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Bidirectional Effect of Long-Term Δ9-Tetrahydrocannabinol Treatment on mTOR Activity and Metabolome

★ ★ ★ ☆ ☆

Paper Summary

Paperzilla title
THC and Mice: A Tale of Two Metabolisms (Caution: Not for Humans Yet!)

This study in mice found that long-term, low-dose THC treatment had distinct effects on brain and body metabolisms. In the brain, it initially increased mTOR activity and energy production, seemingly promoting synapse formation. Subsequently, it reduced mTOR activity and metabolic processes in adipose tissue, similar to the effects seen in calorie restriction. These findings suggest potential cognitive and anti-aging benefits of THC, but more research is needed to confirm these effects in humans.

Explain Like I'm Five

In old mice, long-term, low-dose THC temporarily boosted brain activity and synapse formation, followed by reduced activity in fat tissue, potentially combining cognitive benefits with anti-aging effects.

Possible Conflicts of Interest

None identified.

Identified Limitations

Animal model
The study uses mice as a model organism, and it is not clear if these results translate directly to humans. Further research is needed to determine if long-term, low-dose THC has similar effects on human brains and metabolisms.
Limited sample size
Sample sizes, while adequate for the mouse study, are still relatively small, especially for some of the subgroup analyses. This raises the possibility of spurious correlations or exaggerated effect sizes, impacting the generalizability of the results.
Correlation vs. Causation
The study predominantly observes correlations between THC treatment, mTOR activity, and metabolic changes. Further investigation using causal inference methods is needed to definitively establish THC as the driver of these observed effects.

Rating Explanation

This study uses an animal model and shows correlation, not causation, limiting its applicability to humans and earning a 3 despite interesting findings in mice. The sample size is adequate for the animal model but is not very large. There is no clear conflict of interest.

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Topic Hierarchy

Domain: Life Sciences
Subfield: Pharmacology

File Information

Original Title: Bidirectional Effect of Long-Term Δ9-Tetrahydrocannabinol Treatment on mTOR Activity and Metabolome
Uploaded: August 26, 2025 at 12:47 AM
Privacy: Public