Introduction: The gut-brain axis (GBA) is a complex, bidirectional communication network connecting the gastrointestinal tract and central nervous system. Cannabidiol (CBD) and probiotics have shown promising neuroprotective, anti-inflammatory, and immunomodulatory effects. However, the synergistic potential of these agents on the GBA has not been fully explored. Methods: A systematic review of recent preclinical and clinical studies was conducted using databases such as PubMed, Scopus, Web of Science, Science Direct, and Google Scholar. The review focused on the individual and combined effects of CBD and probiotics on gut microbiota composition, neuroinflammation, neurotransmitter modulation, and immune signalling. Mechanistic insights involving the endocannabinoid system and microbiome-derived metabolites were also analyzed. Results: Evidence suggests that both CBD and probiotics can enhance gut microbial diversity, regulate pro-inflammatory cytokines, and increase neuroactive metabolites like serotonin and short-chain fatty acids. These effects may improve vagus nerve activity and gut-brain communication, indicating therapeutic potential for managing anxiety, depression, and neurodegenerative conditions. However, human studies remain limited in scale and duration. Discussion: The observed benefits of CBD and probiotics suggest a synergistic mechanism through gut-brain axis modulation, addressing both neurological and immunological pathways. While animal studies are promising, translation to clinical practice requires further evidence. Conclusion: CBD and probiotics represent a novel combinatorial approach for managing central nervous system disorders through GBA modulation. Future clinical trials should establish optimal dosing, long-term safety, and therapeutic efficacy to validate their use in neuroimmune conditions.
Chauhan et al. (Tue,) studied this question.