Electroencephalographic Findings in Insomnia Disorder: Treatment Effects Under Cannabinoid Interventions

Abstract

Insomnia disorder - characterised by subjective sleep difficulties causing daytime impairment - is a pervasive, distressing, and costly condition. Cannabinoid therapeutics, such as Δ⁹- tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN), are widely used and prescribed to treat insomnia symptoms, despite an insufficient evidence-base. CBN, a less intoxicating by-product of THC, is marketed as the ‘sleepy’ cannabinoid albeit untested; and THC was shown to worsen sleep and change rapid eye movement (REM) sleep characteristics. Therefore, the overarching aim of this research was to investigate the objective and subjective safety and efficacy of cannabinoid therapeutics used to treat insomnia disorder and explore whether this could enhance our understanding of the pathogenesis of insomnia more broadly. The specific aims were (a) Design a rigorous randomised, double-blind, triple-arm, crossover, dose-ranging, single-night, proof-of-concept clinical trial of CBN for treatment of insomnia disorder; (b) Characterise the effects of acute CBN (30 and 300 mg) on subjective and objective sleep using validated assessments, inlaboratory polysomnography, and quantitative EEG in patients with clinician-diagnosed insomnia disorder; (c) Establish the effects of acute CBN (30 and 300 mg) on next-day neurobehavioral function in insomnia disorder patients; (d) Explore sleep fragmentation in a randomised, placebocontrolled, crossover trial where CBD:THC (20:1) reduced total sleep time and REM sleep duration/onset in insomnia disorder patients; (e) Distinguish normal and maladaptive arousals by examining their characteristics, neural determinants, and consequences to wake versus sleep continuation. Each aim was successfully addressed, leading to several findings that advance the current understanding of cannabinoid therapeutics, insomnia disorder, and sleep instability.