Cannabis in Adolescence: Lasting Cognitive Alterations and Underlying Mechanisms

Scheyer, Andrew F.; Laviolette, Steven R.; Pélissier, A.; Manzoni, Olivier J.

doi:10.1089/can.2022.0183

Cited by 8 publications

(17 citation statements)

References 115 publications

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“…Might THC, which also acts via CBRs, disrupt this age-dependent ECB signaling system and thus leave long-lasting consequences on the brain? If so, the adolescent- developing PFC (Spear, 2000; Peters et al, 2021; Scheyer et al, 2023), and its dopaminergic inputs from ventral tegmental area (VTA), which are actively innervating during this period (Manitt et al, 2011; Hoops and Flores, 2017; Reynolds et al, 2018), are a likely candidate for cognition-relevant neurodevelopmental insults caused by adolescent THC (Renard et al, 2016; Renard et al, 2017; Molla and Tseng, 2020).…”

Section: Introductionmentioning

confidence: 99%

Adolescent THC impacts on mPFC dopamine-mediated cognitive processes in male and female rats

Martinez,

Alizo Vera,

Ruiz

et al. 2024

Preprint

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Adolescent use of cannabis is linked to later-life changes in cognition, learning, and memory. Rodent models suggest this could be a causal effect of Δ9-tetrahydrocannabinol (THC) influencing the development of circuits underlying these processes, especially for the prefrontal cortex (PFC) which undergoes maturation during adolescence. Here we examined how two weeks of daily exposure to THC (5mg/kg IP) during adolescence persistently impacts cognitive processes involving mPFC dopamine. In male and female Long Evans rats treated in adolescence with THC or vehicle, we quantify acquisition of, and stable performance in two mPFC dopamine-dependent cognitive tasks—attentional set shifting and probability-based reward discounting. We also determined how acute pharmacological or chemogenetic augmentation of dopamine signaling impacts cognition in both groups and both sexes. We found that adolescent THC (AdoTHC) sex-dependently impacts acquisition of cue-guided instrumental reward seeking, but has minimal effects on set-shifting or probability discounting in either sex. When we challenged dopamine circuits by acutely potentiating monoamine signaling with amphetamine (0, 0.25, 0.5 mg/kg) during probability discounting, we confirmed prior findings that amphetamine reduced discounting of improbable reward options, and further showed that this amphetamine effect was more robust in rats with a history of adolescent THC. We next asked whether this potentiated effect of amphetamine involves AdoTHC impacts on dopamine circuits in particular, by attempting to recapitulate the amphetamine effect using more specific chemogenetic stimulation of VTA dopamine neurons. In contrast, we found that neither acute chemogenetic stimulation of VTA dopamine neurons (using a Cre-dependent DREADD in tyrosine hydroxylase:Cre rats), nor pathway-specific chemogenetic stimulation of these neurons' projection to mPFC in particular impacted probability discounting, suggesting that AdoTHC's potentiation of amphetamine effects may reflect alterations of non-VTA dopamine neurons influenced by amphetamine. Results confirm the marked specificity in the cognitive processes impacted by adolescent THC exposure, and suggest that some persistent effects of adolescent THC may alter cognitive responses to amphetamine in a manner independent of VTA dopamine projections to mPFC.

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Section: Introductionmentioning

confidence: 99%

Adolescent THC impacts on mPFC dopamine-mediated cognitive processes in male and female rats

Martinez,

Alizo Vera,

Ruiz

et al. 2024

Preprint

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“…Excluding tobacco and alcohol, cannabis stands out as the most prevalent drug among young people aged 15-24, according to the United Nations. On average, around 9% of cannabis users develop use disorders, and this figure rises to over 16% for those initiating use during adolescence [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…This early onset has been associated with mental health disorders, including personality disorders, depression, and suicidality. Moreover, there is evidence that acute consumption, even infrequently, can lead to negative mood states such as anxiety, mental confusion, tension, memory impairment, instability, and paranoia [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

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Neurocognitive Impact of Exposure to Cannabis Concentrates and Cannabinoids Including Vaping in Children and Adolescents: A Systematic Review

