A randomized, double-blind, placebo-controlled decentralized trial to assess sleep, health outcomes, and overall well-being in healthy adults reporting disturbed sleep, taking a melatonin-free supplement

Inadequate sleep is a global health concern. Sleep is multidimensional and complex; new multi-ingredient agents are needed. This study assessed the comparative effects of two multi-ingredient supplements on sleep relative to placebo. Adults (N=620) seeking better sleep were randomly assigned to receive 1 of 3 study products (Sleep A, Sleep B or placebo) for 4 weeks. Both active products contained federally legal hemp-derived cannabinoids, botanical oils, GABA and L-theanine. Sleep disturbance was assessed at baseline and weekly using NIH’s Patient-Reported Outcomes Measurement Information System (PROMIS™) Sleep Disturbance SF 8A survey. Anxiety, stress, pain, and well-being were assessed using validated measures at baseline and weekly. A linear mixed-effects regression model was used to assess the change in health outcome score between active product groups and the placebo. There was a significant difference in sleep disturbance, anxiety, stress, and well-being between Sleep A and placebo. There was no significant difference in any health parameter between Sleep B and placebo. Side effects were mild or moderate. There were no significant differences in the frequency of side effects between the study groups. A botanical blend containing a low concentration of THC improved sleep disturbance, anxiety, stress, and well-being in healthy individuals that reported better sleep as a primary health concern. ### Competing Interest Statement Antonija Kolobaric, Susan Hewlings, Corey Bryant, Jeff Chen and Emily Pauli are employees of Radicle Science, the research organization contracted to conduct this trial. ### Clinical Trial NCT05511818 ### Funding Statement This study was funded by MDbio - The Doctors Brand ### 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: Radicle Rest: A randomized, blinded, controlled, direct-to-consumer study assessing the impact of plant derived cannabinoids on sleep and overall health outcomes was registered on [ClinicalTrials.gov][1] ([NCT05511818][2]) and reviewed and approved by Sterling Independent Review Board (SIRB) (10147). 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 study are available upon reasonable request to the authors [1]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05511818&atom=%2Fmedrxiv%2Fearly%2F2023%2F07%2F11%2F2023.07.02.23292135.atom