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Episode Summary: Dr. Michael Wheeler talks about neuroimmune interactions, exploring how the immune system and brain communicate, particularly through the blood-brain barrier and meninges; how chronic stress and inflammation can alter brain circuits, contributing to mood disorders like depression; how drugs like psilocybin and MDMA may reduce inflammation by modulating immune cells in the meninges, offering potential therapeutic benefits.

About the guest: Michael Wheeler, PhD is an Assistant Professor of Neurology at Harvard Medical School. His lab studies how immune responses influence behavior, mood disorders, and addiction.

Key Conversation Points:

• The blood-brain barrier (BBB) is not as impermeable as once thought, allowing immune signals like cytokines to influence brain function even in healthy states.
• Chronic stress can weaken the BBB, increasing inflammation and affecting mood-regulating circuits, potentially contributing to depression.
• Microglia, the brain’s resident immune cells, help maintain neural circuits by pruning synapses and regulating metabolism.
• Psychedelics like psilocybin and MDMA can reduce inflammation by prompting immune cells (monocytes) to leave the meninges, potentially via vascular effects.
• These psychedelics may act in a context-specific “window,” requiring a dysregulated tissue state to exert anti-inflammatory effects, not as broad-spectrum anti-inflammatories.
• Neuroinflammation may underlie some treatment-resistant depression cases, suggesting immunotherapy could complement traditional psychiatric treatments.
• The brain encodes peripheral immune signals, like gut inflammation, in specific circuits, which can “remember” and recreate inflammatory responses.
• Aging may naturally increase blood-brain barrier leakiness, heightening the brain's susceptibility to peripheral inflammation.
• Future research aims to explore how psychedelics influence plasticity and their potential in treating inflammation-related diseases beyond psychiatry.

Related episode:

• M&M 2: Psilocybin, LSD, Ketamine, Inflammation & Novel

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