A specific group of astrocytes in the nucleus accumbens drives THC-induced cognitive deficits, and selectively reducing their overactivity prevented spatial learning and memory impairments in mice.
Neuroscience researchers and anyone interested in the mechanism behind cannabis-related cognitive effects.
Targeting specific astrocytes prevented THC cognitive impairment
What the researchers found
THC increased astrocytic calcium activity and glutamate release in the nucleus accumbens via the ventral hippocampus circuit. These effects required p38alpha signaling in astrocytes. Using a tool called AstroLight to selectively dampen THC-induced calcium activity in this specific astrocytic ensemble prevented spatial learning and synaptic plasticity impairments.
Why it matters
This study identifies the exact cellular mechanism through which THC impairs cognition and demonstrates that it can be prevented by targeting a specific group of non-neuronal brain cells. This opens a path toward interventions that could preserve cognitive function in medical cannabis users.
The numbers in context
THC increased astrocytic calcium activity in the NAc. Effects absent in p38alpha knockout mice. AstroLight manipulation of the vHip-NAc astrocytic ensemble prevented spatial learning impairments and synaptic plasticity deficits.
How the study worked
Researchers used the AstroLight tool to selectively manipulate a specific astrocytic ensemble associated with the vHip-NAc circuit. Astrocyte-specific p38alpha knockout mice were used to identify the signaling pathway. Calcium imaging, glutamate measurements, and spatial learning tests were performed in THC-exposed mice.
What this study cannot tell us
The AstroLight manipulation tool is a research tool not available for clinical use. Mouse spatial learning tasks may not fully capture human cognitive impairment from THC. Chronic THC exposure in humans involves more complex factors than acute laboratory dosing.
How to read the evidence
Cutting-edge mechanistic study using novel tools for cell-type-specific manipulation. Strong basic science evidence published in Nature Communications, but far from clinical application.
When this study was published
Published in 2025 in Nature Communications.
The bigger picture
The prevailing view has been that THC impairs cognition by acting on neurons. This study shows that astrocytes, the brain's support cells, are actually the critical intermediary. The ability to prevent cognitive impairment by targeting these cells suggests a fundamentally new approach to managing cannabis side effects.
Questions still open
- Could drugs targeting astrocytic p38alpha signaling prevent cognitive side effects of medical cannabis? Do human astrocytes respond to THC in the same way as mouse astrocytes?
Common questions
What are astrocytes?
Could this lead to a drug that prevents cannabis memory problems?
Read the original research
An astrocytic ensemble at vHip-NAc synapses modulates cognitive impairments induced by chronic tetrahydrocannabinol exposure.
Nature communications, 17(1), 471
Citation
Martín-Monteagudo, Cristina; Sánchez Romero, Javier; Adams, Julia M; Puente, Nagore; Grandes, Pedro; Marsicano, Giovanni; Covelo, Ana; Khakh, Baljit S; Navarrete, Marta. (2025). An astrocytic ensemble at vHip-NAc synapses modulates cognitive impairments induced by chronic tetrahydrocannabinol exposure.. Nature communications, 17(1), 471. https://doi.org/10.1038/s41467-025-67166-w
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