Visual Hallucinations in Serotonergic Psychedelics and Lewy Body Diseases
Schizophrenia Bulletin – April 17, 2025
Source: OpenAlex
Summary
Visual hallucinations, a core symptom in Lewy body diseases, astonishingly resemble those induced by psychedelics. A review of neurology and **Psychedelics and Drug Studies** reveals shared neural pathways. Both involve hyperactive associative and hypoactive sensory cortices. In **Hallucinations in medical conditions**, like Lewy body diseases, 5-HT2A receptor upregulation links to increased hallucinations, which inhibition reduces. **Complementary and Alternative Medicine Studies** also highlight serotonin 2A and 1A receptor modulation in psychedelic-induced experiences. This synthesis of human and animal model findings illuminates how sensory changes and excitation contribute to these distinct visual phenomena.
Abstract
Abstract Background and Hypothesis Visual hallucinations (VH) are a core symptom of both Lewy body diseases (LBDs; eg, Parkinson’s disease and dementia with Lewy bodies) and serotonergic psychedelics (SPs; eg, psilocybin and mescaline). While these conditions differ in etiology, overlapping phenomenology, and neural mechanisms suggest shared pathways. This review explores similarities and differences in VH between LBDs and SPs, focusing on phenomenology, cortical function, and serotonergic modulation. Study Design This narrative review synthesizes findings from neurology, cognitive neuroscience, and systems neuroscience to compare VH in LBDs and SPs. The literature includes studies with both human subjects and animal models that examine cortical activity patterns, neuromodulatory mechanisms, and VH phenomenology. Study Results Both LBDs and SPs exhibit distinct visual aberrations, ranging from minor metamorphopsias to complex hallucinations. Some features in LBDs resemble those induced by SPs (eg, illusory motion and entity encounters), suggesting shared neural mechanisms. Neuroimaging studies indicate a common pattern of hyperactive associative cortex and hypoactive sensory cortex. At the neuromodulator level, SP-induced VH involves serotonin 2A and 1A receptor (5-HT2AR and 5-HT1AR) modulation, while in LBDs, 5-HT2A receptor upregulation correlates with increased VH, and its inhibition (eg, with pimavanserin) reduces VH. Two shared cortical signatures are highlighted: reduced visual evoked responses and shifts toward visual excitation. Conclusions Examining cortical and neuromodulatory similarities between LBD- and SP-induced VH may elucidate the link between sensory degradation, excitation, and hallucinogenesis. Future research should employ real-time neuroimaging of discrete hallucinatory episodes to identify shared mechanisms and develop targeted interventions for LBD hallucinations.