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Adult Rat Offspring Exposed to THC during Gestation Exhibit Distinct Biomolecular Changes Identified by X-ray Fluorescence Imaging and Fourier Transform Infrared Spectroscopy in Cortico-Limbic Circuits.

Tallan Black, Rhiannon E Boseley, Amanda Quirk, Kaylen M. Young, Sarah Lunardi-Baccetto, Brett D Muyres, Robert B. Laprairie, John G. Howland

ACS Chemical Neuroscience February 18, 2026 DOI: 10.1021/acschemneuro.5c00752 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Experimental animal study Peer reviewed
Population Rat offspring exposed prenatally to THC or vehicle
Intervention THC
Dose 3 mg/kg
Topics Cannabis
Keywords Gestational Neurodevelopment Phytocannabinoids Prenatal Δ-9-tetrahydrocannabinol
Key findings Gestational THC exposure led to decreased copper in the corpus callosum and altered lipid and protein composition in brain regions including the hippocampus, corpus callosum, and lateral ventricle.

Abstract

Perspectives surrounding Cannabis use have transformed over the past decade. This shift in perspective has been noted in pregnant populations in Canada and the US, where various investigations report that the use of Cannabis in pregnancy is increasingly commonplace. There is some evidence indicating that Δ9-tetrahydrocannabinol (THC), the main intoxicating phytocannabinoid found within Cannabis flower, may influence the biochemical composition of lipids within the developing fetal brain. The aim of this study was to apply multimodal biospectroscopic imaging techniques, X-ray fluorescence imaging (XFI) and Fourier transform mid-infrared spectromicroscopy (FTIR), to investigate the biochemical and biomolecular changes underlying the distinct behavioral phenotypes identified previously. XFI was used to investigate the presence of metal, nonmetal, and alkali dysregulation, while FTIR provided information on neurochemical dysbiosis within the brains of offspring exposed to THC (3 mg/kg; i.p.) or vehicle (VEH). The THC offspring exhibited decreased copper (Cu) concentrations within the perimeter of their corpus callosum, as identified by XFI. FTIR hyperspectral data from the brain revealed noteworthy changes in peaks associated with lipid methylene (CH2as), carbohydrates, and peak ratios identifying changes in the lipid structure and the relative content of lipids, cholesterol esters, and cholesterols to saturated fatty acids. These changes were particularly evident in the hippocampus, where THC offspring exhibited increased CH2as, lipid esters, phosphate, protein, and unsaturation levels of lipids. The biochemical changes seen in the FTIR spectra were modest, with THC offspring showing an increase in the number of structural changes of lipids in the corpus callosum and an increase in protein in the lateral ventricle. This study supports the usefulness of these techniques to detect subtle changes in biomolecular composition within brain tissues exposed to gestational THC. These results contribute to the growing body of knowledge unraveling the complex effects of THC on fetal neurodevelopmental trajectories.

Comparable studies

Other preclinical and animal studies on cannabis, most cited first.

Study Year Design Participants
Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors Mice 2015 Preclinical study
Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). hMDR1- and hBCRP-transfected HEK293 cells and hMDR1- and hBCRP-MDCKII cells 2010 In vitro study
Long-term hippocampal interneuronopathy drives sex-dimorphic spatial memory impairment induced by prenatal THC exposure Mice prenatally exposed to THC, including conditional CB1R knockout mice 2020 Animal experimental study
Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway Mice exposed to chronic THC early in life 2018 Animal experimental study
Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain Spontaneously hypertensive rats (SHRs) and Wistar rats 2014 Animal experimental study

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