Cannabis Use During Pregnancy Disrupted Blood Vessel Function in the Placenta

In placentas from cannabis users, the endocannabinoid system was altered and blood vessels lost their ability to relax in response to cannabinoids, while nitric oxide signaling was also greatly diminished.

Harhangi, Madhavi S et al.·Hypertension (Dallas·2025·Moderate Evidencelaboratory-study
RTHC-06635Laboratory StudyModerate Evidence2025RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
laboratory-study
Evidence
Moderate Evidence
Sample
Not reported

What This Study Found

The study found three distinct patterns: (1) In healthy pregnancies, anandamide relaxed placental arteries via CB1 and CB2 receptors. (2) In preeclampsia, endocannabinoid signaling was altered (lower 2-AG synthesis enzyme) but vessel relaxation was maintained through non-cannabinoid receptor pathways. (3) In cannabis users, endocannabinoid-mediated vessel relaxation was entirely absent, and nitric oxide (NO) signaling was greatly reduced. This provides a mechanistic explanation for why cannabis use during pregnancy is associated with preeclampsia and other vascular complications.

Key Numbers

Three groups compared (healthy, preeclampsia, cannabis users); cannabis users: complete loss of endocannabinoid-mediated vessel relaxation; greatly reduced NO signaling; preeclampsia: lower DAGL-alpha mRNA (2-AG synthesis); cannabis users: higher NAPE-PLD mRNA (AEA synthesis)

How They Did This

Placental biopsies from gestational age-matched healthy pregnant women, women with preeclampsia, and women who used cannabis throughout pregnancy. Measured ECS component mRNA levels, then tested vascular reactivity of chorionic plate arteries with endogenous and synthetic cannabinoid receptor agonists, with and without selective antagonists.

Why This Research Matters

This is the first study to show that cannabis use during pregnancy fundamentally disrupts both the placental endocannabinoid system and nitric oxide signaling in placental blood vessels. These are two critical systems for maintaining healthy placental blood flow.

The Bigger Picture

The finding that cannabis use eliminates the placenta's ability to respond to its own endocannabinoid system provides direct biological evidence against cannabis use during pregnancy, beyond the epidemiological associations already documented.

What This Study Doesn't Tell Us

Small sample sizes typical of placental tissue studies. Cannot determine whether vascular changes are from THC, CBD, other cannabinoids, or smoking. Cross-sectional tissue analysis cannot assess when changes occurred during pregnancy. Cannabis-using group may differ from non-users in other ways.

Questions This Raises

  • ?Are these placental vascular changes reversible if cannabis use stops during pregnancy?
  • ?Does CBD alone have the same placental effects as THC-containing cannabis?

Trust & Context

Key Stat:
Evidence Grade:
Moderate: rigorous multi-method laboratory study with clinical samples, but small numbers and cross-sectional design.
Study Age:
2025 publication
Original Title:
Placental Endocannabinoid System: Focus on Preeclampsia and Cannabis Use.
Published In:
Hypertension (Dallas, Tex. : 1979), 82(5), 804-815 (2025)
Database ID:
RTHC-06635

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study
What do these levels mean? →

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Cite This Study

RTHC-06635·https://rethinkthc.com/research/RTHC-06635

APA

Harhangi, Madhavi S; Simons, Sinno H P; Bijma, Hilmar H; Nguyen, Anna; Nguyen, Tuong-Vi; Kaitu'u-Lino, Tu'uhevaha; Reiss, Irwin K M; Jan Danser, A H; Broekhuizen, Michelle. (2025). Placental Endocannabinoid System: Focus on Preeclampsia and Cannabis Use.. Hypertension (Dallas, Tex. : 1979), 82(5), 804-815. https://doi.org/10.1161/HYPERTENSIONAHA.125.24934

MLA

Harhangi, Madhavi S, et al. "Placental Endocannabinoid System: Focus on Preeclampsia and Cannabis Use.." Hypertension (Dallas, 2025. https://doi.org/10.1161/HYPERTENSIONAHA.125.24934

RethinkTHC

RethinkTHC Research Database. "Placental Endocannabinoid System: Focus on Preeclampsia and ..." RTHC-06635. Retrieved from https://rethinkthc.com/research/harhangi-2025-placental-endocannabinoid-system-focus

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.