Functional neuroimaging of Cannabidiol in stress and anxiety: a systematic review

Cannabidiol (CBD) is a non-intoxicating phytocannabinoid primarily derived from hemp (cannabis sativa L.) that has been investigated for its potential anxiolytic effects. Prior functional neuroimaging studies suggest that CBD may affect brain regions associated with stress and anxiety. However, it remains unclear if there is a consistent pattern of modulation within these regions and if there is a correlation with behavioral or physiological measures. We conducted a systematic review examining adult human neuroimaging investigations comparing CBD with placebo under conditions related to stress or anxiety. We searched PubMed, Web of Science, EBSCO, and ProQuest for studies published before June 30, 2025. The quality of the evidence was assessed with the revised Cochrane Risk of Bias Tool for Randomized Trials (RoB 2), findings were summarized using a Synthesis Without Meta-analysis (SWiM) approach, and certainty of evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. A total of 12 studies with 146 participants in 7 cohorts met the eligibility criteria and were included in the synthesis. Results indicated a wide distribution of reported peaks across many cortical and subcortical regions with mixed directions of activation or perfusion, demonstrating substantial heterogeneity in the reported findings. Risk of bias assessments generally indicated either some concerns or high risk of bias, and the certainty of evidence was judged to be low to very low. Overall, there is a lack of consistent evidence showing the acute effects of CBD on the brain across various study designs. The current literature on the putative anxiolytic effects of CBD is constrained by methodological variability and limited statistical power. Future studies should employ standardized paradigms, improve reporting practices, and include more diverse and adequately powered samples to clarify the neural correlates of CBD-related effects on stress and anxiety.

PROSPERO, CRD420251063369.