Insomnia is increasingly recognized as a manifestation of multisystem dysregulation characterized by sustained physiological hyperarousal. This review situates insomnia within a framework of reciprocal disturbances across neuroendocrine, inflammatory, and autonomic pathways. It examines the potential roles of cannabidiol (CBD), polyunsaturated fatty acids (PUFAs) derived from hemp seed oil (HSO), and lignans from black sesame oil (BSO) as modulators of upstream biological processes relevant to sleep regulation. Rather than acting as direct hypnotics, these compounds are considered for their capacity to influence convergent mechanisms involved in sleep–wake stability. Preclinical evidence suggests that CBD modulates endocannabinoid and serotonergic signaling, potentially contributing to the regulation of physiological processes associated with hyperarousal. Concurrently, HSO-derived fatty acids support mitochondrial function and lipid-mediated resolution. Sesame lignans further contribute through antioxidant properties linked to redox balance, neurometabolic stability, and modulation of neural excitability. However, the current evidence base is predominantly preclinical, and definitive conclusions regarding therapeutic efficacy or optimal dosing in humans remain limited. Future research should prioritize integrative clinical studies that link these specific biological modulations to standardized sleep outcomes to determine their real-world applicability. Nevertheless, the pathways discussed align with biological domains consistently implicated in established insomnia phenotypes. This review integrates these compounds within a shared hyperarousal framework to highlight convergent upstream mechanisms that extend beyond their individual effects.
Kovitkanit et al. (Tue,) studied this question.