Two Synthetic Cannabinoids Boosted Nerve Cell Growth but Damaged Mitochondria in Lab Cells | Research

The takeaway

ADB-FUBINACA and AMB-FUBINACA promoted neurite outgrowth in lab-grown nerve cells through CB1 receptor activation while simultaneously causing mitochondrial dysfunction.

Researchers studying synthetic cannabinoid toxicity and anyone concerned about the neurodevelopmental risks of synthetic cannabinoid exposure.

Both compounds active below 1 micromolar concentration

What the researchers found

Both synthetic cannabinoids enhanced neurite outgrowth at biologically relevant concentrations below 1 micromolar. This effect was blocked by CB1 receptor antagonists. However, both compounds also reduced mitochondrial membrane potential independently of CB1 receptors. ADB-FUBINACA additionally decreased cellular ATP levels through CB1 activation.

Why it matters

Synthetic cannabinoids are used by young adults, including women of childbearing age. These findings suggest that these compounds could interfere with normal neurodevelopment by simultaneously promoting abnormal nerve growth and damaging the cellular energy machinery that developing neurons depend on.

The numbers in context

Effects observed at concentrations below 1 micromolar. ADB-FUBINACA increased cytosolic PGC-1alpha expression (1 pM to 1 micromolar) while decreasing mitochondrial PGC-1alpha (at 1 nM and 1 micromolar). The Parkin-PINK1 mitophagy pathway was not activated at tested concentrations.

How the study worked

Researchers exposed NG108-15 neuronal cell lines to ADB-FUBINACA and AMB-FUBINACA at varying concentrations. They measured neurite outgrowth, mitochondrial membrane potential, ATP levels, and expression of mitochondrial markers including PGC-1alpha, VDAC, NRF-1, and TFAM. CB1 receptor antagonists were used to determine receptor involvement.

What this study cannot tell us

This is an in vitro study using a cell line, not living brain tissue or whole organisms. Effects at the cellular level may not directly translate to neurodevelopmental outcomes in humans. The concentrations used, while biologically relevant, may not reflect actual brain exposure from recreational use.

How to read the evidence

In vitro cell line study provides mechanistic insight but cannot confirm these effects would occur in developing human brains.

When this study was published

Published in 2025.

The bigger picture

The finding that synthetic cannabinoids can enhance neuronal differentiation while simultaneously impairing mitochondrial function raises concerns about neurodevelopmental effects. This dual action - promoting growth while starving cells of energy - could lead to abnormal neural development.

Questions still open

Do these effects occur in developing brains in vivo? Could the combination of enhanced neurite growth and mitochondrial damage produce lasting structural changes in neural circuits?

Common questions

What are ADB-FUBINACA and AMB-FUBINACA?

They are potent indazole-derived synthetic cannabinoids commonly found in products sold as "spice" or "K2." Both bind to CB1 receptors much more strongly than natural THC.

Why is mitochondrial damage concerning for brain development?

Developing neurons require enormous amounts of energy for growth and migration. Mitochondrial dysfunction could impair these processes, potentially leading to abnormal brain wiring.

Read the original research

The synthetic cannabinoids ADB-FUBINACA and AMB-FUBINACA enhance in vitro neurodifferentiation of NG108-15 cells, along with PGC-1α dysregulation and mitochondrial dysfunction.

Toxicology, 517, 154213

View on PubMed ↗Publisher’s paper ↗

Citation

Malheiro, Rui Filipe; Figueiredo, João; Carmo, Helena; Carvalho, Félix; Silva, João Pedro. (2025). The synthetic cannabinoids ADB-FUBINACA and AMB-FUBINACA enhance in vitro neurodifferentiation of NG108-15 cells, along with PGC-1α dysregulation and mitochondrial dysfunction.. Toxicology, 517, 154213. https://doi.org/10.1016/j.tox.2025.154213