Radwan MM, Chandra S, Gul S, ElSohly MA. Cannabinoids, phenolics, terpenes and alkaloids of cannabis. Molecules. 2021;26:2774.

Arnold JC, McCartney D, Suraev A, McGregor IS. The safety and efficacy of low oral doses of cannabidiol: an evaluation of the evidence. Clin Transl Sci. 2023;16:10–30.

Article  PubMed  CAS  Google Scholar 

Banister SD, Arnold JC, Connor M, Glass M, McGregor IS. Dark classics in chemical neuroscience: delta(9)-tetrahydrocannabinol. ACS Chem Neurosci. 2019;10:2160–75.

Article  PubMed  CAS  Google Scholar 

Lintzeris N, Mills L, Abelev SV, Suraev A, Arnold JC, McGregor IS. Medical cannabis use in Australia: consumer experiences from the online cannabis as medicine survey 2020 (CAMS-20). Harm Reduct J. 2022;19:88.

Article  PubMed  PubMed Central  Google Scholar 

Lintzeris N, Mills L, Suraev A, Bravo M, Arkell T, Arnold JC, et al. Medical cannabis use in the Australian community following introduction of legal access: the 2018-2019 Online Cross-Sectional Cannabis as Medicine Survey (CAMS-18). Harm Reduct J. 2020;17:37.

Article  PubMed  PubMed Central  Google Scholar 

Endomba FT, Tchebegna PY, Chiabi E, Angong Wouna DL, Guillet C, Chauvet-Gelinier JC. Epidemiology of insomnia disorder in older persons according to the Diagnostic and Statistical Manual of Mental Disorders: a systematic review and meta-analysis. Eur Geriatr Med. 2023;14:1261–72.

Fietze I, Laharnar N, Koellner V, Penzel T. The different faces of insomnia. Front Psychiatry. 2021;12:683943.

Article  PubMed  PubMed Central  Google Scholar 

Krystal AD, Prather AA, Ashbrook LH. The assessment and management of insomnia: an update. World Psychiatry. 2019;18:337–52.

Article  PubMed  PubMed Central  Google Scholar 

Anderson LL, Ametovski A, Lin Luo J, Everett-Morgan D, McGregor IS, Banister SD, et al. Cannabichromene, related phytocannabinoids, and 5-fluoro-cannabichromene have anticonvulsant properties in a mouse model of Dravet syndrome. ACS Chem Neurosci. 2021;12:330–39.

Article  PubMed  CAS  Google Scholar 

Anderson LL, Heblinski M, Absalom NL, Hawkins NA, Bowen MT, Benson MJ, et al. Cannabigerolic acid, a major biosynthetic precursor molecule in cannabis, exhibits divergent effects on seizures in mouse models of epilepsy. Br J Pharm. 2021;178:4826–41.

Article  CAS  Google Scholar 

Anderson LL, Low IK, Banister SD, McGregor IS, Arnold JC. Pharmacokinetics of phytocannabinoid acids and anticonvulsant effect of cannabidiolic acid in a mouse model of Dravet syndrome. J Nat Prod. 2019;82:3047–55.

Article  PubMed  CAS  Google Scholar 

Assareh N, Gururajan A, Zhou C, Luo JL, Kevin RC, Arnold JC. Cannabidiol disrupts conditioned fear expression and cannabidiolic acid reduces trauma-induced anxiety-related behaviour in mice. Behav Pharmacol. 2020;31:591–96.

Article  PubMed  CAS  Google Scholar 

Rock EM, Limebeer CL, Pertwee RG, Mechoulam R, Parker LA. Therapeutic potential of cannabidiol, cannabidiolic acid, and cannabidiolic acid methyl ester as treatments for nausea and vomiting. Cannabis Cannabinoid Res. 2021;6:266–74.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Pollastro F, Caprioglio D, Marotta P, Moriello AS, De Petrocellis L, Taglialatela-Scafati O, et al. Iodine-promoted aromatization of p-menthane-type phytocannabinoids. J Nat Prod. 2018;81:630–33.

Article  PubMed  CAS  Google Scholar 

Mechoulam R, Hanus L. A historical overview of chemical research on cannabinoids. Chem Phys Lipids. 2000;108:1–13.

Article  PubMed  CAS  Google Scholar 

Corroon J. Cannabinol and sleep: separating fact from fiction. Cannabis Cannabinoid Res. 2021;6:366–71.

PubMed  PubMed Central  Google Scholar 

Lavender I, McGregor IS, Suraev A, Grunstein RR, Hoyos CM. Cannabinoids, insomnia, and other sleep disorders. Chest. 2022;162:452–65.

Article  PubMed  CAS  Google Scholar 

Rhee MH, Vogel Z, Barg J, Bayewitch M, Levy R, Hanus L, et al. Cannabinol derivatives: binding to cannabinoid receptors and inhibition of adenylylcyclase. J Med Chem. 1997;40:3228–33.

