Given how important quality sleep is for optimizing mental and physical wellbeing, it is alarming how pervasive sleep disturbances are throughout society [2,3,4]. The limited effectiveness and risk of undesirable and potentially dangerous side effects of conventional pharmaceutical sleep aids [6,7] result in nearly 50% dissatisfaction rates [5]. Hence, it is not surprising why people with sleep disturbances commonly report regular experimentation with multiple types of sleep aids [26], including alcohol and Cannabis. Our results showed that on average, Releaf App^TM users experienced a statistically and clinically significant improvement (−4.5 points on a 0–10 point scale) in perceived insomnia levels. However, products made with C. sativa were associated with less symptom relief and more negative side effects than products made from C. indica or hybrid plant subtypes. Use of pipes and vaporizers was associated with greater symptom relief and more positive and context-specific side effects as compared to the use of joints, while vaporization was also associated with lower negative effects. CBD potency levels were associated with greater symptom relief than were THC levels, but the cannabinoid contents were generally not associated with differential reported side effects.

The current results are consistent with survey-based studies showing increasing reported usage of cannabis for treating insomnia in healthy people and patients with other primary health conditions [13,14,15], and a patient preference for high CBD products [13,18,27]. In comparison to conventional prescription pharmaceutical sleep aids, CBD is generally believed to be much safer and often is described as non-psychoactive [16]. Prescription sleep aids in contrast, namely antidepressants (e.g., trazodone, amitriptyline, and doxepin), benzodiazepines (e.g., diazepam and lorazepam), gamma-aminobutyric acid (GABA) medications (zolpidem and eszopiclone), and anti-psychotics (aripiprazole, olanzapine, quetiapine and risperidone) are associated with significant clinical drawbacks [6] and heightened risk of morbidity [28,29,30,31]. The phytocannabinoid family of CBDs are known to differ from other cannabinoids such as THC in several ways, including having little affinity to CB1 receptors, serving as an antagonist to the effects of THC, and functioning as anti-inflammatory and immuno-suppressant agents [32,33]. Orexin antagonists, such as suvorexant [34], as well as nemorexant and lemborexant, which are currently in phase 3 clinical trials, are all dual antagonists of the orexin OX1 and OX2 receptors. They are being investigated for their potential use in treating sleep disorders. OX1 and OX2 receptors regulate several functions that overlap with cannabinoids, such as pain, wakefulness, and sleep. Both receptor types can form homo- and heterodimers with one-another and with CB1 receptors; however, orexin potentiation of CB1 signaling may result from orexin-promoted 2-AG (2-arachidonoyl glycerol, a native ligand of CB1 cannabinoid receptors) production and not necessarily from orexin-CB1 heterodimerization [23,35]. The activation of OX1 and OX2 receptors each modulate the effects induced by cannabinoids in different ways [36]. Whereas THC is a partial agonist of the CB1 receptor, CBD has a very low affinity for the CB1 receptor and instead acts as an indirect antagonist [37].

However, the fact that our results did not seem to show a clear relationship between THC or CBD and symptom relief suggests that other cannabinoid chemical(s) (e.g., cannabinols) and terpenes could contribute to changes in sleep experiences. Cannabinoid and terpene profiles vary across strains and we did find that the most frequently used cannabis strains for insomnia treatment were quite distinct in their chemotypic characteristics, highlighting the range of products and associated interactions among sub-compounds across products used by patients even just within flower. Therapeutically, cannabis consumption may also alleviate primary symptoms such as pain and anxiety, which are associated with sleep disturbances [16]. Unfortunately, due to cannabis’ continued Schedule I status and associated barriers to conducting medical cannabis research [24], no practical, naturalistic investigations have been completed on how patient-managed phytocannabinoid consumption affects discrete mechanisms (e.g., ventrolateral preoptic nucleus activation, memory consolidation) and other basic characteristics (e.g., sleep stages, circadian rhythm) involved in normal and aberrant sleep patterns.

Despite the novelty and practical implications of our findings, the observational nature of the research design had unavoidable drawbacks, most notably the absence of a comparison group, which could have resulted in overestimation of the effectiveness of cannabis if unsatisfied users chose not to use the Releaf App^TM, or underestimation of cannabis’ effectiveness if users choose not to use the app as a result of accomplished satisfaction with product choices and their effects. It is also possible that the Releaf App^TM affected how users experience cannabis’ effects, and future research will benefit from examining both the effectiveness and influence of using electronic technology for patient medication management and monitoring. Small sample sizes could have also led to under-powered analyses, i.e., that other product characteristics matter but our sample is too small to pick them up at standard levels of statistical precision. Our study was also limited in the amount of information obtained by users and did not include detailed demographic characteristics, pre-app experience using cannabis, other types of sleep therapies, or type of sleep disorder. Finally, the study was limited to the accuracy of the product characteristics displayed on labels of the products consumed in the study, and there is a common problem of inaccurate (e.g., inflated) labeling practices in the medical cannabis industry in the U.S. [38].

Notwithstanding these limitations, this is the first study to measure how fundamental properties of self-directed Cannabis flower consumption affect immediate symptom relief from insomnia within users’ natural environments. Although no U.S. state has legalized medical cannabis for the treatment of sleep disorders, our results show that consumption of Cannabis flower is associated with significant improvements in perceived insomnia with differential effectiveness and side effect profiles. The widespread apparent use of cannabis as a sleep aid underscores the importance of further medical research regarding its risk-benefit profile and the effectiveness of cannabis as a substitute for other substances, including alcohol, over-the-counter and prescription sleep aids, and scheduled medications (e.g., opioids and sedatives) [14,39,40,41], many of which are used in part as sleep aids.