Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • ASCI Milestone Awards
    • Video Abstracts
    • Conversations with Giants in Medicine
  • Reviews
    • View all reviews ...
    • Neurodegeneration (Mar 2026)
    • Clinical innovation and scientific progress in GLP-1 medicine (Nov 2025)
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • ASCI Milestone Awards
  • Video Abstracts
  • Conversations with Giants in Medicine
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Chronic THC intake modifies fundamental cerebellar functions
Nephi Stella
Nephi Stella
View: Text | PDF
Commentary

Chronic THC intake modifies fundamental cerebellar functions

  • Text
  • PDF
Abstract

Delta9-tetrahydrocannabinol (THC), the principal bioactive component in the Cannabis plant, is truly a captivating drug. Acute and chronic THC intake produces a spectrum of biological effects ranging from transient psychotropic effects to prolonged medicinal benefits, many of which have been fostered for centuries by our society. In the July 2013 issue of the JCI, Cutando et al. combined mouse genetics with classic mouse behavioral analysis to deepen our understanding of the physiological consequence of subchronic THC intake on eyeblink reflexes, a fundamental neuronal adaptive response, revealing that this regimen leads to downregulation of the cannabinoid CB1 receptor (referred to as CB1 in the Cutando et al. article) in cerebellar stress fibers and the activation of microglia, raising provocative new questions about the safety profile of regimented THC intake.

Authors

Nephi Stella

×

Figure 1

In mice, subchronic treatment with THC leads to the downregulation of presynaptic cannabinoid CB1 receptors expressed by parallel fibers that project onto Purkinje cells.

Options: View larger image (or click on image) Download as PowerPoint
In mice, subchronic treatment with THC leads to the downregulation of pr...
Cutando et al. (9) show that the loss of CB1 receptors, either due to TCH-induced downregulation or genetic deletion, triggers a neuroinflammatory response typified by changes in microglial cell morphology and CB2 receptor expression. This adaptive response underlies THC-induced deficits in cerebellar-associated learning functions.

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts