Pioneering scientist reveals breakthrough link between psychedelics and immune system in treating fear
Harvard's Dr. Michael Wheeler illuminates how psychedelic compounds interact with brain-immune pathways to potentially treat both psychiatric and inflammatory disorders
Genomic Press
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Michael A. Wheeler, PhD, Harvard Medical School, Brigham & Women’s Hospital, USA.
view moreCredit: Michael A. Wheeler, PhD
BOSTON, Massachusetts, USA, 6 May 2025 -- In a compelling Genomic Press interview published today, rising scientific star Dr. Michael Wheeler unveils revolutionary findings about how psychedelics reshape communication between the brain and immune system, potentially transforming treatments for psychiatric disorders and inflammatory diseases alike.
Bridging the Mind-Body Divide
As an Assistant Professor at Harvard Medical School and investigator at Brigham and Women's Hospital, Dr. Wheeler stands at the frontier of neuroimmunology, a field exploring how the nervous and immune systems interact. His groundbreaking research, recently validated in Nature (April 23, 2025; https://doi.org/10.1038/s41586-025-08880-9), demonstrates that psychedelics like psilocybin don't just affect neurons: they fundamentally reshape immune responses tied to fear and stress.
"We found that astrocytes in the amygdala use a specific receptor called EGFR to limit stress-induced fear," explains Dr. Wheeler. "When chronic stress disrupts this signaling, it leads to a cascade involving brain-resident cells and immune cells that ultimately increases fear behavior. What is fascinating is that psychedelic compounds can reverse this entire process."
This finding represents a paradigm shift in understanding psychedelics' therapeutic potential. Rather than simply acting on neural pathways, these compounds appear to recalibrate entire neuroimmune circuits. Could this dual action explain why psychedelics show promise across diverse conditions from depression to addiction? And might they eventually prove useful for treating inflammatory disorders that have no apparent psychiatric component?
From Legal Defender to Brain-Immune Explorer
Dr. Wheeler's journey to this breakthrough began in an unexpected place, the Public Defender's office in Baltimore City. "I felt that the actions of the people we defended were so inextricably linked with their environmental circumstances, inclusive of physical or emotional abuse beyond their control, that I was desperate to understand the inner workings of their minds," Dr. Wheeler reflects.
This early experience shaped his scientific mission to unravel how environmental factors—including stress and trauma—reshape our internal neurobiology. Following this passion, he made the courageous decision to join the lab of an immunologist during his postdoctoral training despite having no background in the field.
"One of the most intimidating choices I made was joining the lab of an Immunologist during my post-doc," notes Dr. Wheeler. "I only trained in Neuroscience at that point, so when I looked at Francisco's papers on dendritic cells and T cells, I was nervous about what I was getting into."
This interdisciplinary leap proved transformative. By bringing together insights from neuroscience and immunology, Dr. Wheeler identified previously hidden communication channels between the brain and immune system that may help explain why traditional psychiatric treatments often yield inconsistent results.
Mapping the Brain-Body Interface
Dr. Wheeler's laboratory employs cutting-edge technologies including genomic screening, single-cell analysis, and behavioral studies to create what he describes as a "wiring diagram" of brain-immune communication.
His team's recent Nature publication demonstrates that when chronic stress disrupts normal signaling in the amygdala—a key brain region for processing fear—it triggers an inflammatory cascade involving immune cells in the meninges (the protective membranes surrounding the brain). Remarkably, psychedelics can interrupt this process at multiple points, reducing both immune cell accumulation and fear behaviors.
This research raises intriguing questions about traditional approaches to psychiatric disorders. If mental health conditions have significant immune components, might we need to rethink treatment strategies that focus exclusively on neurotransmitters? Could new therapeutic agents that target both neural and immune pathways prove more effective than current options?
Looking ahead, Dr. Wheeler envisions a revolution in thinking about neuropsychiatric disorders. "I am excited about the prospect of identifying brain-body communication loops as a fundamental feature of physiology," he states. "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."
Team Science and Cross-Disciplinary Collaboration
Dr. Wheeler emphasizes that his success stems from collaborative team science rather than solitary genius. As a laboratory leader, he values bringing together people with diverse scientific backgrounds to create synergistic insights that no individual could achieve alone.
