0371 Acute effects of cannabinoids in insomnia disorder: a randomised, placebo-controlled trial using high-density EEG

Abstract

Abstract Introduction Medicinal cannabis is often cited as a popular alternative to common sleep aids; however, there are limited studies using complex sleep EEG methods examining its’ effects in insomnia disorder. Methods Twenty participants (16 female; mean [SD] age, 47.1 [8.7] years) with insomnia disorder (mean ISI=20.8) completed two 24-hour in-laboratory visits during which they received a single oral dose of ‘CBD/THC’ containing 200 mg cannabidiol (CBD) and 10 mg Δ9-tetrahydrocannabinol (THC) or matched placebo. Co-primary outcomes were total sleep time (TST) and wake after sleep onset (WASO). Secondary outcomes included next-day neurobehavioural function and sleep architecture metrics determined using overnight polysomnography with high-density EEG. Trial registration: ACTRN12619000714189. Results Compared to placebo, CBD/THC significantly decreased TST (-24.5 min, p=0.047) with no significant change to WASO (+10.7 min, p=0.422). CBD/THC significantly decreased time spent in REM sleep (-8.1%, p< 0.001) and increased REM sleep latency (+65.6 min, p=0.008). High-density EEG analysis revealed a significant reduction in high-frequency EEG activity overlying the posterior and frontal cortex during N2 sleep with CBD/THC treatment compared to placebo. CBD/THC treatment also reduced delta activity in the posterior region of the brain during N3 sleep and increased alpha and beta activity during REM sleep in the posterior regions of the brain relative to placebo (all p’s< 0.05). CBD/THC did not impair next-day (+12 h post-treatment) cognitive performance, alertness, or simulated driving performance (all p’s>0.05). Eighty-five mild, non-serious, adverse events were reported (55 during ETC120; most common dry mouth, drowsiness, and fatigue). Conclusion An acute dose of combined 200 mg CBD and 10 mg THC reduced TST with a clear effect of REM sleep suppression. However, no next-day residual impairment on cognitive function, alertness or simulated driving performance were observed. Further research is required to determine the impact of chronic cannabinoid dosing on REM sleep and other objective sleep outcomes in insomnia disorder. Support (if any) The study was funded by the Lambert Initiative for Cannabinoid Therapeutics, a philanthropically funded centre for cannabinoid research at the University of Sydney, Australia.