In pregnant rats, injected THC and CBD increased pro-inflammatory markers in placental and fetal brain tissue, while smoked cannabis generally reduced them, highlighting how the route of administration changes outcomes.
Reproductive toxicology researchers, prenatal cannabis researchers, preclinical pharmacologists
Injected vs. smoked cannabinoids produced opposite inflammatory effects in fetal tissue
What the researchers found
Pregnant rats exposed to high-THC or high-CBD cannabis smoke from gestational day 6-20 showed different inflammatory profiles than those receiving injected THC or CBD. Injected cannabinoids upregulated pro-inflammatory cytokines in placental and fetal brain tissue, while smoke exposure reduced cytokine and chemokine concentrations. Injection also led to fewer offspring and more uterine reabsorption events.
Why it matters
Most preclinical cannabis-pregnancy research uses injected pure cannabinoids, but most human use involves smoking. This study shows these routes produce opposite inflammatory effects, calling into question how well injection studies translate to real-world exposures.
The numbers in context
High-THC smoke: 18% THC, 0.1% CBD; high-CBD smoke: 0.7% THC, 13% CBD; injected doses: 3 mg/kg THC, 10 mg/kg CBD; treatment period: gestational day 6-20
How the study worked
Pregnant Sprague-Dawley rats were treated daily from gestational day 6-20 with room air, vehicle, high-THC smoke (18% THC, 0.1% CBD), high-CBD smoke (0.7% THC, 13% CBD), injected THC (3 mg/kg), or injected CBD (10 mg/kg). Plasma cannabinoid levels, cytokine profiles, and reproductive outcomes were assessed.
What this study cannot tell us
Rat model may not translate directly to human pregnancy. Smoke exposure involves combustion products beyond cannabinoids. Specific cannabinoid doses delivered via smoke are harder to control than injections.
How to read the evidence
Well-controlled animal study with multiple exposure routes, but rat model and combustion variables limit direct human translation.
When this study was published
Published 2023
The bigger picture
The divergent effects by route of administration suggest that the large body of preclinical research using injected cannabinoids may not accurately predict what happens when pregnant people smoke cannabis.
Questions still open
- What drives the opposite inflammatory responses between smoked and injected cannabinoids? Do these route-dependent differences persist in offspring developmental outcomes?
Common questions
Does the way cannabis is consumed matter during pregnancy?
Did cannabis smoke or injection cause more reproductive harm in rats?
Read the original research
Characterization of cannabinoid plasma concentration, maternal health, and cytokine levels in a rat model of prenatal Cannabis smoke exposure.
Scientific reports, 13(1), 21070
Citation
Black, Tallan; Baccetto, Sarah L; Barnard, Ilne L; Finch, Emma; McElroy, Dan L; Austin-Scott, Faith V L; Greba, Quentin; Michel, Deborah; Zagzoog, Ayat; Howland, John G; Laprairie, Robert B. (2023). Characterization of cannabinoid plasma concentration, maternal health, and cytokine levels in a rat model of prenatal Cannabis smoke exposure.. Scientific reports, 13(1), 21070. https://doi.org/10.1038/s41598-023-47861-8
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