Cannabidiol (CBD) and cannabigerol (CBG) significantly improved memory and reversed several signs of brain damage in rats exposed to excessive iron early in life, according to a new study published this week in Neurotoxicity Research.
Researchers from the Federal University of Rio Grande do Sul and University of São Paulo in Brazil examined 63 male Wistar rats using a model designed to produce long-lasting cognitive impairment associated with excessive iron exposure. The researchers note that excess iron accumulation and related inflammation have been associated with neurodegenerative conditions including Alzheimer’s and Parkinson’s diseases.
Rats received iron or a control substance during the second week after birth. At three months old, they were divided into groups receiving CBD, CBG or a placebo once daily for 21 days. Both cannabinoids were administered at 10 milligrams per kilogram.
Animals exposed to excess iron showed impaired recognition memory as adults. Treatment with either CBD or CBG significantly improved their performance on the object recognition test, while neither cannabinoid significantly affected general movement, exploratory activity or anxiety-like behavior.
The researchers also found that iron exposure increased levels of inflammatory markers in the hippocampus. Both CBD and CBG significantly reduced interleukin-1 beta (IL-1β) among iron-exposed rats. CBD did not significantly affect tumor necrosis factor alpha (TNF-α), while CBG produced a more complex response, including increased TNF-α among rats that had not been exposed to excess iron. Neither cannabinoid significantly affected IL-6.
Another notable finding involved occludin, a protein that helps maintain the blood-brain barrier. Iron exposure significantly reduced occludin expression, while both CBD and CBG significantly restored its expression in iron-exposed animals. The effect was statistically significant for CBD and even stronger for CBG.
Researchers cautioned that restoring occludin expression does not prove that normal blood-brain barrier function was restored, because the study did not directly measure barrier permeability. The experiment also involved only male rats, meaning the results cannot yet be generalized to females or humans.
The authors said the study provides the first direct comparison of CBD and CBG in this model of iron-related brain dysfunction, with both cannabinoids showing potential neuroprotective effects through somewhat different mechanisms.
They concluded that “These findings highlight inflammation and BBB disruption as mediators of iron-induced cognitive dysfunction and show that both phytocannabinoids act through distinct but complementary mechanisms, supporting their therapeutic potential in neuroinflammation linked to iron overload.”
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