About

Craig Ferris is a Professor in the Department of Pharmaceutical and Biomedical Sciences at Bouvé College of Health Sciences, Northeastern University. His contact information is listed as being at 125 NI, with a phone number of 617-373-3083. The page does not provide additional details about his research focus, background, or key contributions.

Research topics

• Biology
• Endocrinology
• Neuroscience
• Psychology
• Medicine
• Internal medicine

Selected publications

• Filtering the noise: a cerebellar-centered framework for understanding and treating mental illness -a paradigm shift in psychiatry

  Frontiers in Psychiatry · 2026-04-13

  articleOpen access1st authorCorresponding

  For the past half-century, psychiatric drug development has largely focused on tweaking neurotransmitter receptors and chemical pathways. Yet despite billions of dollars invested and major advances in neuroscience, truly innovative treatments for mental illness remain scarce. Disorders like depression, schizophrenia, and post-traumatic stress disorder (PTSD) continue to be managed with drugs discovered decades ago that often provide only partial relief, with remission rates of approximately 30-40% for treatment-resistant depression and 60-70% of schizophrenia patients experiencing persistent symptoms despite medication. This stagnation has prompted a paradigm shift - what if the key to treating mental illness is not just which receptor a drug targets, but how it changes the brain's processing of sensory information? In this treatise, I propose that many psychiatric conditions stem from breakdowns in the brain's sensory filtering mechanisms, the neural circuits that gate irrelevant stimuli before they consume valuable processing resources, and that effective therapies must restore these filtering functions. While computational psychiatry has long recognized that mental illness may reflect failures in predictive filtering, the specific neural substrate implementing this gating remains underspecified. Here the cerebellum emerges as a critical hub: neuroanatomically positioned to perform bottom-up sensory gating before cortical processing, housing more than half the brain's neurons in an architecture ideally suited for distilling signal from noise and showing state-dependent disruption of cerebellar-cortical connectivity during symptom provocation in PTSD. Intriguingly, psychedelic drugs may act as recalibration triggers for these neural filters, acutely disrupting entrenched filtering architectures and reopening windows of plasticity through which maladaptive sensory weightings can be reset. This cerebellar filtering framework offers a neuroanatomically specified extension of predictive processing theory, generates falsifiable predictions, and suggests novel therapeutic targets for conditions that have resisted a half-century of receptor-focused drug development.

  PublisherOA PDFDOI

• Mescaline Alters Cerebellar Function, Global Connectivity, and Frequency-Selective Acoustic Gating: A BOLD fMRI Study in Awake Rats

  Neuroscience Bulletin · 2026-05-21

  articleOpen accessSenior author

  Mescaline, a 5-HT2A agonist psychedelic used ceremonially for millennia, lacks neuroimaging characterization due to its Schedule 1 status. Using pharmacological and resting-state fMRI in awake rats, we report mescaline's first comprehensive neurobiological profile. Acutely, mescaline produced cerebellar-selective BOLD suppression, suggesting functional disconnection from forebrain structures. Paradoxically, resting-state analysis revealed global hyperconnectivity, with the cerebellum forming enhanced connections to the hippocampus, thalamus, somatosensory cortex, and midbrain. Mescaline abolished normal BOLD responses to rewarding olfactory stimuli, indicating disrupted sensory processing. Pre-pulse inhibition showed frequency-dependent acoustic gating effects: enhancement at 4 kHz (+ 27.6%) and 20 kHz (+ 27.3%), but impairment at 12 kHz (- 16.4%). These findings distinguish mescaline from LSD and psilocybin, implicating the cerebellum as a dysregulated sensory filter that floods forebrain circuits with unprocessed sensorimotor information-a potential mechanism underlying psychedelic-induced perceptual alterations.

  PublisherOA PDFDOI

• Beyond the toad's kiss: Mapping acute 5-MeO-DMT effects on brain connectivity across sex and dose using awake rat neuroimaging

