CBD Raises Anandamide Levels But This Does Not Explain Its Blood Pressure-Lowering Effect

In a crossover RCT of 66 hypertensive patients, CBD raised anandamide levels but this did not correlate with blood pressure reduction, suggesting other mechanisms.

Kumric, Marko et al.·Cannabis and cannabinoid research·2025·Strong EvidenceRandomized Controlled Trial
RTHC-06874Randomized Controlled TrialStrong Evidence2025RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Randomized Controlled Trial
Evidence
Strong Evidence
Sample
N=66

What This Study Found

CBD (225-450 mg/day, 5 weeks) increased AEA by 11.1 ng/mL (p=0.025). AEA change did not correlate with systolic BP change (r=-0.106, p=0.428). BMI, antihypertensives, and glucose predicted AEA increase; BP reduction did not. No 2-AG effect.

Key Numbers

66 patients; AEA +11.1 ng/mL (p=0.025); BP correlation r=-0.106 (p=0.428); no 2-AG effect (p=0.478).

How They Did This

Sub-analysis of HYPER-H21-4 crossover RCT. 66 hypertensive patients. CBD vs. placebo for 5 weeks each. AEA and 2-AG measured.

Why This Research Matters

Dissociates CBD's endocannabinoid effects from its cardiovascular effects, redirecting mechanistic research.

The Bigger Picture

CBD affects the endocannabinoid system and lowers blood pressure, but these may be independent effects.

What This Study Doesn't Tell Us

Plasma may not reflect tissue changes. 5-week period. Only two endocannabinoids measured.

Questions This Raises

  • ?What mechanism drives CBD blood pressure effects?
  • ?Do tissue endocannabinoid changes correlate with BP?

Trust & Context

Key Stat:
AEA rose 11.1 ng/mL but did not predict BP change
Evidence Grade:
Well-designed crossover RCT. Plasma measurements may not capture full picture.
Study Age:
2025 sub-analysis of the landmark HYPER-H21-4 CBD-hypertension trial.
Original Title:
Can Endocannabinoids Explain CBD-Mediated Reduction in Blood Pressure? Insights from a Randomized, Placebo-Controlled, Crossover Trial.
Published In:
Cannabis and cannabinoid research (2025)
Database ID:
RTHC-06874

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled TrialGold standard for testing treatments
This study
Cohort / Case-Control
Cross-Sectional / Observational
Case Report / Animal Study

Participants are randomly assigned to treatment or placebo groups to test cause and effect.

What do these levels mean? →

Frequently Asked Questions

Does CBD lower blood pressure via endocannabinoids?

CBD raised anandamide but this did not correlate with BP reduction, suggesting a different mechanism.

Does CBD affect endocannabinoid levels?

Yes, it raised anandamide but not 2-AG.

Read More on RethinkTHC

Cite This Study

RTHC-06874·https://rethinkthc.com/research/RTHC-06874

APA

Kumric, Marko; Dujic, Goran; Vrdoljak, Josip; Supe Domic, Daniela; Dujic, Zeljko; Bozic, Josko. (2025). Can Endocannabinoids Explain CBD-Mediated Reduction in Blood Pressure? Insights from a Randomized, Placebo-Controlled, Crossover Trial.. Cannabis and cannabinoid research. https://doi.org/10.1177/25785125251392773

MLA

Kumric, Marko, et al. "Can Endocannabinoids Explain CBD-Mediated Reduction in Blood Pressure? Insights from a Randomized, Placebo-Controlled, Crossover Trial.." Cannabis and cannabinoid research, 2025. https://doi.org/10.1177/25785125251392773

RethinkTHC

RethinkTHC Research Database. "Can Endocannabinoids Explain CBD-Mediated Reduction in Blood..." RTHC-06874. Retrieved from https://rethinkthc.com/research/kumric-2025-can-endocannabinoids-explain-cbdmediated

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.