Δ9-Tetrahydrocannabinol Modulates Hippocampal Neurogenesis in Female Wistar Rats: Interaction with Estradiol.
Duarte R Carvalhinho, Sandra I Marques, Sandra Leal, Bruno M Fonseca, José P Andrade, Susana I Sá
Neurochemical Research August 8, 2026 DOI: 10.1007/s11064-026-04857-w (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Sample size | 16 |
| Population | Ovariectomized female Wistar rats |
| Interventions | THC estradiol benzoate |
| Measures | Ki-67, doublecortin, PSA-NCAM, CB1, COX-2, TNF-α |
| Topics | Cannabis Neuroplasticity |
| Keywords | Endocannabinoid system Estradiol Female rats Hippocampal neurogenesis Inflammation |
| Key findings | THC increased hippocampal Ki-67 immunoreactivity, suggesting enhanced cell proliferation, and reduced COX-2 and TNF-α expression in a region-dependent manner in ovariectomized female rats. Combined THC and estradiol benzoate significantly increased CB1 receptor expression in the dentate gyrus and hilus, and a trend toward increased doublecortin expression appeared, particularly with estradiol. The authors argue some effects depend on estradiol status. |
Abstract
The endocannabinoid system (ECS) plays a key role in regulating neurogenesis and inflammatory processes in the brain. The increasing prevalence of Cannabis use among women highlights the importance of understanding sex-specific effects of cannabinoids, particularly in the context of hormonal interactions. This study aimed to investigate the effects of delta-9-tetrahydrocannabinol (THC) and estradiol benzoate (EB) on adult hippocampal neurogenesis (AHN) and inflammation in ovariectomized female Wistar rats. Sixteen rats were allocated to four experimental groups receiving THC, EB, both treatments, and vehicle. Immunohistochemical analyses were conducted to evaluate markers of proliferation (Ki-67), neurogenesis (doublecortin and PSA-NCAM), cannabinoid receptor expression (CB1), and inflammation (COX-2 and TNF-α) in the hippocampal formation. The administration of THC significantly increased Ki-67 immunoreactivity, suggesting enhanced cell proliferation. A trend toward increased doublecortin expression was observed, particularly in EB-treated animals. THC also modulated CB1 receptor expression, with significant increases in the dentate gyrus and hilus following combined THC and EB treatment. Furthermore, THC reduced inflammatory markers, with region-dependent decreases in COX-2 and TNF-α expression. These findings indicate that THC influences markers associated with hippocampal cell proliferation, neurogenesis, cannabinoid signaling and inflammation in female rats, and that some of these effects depend on estradiol status. The interaction between cannabinoids and gonadal hormones may represent an important mechanism underlying sex-specific neurobiological responses and suggests potential targets for therapeutic intervention in neuropsychiatric disorders.
Comparable studies
Other preclinical and animal studies on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Mice | 2023 | Experimental study | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study | |
| The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro Progenitor cells from subventricular and subgranular zones of adult mice brains | 2017 | In vitro experimental study | |
| N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Mice | 2020 | In vitro and in vivo experimental study |
Citations in the library
Cites 6
- Prenatal Exposure to Δ9-Tetrahydrocannabinol Affects Hippocampus-Related Cognitive Functions in the Adolescent Rat Offspring: Focus on Specific Markers of Neuroplasticity. Pharmaceutics February 17, 2023
- Effect of Cannabis on Memory Consolidation, Learning and Retrieval and Its Current Legal Status in India: A Review. Biomolecules January 12, 2023
- Dos(e)Age: Role of Dose and Age in the Long-Term Effect of Cannabinoids on Cognition Molecules February 1, 2022
- Biphasic effects of THC in memory and cognition. European journal of clinical investigation May 2018
- Sex, drugs, and adult neurogenesis: sex-dependent effects of escalating adolescent cannabinoid exposure on adult hippocampal neurogenesis, stress reactivity, and amphetamine sensitization. Hippocampus March 2014
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