Men with PTSD showed depleted endocannabinoid levels while women with PTSD showed elevated inflammatory markers, suggesting sex-specific biological mechanisms.
PTSD researchers, cannabis-based therapy developers, clinicians treating PTSD in men vs women.
Distinct PTSD biology by sex
What the researchers found
Among 88 PTSD patients and 85 matched controls, male PTSD patients had significantly decreased levels of AEA, arachidonic acid, and OEA compared to male controls and female subgroups. Female PTSD patients showed elevated levels of IL-6 and IL-8 compared to other subgroups. These distinct profiles persisted after controlling for the FAAH gene variant and in the subgroup with comorbid depression.
Why it matters
PTSD predominantly affects women, yet most biological research has focused on mixed samples. This study reveals that men and women with PTSD may have fundamentally different underlying biological disruptions: endocannabinoid depletion in men versus inflammatory elevation in women. This could explain why treatments work differently by sex.
The numbers in context
88 PTSD patients, 85 controls. Males: decreased AEA, AA, OEA (p < 0.001 to 0.05). Females: elevated IL-6 and IL-8 (p < 0.010). Results persisted after controlling for FAAH genotype and comorbid MDD.
How the study worked
Case-control study retrospectively selecting 88 PTSD patients and 85 sex- and age-matched healthy controls from the Mass General Brigham Biobank. Serum samples measured endocannabinoids (AEA, 2-AG, OEA, AA) and inflammatory markers (IL-1beta, IL-6, IL-8, IL-18, TNF-alpha, CRP). Analyses controlled for FAAH 385A genotype.
What this study cannot tell us
Cross-sectional biobank study cannot determine whether biomarker changes cause or result from PTSD. Retrospective selection may introduce bias. Serum endocannabinoid levels may not reflect brain levels. Cannot determine whether differences existed before PTSD onset. Single timepoint measurement.
How to read the evidence
Moderate: well-designed biobank study with appropriate controls and genetic adjustment, though cross-sectional design limits causal inference.
When this study was published
2025 study
The bigger picture
If PTSD operates through different biological pathways in men versus women, then treatments targeting the endocannabinoid system (like cannabis) might be more effective for men, while anti-inflammatory approaches might better serve women. This has direct implications for the growing interest in cannabis-based PTSD treatments.
Questions still open
- Would endocannabinoid supplementation (via cannabis) be more effective for men with PTSD? Could anti-inflammatory treatments benefit women with PTSD more than current approaches? Do these sex differences explain variable response to cannabis-based PTSD treatments in clinical trials?
Common questions
Does PTSD affect men and women differently biologically?
Could this explain why cannabis helps some PTSD patients but not others?
Read the original research
Sex differences in endocannabinoid and inflammatory markers associated with posttraumatic stress disorder.
Progress in neuro-psychopharmacology & biological psychiatry, 142, 111501
Citation
Rajasekera, Therese A; Joseph, Anna; Pan, Hui; Dreyfuss, Jonathan M; Fida, Doruntina; Wilson, Julia C; Behee, Madeline; Fichorova, Raina N; Cinar, Resat; Spagnolo, Primavera A. (2025). Sex differences in endocannabinoid and inflammatory markers associated with posttraumatic stress disorder.. Progress in neuro-psychopharmacology & biological psychiatry, 142, 111501. https://doi.org/10.1016/j.pnpbp.2025.111501
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