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.

Introduction: Prescription sleep aids often have side effects, making alternative solutions necessary. Melatonin is an efficacious sleep aid and is often the comparator for alternatives. The phytocannabinoid cannabinol (CBN), has a potential mechanism of action but minimal evidence to support its effectiveness. Methods: TruCBN is a hemp-derived cannabinol (CBN) sleep aid. The primary aim of this randomized, double-blind, placebo-controlled study was to assess the safety and effects of three formulations of TruCBN [25 mg (n=206), 50 mg (n=205), 100 mg (n=203)], on sleep quality measured by PROMIS Sleep Disturbance 8A scale, relative to placebo (n=204). As a secondary aim, the effectiveness and safety of these formulations relative to a 4 mg melatonin (n=202) were assessed. Exploratory measures were stress (PROMIS Stress 4A), anxiety (Anxiety 4A), pain (PROMIS PEG) and well-being (WHO 5). Results: All treatment groups (25, 50 and 100 mg TruCBN) and the 4 mg melatonin group experienced significant improvement in sleep quality relative to placebo. There were no significant differences between any of the TruCBN groups and melatonin for improving sleep. Participants taking 100 mg TruCBN showed a larger decrease in stress compared to the placebo group. There were no significant differences in anxiety, pain, well-being or frequency of side effects between any TruCBN group and placebo. There was no significant difference in improvements in sleep quality between any of the treatment groups and 4mg melatonin. Discussion: Orally ingested TruCBN, 25 mg, 50 mg and 100 mg, is a safe and effective alternative for the improvement of sleep. ### Competing Interest Statement A. Kolobaric, J. Saleska, S. Hewlings, Corey Bryant, J. Chen, E. Pauli are employed by Radicle Science, the company who conducted the study. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript. ### Clinical Trial NCT05511818 ### Funding Statement Funders and Support Radicle Science is conducting the evaluation of the effectiveness of the product under contract with the funder (Floraworks). Data collected for this article was funded by the client for the purposes of the evaluation. The funding source(s) had no role in the design and conduct of the study; in the collection, management, analysis, and interpretation of the data; preparation, or approval of the manuscript. The funders were able to review the manuscript, but their approval was not required. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Sterling Institutional Review Board (SIRB) approved the study [10147-EKPauli]. The study was registered on ClinicalTrials.gov [[NCT05511818][1]] on August 21, 2023. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05511818&atom=%2Fmedrxiv%2Fearly%2F2023%2F11%2F08%2F2023.11.07.23298230.atom