2 agonists 4% Previous medications: details not provided
Interventions	Intervention (pure cannabinoids): 99% pure cannabidiol (CBD) and 99% pure tetrahydrocannabinol in a 20:1 ratio at 1 mg/kg cannabidiol/d, up‐titrated until intolerance or to a maximum dose of 10 mg/kg CBD/d, divided to 3 daily doses, for 3 months Comparator (placebo): oral olive oil and flavors that mimic in texture and flavour the cannabinoid solution.
Outcomes	Primary outcomes: AEs Secondary outcomes: none reported Timing of outcome assessments: 1 month, 2 months, and 3 months (endpoint)
Notes	Study start date: January 2017 Study end date: December 2018 Funding: the study was funded by BOL Pharma, Revadim, Israel and the National Institute for Psychobiology in Israel (#203‐17‐18). Conflicts of interest: details not provided
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Allocation to treatment arm was based on a randomisation list. Randomisation scheme was generated by BioStats Statistical Consulting Ltd.
Allocation concealment (selection bias)	Low risk	Allocation to treatment arm was based on a randomisation list. Randomisation scheme was generated by BioStats Statistical Consulting Ltd.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The code key was kept by BioStats Statistical Consulting Ltd. until study end. Neither the principal investigator nor any other team member or individual had access to the codes until study end. No unblinding occurred during the study.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The code key was kept by BioStats Statistical Consulting Ltd. until study end. Neither the principal investigator nor any other team member or individual had access to the codes until study end. No unblinding occurred during the study.
Incomplete outcome data (attrition bias) All outcomes	Low risk	12% overall attrition, doesn't appear to be bias in dropout reason
Selective reporting (reporting bias)	Low risk	it appears that all outcomes listed on trial registry have been reported
Other bias	High risk	The study was funded by BOL Pharma, Revadim, Israel.