"My favorite part is bringing people into the lab and onto our team with completely different scientific (and personal) backgrounds to have everyone work together," says Dr. Wheeler. "This facilitates cross-pollination between ideas that could only happen on the organizational level."
This approach reflects Dr. Wheeler's conviction, formed during his undergraduate years at Johns Hopkins, that "you cannot do great science alone, everyone needs a great team." It's a philosophy that has guided his academic journey and research approach.
Dr. Michael Wheeler's Genomic Press interview is part of a larger series called Innovators & Ideas that highlights the people behind today's most influential scientific breakthroughs. Each interview in the series offers a blend of cutting-edge research and personal reflections, providing readers with a comprehensive view of the scientists shaping the future. By combining a focus on professional achievements with personal insights, this interview style invites a richer narrative that both engages and educates readers. This format provides an ideal starting point for profiles that delve into the scientist's impact on the field, while also touching on broader human themes. More information on the research leaders and rising stars featured in our Innovators & Ideas -- Genomic Press Interview series can be found in our publications website: https://genomicpress.kglmeridian.com/.
The Genomic Press Interview in Psychedelics titled "Michael A. Wheeler: Psychedelics and neuroimmune circuits—what a strange trip, indeed," is freely available available via Open Access on 6 May 2025 in Psychedelics at the following hyperlink: https://doi.org/10.61373/pp025k.0011.
About Psychedelics: Psychedelics: The Journal of Psychedelic and Psychoactive Drug Research (ISSN: 2997-2671, online and 2997-268X, print) is a peer reviewed medical research journal published by Genomic Press, New York. Psychedelics is dedicated to advancing knowledge across the full spectrum of consciousness altering substances, from classical psychedelics to stimulants, cannabinoids, entactogens, dissociatives, plant derived compounds, and novel compounds including drug discovery approaches. Our multidisciplinary approach encompasses molecular mechanisms, therapeutic applications, neuroscientific discoveries, and sociocultural analyses. We welcome diverse methodologies and perspectives from fundamental pharmacology and clinical studies to psychological investigations and societal-historical contexts that enhance our understanding of how these substances interact with human biology, psychology, and society.
Visit the Genomic Press Virtual Library: https://issues.genomicpress.com/bookcase/gtvov/
Our full website is at: https://genomicpress.kglmeridian.com/
Members of the Wheeler lab are out having dinner in Boston in early 2024.
Credit
Michael A. Wheeler, PhD
Michael A. Wheeler: Psychedelics and neuroimmune circuits—what a strange trip, indeed
Credit
Michael A. Wheeler
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Psychedelics
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Article Title
Michael A. Wheeler: Psychedelics and neuroimmune circuits—what a strange trip, indeed
Article Publication Date
6-May-2025
Beyond psychedelics: New journal broadens the scope of consciousness research
Genomic Press publication redefines boundaries in the study of mind-altering substances and their role in human experience
Genomic Press
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The unfinished process of creation. The image illustrates the endless process of revision and reformulation described by Drummond de Andrade, where humans continually attempt to compose definitive versions of knowledge and self without ever reaching completion.
view moreCredit: From “Diagnosing Madness," by Julio Licinio, 2013, Science, 340(6139), p. 1406. Illustration by Joe Sutliff/www.cdad.com/joe. Reprinted with permission from AAAS.
NEW YORK, USA, 6 May 2025 -- In a thought-provoking Genomic Press editorial, the Psychedelics journal has formally expanded its scope beyond classical psychedelic compounds to embrace the broader landscape of consciousness-altering substances. The publication, which previously focused primarily on serotonergic compounds, now explicitly includes all psychoactive drugs in its research purview.
A Quiet Correction, Not a Rebranding
The editorial, authored by Editor-in-Chief Dr. Julio Licinio, reflects on the inherent limitations of categorizing mind-altering substances solely by their pharmacological properties. "From the outset, our journal's indexed title, Psychedelics, has served a practical purpose," writes Dr. Licinio. "But even in our earliest planning, we knew this name alone could never hold the full scale of what we hoped to publish."
