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.
OB-GYN providers, placental researchers, cannabis-using pregnant individuals
What the researchers 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.
Why it 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 numbers in context
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 the study worked
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.
What this study cannot 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.
How to read the evidence
Moderate: rigorous multi-method laboratory study with clinical samples, but small numbers and cross-sectional design.
When this study was published
2025 publication
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.
Questions still open
- Are these placental vascular changes reversible if cannabis use stops during pregnancy?
- Does CBD alone have the same placental effects as THC-containing cannabis?
Read the original research
Placental Endocannabinoid System: Focus on Preeclampsia and Cannabis Use.
Hypertension (Dallas, Tex. : 1979), 82(5), 804-815
Citation
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
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