Endocannabinoids are compartmentalized within adrenal gland zones and stored in chromaffin granules alongside stress hormones, where they modulate progesterone and testosterone production.
Endocrinologists, endocannabinoid system researchers, and neuroscientists studying stress physiology.
Anandamide in cortex; 2-AG in medulla; both modulate hormones
What the researchers found
N-acylethanolamines including anandamide predominated in the adrenal cortex while 2-AG was concentrated in the medulla. Anandamide and the peptide endocannabinoid RVD-hemopressin increased progesterone and decreased testosterone secretion in adrenal cells. N-linoleoylethanolamine (LEA) and L-leucine were markedly enriched in chromaffin granules alongside neurotransmitters.
Why it matters
The endocannabinoid system is known to regulate the central stress response, but its role in the adrenal glands (where stress hormones are actually produced) has been largely unexplored. This study reveals an entire layer of local endocannabinoid regulation.
The numbers in context
Anandamide and N-acylethanolamines predominated in cortex. 2-AG concentrated in medulla. LEA enriched in chromaffin granules. Anandamide increased progesterone and decreased testosterone in adrenal cells. RVD-hemopressin potentiated anandamide effects on progesterone.
How the study worked
Targeted metabolomics of bovine adrenal gland zones and isolated chromaffin granules. Novel VMAT2-targeting fluorescent probe (CV-28) for flow cytometry of large dense-core vesicles. Hormone secretion assays in NCI-H295R adrenal cells.
What this study cannot tell us
Bovine adrenal tissue may differ from human. In vitro hormone effects may not translate to in vivo physiology. The peptide endocannabinoids (pepcans) were absent from chromaffin granules, contradicting some prior hypotheses.
How to read the evidence
Novel basic science study using advanced metabolomics and custom molecular probes, but conducted in bovine tissue and cell lines.
When this study was published
2026 study.
The bigger picture
This finding connects the endocannabinoid system directly to adrenal hormone production, potentially explaining some of the hormonal effects reported in cannabis users. If cannabis disrupts this local ECS regulation, it could alter stress hormone output.
Questions still open
- Does cannabis use alter adrenal endocannabinoid signaling and stress hormone production? Could this explain some of the hormonal and stress-response changes reported in chronic cannabis users?
Common questions
What does this mean for cannabis and stress hormones?
Are endocannabinoids released with adrenaline?
Read the original research
Illuminating chromaffin granules: compartmentalization of endocannabinoids in bovine adrenal glands supports role in hormone modulation.
Biochemical pharmacology, 248, 117827
Citation
Roukens, Jaap-Jan; Meier, Philip; Simão, Ana Catarina; Chicca, Andrea; Bregy, Rachel; Altmann, Karl-Heinz; Gertsch, Jürg. (2026). Illuminating chromaffin granules: compartmentalization of endocannabinoids in bovine adrenal glands supports role in hormone modulation.. Biochemical pharmacology, 248, 117827. https://doi.org/10.1016/j.bcp.2026.117827
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