Sexually Dimorphic Effects of a Single Neonatal Δ9-tetrahydrocannabinol Exposure on Neuronal Dendritic Morphology and Cognitive Functions in Rats.
Meetu Wadhwa, Gregory A Chinn, Katrina Duong, Jennifer Sasaki Russell, Judith Hellman, Jeffrey W Sall
Cannabis and Cannabinoid Research February 1, 2026 DOI: 10.1177/25785125251387835 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Male and female Sprague Dawley rat pups |
| Intervention | THC |
| Dose | 5 mg/kg |
| Duration | Single injection at postnatal day 3; behavioral testing at postnatal weeks 6-8 |
| Topics | Cannabis Neuroplasticity |
| Keywords | Cannabinoids Cortex Dendrite Hippocampus Pyramidal neurons Sexual dimorphism Spatial memory |
| Key findings | Neonatal THC exposure induced spatial memory deficits in female but not male rats and reduced dendritic complexity and spine density in cortical and hippocampal neurons of both sexes. |
Abstract
Cannabis consumption among adults, including pregnant and breastfeeding women, continues to rise. However, the long-term effects of early-life exposure to cannabinoids on brain development remain unclear. Δ9-tetrahydrocannabinol (THC) is the main psychoactive cannabinoid in cannabis and is an agonist of cannabinoid type 1 receptor, a critical component of the endocannabinoid system (ECS) that functions in normal pre- and postnatal brain development. We hypothesized that perinatal exposure to THC perturbs ECS-regulated neurodevelopment and leads to lasting cognitive effects in later life. Male and female Sprague Dawley rat pups received a single intraperitoneal injection of THC (5 mg/kg) or vehicle (sesame oil) at postnatal day 3. At postnatal weeks 6-8, animals were assessed for spatial memory and anxiety-like behavior using the Barnes maze, open field, and elevated plus maze. Following behavioral testing, brains were processed using Golgi-Cox staining to examine dendritic morphology and spine density in the frontal cortex and hippocampus. THC exposure during the neonatal period induced a spatial memory deficit later in young adult female, but not male, rats. Anxiety-like behavior was not altered in either sex. THC-exposed animals of both sexes exhibited decreased spine density reductions, as well as decreases in dendritic length, branching, and complexity in cortical and hippocampal (cornu ammonis 1 [CA1], CA3, dentate gyrus) neurons. These findings demonstrate that a single neonatal THC exposure induces long-lasting, sex-dependent cognitive impairment and structural alterations in cortical and hippocampal neurons in rats. Our results underscore the vulnerability of the developing brain to cannabinoid exposure.
Comparable studies
Other experimental studies on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Smoked Cannabis' Psychomotor and Neurocognitive Effects in Occasional and Frequent Smokers Occasional (<2x/week) and frequent (≥4x/week) cannabis smokers | 2015 | Controlled within-subjects study | n = 25 |
| Dissociable effects of cannabis with and without cannabidiol on the human brain’s resting-state functional connectivity Healthy volunteers experienced with cannabis but not regular users | 2019 | Within-subjects experimental design | n = 17 |
| Which biological and self-report measures of cannabis use predict cannabis dependency and acute psychotic-like effects? Young cannabis users | 2018 | Observational study (naturalistic, within-subject counterbalanced design) | n = 410 |
| Cannabis Essential Oil: A Preliminary Study for the Evaluation of the Brain Effects Healthy volunteers | 2018 | Experimental study | n = 5 |
| Coming off cannabis: a cognitive and magnetic resonance imaging study in patients with multiple sclerosis Patients with multiple sclerosis who began using cannabis after disease onset, used it... | 2019 | Quasi-experimental study with odd-even allocation | n = 40 |
Citations in the library
Cites 5
- THC and CBD: Similarities and differences between siblings. Neuron February 1, 2023
- Cannabis and synaptic reprogramming of the developing brain. Nature Reviews Neuroscience July 2021
- Prenatal THC exposure produces a hyperdopaminergic phenotype rescued by pregnenolone Nature Neuroscience September 11, 2019
- Persistent inhibitory circuit defects and disrupted social behaviour following in utero exogenous cannabinoid exposure. Molecular Psychiatry January 2017
- The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. British Journal of Pharmacology January 2008