Article  PubMed  CAS  Google Scholar 

Hillard CJ. Circulating endocannabinoids: from whence do they come and where are they going? Neuropsychopharmacology. 2018;43:155–72.

Article  PubMed  CAS  Google Scholar 

Pava MJ, den Hartog CR, Blanco-Centurion C, Shiromani PJ, Woodward JJ. Endocannabinoid modulation of cortical up-states and NREM sleep. PLoS ONE. 2014;9:e88672.

Article  PubMed  PubMed Central  Google Scholar 

Pava MJ, Makriyannis A, Lovinger DM. Endocannabinoid signaling regulates sleep stability. PLoS ONE. 2016;11:e0152473.

Article  PubMed  PubMed Central  Google Scholar 

Felder CC, Joyce KE, Briley EM, Mansouri J, Mackie K, Blond O, et al. Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors. Mol Pharmacol. 1995;48:443–50.

PubMed  CAS  Google Scholar 

MacLennan SJ, Reynen PH, Kwan J, Bonhaus DW. Evidence for inverse agonism of SR141716A at human recombinant cannabinoid CB1 and CB2 receptors. Br J Pharmacol. 1998;124:619–22.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Perez-Reyes M, Timmons MC, Davis KH, Wall EM. A comparison of the pharmacological activity in man of intravenously administered delta9-tetrahydrocannabinol, cannabinol, and cannabidiol. Experientia. 1973;29:1368–9.

Article  PubMed  CAS  Google Scholar 

Takahashi RN, Karniol IG. Pharmacologic interaction between cannabinol and delta9-tetrahydrocannabinol. Psychopharmacologia. 1975;41:277–84.

Article  PubMed  CAS  Google Scholar 

Bonn-Miller MO, Feldner MT, Bynion TM, Eglit GML, Brunstetter M, Kalaba M, et al. A double-blind, randomized, placebo-controlled study of the safety and effects of CBN with and without CBD on sleep quality. Exp Clin Psychopharmacol. 2024;32:277-–84.

Kolobaric A, Saleska J, Hewlings SJ, Bryant C, Colwell CS, D’Adamo CR, et al. A randomized, double-blind, placebo-controlled trial to assess the effectiveness and safety of melatonin and three formulations of floraworks proprietary TruCBN for improving sleep. Pharmaceuticals. 2024;17:977.

Betschart C, Hintermann S, Behnke D, Cotesta S, Fendt M, Gee CE, et al. Identification of a novel series of orexin receptor antagonists with a distinct effect on sleep architecture for the treatment of insomnia. J Med Chem. 2013;56:7590–607.

Article  PubMed  CAS  Google Scholar 

Toth LA, Bhargava P. Animal models of sleep disorders. Comp Med. 2013;63:91–104.

PubMed  PubMed Central  CAS  Google Scholar 

Depoortere H, Francon D, van Luijtelaar EL, Drinkenburg WH, Coenen AM. Differential effects of midazolam and zolpidem on sleep-wake states and epileptic activity in WAG/Rij rats. Pharm Biochem Behav. 1995;51:571–6.

Article  CAS  Google Scholar 

Morairty SR, Hedley L, Flores J, Martin R, Kilduff TS. Selective 5HT2A and 5HT6 receptor antagonists promote sleep in rats. Sleep. 2008;31:34–44.

Article  PubMed  PubMed Central  Google Scholar 

Raymond JS, Everett NA, Gururajan A, Bowen MT. Quiet wakefulness: the influence of intraperitoneal and intranasal oxytocin on sleep-wake behavior and neurophysiology in rats. Sleep. 2023;46:zsad112.

Kevin RC, Vogel R, Doohan P, Berger M, Amminger GP, McGregor IS. A validated method for the simultaneous quantification of cannabidiol, Delta(9) -tetrahydrocannabinol, and their metabolites in human plasma and application to plasma samples from an oral cannabidiol open-label trial. Drug Test Anal. 2021;13:614–27.

Article  PubMed  CAS  Google Scholar 

Sparkes E, Boyd R, Chen S, Markham JW, Luo JL, Foyzun T, et al. Synthesis and pharmacological evaluation of newly detected synthetic cannabinoid receptor agonists AB-4CN-BUTICA, MMB-4CN-BUTINACA, MDMB-4F-BUTICA, MDMB-4F-BUTINACA and their analogs. Front Psychiatry. 2022;13:1010501.

Article  PubMed  PubMed Central  Google Scholar 

R Core Team. R: a language and environment for statistical computing. R Foundation for Statistical Computing; 2022. https://www.R-project.org/

Fox J, Weisberg S. An R companion to applied regression. 3rd ed. Thousand Oaks, CA: Sage Publications; 2018.

Lenth R. emmeans package (The University of Iowa Iowa City, IA, 2022).

Killander D, Sterner O. Synthesis of the bioactive benzochromenes pulchrol and pulchral, metabolites of Bourreria pulchra. Eur J Org Chem. 2014;2014:1594–96.

Article  CAS