Two Synthetic Cannabinoids Boosted Nerve Cell Growth but Damaged Mitochondria in Lab Cells
ADB-FUBINACA and AMB-FUBINACA promoted neurite outgrowth in lab-grown nerve cells through CB1 receptor activation while simultaneously causing mitochondrial dysfunction.
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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.
Why This Research 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 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.
What This Study Doesn't 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.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- Both compounds active below 1 micromolar concentration
- Evidence Grade:
- In vitro cell line study provides mechanistic insight but cannot confirm these effects would occur in developing human brains.
- Study Age:
- Published in 2025.
- Original Title:
- The synthetic cannabinoids ADB-FUBINACA and AMB-FUBINACA enhance in vitro neurodifferentiation of NG108-15 cells, along with PGC-1α dysregulation and mitochondrial dysfunction.
- Published In:
- Toxicology, 517, 154213 (2025)
- Database ID:
- RTHC-07027
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked 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 More on RethinkTHC
- THC-purity-potency-label-meaning
- dab-concentrate-addiction-withdrawal
- delta-8-addiction-withdrawal
- edible-addiction-withdrawal-different
- edibles-psychosis-emergency-room
- healthiest-way-to-consume-cannabis
- how-cannabis-products-made-concentrates-edibles
- laced-weed-fentanyl-contaminated-vape
- legal-weed-vs-street-weed-quality-safety
- quitting-dabs-withdrawal
- quitting-edibles-withdrawal
- sativa-vs-indica-difference-myth
- weed-potency-withdrawal
Cite This Study
https://rethinkthc.com/research/RTHC-07027APA
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
MLA
Malheiro, Rui Filipe, et al. "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, 2025. https://doi.org/10.1016/j.tox.2025.154213
RethinkTHC
RethinkTHC Research Database. "The synthetic cannabinoids ADB-FUBINACA and AMB-FUBINACA enh..." RTHC-07027. Retrieved from https://rethinkthc.com/research/malheiro-2025-the-synthetic-cannabinoids-adbfubinaca
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.