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.
Quick Facts
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)
- Authors:
- Harhangi, Madhavi S(2), Simons, Sinno H P(2), Bijma, Hilmar H(2), Nguyen, Anna, Nguyen, Tuong-Vi, Kaitu'u-Lino, Tu'uhevaha, Reiss, Irwin K M, Jan Danser, A H, Broekhuizen, Michelle
- Database ID:
- RTHC-06635
Evidence Hierarchy
Read More on RethinkTHC
Cite This Study
https://rethinkthc.com/research/RTHC-06635APA
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.