4. Discussion
sleep disturbances, insomnia, sleep disturbance, anxiety
We presented a randomized, double-blinded, placebo-controlled trial to evaluate the effectiveness and safety of two orally ingested softgel dietary supplements, Sleep A and Sleep B, compared to a placebo over four weeks of treatment. We observed a significant difference in effect on four health outcomes (sleep disturbance, anxiety, stress, and overall well-being) between Sleep A formula and placebo control. We observed no significant difference in effect on any health outcomes between Sleep B formula and placebo control. Importantly, both supplements exhibited favorable safety profiles, as all side effects were mild or moderate and there were no significant differences in the frequency of reported side effects between the active and placebo arms.We hypothesize that the change in the quality of sleep between the baseline and the first week of treatment is directly related to the use of study products, meaning that the placebo effect was the reason for the increase in both groups. The change in placebo group remained consistent over the course of the study, while the treatment group continued to improve. This is consistent with the literature investigating the change in placebo effect over time, which suggests that the change remains constant over the course of a study lasting as long as 12 months, especially in study designs utilizing subjective outcome measures [This study is among the first to investigate the effectiveness and safety of supplements that aim to enhance sleep and overall health in a large participant sample. These supplements were specifically designed to harness the potential synergistic effects of botanical ingredients that demonstrated favorable outcomes in promoting better sleep. Our primary analyses indicate that over the course of four weeks using the study product, the Sleep A group experienced a significantly greater reduction in sleep disturbance compared to the placebo group. Additionally, participants in the Sleep A group also showed significantly greater improvements in anxiety, stress, and overall well-being compared to those in the placebo group. These results are expected, given the intricate connections between sleep, anxiety, stress, and overall well-being [Interestingly, we observed no significant differences in any of the health outcomes between Sleep B and placebo. It is important to note that both Sleep A and B formulas contained the same amount of CBD, CBN, and L-Theanine, while Sleep formula A contained a lower amount of THC and higher amounts of GABA, hops oil, and valerian oil than the Sleep B formula. Since the current study did not employ a factorial design to examine the individual effects of all ingredients, as well as their potential interactions, we are unable to determine the main driver(s) between the different impacts Sleep A and Sleep B had on behavioral outcomes. We put forward a hypothesis regarding the potential reasons for the superior performance of Sleep A in reducing sleep disturbances compared to Sleep B. There are two primary factors that we believe contribute to this outcome. Firstly, Sleep A contains a lower amount of THC compared to Sleep B. One study found that those participants who use cannabis multiple times a week for its sleeping effects prefer strains with lower amounts of THC, suggesting that the strains with lower THC may be more effective at promoting sleep [The data obtained in the present study are consistent with previous findings that a combination of cannabinoids could improve sleep. For example, a randomized, controlled crossover trial administering a combination product, containing THC 20 mg/mL, CBN 2 mg/mL, CBD 1 mg/mL, and naturally occurring terpenes (extracted from the cannabis plant) in pharmaceutical grade sunflower oil for 2 weeks, demonstrated an improvement in sleep quality in subjects with insomnia when compared to placebo [This study was intended to approximate the “real world” effectiveness of the study products by administering them to a broad population that used the products in a manner and setting similar to that of actual consumers. Unlike conventional clinical trials, which often have restrictive eligibility criteria and rigorous monitoring, the data in question may exhibit higher levels of missingness and heterogeneity. Nonetheless, conventional clinical trials involving natural products frequently suffer from limited sample sizes and lack external validity, as the participants’ characteristics and behaviors may not accurately represent those of real-world users. Consequently, studies such as this try to reflect the real-world effects of such products and possess distinct value in their capacity to provide evidence for regulatory and clinical decision-making and additional clinical trial design [Whether or not the results of our study reflect botanical synergy, meaning that the higher levels of the hops, valerian, and GABA allowed for the lower level of THC to be effective, was not directly investigated in this study. However, it poses interesting questions and warrants further investigation.This study has multiple limitations. First, approximately 26% of participants did not complete any follow-up surveys. However, the overall attrition level was still below our anticipated attrition (45%) and the study remained adequately powered to detect significant sleep changes. Furthermore, because the products used in this study were combinatorial, we are unable to pinpoint the exact drivers of the observed changes. Additionally, as stated in the methods, subjects reported that they were healthy but were not screened for any diagnosed conditions. We feel this best represents a real-world consumer likely to seek sleep support.Considering the complex combinations of products examined in this study, further investigations are warranted to identify the specific active ingredient(s) responsible for the observed significant effects. To achieve this, a rigorous study employing a factorial design with multiple arms would be beneficial. This design would systematically vary the ingredients in different combinations, allowing for the examination of both their individual effects and potential interactions on behavioral outcomes. Such an approach would enhance our understanding of the precise drivers behind the observed effects.