Cannabinol for Acute Treatment of Insomnia Disorder in a Randomized Placebo-Controlled Crossover Trial
Isobel G Lavender 1 2 3, Nathaniel S Marshall 1 4, Danielle McCartney 1 2 3, Garry Cho 1, Chris Irwin 5, Anastasia Suraev 2, Rebecca Gordon 3, Jonathon C Arnold 3 6, Angela L D'Rozario 1 7, Christopher J Gordon 1 4, Bandana Saini 1, Sheila Sivam 1 8 9, Yizhong Zheng 1 8 9, Ronald R Grunstein 1 8 10 11, Brendon J Yee 1 8 9 10, Iain S McGregor 2 3, Camilla M Hoyos 1 4
- 1Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research, Macquarie University, Sydney, New South Wales, Australia.
- 2School of Psychology, Faculty of Science, The University of Sydney, Sydney, New South Wales, Australia.
- 3Lambert Initiative for Cannabinoid Therapeutics, Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia.
- 4Department of Health Science, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia.
- 5School of Health Sciences and Social Work, Griffith University, Gold Coast, Queensland, Australia.
- 6Discipline of Pharmacology, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
- 7School of Psychological Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia.
- 8School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
- 9Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
- 10Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia.
- 11CPC-RPA Clinic, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
Affiliationer
Insomnia disorder is harmful and requires novel treatments. Cannabinol, an oxidative by-product of Δ9-tetrahydrocannabinol, is claimed to be a hypnotic, but its effects on objective sleep and insomnia remain unknown. This randomized, double-blind, placebo-controlled, three-arm, single-night crossover trial evaluated the acute efficacy and safety of cannabinol for insomnia disorder. Twenty adults (aged 25-65) with physician-diagnosed insomnia disorder (meeting DSM-5 and ICSD-3 criteria; Insomnia Severity Index ≥ 15) were enrolled at the Woolcock Institute of Medical Research (Sydney, Australia) between August 2022 and September 2023. Participants received a single 2 mL oral dose of 30 mg (1.5%) or 300 mg (15%) cannabinol, or matched placebo (2-week washout). All participants (17 female and 3 males; mean ± SD age 42 ± 13 years) completed the protocol and were statistically analysed. The primary outcome was wake after sleep onset (WASO) minutes, measured by overnight polysomnography. Cannabinol did not significantly change WASO (300 mg: -6.3 min [95% CI: -18.2, +5.5], p = 0.29, dz = -0.22; 30 mg: -4.0 min [-15.9, +7.9], p = 0.50, dz = 0.11). However, 300 mg cannabinol increased non-rapid eye movement-2 sleep (p = 0.03, dz = 0.54), subjective sleep quality (p = 0.005, dz = 0.56); and reduced sleep onset latency (p = 0.004, dz = -0.74) and electroencephalographic arousal indices (p = 0.02, dz = -0.65). There were 247 mild-to-moderate adverse events across arms. Larger, longer trials are warranted.
