Research study · Frontiers in Neuroimaging · 2026
Functional neuroimaging of Cannabidiol in stress and anxiety: a systematic review
Verified on PubMed Systematic review or meta-analysis
A 2026 systematic review in Frontiers in Neuroimaging tested cannabidiol in anxiety. The results were mixed and did not point to a clear effect. This review shows that the brain-scan evidence for cannabidiol and anxiety is small, scattered, and hard to repeat, so it cannot yet confirm how the substance works in the brain.
In plain language
Study overview
This review gathered brain scan studies in adults that gave cannabidiol, a non-intoxicating part of the cannabis plant, and compared it with a dummy pill while people were stressed or anxious. The authors combined the results from twelve small studies.
Findings
The results were mixed and did not point to a clear effect. The brain changes seen were scattered across many areas and went in different directions, and most people did not report feeling less anxious.
The deeper readScientific analysis
Cannabidiol (CBD) is a non-intoxicating phytocannabinoid primarily derived from hemp that has been investigated for its potential anxiolytic effects. This systematic review examined adult human neuroimaging investigations comparing CBD with placebo under conditions related to stress or anxiety. Searches of PubMed, Web of Science, EBSCO, and ProQuest covered studies published before June 30, 2025. Twelve studies with 146 participants in 7 cohorts were included. Results showed a wide distribution of reported peaks across many cortical and subcortical regions with mixed directions of activation or perfusion and substantial heterogeneity. Risk of bias was generally some concerns or high, and certainty of evidence was low to very low. The authors conclude there is a lack of consistent evidence showing acute effects of CBD on the brain, and that the literature on putative anxiolytic effects is constrained by methodological variability and limited statistical power.
The paper
Citation
Rutledge O, Goyette RB, Wang KL, Park MS, Gabrieli JDE Functional neuroimaging of Cannabidiol in stress and anxiety: a systematic review. Frontiers in Neuroimaging (2026). PubMed 42494831 · DOI
Read the abstract as published
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.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD420251063369.
Abstract text as indexed by PubMed for this identifier.
Limitations the authors noted
Small sample sizes and limited statistical power across studies. Overlapping participant cohorts reducing independence of evidence. Heterogeneous paradigms, imaging modalities, dosing, and analytic approaches precluding meta-analysis. Reliance on reported peak coordinates rather than unthresholded maps or standardized effect sizes. Predominantly male samples limiting generalizability. Concerns about missing outcome data, selective reporting, and limited assessment of publication bias.
In practice
Why this matters
This review shows that the brain-scan evidence for cannabidiol and anxiety is small, scattered, and hard to repeat, so it cannot yet confirm how the substance works in the brain. It does not prove cannabidiol does nothing, since the studies used single doses, mostly men, and few participants. Future larger, consistently designed trials are needed before drawing firm conclusions.
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Reviewed by Dr. Caplan on October 15, 2026.
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