Synthetic cannabinoids and THC kill placental cells through programmed cell death
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.
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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.
Why This Research 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 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.
What This Study Doesn't 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.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- Synthetic cannabinoids more potent than THC at killing placental cells
- Evidence Grade:
- Well-designed in vitro study, but cell line data cannot directly predict clinical outcomes.
- Study Age:
- 2020 in vitro study.
- Original Title:
- Synthetic cannabinoids JWH-018, JWH-122, UR-144 and the phytocannabinoid THC activate apoptosis in placental cells.
- Published In:
- Toxicology letters, 319, 129-137 (2020)
- Authors:
- Almada, Marta, Alves, Patrícia, Fonseca, Bruno M(4), Carvalho, Félix, Queirós, Cláudio R, Gaspar, Helena, Amaral, Cristina, Teixeira, Natércia A, Correia-da-Silva, Georgina
- Database ID:
- RTHC-02378
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
Can cannabis harm the placenta?
This lab study found that THC and three synthetic cannabinoids all triggered programmed cell death in human placental cells, with synthetic cannabinoids being more potent than THC.
Are synthetic cannabinoids worse than THC during pregnancy?
In this cell study, synthetic cannabinoids disrupted placental cells at lower concentrations than THC, suggesting they may pose greater risk, though this has not been confirmed in human pregnancies.
Read More on RethinkTHC
Cite This Study
https://rethinkthc.com/research/RTHC-02378APA
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
MLA
Almada, Marta, et al. "Synthetic cannabinoids JWH-018, JWH-122, UR-144 and the phytocannabinoid THC activate apoptosis in placental cells.." Toxicology letters, 2020. https://doi.org/10.1016/j.toxlet.2019.11.004
RethinkTHC
RethinkTHC Research Database. "Synthetic cannabinoids JWH-018, JWH-122, UR-144 and the phyt..." RTHC-02378. Retrieved from https://rethinkthc.com/research/almada-2020-synthetic-cannabinoids-jwh018-jwh122
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.