The long-term effects of adolescent Δ9-tetrahydrocannabinol on brain structure and function assessed through neuroimaging techniques in male and female rats

Orihuel, Javier; Capellán, Roberto; Casquero-Veiga, Marta; Soto-Montenegro, María Luisa; Desco, Manuel; Oteo-Vives, Marta; Ibáñez-Moragues, Marta; Magro-Calvo, Natalia; Luján, Víctor M.; Morcillo, Miguel Ángel; Ambrosio, Emilio; Higuera-Matas, Alejandro

doi:10.1016/j.euroneuro.2023.05.005

Cited by 2 publications

(1 citation statement)

References 79 publications

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“…Cannabis, primarily through the psychoactive compound delta-9-tetrahydrocannabinol (THC), interacts with the developing endocannabinoid system (ECS) during adolescence, a period marked by ECS maturation and a higher density of CB1 receptors in the brain. Preclinical evidence suggests that the activation of CB1 receptors may play a crucial role in regulating structural brain development, influencing synaptic plasticity and impacting processes like synaptic pruning, dendritic arborization, and synaptogenesis, thereby shaping the brain’s structural organization [ 51 , 52 ]. Studies involving adolescents and emerging adults have reported varying findings regarding the impact of cannabis use [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

The Combined Effects of Nicotine and Cannabis on Cortical Thickness Estimates in Adolescents and Emerging Adults

Hernandez Mejia,

Courtney,

Wade

et al. 2024

Brain Sciences

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Early life substance use, including cannabis and nicotine, may result in deleterious effects on the maturation of brain tissue and gray matter cortical development. The current study employed linear regression models to investigate the main and interactive effects of past-year nicotine and cannabis use on gray matter cortical thickness estimates in 11 bilateral independent frontal cortical regions in 223 16–22-year-olds. As the frontal cortex develops throughout late adolescence and young adulthood, this period becomes crucial for studying the impact of substance use on brain structure. The distinct effects of nicotine and cannabis use status on cortical thickness were found bilaterally, as cannabis and nicotine users both had thinner cortices than non-users. Interactions between nicotine and cannabis were also observed, in which cannabis use was associated with thicker cortices for those with a history of nicotine and tobacco product (NTP) use in three left frontal regions. This study sheds light on the intricate relationship between substance use and brain structure, suggesting a potential modulation of cannabis’ impact on cortical thickness by nicotine exposure, and emphasizing the need for further longitudinal research to characterize these interactions and their implications for brain health and development.

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Section: Discussionmentioning

confidence: 99%

The Combined Effects of Nicotine and Cannabis on Cortical Thickness Estimates in Adolescents and Emerging Adults

Hernandez Mejia,

Courtney,

Wade

et al. 2024

Brain Sciences

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A hidden mark of a troubled past: neuroimaging and transcriptomic analyses reveal interactive effects of maternal immune activation and adolescent THC exposure in the absence of overt behavioural disruptions

Moreno-Fernández,

Luján,

Baliyan

et al. 2024

Preprint

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Maternal exposure to infections during gestation has been shown to predispose individuals to the development of schizophrenia. Additionally, clinical data suggest that cannabis use could trigger the onset of schizophrenia in vulnerable individuals. However, the direction of causality remains unclear. To elucidate this issue, we utilised a rat model of maternal immune activation, combined with exposure to increasing doses of THC during adolescence, in both male and female rats. We investigated several behaviours in adulthood that resemble specific symptoms of schizophrenia, including impairments in working memory, deficits in sensorimotor gating, alterations in social behaviour, anhedonia, and potential changes in implicit learning (conditioned taste aversion). Furthermore, we conducted a longitudinal positron emission tomography (PET) study to identify affected brain regions and subsequently collected brain samples from one of these regions (the orbitofrontal cortex) for RNA sequencing analyses. These analyses were also performed on peripheral blood mononuclear cells to identify peripheral biomarkers. Notably, while no overt behavioural disruptions were observed, our PET scans revealed several brain alterations dependent on the combination of both exposures. Additionally, the transcriptomic studies demonstrated that maternal immune activation affected glutamatergic and serotoninergic genes, with the combination of both exposures shifting the expression from down-regulation to up-regulation. In peripheral cells, interactive effects were observed on inflammatory pathways, and some genes were proposed as biomarkers of the disease. These results suggest that the combination of these two vulnerability factors leaves a lasting mark on the body, potentially predisposing individuals to the disease even before behavioural alterations manifest.

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The long-term effects of adolescent Δ9-tetrahydrocannabinol on brain structure and function assessed through neuroimaging techniques in male and female rats

Cited by 2 publications

References 79 publications

The Combined Effects of Nicotine and Cannabis on Cortical Thickness Estimates in Adolescents and Emerging Adults

The Combined Effects of Nicotine and Cannabis on Cortical Thickness Estimates in Adolescents and Emerging Adults

A hidden mark of a troubled past: neuroimaging and transcriptomic analyses reveal interactive effects of maternal immune activation and adolescent THC exposure in the absence of overt behavioural disruptions

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