  Neuropharmacology · 2026-03-06 · 1 citations

  articleOpen accessSenior authorCorresponding

  5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a potent serotonergic psychedelic with rapid therapeutic potential for depression and anxiety disorders. Despite growing clinical interest, the neurobiological mechanisms underlying 5-MeO-DMT's acute brain effects remain poorly understood, and potential sex differences in response have not been investigated. We conducted the first functional MRI study of 5-MeO-DMT in awake, drug-naïve rats using BOLD imaging. Male (n = 24) and female (n = 24) rats received I.P. injections of vehicle or 5-MeO-DMT (0.01, 0.1, or 1.0 mg/kg) during scanning sessions. BOLD signal changes and resting-state functional connectivity were assessed across 169 brain regions. Negative and positive BOLD volume activations were quantified during acute (1-10 min) and sustained (11-20 min) time windows post-injection, with sex-stratified analyses performed. Females demonstrated markedly enhanced sensitivity to low-dose 5-MeO-DMT (0.1 mg/kg), exhibiting extensive negative BOLD responses that were largely absent in males at the same dose. The 1.0 mg/kg dose induced widespread negative BOLD responses across multiple brain regions in both sexes during the acute window (1-10 minutes post-injection), with effects substantially diminishing thereafter. Global functional connectivity was significantly reduced across all doses (p<0.0001), with regional specificity observed in hypothalamic and cerebellar networks. Temporal analysis revealed peak neurobiological effects within the first 10 minutes, consistent with 5-MeO-DMT's known rapid pharmacokinetics. To our knowledge, this is the first fMRI characterization of 5-MeO-DMT in any species, and it reveals a previously unreported sex difference in psychedelic response. The rapid onset and brief duration of peak effects align with 5-MeO-DMT's unique pharmacological profile and clinical reports. • The first fMRI investigation of 5-MeO-DMT's acute neurobiological effects in conscious animals. • Fills a critical knowledge gap by providing the first detailed mapping of 5-MeO-DMT's effects on brain activity and connectivity patterns. • There are profound sex differences in psychedelic drug sensitivity. • Female rats demonstrated markedly enhanced sensitivity to low-dose 5-MeO-DMT (0.1 mg/kg), • These finding suggest that sex-specific protocols may be essential for optimal therapeutic outcomes. • The rapid onset and brief duration of peak effects align with 5-MeO-DMT's known pharmacokinetic profile and clinical reports, supporting the translational validity of our awake rodent model.

  PublisherDOI

• Sex-dependent developmental changes in behavior, brain structure, functional connectivity, and sensory perception following exposure to psilocybin during adolescence

  Neuropsychopharmacology · 2026-02-18

  articleOpen accessSenior author

  Psilocybin is a hallucinogen with complex neurobiological and behavioral effects. Underlying these effects are changes in brain neuroplasticity. We hypothesized psilocybin given during adolescence, a time of heightened neuroplasticity, particularly in the forebrain, would affect emotional behavior and the associated underlying neuroanatomy, neurocircuitry, and epigenetics. Female and male mice were given vehicle or 3.0 mg/kg psilocybin every other day by oral gavage from postnatal days 40-50 for a total of five exposures. Between postnatal days 90-120 mice were imaged and evaluated for affective behavior and perception of rewarding and aversive stimuli. MRI data from voxel-based morphometry, diffusion weighted imaging, and BOLD resting state functional connectivity were registered to a mouse 3D MRI atlas with 139 brain regions providing site-specific differences in global brain structure and functional connectivity between experimental groups. The prefrontal cortex was measured for changes in proteins associated with epigenetics. Mice showed no significant differences in the light/dark box test, but female mice exposed to psilocybin showed reduced mobility in the open field as compared to controls. Mice with early psilocybin exposure showed reduced brain sensitivity to both rewarding and aversive odors during scanning sessions. There were regional reductions in brain volume and alteration in water diffusivity affecting males more than females. Global and regional functional connectivity were increased in both sexes with the prefrontal cortex showing enhanced connections to the hypothalamus, thalamus and midbrain. Males showed reduced levels of epigenetic and neuroplasticity protein markers in the prefrontal cortex. The pronounced changes in brain volume, water diffusivity - a surrogate marker of gray matter microarchitecture, increase in functional connectivity, altered perception of rewarding and aversive stimuli and altered levels of protein markers of neuroplasticity provide compelling evidence that exposure to psilocybin during adolescence has long term developmental consequences, particularly in males.

  PublisherOA PDFDOI

• Pharmacologic <scp>MRI</scp> Brain Imaging Studies of Serotonin 5‐ <scp> HT ₁ </scp> Receptor Agonists in Awake Mice

