Cannabinoids shaped brain activity and new neuron growth in zebrafish | Research

The takeaway

In adult zebrafish, CB1 cannabinoid receptors maintained baseline brain excitatory activity in cognitive regions, while cannabinoid exposure reduced stem cell proliferation but increased the survival of newly born neurons.

Neuroscience researchers and readers interested in how cannabinoids affect brain cell formation.

Cannabinoids reduced stem cell proliferation but increased new neuron survival in the brain

What the researchers found

CB1 receptors were found in glutamatergic neurons of the zebrafish pallium. Blocking CB1 with rimonabant reduced spontaneous excitatory activity and ERK phosphorylation, suggesting CB1 maintains tonic excitatory signaling. Acute cannabinoid exposure reduced neural stem cell proliferation, but during the maturation window (12-24 days), cannabinoid treatment increased the number of surviving new neurons, an effect reversed by rimonabant.

Why it matters

The zebrafish brain undergoes continuous adult neurogenesis, making it a powerful model for understanding how cannabinoids affect new brain cell formation. The finding that cannabinoids reduce initial stem cell proliferation but increase neuron survival suggests a complex regulatory role that may be relevant to mammalian brains.

The numbers in context

CB1 receptors mapped in dorsomedial (Dm) and dorsolateral (Dl) pallial regions, predominantly in glutamatergic neurons. Rimonabant reduced sEPSC frequency without affecting other synaptic properties. 13-day rimonabant treatment reduced ERK phosphorylation. Cannabinoid treatment increased 25-day-old BrdU+/HuC/D+ neurons in both Dm and Dl regions.

How the study worked

Researchers mapped CB1 receptor expression in the zebrafish pallium using immunofluorescence and single-cell mRNA analysis. Electrophysiology measured synaptic activity with and without rimonabant. Neural stem cell proliferation was assessed after acute cannabinoid exposure, and neuronal maturation was tracked using BrdU labeling over 25 days with cannabinoid treatment during the 12-24 day maturation window.

What this study cannot tell us

Zebrafish neurogenesis is far more robust than in adult mammals, so translation to human brains is uncertain. The specific cannabinoids used and their concentrations were not detailed in the abstract. Only acute and sub-chronic exposures were tested.

How to read the evidence

Well-designed zebrafish study using multiple techniques (electrophysiology, immunofluorescence, BrdU tracking), but zebrafish-to-human translation is uncertain.

When this study was published

Published in 2025.

The bigger picture

This study reveals a conserved role for the endocannabinoid system in regulating neurogenesis across vertebrates. The dual effect (suppressing proliferation but enhancing survival) mirrors some findings in mammalian studies and suggests the endocannabinoid system may act as a quality control mechanism for new neuron integration.

Questions still open

Does this proliferation-survival tradeoff occur in mammalian adult neurogenesis? Could cannabinoid modulation of neurogenesis explain some cognitive effects of cannabis use? Would chronic cannabinoid exposure eventually deplete the stem cell pool?

Common questions

Do cannabinoids help or hurt brain cell growth?

Both, in this zebrafish study. They reduced the initial proliferation of neural stem cells but increased the survival of neurons that were already developing, suggesting a complex regulatory role rather than simple promotion or suppression.

Why study zebrafish?

Zebrafish continuously produce new neurons throughout adulthood at much higher rates than mammals, making them ideal for studying how cannabinoids affect neurogenesis over relatively short time periods.

Read the original research

Cannabinoids Shape Synaptic Activity and Adult Neurogenesis in the Zebrafish Pallium.

Journal of neurochemistry, 169(11), e70289

View on PubMed ↗Publisher’s paper ↗

Citation

Deleglise, Emilia Beatriz; Carnevale, Gonzalo; Mazzaro, Luz; Lobera, José; Bellora, Nicolás; Mongiat, Lucas Alberto. (2025). Cannabinoids Shape Synaptic Activity and Adult Neurogenesis in the Zebrafish Pallium.. Journal of neurochemistry, 169(11), e70289. https://doi.org/10.1111/jnc.70289