Modulowanie pobudliwości neuronów w epilepsji: systemowa perspektywa sygnalizacji kannabinoidów i terpenów
Modulating Neural Excitability in Epilepsy: A Systems-Level Perspective on Cannabinoid–Terpene Signaling
W skrócie
[Preprint - wstępne wyniki] Epilepsja to choroba, w której dochodzi do zaburzenia równowagi między pobudzającymi a hamującymi sygnałami w mózgu, co prowadzi do napadów padaczkowych. Naukowcy sugerują, że pewne związki z konopi, takie jak kannabinoidów i terpeny, mogą działać na wiele celów molekularnych jednocześnie, aby przywrócić równowagę w mózgu i zmniejszyć częstość napadów. Propozycja dotyczy zastosowania kombinacji kilkunastu składników konopi w przyszłych badaniach, które mogą otworzyć nowe drogi leczenia epilepsji.
Oryginalny abstract (angielski)
Epilepsy is increasingly understood as a disorder of neural circuit hyperexcitability arising from disruptions in the balance between excitatory glutamatergic and inhibitory GABAergic signaling. In many forms of epilepsy, recurrent seizures are associated with excessive glutamate release and calcium influx, along with inflammatory signaling, oxidative stress, and maladaptive changes in synaptic transmission. These processes can further destabilize vulnerable networks, particularly within hippocampal and cortical circuits. Endogenous mechanisms that normally constrain hyperexcitability—including endocannabinoid signaling through CB1 receptors—may become insufficient or dysregulated in chronic epilepsy, creating conditions that favor recurrent seizure generation. Here, we propose that multi-phytocompound combinations may influence neural balance in epilepsy by engaging several molecular systems that regulate neuronal excitability and seizure threshold. Cannabinoids and terpenes derived from Cannabis sativa interact with diverse molecular targets implicated in epilepsy, including CB1 receptors, GPR55, transient receptor potential (TRP) channels, GABAA receptors, voltage-gated ion channels, glycine and serotonergic receptors, as well as endocannabinoid metabolic pathways. Through these convergent mechanisms, phytocannabinoids and terpenes may influence excitatory and inhibitory signaling, limit excitotoxic processes, and modulate pathways associated with neuroinflammation and oxidative stress. Within this context, we outline a theoretical multi-compound approach composed of a dozen cannabinoids and terpenes selected for their potential synergy and interactions with pathways implicated in seizure generation, synaptic transmission, and neuroprotection, yielding testable predictions for future experimental and clinical investigation. This perspective provides a systems-level model for understanding how coordinated, multi-target modulation of neural signaling pathways may influence circuit stability in epilepsy and offers a foundation for future experimental validation of multi-compound strategies.