This expansion is formalized in the journal's revised subtitle: "The Journal of Psychedelic and Psychoactive Drug Research," which Dr. Licinio describes not as rebranding but as "a quiet correction of what was always slightly misaligned." This change acknowledges the publication was "never just about psychedelics" but rather "the pharmacopeia of mind alteration."
Challenging Traditional Classifications
The decision raises fascinating questions about how we categorize consciousness-altering substances. What precisely defines a "psychedelic" experience? Is it determined by molecular structure, receptor targets, subjective effects, or cultural context? These classifications, while useful, are ultimately human constructs that evolve as our understanding deepens.
"Our compounds of interest are part of humanity's ongoing attempt to transcend our incompleteness," explains Dr. Licinio, borrowing from Brazilian poet Carlos Drummond de Andrade's metaphor of humans continually trying to compose definitive versions of knowledge and self without ever reaching completion.
Beyond Traditional Boundaries
The editorial acknowledges that this expanded focus includes substances like MDMA, ketamine, and ibogaine – compounds that resist neat categorization and exist at the margins of established taxonomies. These pharmacologically diverse substances challenge our understanding of consciousness alteration while offering promising therapeutic applications.
"The boundaries we rely on are 'concocted hour after hour without ever attaining our own convincing edition,'" Dr. Licinio notes, suggesting that these classifications, while useful, are never final. This philosophical approach positions the journal at the intersection of neuroscience, psychiatry, and the humanities.
Implications for Therapeutic Research
This refined focus comes at a pivotal moment in psychoactive drug research. Recent years have seen unprecedented interest in these compounds' therapeutic potential, from psilocybin for depression to MDMA for PTSD. How might broadening our understanding of consciousness-altering substances lead to novel therapeutic approaches? Could previously overlooked compounds offer unique benefits by acting through different neurological mechanisms?
Embracing Intellectual Discomfort
Dr. Licinio's approach encourages researchers to embrace the contradictions and incomplete understanding inherent in this field. "We have room for writing that resists the urge to wrap things up," he writes. "Sometimes, staying with the discomfort tells us more than reaching a quick conclusion."
This perspective raises intriguing questions about the future of consciousness research. How might our understanding of these substances evolve as we move beyond rigid classifications? What unexpected therapeutic applications might emerge from compounds currently at the margins of research? And how does studying these substances illuminate the fundamental nature of human consciousness?
A Platform for Ongoing Scientific Conversation
The editorial concludes with an invitation to anticipate contradiction, acknowledging that "some compounds will not fit" and "some theories are still in the middle of becoming something else." This admission of the field's evolving nature positions Psychedelics journal as a platform for ongoing scientific conversation rather than definitive conclusions.
The Psychedelics Editorial titled "Psychedelics, Yes—but Not Only: Redefining the boundaries of consciousness research as part of humanity's ongoing attempt to transcend our incompleteness," is freely available via Open Access on 6 May 2025 in Psychedelics at the following hyperlink: https://doi.org/10.61373/pp025d.0014.
About Psychedelics: Psychedelics: The Journal of Psychedelic and Psychoactive Drug Research (ISSN: 2997-2671, online and 2997-268X, print) is a peer reviewed medical research journal published by Genomic Press, New York. Psychedelics is dedicated to advancing knowledge across the full spectrum of consciousness altering substances, from classical psychedelics to stimulants, cannabinoids, entactogens, dissociatives, plant derived compounds, and novel compounds including drug discovery approaches. Our multidisciplinary approach encompasses molecular mechanisms, therapeutic applications, neuroscientific discoveries, and sociocultural analyses. We welcome diverse methodologies and perspectives from fundamental pharmacology and clinical studies to psychological investigations and societal-historical contexts that enhance our understanding of how these substances interact with human biology, psychology, and society. Visit the Genomic Press Virtual Library: https://issues.genomicpress.com/bookcase/gtvov/
Journal
Psychedelics
Method of Research
News article
Subject of Research
People
Article Title
Psychedelics, Yes—but Not Only: Redefining the boundaries of consciousness research as part of humanity's ongoing attempt to transcend our incompleteness
Article Publication Date
6-May-2025
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