Related Experiment Video
Updated: Aug 10, 2026
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Preclinical Model of Prenatal Delta-9-Tetrahydrocannabinol Exposure to Assess Its Impact on Neurodevelopmental Outcomes
Published on: February 28, 2025
Δ9-Tetrahydrocannabinol Modulates Hippocampal Neurogenesis in Female Wistar Rats: Interaction with Estradiol
Duarte R Carvalhinho1, Sandra I Marques2,3, Sandra Leal3,4
1Unit of Anatomy, Department of Biomedicine, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.
Neurochemical Research
|August 8, 2026
Summary
Delta-9-tetrahydrocannabinol (THC) promotes cell proliferation and reduces inflammation in the female rat hippocampus. These effects are influenced by estradiol, suggesting hormone interactions in cannabinoid neurobiology.
Area of Science:
- Neuroscience
- Endocrinology
- Pharmacology
Background:
- The endocannabinoid system (ECS) is crucial for brain neurogenesis and inflammation.
- Cannabis use is rising, necessitating research into sex-specific cannabinoid effects, especially concerning hormonal interactions.
Purpose of the Study:
- To investigate the impact of delta-9-tetrahydrocannabinol (THC) and estradiol benzoate (EB) on adult hippocampal neurogenesis (AHN) and inflammation.
- To explore sex-specific neurobiological responses and potential therapeutic targets in neuropsychiatric disorders.
Main Methods:
- Ovariectomized female Wistar rats were used, divided into four groups: THC, EB, combined THC+EB, and vehicle.
- Immunohistochemistry assessed markers for proliferation (Ki-67), neurogenesis (doublecortin, PSA-NCAM), cannabinoid receptor 1 (CB1), and inflammation (COX-2, TNF-α) in the hippocampus.
Main Results:
- THC significantly increased Ki-67, indicating enhanced cell proliferation.
- A trend of increased doublecortin expression was noted, particularly with EB treatment.
- THC modulated CB1 receptor expression, with combined THC+EB showing significant increases in the dentate gyrus and hilus.
- THC reduced inflammatory markers (COX-2, TNF-α) in a region-dependent manner.
Conclusions:
- THC influences hippocampal cell proliferation, neurogenesis, cannabinoid signaling, and inflammation in female rats.
- Estradiol status affects some of these THC-induced changes.
- The interaction between cannabinoids and gonadal hormones is a key mechanism for sex-specific neurobiological responses and potential therapeutic strategies.
