Evaluation of the efficacy of a full-spectrum medicinal cannabis plant extract with less than 0.3% Delta9-tetrahydrocannabinol in in vitro models of inflammation and excitotoxicity

The rapid development of research on the therapeutic benefits of medicinal cannabis, in parallel with an increased understanding of the endocannabinoid system, has driven research of Cannabis sativa constituents for managing neurological conditions. While most studies have focused on the therapeutic potential of the major components of cannabis plant extract isolated or combined, limited research has explored the pharmacological benefits of whole cannabis plant extract. In this study, we investigated the potential anti-inflammatory and neuroprotective effects of NTI-164, a novel full-spectrum cannabis extract with negligible Delta9-tetrahydrocannabinol (THC), compared with cannabidiol (CBD) alone in BV-2 microglial and SHSY-5Y neuronal cells. The inflammation-induced upregulation of microglial inflammatory mediators, being tumour necrosis factor α (TNFalpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), inducible nitric oxide synthase (iNOS), and Arginase-1 (Arg-1), were significantly attenuated by NTI-164. This immunomodulatory effect was not observed upon treatment with isolated CBD. Compared to CBD alone, NTI-164 prevented elevated mitochondrial activity while normalising cell numbers in immune-activated microglia cells. NTI-164 also promoted the proliferation of undifferentiated neurons and the survival of differentiated neurons under excitotoxic conditions. Overall, our work shows that the anti-inflammatory and neuroprotective effects of NTI-164 as a full-spectrum cannabis extract are enhanced relative to that of CBD alone, highlighting the potential therapeutic efficacy of NTI-164 for the treatment of neuropathologies such as autism spectrum disorder (ASD) and related neuropathologies. This study has further shown that understanding the synergistic effect of phytocannabinoids is integral to realising the therapeutic potential of full-spectrum cannabis extract to inform the design of botanical-derived treatments for managing neurological disorders. ### Competing Interest Statement We have read the journal's policy and Esra Iskigel has the following competing interests: employee and shareholder of organisation funding the research.