  Pharmacology Research & Perspectives · 2026-04-23

  articleOpen access

  ABSTRACT Serotonin (5‐hydroxytryptamine, 5‐HT) type‐1 G protein‐coupled receptors are expressed throughout the central nervous system. 5‐HT 1A R activation is the putative mechanism of approved drugs for generalized anxiety disorder and major depressive disorder and is being studied in the treatment of autism and neurological disorders. The 5‐HT 1B and 5‐HT 1D Rs are the putative therapeutic targets for “triptan”‐type migraine drugs, and the 5‐HT 1B R is associated with prosocial effects, relative to autism treatment, consistent with its high expression in limbic and cortical brain regions. Under study is a recently developed drug candidate for autism, ( S )‐5‐(2′‐fluorophenyl)‐2‐dimethylaminotetralin (FPT), that is a full efficacy pan‐5‐HT 1 R agonist (pEC50 = 7.4, 9.4, and 8.6 at 5‐HT1 A , 5‐HT1 B , and 5‐HT1 D Rs, respectively). FPT demonstrates anti‐seizure, anxiolytic, and prosocial properties, as well as reduces stereotypic movements in Fmr1 knockout mice, a model for autism. The goal of this study was to compare brain activation patterns of the pan‐5‐HT 1 R agonist FPT to NLX‐112, a highly selective 5‐HT 1A R full agonist (pEC 50 = 7.5) which also prevents seizures in Fmr1 knockout mice, to help establish therapeutic mechanisms in autism. We used pharmacological magnetic resonance imaging (phMRI) in awake C57BL/J6 mice to assess activation of integrated neuronal circuits as measured by blood oxygen level dependent volume of activation changes, comparing dose‐related effects of FPT and NLX‐112. The selective 5HT 1A R agonist NLX‐112 broadly inhibited brain activity in a dose‐dependent manner. In contrast, FPT increased global brain activity; however, dose‐related effects were complex, suggesting FPT's polypharmacology at 5‐HT 1 Rs and perhaps other receptors are involved in its brain activation pattern.

  PublisherDOI

• Functional and microstructural biomarkers of repetitive mild head injury in a conscious momentum exchange mouse model

  Journal of Neuroscience Methods · 2026-05-01

  articleSenior authorCorresponding
  PublisherDOI

• Dynamic interaction between stress hormones and neutrophils promotes neutrophil extracellular trap formation with behavioral consequences

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-13

  preprintOpen access

  Abstract Recent studies have highlighted the crosstalk between neuroendocrine responses and the immune system but the mechanisms underlying this cooperation are still not well understood. The stress response is associated with peripheral inflammation suggesting that stress hormones including glucocorticoids and catecholamines could modulate the function of innate immune cells like neutrophils. Likewise, inflammatory mediators produced by immune cells are known to contribute to psychiatric diseases like major depressive disorder. Here we investigated the dynamic relationship between stress hormones and neutrophils and their contribution to mood disorders. We found that chronic restraint stress leads to plasma elevation of neutrophil extracellular traps (NETs) and increased NET formation in mice. Interestingly, the stress hormones, cortisol and epinephrine induce NET formation in human neutrophils ex vivo. Activation of neutrophils to form NETs leads to their increased expression of adrenergic and glucocorticoid receptors and neutrophil production of both cortisol and epinephrine indicating an autocrine/paracrine mechanism for the regulation of neutrophil inflammatory response by stress hormones. Strikingly, administration of NET components to mice induces depressive-like behavior. Moreover, activation of the glucocorticoid receptor in human volunteers leads to increase in gene expression of NET proteins. Furthermore, patients with major depressive disorder show gene upregulation of NET proteins. Our data highlights the bi-directional relationship between neuroendocrine processes and neutrophils that contribute to stress-induced increase in inflammation and the role of neutrophil inflammatory responses in propagation of behavioral changes following stress.

  PublisherOA PDFDOI

• Psilocybin as a Treatment for Repetitive Mild Head Injury: Evidence from Neuroradiology and Molecular Biology

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-02-06 · 2 citations

  preprintOpen accessSenior authorCorresponding

  Repetitive mild head injuries incurred while playing organized sports, during car accidents and falls, or in active military service are a major health problem. These head injuries induce cognitive, motor, and behavioral deficits that can last for months and even years with an increased risk of dementia, Parkinson's disease, and chronic traumatic encephalopathy. There is no approved medical treatment for these types of head injuries. To this end, we tested the healing effects of the psychedelic psilocybin, as it is known to reduce neuroinflammation and enhance neuroplasticity. Using a model of mild repetitive head injury in adult female rats, we provide unprecedented data that psilocybin can reduce vasogenic edema, restore normal vascular reactivity and functional connectivity, reduce phosphorylated tau buildup, enhance levels of brain-derived neurotrophic factor and its receptor TrkB, and modulate lipid signaling molecules.

