This was an open-label, single-arm trial of medicinal cannabis, with participants with a body weight <50 kg receiving a maximum Δ9-tetrahydrocannabinol dose of 10 mg/day and those with a body weight ≥50 kg receiving a maximum Δ9-tetrahydrocannabinol dose of 20 mg/day.

This study was conducted in accordance with the Consolidated Standards of Reporting Trials guidelines, and ethical approval was granted from the South-Western Sydney Local Health District Ethics Committee (approval number 2021/ETH11096). It was registered with the Australian and New Zealand Clinical Trials Registry (identifier ACTRN12622000031763).

Adolescents aged 12–18 years, with a DSM-5 diagnosis of Tourette syndrome, a total tic severity score of ≥20 on the Yale Global Tic Severity Scale (YGTSS) ⁸ and no change to medication/interventions for the previous 4 weeks were enrolled from 14 April 2022 to 19 October 2023. All participants had been treated with psychotropic medication (and six had also received behavioural treatments), but had failed to achieve meaningful improvement despite appropriate trial at therapeutic doses and duration. All parents and participants (aged >16 years) provided written informed consent. Exclusion criteria included non-English-speaking parents, a personal/family history of serious mental disorders such as psychosis, abnormal liver function, recent illicit drug or certain medication use, pregnancy or breastfeeding, and clinically significant suicidal ideation in the previous 12 months.

Medicinal cannabis oil with a concentration of Δ9-tetrahydrocannabinol 10 mg/mL and cannabidiol 15 mg/mL (Cann Group, Australia) was used.

The dose was stratified by participant weight (<50 kg and ≥50 kg) at enrolment. The titration schedule included an initial dose of 1 mg/day, followed by uptitration over 21 days by 1 mg every 4–5 days to reach 5 mg/day for participants weighing <50 kg, and 1 mg every 2–3 days to reach 10 mg/day for participants weighing ≥50 kg by day 29. This was administered once daily, with a recommendation for it to be taken in the evening, except when twice a day divided dosage was used where side-effects were experienced. Participants achieving a 55% reduction from baseline on the Parent Tic Questionnaire (PTQ) and a favourable Clinical Global Impression – Improvement score (1 or 2) with tolerable side-effects were considered responders and stayed on this dose until day 85. Non-responders continued uptitration over 21 days, to 10 mg (<50 kg) or 20 mg (≥50 kg).

Tics were evaluated using the clinician-administered YGTSS ⁸ and parent-administered PTQ. ⁹ Acceptability and adverse events were ascertained using a weekly log and the Modified Liverpool Adverse Events Profile (LAEP) questionnaire. ¹⁰ Clinicians completed Clinical Global Impression – Severity and Improvement scales and the Premonitory Urge for Tics Scale (PUTS). ¹¹ Tics and associated features and comorbid conditions were assessed by a clinician, using the National Hospital Interview Schedule (NHIS), ¹² and parents completed the ADHD Rating Scale, ¹³ the Strengths and Difficulties Questionnaire (SDQ) ¹⁴ for behavioural and emotional issues, and the Gilles de la Tourette Syndrome-Quality of Life Scale (GTS-QOL). ¹⁵ Urine testing for illicit drugs and blood tests for urea and electrolytes at screening and liver function during screening and on day 85 were done. See Supplementary Table 1 for the schedule of activities.

We conducted equivalence tests for tic-related symptoms and QoL by using paired t-tests with two-sided P-values. Comparisons of baseline features for responders and non-responders, as well as experience of adverse events, were conducted with Mann–Whiney U-tests. Effect sizes were estimated for both types of statistical tests. Given that this is a feasibility study, we employed exploratory analyses designed to guide the development of a larger trial. To align with the study’s preliminary nature, these analyses did not account for covariates, and adjustments for multiple testing were not performed.