Synthetic cannabinoid AB-FUBINACA damaged memory and hippocampal cells in mice | Research

The takeaway

Chronic administration of the synthetic cannabinoid AB-FUBINACA impaired recognition memory in mice and caused hippocampal damage through oxidative stress, neuroinflammation, and reduced BDNF expression.

People exposed to synthetic cannabinoids, neuroscience researchers, substance abuse clinicians

Reduced BDNF and NMDA receptor expression

What the researchers found

AB-FUBINACA caused significant recognition memory impairment along with hippocampal histopathological changes. These effects correlated with increased oxidative stress, neuroinflammation, apoptosis markers, reduced brain-derived neurotrophic factor (BDNF), and decreased NR1 subunit expression of NMDA receptors.

Why it matters

Synthetic cannabinoids are far more potent than natural cannabis and are linked to psychiatric emergencies, but the molecular mechanisms behind their neurotoxicity are poorly understood. This study maps specific pathways of hippocampal damage.

The numbers in context

Significant decreases in BDNF expression and NR1 (NMDA receptor subunit). Increased markers of oxidative stress, neuroinflammation, and apoptosis in hippocampal tissue.

How the study worked

Mouse study evaluating chronic AB-FUBINACA administration effects on hippocampus through behavioral testing (recognition memory), histopathology, and molecular markers of oxidative stress, inflammation, apoptosis, BDNF, and NMDA receptor expression.

What this study cannot tell us

Mouse model may not fully translate to human neurotoxicity. Specific doses and administration routes may not match human use patterns. Only studied one synthetic cannabinoid (AB-FUBINACA) out of hundreds.

How to read the evidence

Animal study with detailed molecular analysis, but findings may not directly translate to human neurotoxicity.

When this study was published

2024 mouse study examining AB-FUBINACA neurotoxicity

The bigger picture

The reduced NR1 expression is particularly noteworthy because NMDA receptor dysfunction is implicated in toxic psychosis, a known risk of synthetic cannabinoid use. This provides a molecular link between synthetic cannabinoid exposure and the psychotic episodes reported in users.

Questions still open

Are these hippocampal changes reversible after cessation? Do different synthetic cannabinoids produce similar molecular damage patterns? What doses in humans would correspond to the neurotoxic levels in mice?

Common questions

What is AB-FUBINACA?

AB-FUBINACA is a synthetic cannabinoid, a lab-made chemical designed to bind to the same brain receptors as THC but often with much greater potency. It has been found in products sold as "spice" or "K2."

How does this differ from natural cannabis effects on the brain?

Synthetic cannabinoids are typically far more potent CB1 receptor agonists than THC. This study found molecular damage (oxidative stress, apoptosis, NMDA disruption) more severe than typically seen with natural cannabis in animal studies.

Read the original research

Delineating the molecular mechanisms of hippocampal neurotoxicity induced by chronic administration of synthetic cannabinoid AB-FUBINACA in mice.

Neurotoxicology, 103, 50-59

View on PubMed ↗Publisher’s paper ↗

Citation

Alzu'bi, Ayman; Abu-El-Rub, Ejlal; Almahasneh, Fatimah; Tahat, Lena; Athamneh, Rabaa Y; Khasawneh, Ramada; Alzoubi, Hiba; Ghorab, Doaa S; Almazari, Rawan; Zoubi, Mazhar Salim Al; Al-Zoubi, Raed M. (2024). Delineating the molecular mechanisms of hippocampal neurotoxicity induced by chronic administration of synthetic cannabinoid AB-FUBINACA in mice.. Neurotoxicology, 103, 50-59. https://doi.org/10.1016/j.neuro.2024.05.009