Prenatal THC and maternal infection each impaired offspring cognition through different cannabinoid receptors in mice
THC exposure during pregnancy impaired adult offspring cognition via CB1 receptors, while maternal immune activation operated through CB2 receptors, and surprisingly, combining both exposures cancelled out the cognitive deficits.
Quick Facts
What This Study Found
PCE impaired novel object recognition and working memory in males via CB1 receptors; MIA impaired the same tasks via CB2 receptors; combined PCE+MIA did not produce cognitive deficits; CB2 knockout prevented the protective effect of combined exposure.
Key Numbers
THC 3 mg/kg daily from GD5 to PND10; Poly I:C at GD16.5; male offspring showed impaired novel object recognition and working memory from either PCE or MIA alone; females showed more modest changes; combined exposure negated deficits in wildtype males.
How They Did This
Compared wildtype, CB1 knockout, and CB2 knockout mice across four conditions: control, perinatal cannabis exposure (3 mg/kg THC daily GD5-PND10), maternal immune activation (Poly I:C at GD16.5), and combined; tested adult offspring on emotional and cognitive behaviors.
Why This Research Matters
Many pregnant women face both infection and cannabis exposure, and understanding how these interact at the receptor level is important for assessing combined risk.
The Bigger Picture
The finding that two harmful exposures can paradoxically cancel each other out reveals unexpected complexity in how prenatal insults interact, with implications for risk assessment in real-world scenarios.
What This Study Doesn't Tell Us
Mouse model; single THC dose level; MIA model using Poly I:C may not fully represent human infections; the protective effect of combined exposure may not translate to humans; behavioral tests capture limited cognitive domains.
Questions This Raises
- ?What mechanism allows combined PCE and MIA to cancel cognitive deficits?
- ?Does this paradoxical protection occur in humans?
- ?Would different THC doses or infection timing change the interaction?
Trust & Context
- Key Stat:
- Combined prenatal THC and maternal infection paradoxically cancelled cognitive deficits seen with either exposure alone
- Evidence Grade:
- Well-designed knockout study with multiple comparison groups and sex-stratified analysis, but single THC dose and mouse model limit clinical translation.
- Study Age:
- Published 2025
- Original Title:
- CB1 and CB2 receptors differentially modulate the cognitive impact of maternal immune activation and perinatal cannabinoid exposure.
- Published In:
- Behavioural brain research, 485, 115543 (2025)
- Authors:
- Chen, Han-Ting, Mackie, Ken(22)
- Database ID:
- RTHC-06199
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
Did prenatal THC affect offspring brain function?
Yes. Male offspring exposed to THC during pregnancy and early life showed impaired object recognition and working memory as adults, and this required CB1 receptors.
What happened when both THC and infection were present?
Surprisingly, combining prenatal THC exposure with maternal immune activation cancelled the cognitive deficits seen with either exposure alone. CB2 receptors were necessary for this protective interaction.
Read More on RethinkTHC
Cite This Study
https://rethinkthc.com/research/RTHC-06199APA
Chen, Han-Ting; Mackie, Ken. (2025). CB1 and CB2 receptors differentially modulate the cognitive impact of maternal immune activation and perinatal cannabinoid exposure.. Behavioural brain research, 485, 115543. https://doi.org/10.1016/j.bbr.2025.115543
MLA
Chen, Han-Ting, et al. "CB1 and CB2 receptors differentially modulate the cognitive impact of maternal immune activation and perinatal cannabinoid exposure.." Behavioural brain research, 2025. https://doi.org/10.1016/j.bbr.2025.115543
RethinkTHC
RethinkTHC Research Database. "CB1 and CB2 receptors differentially modulate the cognitive ..." RTHC-06199. Retrieved from https://rethinkthc.com/research/chen-2025-cb1-and-cb2-receptors
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.