Molecular Pathways Potentially Involved in Hallucinatory Experiences During Sleep Paralysis: The Emerging Role of β-Arrestin-2
International Journal of Molecular Sciences July 26, 2025 Lena M. Rudy, Michał M. Godlewski 2 citations
Sleep paralysis involves regaining awareness during REM sleep while the body remains paralyzed, often accompanied by vivid, distressing hallucinations such as sensing an evil presence, chest pressure, and intense fear. The paralysis mechanism is understood, but how hallucinations arise is not. Serotonergic activation of the 5-HT2A receptor is critical, and these hallucinations share features with those induced by psychedelics like LSD and psilocybin, which also target 5-HT2A but through different molecular mechanisms. This review proposes that the β-arrestin-2 signaling pathway does not directly cause hallucinations but creates a state of network susceptibility that allows them to emerge abruptly in sensory brain areas. Understanding these pathways may aid treating neuropsychiatric disorders involving serotonin receptor dysfunction.