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Cell. 2013 Nov 21;155(5):1154-1165. doi: 10.1016/j.cell.2013.10.042.

Δ9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling.

Author information

1
Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
2
Department of Cell Biology and Anatomy, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
3
Department of Otorhinolaryngology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
#
Contributed equally

Erratum in

  • Cell. 2014 Jan 30;156(3):618.

Abstract

Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here, we show that synaptic and cognitive impairments following repeated exposure to Δ(9)-tetrahydrocannabinol (Δ(9)-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids in the brain. COX-2 induction by Δ(9)-THC is mediated via CB1 receptor-coupled G protein βγ subunits. Pharmacological or genetic inhibition of COX-2 blocks downregulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated Δ(9)-THC exposures. Ablation of COX-2 also eliminates Δ(9)-THC-impaired hippocampal long-term synaptic plasticity, working, and fear memories. Importantly, the beneficial effects of decreasing β-amyloid plaques and neurodegeneration by Δ(9)-THC in Alzheimer's disease animals are retained in the presence of COX-2 inhibition. These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2.

Comment in

PMID:
24267894
PMCID:
PMC3918429
DOI:
10.1016/j.cell.2013.10.042
[Indexed for MEDLINE]
Free PMC Article

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