Harvard Study Finds Psychedelics May Reset Brain-Immune Signals

Scientists at Harvard University have put forward a potentially fundamental shift in how psychedelics and their therapeutic promise are understood.

Research using mouse models and human cells indicates that hallucinogens may alter the way brain cells communicate with the immune system.

"Our study underscores how psychedelics can do more than just change perception; they can help dial down inflammation and reset brain-immune interactions," explains neuroimmunologist Michael Wheeler from Harvard and Brigham and Women's Hospital.

"This could reshape how we think about treatment for inflammatory disorders and conditions like anxiety and depression."

Psychedelics, inflammation and astrocytes

A growing body of research indicates that brain inflammation could raise the risk of major psychiatric disorders. Astrocytes, a particular type of cell, appear to have an important role in this immune response.

Astrocytes are the most abundant cells in the central nervous system. Recent mouse research suggests that intense, persistent activation of these neural cells can heighten inflammation in the brain, leading to anxiety and stress responses.

Although much remains unclear about psychedelics and their effects on human health, some evidence suggests that hallucinogens such as LSD are powerful anti-inflammatory agents capable of regulating astrocyte activity.

To investigate this possibility in greater depth, Wheeler and his team studied mice exposed to short-term stress for 7 days and chronic stress for 18 days.

EGFR signalling under stress

Through genome analysis and behavioural testing, the researchers found that mouse brains exposed to brief periods of stress were generally resilient. In mice subjected to seven days of stress, astrocytes in the amygdala, a brain region essential for emotional control, were associated with fewer fear responses brought on by stress.

This resilience was connected to the expression of a particular astrocyte receptor: EGFR, or epidermal growth factor receptor. The receptor appears to limit the ‘crosstalk’ between neurons and immune cells.

By contrast, when mice underwent chronic, overwhelming stress for 18 days, EGFR expression declined. This set off a cascade of inflammatory reactions and fearful behaviours.

"What is fascinating is that psychedelic compounds can reverse this entire process," says Wheeler.

When Wheeler and his colleagues gave psilocybin or MDMA to mice with impaired EGFR function, they observed fewer inflammatory cells around the brain as well as reduced fear behaviours.

Human cells and psychedelic immune responses

The researchers then examined human cells to determine whether the same effect could occur in people. The Harvard team identified comparable stress signals in human brain cells. They also assessed human gene-expression data from people with major depressive disorder and found altered EGFR signalling.

More experiments are required to establish how psychedelics affect EGFR expression and how this subsequently influences inflammation in the brain. Still, the evidence that psychedelics can alter immune responses within the central nervous system is compelling.

Inflammation is associated with numerous neurodegenerative diseases and mood disorders. These results point to "potential direct and indirect mechanisms by which psychedelics influence physiological responses to chronic stress and neuroimmune interactions."

"We're not saying that psychedelics are a cure-all for inflammatory diseases or any other health condition," explains 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."

The study was published in Nature.