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2025, Number 5

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Rev Fac Med UNAM 2025; 68 (5)

Endocannabinoids and Orexins in the Modulation of the Sleep-Wake Cycle and Substance Abuse

Ostos-Valverde A, Daval-Marín-Lozano V, Gómez-Villatoro JP, Méndez-Díaz M, Herrera-Solís A, Ruiz-Contreras AE, Prospéro-García ÓE

Language: Spanish
References: 31
Page: 8-18
PDF size: 419.16 Kb.


ABSTRACT

Wakefulness and sleep are essential physiological states that alternate cyclically in humans and other species. Sleep, characterized by a reversible loss of consciousness and modulation of autonomic functions, is organized into distinct phases: non-rapid eye movement sleep (NREM), subdivided into N1, N2, and N3, and rapid eye movement sleep (REM). These phases play critical roles in metabolic restoration, information processing, and the consolidation of different types of memory. Wakefulness, in contrast, is defined as an active state of consciousness oriented toward environmental interaction, sustained by the coordinated activity of multiple neurotransmitters.
The sleep–wake cycle is explained through the two-process model: a circadian component (process C), regulated by the suprachiasmatic nucleus and synchronized with the light–dark cycle, and a homeostatic component (process S), dependent on the accumulation of substances such as adenosine and cortistatin during wakefulness. These processes interact with neurochemical systems that include acetylcholine, dopamine, serotonin, norepinephrine, histamine, hypocretins/orexins, and neuropeptides such as VIP, CCK, and IL-1β. Their precise regulation is indispensable for the maintenance of physiological and cognitive health, whereas their dysfunction is associated with sleep disorders and increased vulnerability to substance addiction.
This work represents the first part of an integrative analysis of the neurobiological systems that link sleep regulation with vulnerability to drug use. A second publication will address the role of the endocannabinoid and orexin systems in the regulation of diverse physiological functions, including the sleep–wake cycle, as well as their contribution to the development of sleep disorders and the mechanisms underlying substance abuse.


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