  PublisherOA PDFDOI

• SST-DUNet: Smart Swin Transformer and Dense UNet for automated preclinical fMRI skull stripping

  Journal of Neuroscience Methods · 2025-08-09 · 3 citations

  articleOpen access

  BACKGROUND: Skull stripping is a common preprocessing step in Magnetic Resonance Imaging (MRI) pipelines and is often performed manually. Automating this process is challenging for preclinical data due to variations in brain geometry, resolution, and tissue contrast. Existing methods for MRI skull stripping often struggle with the low resolution and varying slice sizes found in preclinical functional MRI (fMRI) data. NEW METHOD: This study proposes a novel method that integrates a Dense UNet-based architecture with a feature extractor based on the Smart Swin Transformer (SST), called SST-DUNet. The Smart Shifted Window Multi-Head Self-Attention (SSW-MSA) module in SST replaces the mask-based module in the Swin Transformer (ST), enabling the learning of distinct channel-wise features while focusing on relevant dependencies within brain structures. This modification allows the model to better handle the complexities of fMRI skull stripping, such as low resolution and variable slice sizes. To address class imbalance in preclinical data, a combined loss function using Focal and Dice loss is applied. RESULTS: The model was trained on rat fMRI images and evaluated across three in-house datasets, achieving Dice similarity scores of 98.65%, 97.86%, and 98.04%. COMPARISON WITH EXISTING METHODS: We compared our method with conventional and deep learning-based approaches, demonstrating its superiority over state-of-the-art methods. CONCLUSIONS: The fMRI results using SST-DUNet closely align with those from manual skull stripping for both seed-based and independent component analyses, indicating that SST-DUNet can effectively substitute manual brain extraction in rat fMRI analysis.

  PublisherDOI

• Sex Differences in Plasma Levels of Endocannabinoids and Related Lipids Before and After acute and repeated mTBI: an exploratory study for plasma biomarkers for mTBI

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-15

  preprintOpen access

  Mild traumatic brain injury (mTBI) is common diagnosis across all age groups and while most symptoms resolve within a few weeks; between 10 and 25 percent of mTBI patients suffer long-term problems. Known as post-concussion syndrome (PCS), symptoms include headache, a range of cognitive deficits, and depression. Currently, there are no established treatments for PCS and no clear predictive biometrics to determine which patients are at increased risk. Previous studies have identified some protein-derived plasma biomarkers for mTBI, however, the effects of mTBI on lipid signaling molecules and metabolites in blood is largely unknown. Endogenous lipids (endolipids) such as the endocannabinoids (eCBs) and their congeners are lipid signaling molecules that are associated with promoting neuroprotective responses after head trauma in animal models. Here, we examine the plasma lipidome using a rat model of acute and repeated mTBI that we previously demonstrated had a sex dependent change in neuroinflammation wherein females showed a higher degree of neurodegeneration after repeated head-injury than males. Key results of this exploratory lipidomics screen here demonstrates that acute head injury drives significantly more changes in plasma endolipids in males (32%) than females (8%), whereas, on the second day of head injury, only 11% change in males but 15% in females. Some key endolipids were modified in both males are precursors for resolving molecules and this was lacking in females. Given that females with repeated mTBI in this model demonstrated aspects of PCS, this could be an important component in evaluating clinical cases. Endolipids in the screen were measurable in plasma using only 100μL, a volume necessary to be able to perform multiple blood draws on these rodent subjects. This threshold provides evidence that the levels of these endolipids could be readily measured throughout a patient's recovery. Therefore, this family of endolipids has the potential to provide data on the progression of the injury and could be another crucial aspect in predicting mTBI outcomes.

  PublisherOA PDFDOI

Recent grants

• NIH Grant P51RR000167

  NIH · $61.8M · 2013

• NIH Grant R01MH058700

  NIH · $1.1M · 2004

• NIH Grant R01NS023557

  NIH · $585k · 1990

• NIH Grant R23HD018022

  NIH · $67k · 1986

• NIH Grant R42MH059501

  NIH · $669k · 2001

Frequent coauthors

• Jason R. Yee

  Northeastern University

  105 shared

• William M. Kenkel

  University of Delaware

  101 shared

• Allison M. Perkeybile

  University of Virginia

  87 shared

• Stephen W. Porges

  83 shared

• C. Sue Carter

  University of Illinois Chicago

  83 shared

• Jessica J. Connelly

  University of Virginia

  83 shared

• Hossein Pournajafi‐Nazarloo

  Indiana University Bloomington

  82 shared

• Evan L. MacLean

  University of Arizona

  81 shared

Education

• Ph.D., Pharmaceutical Sciences

  University of ...

  2005

• M.S., Pharmaceutical Sciences

  University of ...

  2001

• B.S., Pharmaceutical Sciences

  University of ...

  1999