Cellular responses to cannabidiol in neuronal models: a scoping review of in vitro studies

Cannabidiol (CBD) has attracted increasing interest because of its reported antioxidant, anti-inflammatory, and neuromodulatory properties; however, its effects in neuronal systems appear to vary according to concentration and experimental context. This scoping review mapped the available in vitro evidence on the effects of CBD and its metabolites in neurons and neuron-like cells. PubMed, Scopus, and Web of Science were searched for eligible studies published up to 11 December 2025, with no publication-date restriction. Of 2,874 records screened, 10 studies met the predefined eligibility criteria. Data on neuronal models, exposure conditions, cell viability, and associated cellular and molecular responses were extracted, and methodological quality was independently assessed by two reviewers using an adapted Joanna Briggs Institute tool. The included studies investigated primary rat hippocampal and cortical neurons and several neuron-like cell lines, including SH-SY5Y, HT22, NSC-34, and mHypoA-2/12 cells, with CBD concentrations reported in molar units rangftring from 0.01 to 100 µM, while one study reported concentrations of commercial CBD preparations in µg/mL. Across the included studies, lower-to-moderate CBD concentrations were more frequently associated with neutral or potentially protective cellular responses, including activation of antioxidant and pro-survival pathways such as Nrf2/HO-1 signalling. In contrast, higher concentrations were more frequently associated with reduced cell viability, mitochondrial dysfunction, ATP depletion, oxidative stress, calcium dysregulation, and apoptosis, although the magnitude and direction of these effects varied across experimental models and conditions. Some studies implicated TRPV1-associated calcium dysregulation, whereas cannabinoid receptor involvement was not consistently demonstrated or assessed. Evidence regarding the neuronal effects of CBD metabolites was limited. Overall, the findings indicate substantial variability in the in vitro effects of CBD across concentrations and experimental contexts, and the available evidence does not establish a universal concentration threshold for either neuroprotection or neurotoxicity. Future studies should prioritise physiologically relevant exposure conditions, longer and repeated exposures, neuron–glia systems and other human-relevant neuronal models, and systematic investigation of major CBD metabolites to improve the evidence’s translational relevance.