Endocannabinoids and Kisspeptin Both Slow New Brain Cell Growth Through a Shared Pathway | Research

The takeaway

Anandamide (the brain's main endocannabinoid) and kisspeptin both inhibited hippocampal neurogenesis in adolescent rats through the TRPV1 receptor, revealing a new regulatory system for adult brain cell production.

Neuroscience researchers and anyone interested in how the endocannabinoid system regulates brain plasticity.

TRPV1 identified as shared pathway between endocannabinoid and kisspeptin systems

What the researchers found

Both anandamide and kisspeptin-10 reduced hippocampal neurogenesis by dampening ERK signaling. The TRPV1 ion channel receptor was upregulated by both treatments, suggesting it serves as a common mediator. Kisspeptin reduced CB1 receptor expression in the dentate gyrus, but anandamide did not affect kisspeptin receptors, indicating an asymmetric interaction between the two systems.

Why it matters

Adult neurogenesis in the hippocampus is important for learning and memory. This study reveals a previously unknown regulatory partnership between the endocannabinoid and kisspeptin systems, both of which can slow new brain cell production. Understanding these mechanisms could inform approaches to cognitive decline and neurodevelopmental conditions.

The numbers in context

Both KP10 and AEA enhanced TRPV1 expression. KP10 reduced CB1R in the dentate gyrus. KP10 upregulated SIRT1, BDNF, c-Jun, and estrogen receptor alpha. AEA did not affect kisspeptin receptor expression. Both systems reduced ERK signaling.

How the study worked

Male adolescent rats received kisspeptin-10 and/or anandamide, with or without the CB1 antagonist SR141716A. Expression of Kiss1, Kiss1R, CB1R, and TRPV1 was characterized in rat hippocampus. Neurogenesis was assessed alongside ERK signaling, SIRT1, BDNF, estrogen receptor alpha, and GAPDH expression.

What this study cannot tell us

Only male adolescent rats were studied; sex differences and adult effects are unknown. The doses and routes of administration may not reflect physiological conditions. The interaction between these systems in humans has not been studied.

How to read the evidence

Novel mechanistic animal study identifying a new regulatory interaction. Preliminary evidence that requires replication and extension to females and humans.

When this study was published

Published in 2025.

The bigger picture

The endocannabinoid system is already known to influence neurogenesis. This study adds the kisspeptin system as a partner in this regulation and identifies TRPV1 as a shared pathway, expanding the network of systems that fine-tune adult brain plasticity.

Questions still open

Does chronic cannabis use alter kisspeptin signaling in the hippocampus? Could targeting TRPV1 restore neurogenesis impaired by endocannabinoid or kisspeptin system dysfunction?

Common questions

What is kisspeptin?

A neuropeptide best known for regulating puberty and reproduction. This study reveals it also regulates hippocampal neurogenesis, a role that was previously unknown.

Does cannabis use reduce brain cell production?

This study shows that anandamide (a natural endocannabinoid) inhibits neurogenesis. Since THC activates the same CB1 receptors, chronic cannabis use could theoretically have similar effects, though this has not been directly tested in this study.

Read the original research

Adult Neurogenesis Is Regulated by the Endocannabinoid and Kisspeptin Systems.

International journal of molecular sciences, 26(9)

View on PubMed ↗Publisher’s paper ↗

Citation

Marino, Marianna; Di Pietro, Paola; D'Auria, Raffaella; Lombardi, Martina; Pastorino, Grazia Maria Giovanna; Troisi, Jacopo; Operto, Francesca Felicia; Carrizzo, Albino; Vecchione, Carmine; Viggiano, Andrea; Meccariello, Rosaria; Santoro, Antonietta. (2025). Adult Neurogenesis Is Regulated by the Endocannabinoid and Kisspeptin Systems.. International journal of molecular sciences, 26(9). https://doi.org/10.3390/ijms26093977