Adolescent cannabinoid exposure interacts with other risk factors in schizophrenia: A review of the evidence from animal models

Dunn, Ariel; Michie, Patricia T.; Hodgson, Deborah M.; Harms, Lauren

doi:10.1016/j.neubiorev.2020.06.028

Cited by 12 publications

(8 citation statements)

References 309 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…adolescence is a critical period for the eCS development and its interaction with other biological organisations, particularly the immune system (Dunn, Michie, Hodgson, & Harms, 2020). Our evidence is in line with a two-hit hypothesis proposed for psychoses, which implies that biologically predisposed individuals are more sensitive to the effects of seconds hits, i.e.…”

Section: Inflammation As a Moderatorsupporting

confidence: 89%

“…Indeed, there are concerns about exposure to cannabinoids during critical periods, given the potential toxic effect of exocannabinoids on the developing brain (Arseneault et al, 2002). The eCS is involved in neuroplasticity and neurodevelopment, with rodent models showing that adolescence is a critical period for the eCS development and its interaction with other biological organisations, particularly the immune system (Dunn, Michie, Hodgson, & Harms, 2020). Our evidence is in line with a two-hit hypothesis proposed for psychoses, which implies that biologically predisposed individuals are more sensitive to the effects of seconds hits, i.e.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The independent and combined effects of cannabis use and systemic inflammation during the early stages of psychosis: exploring the two-hit hypothesis

et al. 2021

View full text Add to dashboard Cite

Background Cannabis consumption is a modifiable risk factor associated with psychosis, but not all cannabis users develop psychosis. Animal studies suggest that an antecedent active immune system interacts with subsequent cannabis exposure and moderates the cannabis–psychosis association, supporting the two-hit hypothesis. The clinical investigations are few, and it is unclear if the immune system is a biological candidate moderating the cannabis–psychosis association or whether cannabis increases inflammation, which in turn, augments psychosis likelihood. Methods We explored the mediating and moderating role of blood inflammation using PROCESS macro. We used data from a cross-sectional study, including 153 first-episode psychosis patients and 256 community-based controls. Participants answered the Cannabis Experience Questionnaire (cannabis frequency, age of onset, and duration), and plasma cytokines were measured [interleukin (IL)-1β, IL-6, IL-4, IL-10, tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ), transforming growth factor-β (TGF-β); multiplex]. We computed an inflammatory composite score (ICS) to represent the systemic inflammatory state. Confounders included sex, age, ethnicity, educational level, body mass index, tobacco smoking, lifetime use of other drugs, and antipsychotic treatment. Results Mediation: Cannabis consumption was not associated with increased inflammation, thus not supporting a mediating effect of inflammation. Moderation: Daily use and age of onset <17 interacted significantly with the ICS to increase the odds of psychosis beyond their individual effects and were only associated with psychosis among those scoring medium–high in the ICS. Conclusions Immune dysregulation might be part of the pathophysiology of psychosis, not explained by cannabis use or other confounders. We provide the first and initial evidence that immune dysregulation modifies the cannabis–psychosis association, in line with a two-hit hypothesis.

show abstract

Section: Inflammation As a Moderatorsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

The independent and combined effects of cannabis use and systemic inflammation during the early stages of psychosis: exploring the two-hit hypothesis

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The long-term outcomes related to cannabis exposure during adolescence are complex and can be the result of multiple factors. Specifically, not only THC exposure itself during brain development increases vulnerability for psychiatric disorders, but co-occurrence with other multivariate factors may heighten these risks (see [121] for an extensive review). For instance, while some genetic polymorphisms have been reported in this review as protective factors, others have been found to induce adverse and synergistic effects and increase the vulnerability to cannabis-related developmental insults.…”

Section: Discussionmentioning

confidence: 99%

Reversing the Psychiatric Effects of Neurodevelopmental Cannabinoid Exposure: Exploring Pharmacotherapeutic Interventions for Symptom Improvement

Felice

Laviolette

2021

IJMS

View full text Add to dashboard Cite

Neurodevelopmental exposure to psychoactive compounds in cannabis, specifically THC, is associated with a variety of long-term psychopathological outcomes. This increased risk includes a higher prevalence of schizophrenia, mood and anxiety disorders, and cognitive impairments. Clinical and pre-clinical research continues to identify a wide array of underlying neuropathophysiological sequelae and mechanisms that may underlie THC-related psychiatric risk vulnerability, particularly following adolescent cannabis exposure. A common theme among these studies is the ability of developmental THC exposure to induce long-term adaptations in the mesocorticolimbic system which resemble pathological endophenotypes associated with these disorders. This narrative review will summarize recent clinical and pre-clinical evidence that has elucidated these THC-induced developmental risk factors and examine how specific pharmacotherapeutic interventions may serve to reverse or perhaps prevent these cannabis-related risk outcomes.

show abstract

“…Over the years, a growing body of research has investigated the impact of cannabinoids on schizophrenia-like behaviours in rodents (12)(13)(14)(15)(16). While providing useful preliminary evidence, these studies have substantial variability in factors like cannabinoid type and dosage, timing of exposure, sex, and species of animals used (14).…”

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

View full text Add to dashboard Cite

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.

show abstract

Adolescent cannabinoid exposure interacts with other risk factors in schizophrenia: A review of the evidence from animal models

Cited by 12 publications

References 309 publications

The independent and combined effects of cannabis use and systemic inflammation during the early stages of psychosis: exploring the two-hit hypothesis

The independent and combined effects of cannabis use and systemic inflammation during the early stages of psychosis: exploring the two-hit hypothesis

Reversing the Psychiatric Effects of Neurodevelopmental Cannabinoid Exposure: Exploring Pharmacotherapeutic Interventions for Symptom Improvement

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

Contact Info

Product

Resources

About