Molecular Pathways Potentially Involved in Hallucinatory Experiences During Sleep Paralysis: The Emerging Role of β-Arrestin-2
Lena M. Rudy, Michał M. Godlewski
International Journal of Molecular Sciences July 26, 2025 DOI: 10.3390/ijms26157233 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Serotonin |
| Keywords | Sleep paralysis Sensory system Sensation Narcolepsy Receptor |
| Citations | 2 |
| Key findings | The β-arrestin-2 signaling pathway is proposed to create network susceptibility that facilitates the abrupt emergence of hallucinations in sensory areas during sleep paralysis, rather than directly inducing them. |
Abstract
Sleep paralysis (SP), an REM parasomnia, can be characterized as one of the symptoms of narcolepsy. The SP phenomenon involves regaining meta-consciousness by the dreamer during REM, when the physiological atonia of skeletal muscles is accompanied by visual and auditory hallucinations that are perceived as vivid and distressing nightmares. Sensory impressions include personification of an unknown presence, strong chest pressure sensation, and intense fear resulting from subjective interaction with the unfolding nightmare. While the mechanism underlying skeletal muscle atonia is known, the physiology of hallucinations remains unclear. Their complex etiology involves interactions among various membrane receptor systems and neurotransmitters, which leads to altered neuronal functionality and disruptions in sensory perception. According to current knowledge, serotonergic activation of 5-hydroxytryptamine-receptor-2A (5-HT2A)-associated pathways plays a critical role in promoting hallucinogenesis during SP. Furthermore, they share similarities with psychedelic-substance-induced ones (i.e., LSD, psilocybin, and 2,5-dimethoxy-4-iodoamphetamine). These compounds also target the 5-HT2A receptor; however, their molecular mechanism varies from serotonin-induced ones. The current review discusses the intracellular signaling pathways responsible for promoting hallucinations in SP, highlighting the critical role of β-arrestin-2. We propose that the β-arrestin-2 signaling pathway does not directly induce hallucinations but creates a state of network susceptibility that facilitates their abrupt emergence in sensory areas. Understanding the molecular basis of serotonergic hallucinations and gaining better insight into 5-HT2A-receptor-dependent pathways may prove crucial in the treatment of multifactorial neuropsychiatric disorders associated with the dysfunctional activity of serotonin receptors.
Comparable studies
Other narrative reviews on serotonin, most cited first.
Citations in the library
Cites 35
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and 30 more in the library