ArticlePsychopharmacology2026
Cannabidiol (CBD) potentiates physiological and behavioral markers of hypothalamic-pituitary-adrenal (HPA) axis responsivity in female and male mice.
Article in Psychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Selective hippocampal transcriptional adaptation to long-term cannabidiol exposure in mice.BMC genomics · 2026Article
- Non-Psychoactive Cannabis Extract Disrupts Reinstatement and Reconsolidation in Cocaine-Induced Conditioned Place Preference in Mice.Brain sciences · 2026Article
- EBPS2023 special issue: Stress, trauma and cannabinoids.Psychopharmacology · 2026Article
- A comparative network analysis to explore cancer patient experiences with cannabis.Frontiers in psychiatry · 2026Article
- Elucidating the transcriptomic response of adult-derived mHypoA-2/12 mouse hypothalamic neuron cell line to cannabidiol (CBD) exposure.Journal of applied genetics · 2025Article
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Authors and funding
5 authors.
Funding
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Abstract
rationaleClinical literature indicates there may be a therapeutic use of cannabidiol (CBD) for stress-related disorders. Preclinical literature remains conflicted regarding the underlying neurobehavioral mechanisms, reporting mixed effects of CBD (increased, decreased, or no effect) on anxiety- and fear-related behaviors. Preclinical data demonstrated that CBD modulates hypothalamus-pituitary-adrenal (HPA) axis gene expression; it is unknown whether CBD changes HPA axis responsivity and how this relates to altered behavior.
objectivesWe aimed to evaluate whether acute or chronic CBD administration would alter physiological and behavioral measures of HPA axis responsivity in male or female mice.
methodsC57BL/6 mice of both sexes were injected with vehicle or CBD (30 mg/kg, i.p.) daily for 26 days. Plasma corticosterone (CORT) levels were evaluated following dexamethasone suppression and adrenocorticotropin hormone stimulation tests after acute and chronic CBD exposure. After chronic CBD, mice were tested for anxiety-like behavior using an elevated plus maze (EPM) and associative fear learning and memory using a trace fear conditioning (FC) protocol.
resultsCompared to vehicle, CBD induced a state of HPA axis hyperactivation, an effect which was significant in males; it also normalized anxiety-like behavior in female mice classified as having HPA axis hypofunction and primed all female mice for enhanced conditioned responding. Significant sex differences were also detected: females had greater plasma CORT levels and HPA axis responsivity than males, exhibited less EPM anxiety-like behavior, and were more responsive during FC.
conclusionsCBD potentiated physiological and behavioral markers of HPA axis function and normalized anxiety-like behavior in a sex-specific manner. This observation has implications for cannabinoid-based drug development targeting individuals with stress-related disorders involving HPA axis hypofunction pathology.
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