Blood levels of the body's own cannabinoids showed limited connection to pain sensitivity in healthy adults
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.
Quick Facts
What This Study 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).
Key Numbers
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 They Did This
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.
Why This Research 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 Bigger Picture
The disconnect between animal and human findings suggests peripheral blood eCB levels may not capture central nervous system activity driving pain modulation.
What This Study Doesn't 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.
Questions This Raises
- ?Would CSF eCB levels show stronger associations?
- ?Do levels predict pain in chronic pain patients?
Trust & Context
- Key Stat:
- Only pressure pain thresholds correlated with blood endocannabinoid levels
- Evidence Grade:
- Well-designed study combining genetics, biochemistry, and psychophysics, but mostly null findings highlight limitations of peripheral eCB measurement.
- Study Age:
- Published in 2025.
- Original Title:
- The contribution of baseline circulating endocannabinoids to individual differences in human pain sensitivity: a quantitative sensory testing study.
- Published In:
- Pain (2025)
- Authors:
- 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
- Database ID:
- RTHC-06437
Evidence Hierarchy
A snapshot of a population at one point in time.
What do these levels mean? →Frequently Asked Questions
Do your natural cannabinoid levels affect pain?
In healthy adults, blood levels were not broadly associated with pain sensitivity. Only pressure pain showed a link to anandamide.
Does the FAAH gene variant affect pain?
In this study, FAAH C385A did not predict any pain sensitivity measures despite prior research suggesting it should.
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Cite This Study
https://rethinkthc.com/research/RTHC-06437APA
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
MLA
Fatemi, S A, et al. "The contribution of baseline circulating endocannabinoids to individual differences in human pain sensitivity: a quantitative sensory testing study.." Pain, 2025. https://doi.org/10.1097/j.pain.0000000000003850
RethinkTHC
RethinkTHC Research Database. "The contribution of baseline circulating endocannabinoids to..." RTHC-06437. Retrieved from https://rethinkthc.com/research/fatemi-2025-the-contribution-of-baseline
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.