Page 31 - JCBP-2-1

Journal of Clinical and
Basic Psychosomatics The endocannabinoid system

cytokines and prostaglandins, by influencing the the conventional expression of these genes, culminating
expression of genes involved in the inflammatory response. in imbalances within the body’s intrinsic chronometer
This intricate network of transcriptional regulation and and disrupting the precise timing of sleep-wake cycles.
neurotransmitter modulation collectively contributes to This discordance can further compromise the pineal
the overall sensitivity of nociceptors to painful stimuli. gland’s proficiency in generating melatonin, the hormone
Moreover, cortisol may participate in the endogenous paramount for regulating the sleep process. Normally,
pain modulation system by influencing the expression of melatonin experiences a surge in production during the
genes related to endorphins and enkephalins, which are evening hours, signaling to the body that it is time to
natural pain-relieving substances. This complex interplay embrace slumber. Dysregulated cortisol levels, however,
highlights the multifaceted role of cortisol in shaping can interrupt this harmonious process, making the onset
nociceptor function and the intricate molecular processes of sleep more elusive [90-94] .
that contribute to the perception and modulation of pain The repercussions of dysregulated cortisol are not
in response to various stimuli [81-85] .
confined to the realm of hormonal fluctuations but extend
This complex interplay additionally contributes to to the autonomic nervous system as well. Increased
the amplification of visceral pain perception, thereby sympathetic nervous system activity, a hallmark of
intensifying the patient’s discomfort and introducing the body’s fight-or-flight response, perpetuates a state
another layer of complexity to the symptomatology of of heightened alertness and readiness to grapple with
PSD . stressors. This state of hyperarousal can render relaxation
[86]
[88]
2.5. Disturbances in sleep patterns and the initiation of sleep a challenging endeavor .
The intricate functioning of the HPA axis holds significant In addition, the hippocampus, a cerebral region
ramifications for the regulation of the human body’s intricately involved in memory and stress regulation, is
circadian rhythm, rendering it an influential factor in densely populated with GRs. Altered cortisol function can
sleep patterns. Dysregulation of HPA axis activity can lead to a detriment in hippocampal performance, thus
give rise to a cascade of sleep disturbances, encompassing adversely affecting sleep quality and the consolidation of
insomnia, sleep fragmentation, and modifications in sleep memories. Furthermore, it paves the way for the upsurge
architecture. These perturbations in sleep are frequently of proinflammatory cytokines, which are notorious for
observed in individuals grappling with PSD, thereby disrupting sleep patterns and fomenting the scourge of
further exacerbating their overall symptomatology . insomnia [88-96] .
[87]
The dysregulated activity of the HPA axis serves as 3. Endocannabinoid system
a harbinger of sleep disturbances through a sequence The endocannabinoid system (ECS) constitutes a
of intricate molecular mechanisms. As a central player
in orchestrating the body’s stress response, the HPA multifaceted signaling network that pervades the human
axis possesses the capacity to disrupt the finely tuned body, originally unearthed through research into the
equilibrium of the circadian rhythm and influence various pharmacological effects of compounds derived from
elements that impact the sleep-wake cycle [87,88] . the cannabis plant. Over time, it has evolved into an
indispensable regulatory system crucial for maintaining
Ordinarily, cortisol adheres to a diurnal pattern, with equilibrium across a myriad of physiological and
its levels peaking in the morning and tapering off as psychological domains [97,100] .
night descends. Dysregulated HPA axis activity, however,
can precipitate a disruption in this rhythm, giving rise The ECS encompasses a constellation of components,
to untimely surges in cortisol levels, notably during the including endogenous cannabinoids (endocannabinoids),
evening and nighttime hours . cannabinoid receptors labeled as cannabinoid type 1
[88]
receptors (CB1Rs) and cannabinoid type 2 receptors
These erratic cortisol levels can precipitate a deleterious (CB2Rs), and a suite of enzymes entrusted with the
impact on the GABAergic system, a pivotal inhibitory synthesis and degradation of endocannabinoids. Within
neural network. A diminution in GABAergic inhibition all the endocannabinoids, Anandamide (AEA) and
can translate into heightened neural excitability, rendering 2-arachidonoylglycerol (2-AG) are of primary interest.
the initiation and sustenance of sleep a herculean task . Unlike conventional neurotransmitters, endocannabinoids
[89]
Moreover, the HPA axis engages in a complex interplay are not stockpiled within synaptic vesicles but are rather
with genes associated with the circadian clock, such as synthesized by neurons as the need arises, making use of
PER1 and PER2. Dysregulated cortisol release can disturb the lipid constituents of cell membranes [101] .

Volume 2 Issue 1 (2024) 7 https://doi.org/10.36922/jcbp.2288