Effect of cannabigerol on sleep and quality of life in Veterans: A decentralized, randomized, placebo-controlled trial

Background/Objective This decentralized, randomized, triple-blind, placebo-controlled study evaluated the efficacy and safety of an oral cannabigerol (CBG) formulation in Veterans with sleep issues. Methods After inclusion, randomization and a two-week run-in phase, participants received CBG (25 mg daily for two weeks, escalated to 50 mg daily for a further two weeks) or placebo. The primary endpoint was change in sleep quality, assessed via the Medical Outcomes Study Sleep Problems Index II (MOS-SS SPI-II). Additional endpoints included change in quality of life (WHODAS-2.0–12), post-traumatic stress disorder symptoms (PCL-5) and sleep actigraphy data. Safety was assessed based on adverse event reporting. Results A total of 63 participants were randomized to receive CBG (n=33) or placebo (n=30) and formed the intention-to-treat (ITT) population. Of these, 35 completed the study without major protocol deviations (CBG [n=18]; placebo [n=17]) and formed the per-protocol (PP) population. During active treatment (between day 14 and day 42) MOS-SS SPI-II scores declined numerically (indicating improved sleep) in both treatment groups (in both the ITT and the PP populations) with no statistically discernible difference between the CBG and placebo groups. Similar patterns were observed for WHODAS-2.0–12 and PCL-5 scores. Actigraphy data indicated no discernible difference in sleep patterns between the treatment groups. Five mild, nonserious, adverse events were reported with CBG. Conclusions Both CBG and placebo tended towards sleep and QoL improvement in Veterans. While no firm conclusion on the efficacy of CBG in improving sleep can be made, the favorable safety profile supports future studies to investigate the benefit of CBG. ### Competing Interest Statement C.R.E. is an employee, shareholder, and fiduciary officer of Metta Medical (dba LEVEL). C.E.W. is an employee of nymbly, which was contracted by Metta Medical for the conduct of this study. E.J.D., B.J.K and M.T are external consultants declaring personal fees from nymbly/Metta Medical (dba LEVEL). No other potential conflicts of interest relevant to this article are reported. ### Clinical Trial NCT05088018 ### Clinical Protocols ### Funding Statement This study and costs associated with development of this manuscript were supported by Metta Medical (dba LEVEL). ### 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: The Institutional Review Board of Advarra gave ethical approval for this work (Advarra; Pro00056526) 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 The data underlying this article will be shared on reasonable request to the corresponding author.