0394 The CANnabidiol Use for RElief of Short-Term Insomnia (CAN-REST). a Randomised Placebo-Controlled Clinical Trial

Abstract Introduction Cannabidiol (CBD) is a non-intoxicating cannabinoid which Australian regulators (TGA) have proposed down-scheduling to an over-the-counter pharmacist-only medicine pending positive efficacy trials. This trial compared the effect of 50mg and 100mg/day of an oral capsule CBD medicine with placebo over 8 weeks on insomnia symptoms, stress and mood. Methods This was a sponsor-initiated (NCT05253417) randomised, double-blind, 3-arm parallel superiority trial. This study was undertaken remotely without in-person visits. Participants were randomised (1:1:1) via a centralised computerised secure system. Potential participants were recruited through social and other media advertising with all participants initially directed to an online screening platform. Those who met initial eligibility were invited to a telehealth screening and informed consent visit. Inclusion criteria included adults aged 18-65 years with an Insomnia Severity Index (ISI) of 8-21. All questionnaires were collected through the online platform, and we couriered actigraphy devices and blinded study drug to participants. Safety blood and urinary drug screening was performed before and after treatment by local pathology services. The primary outcome was ISI and secondary outcomes were actigraphy-derived wake after sleep onset, stress and anxiety (DASS-21 questionnaire). The critical p-value for the primary hypotheses was < 0.025 and < 0.0083 for any of the 3 secondary outcomes to maintain an overall false discovery rate of 5% in each of the primary and secondary comparisons. Results Recruitment was ceased (n=206) when we reached our pre-defined sample size (50mg=64; 100mg=62; placebo=80; 146 females; mean age 47 years [19-65]; ISI=16.8 [8-21]). All participants were analysed under the intention-to-treat principle. At 8-week follow-up there was no difference between placebo and 100mg (-1.3, 95%CI [-2.8 to 0.3], p=0.10) or 50 mg (0.1, [-1.4 to 1.6], p=0.89) on the ISI. No secondary outcomes were positively affected (all p≥0.04). All adverse events were minor and consistent with the known pattern of events for CBD. Conclusion There was no significant effect of 8 weeks of a low-dose CBD medicine on insomnia symptoms in intention-to-treat analyses. It is possible that higher doses of CBD and identifying insomnia subgroups responsive to CBD may be effective and are warranted for future research. Support (if any) BOD Science, Australia