Psychedelics may reverse brain-immune interactions that boost fear, research suggests

A new study indicates that psychedelic compounds interact with brain-immune system pathways and “fundamentally reshape” immunity responses tied to fear and stress. As such, the study reveals that psychedelics can do more than change perception — they can help dial down inflammation and reset brain-immune interactions.

The authors say their findings could potentially transform treatments for psychiatric disorders and inflammatory diseases. They used a mouse model of chronic stress to determine that increased communication between cells (astrocytes) in the brain’s fear center, the amygdala, boosted fear behaviors, elevated inflammatory signaling, and activated fear-promoting neurons. 

“We found that astrocytes in the amygdala use a specific receptor called EGFR (epidermal growth factor receptor) to limit stress-induced fear,” explains co-author Dr. Michael Wheeler, assistant professor at Harvard Medical School and investigator at Brigham and Women’s Hospital, US. 

“When chronic stress disrupts this signaling, it leads to a cascade involving brain-resident cells and immune cells, ultimately increasing fear behavior. What is fascinating is that psychedelic compounds can reverse this entire process.”

“Paradigm shift”

The researchers note that their findings, published in Nature, represent a “paradigm shift” in understanding psychedelics’ therapeutic potential. The study brings together insights from neuroscience and immunology to identify the previously hidden communication channels between the brain and immune system. 

“We’re not saying that psychedelics are a cure-all for inflammatory diseases or any other health condition,” says Wheeler. “But we do see evidence that psychedelics have some tissue-specific benefits and that learning more about them could open up entirely new possibilities for treatments.”

In addition to psychedelics’ impact on the amygdala, the study indicates that monocytes, — inflammatory immune cells — migrated from other parts of the body to the brain during chronic stress. Artificially manipulating these cells impacted fear behaviors. 

Wheeler says that learning more about psychedelics could open up entirely new possibilities for treatments.However, when the researchers treated stressed mice with the psychedelics psilocybin and MDMA, they prevented monocytes from accumulating in the brain and thus lowered fear behaviors. 

The team found similar response signals to stress in human brain cells and in gene expression datasets from patients suffering from major depressive disorder. They explain that this suggests that the same interactions between the immune system and the brain may play a role in neuropsychiatric disorders. 

Next steps

The authors note that further research is needed to fully understand how psychedelics affect immune cells and brain communication. Other next steps include examining the long-term effects of psychedelic treatment on patients with major depressive disorder or inflammatory diseases. 

Wheeler is collaborating with researchers from the Massachusetts General Hospital Center for the Neuroscience of Psychedelics on a clinical trial with patients with depression treated with psychedelics. He will examine the patients’ tissue samples. 

In the future, Wheeler envisions a new way of thinking about neuropsychiatric disorders. “I am excited about the prospect of identifying brain-body communication loops as a fundamental feature of physiology.” 

“Often, we think of mental health disorders based on their behavioral symptoms. However, we are likely leaving much underlying biology on the table by focusing solely on the brain.”

Recent research on psychedelics found that a single dose boosted cognitive flexibility for weeks, with potential impacts on treatments for depression, post-traumatic stress disorder, and neurodegenerative diseases such as Alzheimer’s disease. 

Meanwhile, another study revealed that the natural compound psilocybin can boost mood and brain health for patients with Parkinson’s disease. Research also suggests the compound from magic mushrooms is a more effective treatment for symptoms of depression than controls.