A pilot randomised controlled trial testing the efficacy of cannabidiol for anxiety in Tourette Syndrome

INTERVENTION: This is a randomised, double‐blind, placebo‐controlled cross‐over trial to assess the efficacy of Cannabidiol (CBD) administered as Epidiolex. Epidiolex is a purified cannabidiol oral solution that will be administered orally or via gastrostomy and nasogastric feeding tubes. All participants will undergo a screening process. Eligible participants will be randomised to begin either 16‐weeks of treatment with CBD or 16‐weeks of treatment with placebo. Each treatment block includes 6 weeks of titration, 8 weeks on the maintenance dose and 2 weeks of drug tapering. Following the initial 16‐weeks of either treatment or placebo, patients will immediately cross‐over and begin a further 16‐weeks of the alternative treatment. Allocation to treatment group will be randomised and blinded for both participants and study personnel. Treatment group A (Epidiolex) Parents/caregivers will administer the study drug orally/via gastrostomy/via nasogastric tube in two divided doses (12 hours +/‐ 2 hours) daily. Dosage will be titrated over 6 weeks until maximum or best tolerated dose is reached. Maximum or best tolerated dose will be maintained for 8 weeks. Participants are then titrated down over a two week period, before crossing over to the alternative treatment arm. Dosing schedule: Week 1‐2: 2.5mg/kg/day via two divided doses Week 3‐4: 5mg/kg/day via two divided doses Week 5‐6: 10mg/kg/day via two divided doses Week 7‐14: 15mg/kg/day Week 15‐16: 5mg/kg/day (Week 15); 2.5mg/kg/day (Week 16) Four weeks after final dose, participants will be followed up in clinic prior to discharge from the study. Compliance with study medication will be reviewed at each "in‐clinic" appointment. Pharmacy staff will calculate the expected number of bottl CONDITION: Mental Health ‐ Anxiety Neurological ‐ Other neurological disorders Tourette Syndrome;Anxiety; ; Tourette Syndrome ; Anxiety PRIMARY OUTCOME: Any change in the total anxiety score on the Revised Children’s Anxiety and Depression Scale (RCADS) when compared with placebo.[Treatment Group A: Assessed periodically at Week 0 (Baseline), Week 6, Week 10 and Week 14.; Treatment Group B: Assessed periodically at Week 0 (Baseline), Week 6, Week 10 and Week 14.; ] SECONDARY OUTCOME: Any change in objective sleep parameters (including sleep duration) as measured by a sleep diary.[Treatment Group A: Diary provided at Screening for 2 weeks of sleep tracking. Re‐assessed during dose maintenance. Diary provided for 2 weeks of tracking at Week 10. ; Treatment Group B: Diary provided at Screening for 2 weeks of sleep tracking. Re‐assessed during dose maintenance. Diary provided for 2 weeks of tracking at Week 10.] Any change in subjective sleep parameters (including sleep quality, sleep duration and sleep efficiency) as measured by sleep actigraphy device.[Treatment Group A: Actigraphy device provided at Screening for 2 weeks of monitoring and re‐assessed at Week 10 for 2 weeks of monitoring. ; Treatment Group B: Actigraphy device provided at Screening for 2 weeks of monitoring and re‐assessed at Week 10 for 2 weeks of monitoring.] Any change in obsessive compulsive behaviour as measured by the Children’s Yale‐Brown Obsessive‐Compulsive Scale when compared with placebo.[Treatment Group A: Assessed periodically at Screening, Week 6, Week 10 and Week 14. ; Treatment Group B: Assessed periodically at Screening, Week 6, Week 10 and Week 14. ; Treatment Group B: Assessed periodically at Week 0 (Baseline), Week 6, Week 10 and Week 14. ; Treatment Group B: Assessed periodically at Week 0 (Baseline), Week 10 and Week 14. ; Treatment Group B: Assessed periodically at Week 0 (Baseline), Week 6, Week 10 and Week 14. ; Treatment Group B: Assessed periodically at Screening, Week 6 and Week 14. ; Treatment Group B: Assessed periodically at Screening, Week 6 and Week 14.] ; ] Any change in problem behaviours as measured by the Strengths and Difficulties Questionnaire when compared with placebo.[Treatment Group A: Assessed periodically at Week 0 (Baseline), Week 6, Week 10 and Week 14. ; ] Any change in quality of life as assessed via the Paediatric Quality of Life Scale when compared with placebo.[Treatment Group A: Assessed periodically at Week 0 (Baseline), Week 10 and Week 14. ; ] Any change in the depression scores on the Revised Children’s Anxiety and Depression Scale (RCADS) depression subscale when compared with placebo.[Treatment Group A: Assessed periodically at Week 0 (Baseline), Week 6, Week 10 and Week 14. ; ] Any change in the number of tics as assessed by the Yale Global Tic Severity Scale in Group A (active) when compared with Group B (placebo).[Treatment Group A: Assessed periodically at Screening, Week 6 and Week 14. ; ] Any changes in the premonitory urges for tics as assessed by the Yale Global Tic Severity Scale in Group A (active) when compared with Group B (placebo).[Treatment Group A: Assessed periodically at Screening, Week 6 and Week 14. INCLUSION CRITERIA: ‐ Male or female children/adolescents aged 6‐17 years old. ‐ Participants must have a diagnosis of Tourette Syndrome [confirmed by psychiatric diagnosis], and who have either (1) trialled a course of pharmaceutical (e.g. Clonidine), and psychological (e.g. cognitive behavioural therapy) treatment unsuccessfully; or, (2) who have significant contra‐indications to standard methods of treatment ‐ Participants must be experiencing severe symptoms of anxiety as assessed by the PI at screening ‐ If participants are receiving non‐pharmacological educational, behavioural, and/or dietary interventions, they must be stable and have been doing so for 2 months prior to screening. ‐ Participants must be willing to continue to be reviewed by their primary treating doctor/psychiatrist/paediatrician during the trial.