Hippocampal apoptosis: Molecular mechanisms triggered by toxic cannabinoid exposure: A narrative review

Abstract

Hippocampal apoptosis is increasingly recognized as a significant consequence of toxic cannabinoid exposure, with profound implications for cognitive function and mental health. This narrative review comprehensively examines the molecular mechanisms underlying cannabinoid-induced apoptosis, focusing on the interplay of various bioactive compounds and their effects on neuronal integrity. We begin by discussing the key players in cannabinoid biology, followed by a synthesis of findings from animal and clinical studies that highlight the neurotoxic potential of cannabinoids. Central to our analysis are the roles of neuroinflammation and oxidative stress, which exacerbate neuronal damage and contribute to cell death. The activation of cannabinoid receptors, particularly CB1 and CB2, is scrutinized for its dual role in mediating neuroprotective and neurotoxic effects. We explore calcium dysregulation as a critical mechanism that leads to excitotoxicity, mitochondrial dysfunction, and the activation of pro-apoptotic pathways. Additionally, we address the inhibition of anti-apoptotic proteins, induction of endoplasmic reticulum (ER) stress, and disruption of neurotransmitter systems, all of which further facilitate apoptosis in hippocampal neurons. Alterations in neurotrophic factor levels are also examined, as they play a vital role in neuronal survival and plasticity. Ultimately, this review underscores the multifaceted nature of cannabinoid-induced hippocampal apoptosis and calls for further research to elucidate these complex interactions, aiming to inform clinical practices and public health policies regarding cannabinoid use. The findings presented herein highlight the urgent need for a nuanced understanding of the risks associated with cannabinoid exposure, particularly in vulnerable populations.