Saavedra,

Thota,

Peresuodei

et al. 2024

Cureus

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During adolescence, significant changes unfold in the brain's maturation process. The density of white matter increases, accompanied by the pruning back of gray matter. This critical and vulnerable period becomes especially noteworthy in the context of drug use, as adolescents are extensively exposed to substances such as tobacco, alcohol, and cannabis. The concern is heightened now that cannabis has been legalized for recreational use in many places, leading to increased exposure levels. Additionally, knowledge about the impact of cannabis on neurocognitive development during this stage is limited. This knowledge gap compounds the issue, making it even more concerning. Therefore, a systematic review was carried out based on the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, using medical databases such as PubMed, PubMed Central (PMC), Medline, Cochrane Library, Internet Archive Scholar, and Embase-Elsevier for relevant medical literature. The identified articles were reviewed, eligibility criteria were applied, and 19 research articles were identified. The final papers explored the correlation between children's and adolescents' exposure to cannabis-containing compounds and subsequent changes in the central nervous system (CNS). Findings revealed a considerable impact, ranging from transient alterations in mood to permanent cognitive function and sensory processing changes, affecting the deterioration of the quality of life of these individuals in adulthood. Presently, most studies were conducted on animals, and the few studies on humans have considerable limitations, such as the type of study, age of the population, and small samples, among others. For this reason, it is essential for the scientific community and public health organizations, in general, to conduct more studies that demonstrate the true neurobiological impact of this drug and its accessibility to young people and, based on the results, consider its legalization or propose regulations for its use and commercialization.

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“…To address these questions, we conducted a systematic review and meta-analysis of rodent experiments that modelled chronic cannabis use and assessed its link with schizophrenia-like behaviours. We focused on studies that administered cannabinoids during adolescence, a critical neurodevelopmental period with heightened vulnerability to substance impacts (17)(18)(19)(20)(21). Through this meta-analysis, we aimed to 1) summarise existing behavioural data of rodent experiments that modelled adolescent cannabis exposure, 2) compare the impacts of distinct cannabinoids, particularly THC and cannabidiol (CBD), 3) explore the potential moderating factors of sex, species, age of treatment onset, time lapse between treatment and assessment (short-term vs long-term), and 4) discuss the implications for future research and identify open questions in the field of rodent models of cannabinoids exposure.…”

Section: Introductionmentioning

confidence: 99%

Systematic review and meta-analysis on the effects of chronic peri-adolescent cannabinoid exposure on schizophrenia-like behaviour in rodents

Li,

Mukherjee,

Duric

et al. 2023

Preprint

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BackgroundThe link between cannabis use and schizophrenia is well-established in epidemiological studies, especially among adolescents with early-onset use. However, this association in rodent models is less clear. This meta-analysis examined the effects of adolescent cannabinoid exposure on distinct schizophrenia-like behaviours in rodents and how experimental variations influence outcomes.MethodsFollowing a pre-registered protocol (CRD42022338761), we searched PubMed, Ovid Medline, Embse and APA PsychInfo for English-language original studies until 2022. We synthesised data from experiments on schizophrenia-like behaviour in rats and mice after repeated peri-pubertal (onset between P23-P45) cannabinoid exposure. Risk of bias was assessed using the SYRCLE’s tool.ResultsWe included 291 experiments from 91 articles across 9 behavioural tests. We found meta-analytic evidence supporting that CB1R agonists, both natural and synthetic, elicited broad schizophrenia-like behavioural alterations, including impaired working memory (g =-0.58 [CI: -1.00,-0.16]), novel object recognition (g=-0.63 [CI: -0.97,-0.30]), novel object location recognition (g=-0.70 [CI: -1.22,-0.28]), social motivation (g=-0.40 [CI: -0.63, -0.16]), pre-pulse inhibition (g=-0.48 [CI: -0.89, -0.08]), and sucrose preference (g=-0.92 [CI: -1.87,0.04]). By contrast, effects on novelty-induced locomotion were negligible. Subgroup analyses revealed similar effects across sexes and species. Substantial variance in the protocols and moderate-to-high heterogeneity in behavioural outcomes were observed. We found CBD may attenuate novelty-induced locomotion in an open field and enhance fear memory recall, but data was limited.DiscussionThis is the first meta-analysis to comprehensively assess the link between cannabinoids and schizophrenia-like behaviours in rodents. Our results support epidemiological links between early cannabis use and schizophrenia-like phenotypes, confirming the utility of animal models. Standardising protocols will optimise models to strengthen reproducibility and comparisons, our work provides a framework for refining rodent models to elucidate biological pathways linking cannabis and schizophrenia.

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Cannabis in Adolescence: Lasting Cognitive Alterations and Underlying Mechanisms

Cited by 8 publications

References 115 publications

Adolescent THC impacts on mPFC dopamine-mediated cognitive processes in male and female rats

Adolescent THC impacts on mPFC dopamine-mediated cognitive processes in male and female rats

Neurocognitive Impact of Exposure to Cannabis Concentrates and Cannabinoids Including Vaping in Children and Adolescents: A Systematic Review

Systematic review and meta-analysis on the effects of chronic peri-adolescent cannabinoid exposure on schizophrenia-like behaviour in rodents

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