Translated from our German original by AI. The German text was researched, written, and edited by the Psychedelia Foundation team and remains the authoritative version.
A new study provides evidence that the serotonin system plays a role in the immune defense against colorectal cancer that has been underestimated so far. As the researchers were able to show, targeted activation of the serotonin receptor 5-HT2A strengthens the antitumor immune response in preclinical models and inhibits the growth of colorectal cancer.
In the experiment, LSD (lysergic acid diethylamide) produced a stronger immune reaction against tumor cells, mediated by CD8⁺ T cells. To make therapeutic use of this mechanism without triggering central nervous or psychedelic side effects, the scientists developed the compound IHCH-8110. The novel 5-HT2A agonist does not cross the blood-brain barrier and therefore acts selectively on peripheral receptors.
As the central mechanism of action, the team identified 5-HT2A receptors on enteric glial cells in the gut. Stimulating them leads to increased release of the signaling molecules CXCL10 and interleukin-18 (IL-18). This promotes the targeted recruitment and activation of CD8⁺ T cells in the tumor environment. By turning immunologically inactive (“cold”) tumors into a responsive milieu, IHCH-8110 was also able to increase significantly the efficacy of an accompanying PD-1 immune blockade.
The results document a complex interplay between the serotonin system, the enteric nervous system and tumor immunology. Since these are findings from preclinical models, the study does not yet demonstrate efficacy in humans. Whether peripheral 5-HT2A agonists can be established in future as an addition to existing immunotherapies for colorectal cancer will have to be shown by further preclinical and later clinical studies.
