Extracellular vesicles in Drosophila and mammals: Conserved mechanisms and emerging functional roles.

Cannabidiol (CBD), a major non-intoxicating phytocannabinoid extracted from , has attracted significant clinical and scientific attention. In the United States, pure CBD is sanctioned by the U.S. Food and Drug Administration as an antiseizure treatment and is sold under the brand name Epidiolex []. In addition to its anticonvulsant properties, CBD has been documented to possess anti-inflammatory, antioxidant, anxiolytic, antipsychotic, neuroprotective, and analgesic activities []. Despite thorough investigation, the molecular mechanisms underlying these varied biological activities remain only partially elucidated and likely to require intricate and partially overlapping signaling pathways. An extensive body of research demonstrates that CBD has notable effects on the central nervous system, especially in the hippocampus [–]. The hippocampus is fundamentally engaged in spatial navigation by creating cognitive maps facilitated by place cell activity, and is vital for memory consolidation []. Alongside the amygdala, it plays a role in the regulation of stress and anxiety-related processes [, ], areas often noted to be influenced by CBD. Experimental investigations indicate that CBD affects various physiological parameters in the hippocampus. It mitigates hippocampus hyperexcitability, partially by antagonizing the pro-excitatory actions of lysophosphatidylinositol at GPR55 receptors []. In neurodegenerative models, CBD improves neuronal survival and decreases oxidative stress, alleviating amyloid-β-induced neurotoxicity in hippocampal neurons []. Transcriptomic analyses reveal that CBD administration alters hippocampal gene expression, resulting in the downregulation of genes related to mitochondrial electron transport and ribosome biogenesis, as well as the upregulation of genes involved in chromatin remodelling and synaptic organization in the CA1 region []. These findings indicate that CBD may affect cellular metabolism, protein synthesis, and synapse structure, therefore leading to changes in neuroplasticity. Furthermore, CBD has been reported to change hippocampal ripple dynamics during sleep, potentially influencing memory consolidation processes [].