In 91 healthy adults, baseline blood endocannabinoid levels were not broadly associated with pain sensitivity measures, though anandamide and OEA were linked to pressure pain thresholds.
Pain researchers, endocannabinoid scientists, biomarker developers.
Only pressure pain thresholds correlated with blood endocannabinoid levels
What the researchers found
Serum eCB/NAE concentrations were not affected by sex, FAAH genotype, or cannabis use. FAAH C385A genotype did not predict pain sensitivity. Only pressure pain thresholds were associated with AEA and OEA levels (p=0.003).
Why it matters
Despite strong animal evidence that endocannabinoids modulate pain, this study's mostly null results suggest blood levels may not reflect the local eCB activity that matters for pain.
The numbers in context
91 participants. No sex, genotype, or cannabis use effects on eCB levels. Pressure pain thresholds associated with AEA and OEA (p=0.003). No other QST measures significant.
How the study worked
91 healthy participants (39 males, 52 females) assessed with quantitative sensory testing and serum endocannabinoid measurements. FAAH C385A genotyping. Linear regressions across 13 QST measures.
What this study cannot tell us
Blood levels may not reflect tissue-level concentrations. QST in healthy volunteers may not capture eCB modulation relevant in chronic pain. Single timepoint.
How to read the evidence
Well-designed study combining genetics, biochemistry, and psychophysics, but mostly null findings highlight limitations of peripheral eCB measurement.
When this study was published
Published in 2025.
The bigger picture
The disconnect between animal and human findings suggests peripheral blood eCB levels may not capture central nervous system activity driving pain modulation.
Questions still open
- Would CSF eCB levels show stronger associations? Do levels predict pain in chronic pain patients?
Common questions
Do your natural cannabinoid levels affect pain?
Does the FAAH gene variant affect pain?
Read the original research
The contribution of baseline circulating endocannabinoids to individual differences in human pain sensitivity: a quantitative sensory testing study.
Pain
Citation
Fatemi, S A; Abssy, S S; Bourke, S L; Murray, K B; Kyeremaa-Adjei, C; Honigman, L; Mohabir, N; Sexton, C; Cormie, M A; Tomin, R; Boileau, I; Atlas, L Y; Finn, D P; Moayedi, M. (2025). The contribution of baseline circulating endocannabinoids to individual differences in human pain sensitivity: a quantitative sensory testing study.. Pain. https://doi.org/10.1097/j.pain.0000000000003850
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