Abstract

Study Objectives: 
This randomized, double-blind, placebo-controlled, cross-over study was conducted to evaluate the safety and efficacy of two-weeks of nightly sublingual cannabinoid extract (ZTL-101) in treating chronic insomnia (symptoms ≥three months).

Methods: 
Co-primary study endpoints were safety of the medication based on adverse event reporting and global insomnia symptoms (Insomnia Severity Index; ISI). Secondary endpoints included: self-reported (sleep diary), actigraphy-derived and polysomnography measurements of sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), sleep efficiency (SE); and self-reported assessments of sleep quality (sSQ) and feeling rested upon waking. Adjusted mean differences between placebo and ZTL-101 were calculated.

Results: 
Twenty-three of 24 randomized participants (n=20 female, mean age 53±9years) completed the protocol. No serious adverse events were reported. Forty mild, non-serious, adverse events were reported (36 during ZTL-101) with all but one resolving overnight or soon after waking. Compared to placebo, ZTL-101 decreased ISI (-5.07units [95%CI: -7.28 to -2.86]; p=0.0001) and self-reported SOL (-8.45mins [95%CI: -16.33 to -0.57]; p=0.04) and increased self-reported TST (64.6mins [95%CI: 41.70 to 87.46]; p<.0001), sSQ, (0.74units [95%CI: 0.51 to 0.97]; p<0.0001) and feeling of being rested on waking (0.51units [95%CI: 0.24 to 0.78]; p=0.0007). ZTL-101 also decreased actigraphy-derived WASO (-10.2mins [95%CI: -16.2 to -4.2]; p=0.002), and increased actigraphy-derived TST (33.4mins [95%CI: 23.07 to 43.76]; p<0.001) and SE (2.9% [95%CI: 2.0 to 3.8]; p=0.005).

Conclusion: 
Two-weeks of nightly sublingual administration of a cannabinoid extract (ZTL-101) is well tolerated and improves insomnia symptoms and sleep quality in individuals with chronic insomnia symptoms.