Three synthetic cannabinoids (JWH-018, JWH-122, UR-144) and THC all triggered programmed cell death in human placental cells, with synthetic cannabinoids being more potent than THC, raising concerns about use during pregnancy.
Pregnant women, researchers studying pregnancy outcomes, and toxicologists.
Synthetic cannabinoids more potent than THC at killing placental cells
What the researchers found
All four cannabinoids decreased cell viability without membrane damage (indicating apoptosis, not necrosis). Cell cycle arrest at G2/M phase was observed. JWH-018 and JWH-122 increased reactive oxygen species. THC, UR-144, and JWH-122 caused mitochondrial membrane potential loss. All compounds activated caspase-9 and caspase-3/-7 (apoptotic markers). The mechanisms varied: UR-144 acted through CB1 only, JWH-018 and THC through both CB1 and CB2, and JWH-122 was receptor-independent.
Why it matters
Placental trophoblast turnover relies on balanced proliferation and apoptosis. Cannabinoid-induced apoptosis could disrupt normal placental development, potentially explaining associations between cannabis use and adverse pregnancy outcomes.
The numbers in context
Four cannabinoids tested. All induced caspase-9 and caspase-3/-7 activation. Synthetic cannabinoids affected cells at lower concentrations than THC. Three different receptor-mediated mechanisms identified.
How the study worked
In vitro study using BeWo human placental cytotrophoblast cell line. Cells were exposed to synthetic cannabinoids (JWH-018, JWH-122, UR-144) and THC. Cell viability, cell cycle, ROS, mitochondrial function, and caspase activation were measured.
What this study cannot tell us
In vitro study using a cell line, not intact placental tissue. Concentrations used may not reflect physiological levels. Cannot directly predict in vivo pregnancy outcomes.
How to read the evidence
Well-designed in vitro study, but cell line data cannot directly predict clinical outcomes.
When this study was published
2020 in vitro study.
The bigger picture
Synthetic cannabinoids are increasingly used recreationally, including by women of childbearing age. Their greater potency at disrupting placental cells compared to THC suggests potentially greater pregnancy risk.
Questions still open
- Do these effects occur at the cannabinoid concentrations actually reached in the placenta during use? Are the effects reversible or do they cause permanent placental damage?
Common questions
Can cannabis harm the placenta?
Are synthetic cannabinoids worse than THC during pregnancy?
Read the original research
Synthetic cannabinoids JWH-018, JWH-122, UR-144 and the phytocannabinoid THC activate apoptosis in placental cells.
Toxicology letters, 319, 129-137
Citation
Almada, Marta; Alves, Patrícia; Fonseca, Bruno M; Carvalho, Félix; Queirós, Cláudio R; Gaspar, Helena; Amaral, Cristina; Teixeira, Natércia A; Correia-da-Silva, Georgina. (2020). Synthetic cannabinoids JWH-018, JWH-122, UR-144 and the phytocannabinoid THC activate apoptosis in placental cells.. Toxicology letters, 319, 129-137. https://doi.org/10.1016/j.toxlet.2019.11.004
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