Chronic THC intake modifies fundamental cerebellar functions
Nephi Stella
Nephi Stella
Published August 1, 2013; First published July 1, 2013
Citation Information: J Clin Invest. 2013;123(8):3208-3210. https://doi.org/10.1172/JCI70226.
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Commentary

Chronic THC intake modifies fundamental cerebellar functions

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

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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.

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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.