Exploring cancer neuroscience with psychedelics: Brain-body crosstalk, neuroimmune modulation, and implications from tumor biology to end-of-life support

Recent advancements in cancer neuroscience highlight the intricate bidirectional interactions among tumors, the nervous system, and immune mechanisms, revealing new conceptual avenues for investigation. Serotonergic psychedelics, historically explored for their profound effects on consciousness, are increasingly recognized as modulators of neural circuits and neuroimmune pathways, and as interventions that can alleviate existential distress in cancer-related contexts. This review synthesizes current evidence and conceptual frameworks suggesting that psychedelics may engage cancer-related neural and neuroimmune processes, influence immune signaling within tumor microenvironments, and provide psychological relief in palliative care settings, while emphasizing that most oncology-relevant mechanisms remain preclinical or theoretical. We explore potential pathways through which psychedelics could, in principle, influence tumor-host interactions, including neuron-glioma synapses, autonomic and sensory innervation of peripheral tumors, and systemic neuroimmune communication. Additionally, we critically examine preclinical and emerging clinical data on psychedelic-associated modulation of serotonin receptor signaling, vagal and sympathetic nerve activity, and anti-inflammatory processes with relevance to oncology. Moreover, we highlight the most robust clinical evidence to date for psychedelic-assisted therapy in cancer populations, which supports improvements in cancer-related anxiety, depression, and existential distress in carefully supported settings, while evidence for pain-related outcomes is more heterogeneous and remains less well established. Across domains, clinical evidence is strongest for distress-related outcomes, whereas oncology-specific biological effects and tumor-related endpoints remain largely untested and should be considered hypothesis-generating. Finally, this review underscores the need for rigorous, multidisciplinary research integrating oncology, neuroscience, immunology, and psychedelic pharmacology to clarify mechanistic boundaries and inform the cautious future integration of psychedelic-assisted approaches aimed at improving patient-centered outcomes in cancer care.