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Journal of Clinical and
Basic Psychosomatics The endocannabinoid system

Figure 1. Mechanisms of stress response in psychosomatic disorders. This schematic representation illustrates the intricate molecular processes involved
in the stress response within the neuroendocrine axis. (A) Released ACTH travels through the bloodstream to the adrenal cortex. ACTH stimulates the
synthesis and release of cortisol. (B) Stressors activate neurons in the hypothalamus, leading to the release of CRH. CRH binds to its receptor on corticotropes
in the anterior pituitary. (C) Cortisol binds to GRs on immune cells, modulating gene expression and suppressing the release of proinflammatory cytokines.
Simultaneously, cortisol activates GRs on sensory neurons, influencing neuronal signaling. (D) This activation leads to the release of neurotransmitters
and neuropeptides, aggravating neurogenic inflammation. The released neuropeptides, such as substance P, contribute to increased vascular permeability
and immune cell recruitment, exacerbating the inflammatory response. (E) CB2R activation induces an anti-inflammatory phenotype in immune cells
2+
by inhibiting the ERK pathway. (F) Activation of presynaptic CB1Rs attenuates Ca influx into the presynaptic terminal, blocking vesicle fusion and thus
decreasing transmitter release. Figure 1 is modified from Baral et al. [161]
Abbreviations: ACTH: Adrenocorticotropic hormone; cAMP: cyclic adenosine monophosphate; CB1R: Cannabinoid type 1 receptor; CB2R: Cannabinoid
type 2 receptor; CREB: cAMP response element-binding protein; CRH: Corticotropin-releasing hormone; DRG: Dorsal root ganglion; ERK: Extracellular
signal-regulated kinase; GRs: Glucocorticoid receptors; PKC: Protein kinase C.
gland. The binding of CRH to its receptor on corticotropes activation of adenylate cyclase and leading to an increase
activates intracellular signaling pathways, involving the in intracellular cAMP levels. Elevated cAMP, in turn,

Volume 2 Issue 1 (2024) 3 https://doi.org/10.36922/jcbp.2288