Abstract The endocannabinoid system (ECS) is ubiquitous in most human tissues, and involved in the regulation of mental health. Consequently, its dysregulation is associated with neuropsychiatric and neurodegenerative disorders. Together, the ECS and the expanded endocannabinoidome (eCBome) are composed of genes coding for CB1 and CB2 cannabinoid receptors (CB1R, CB2R), endocannabinoids (eCBs), and the metabolic enzyme machinery for their synthesis and catabolism. The activation of CB1R is associated with adverse effects on the central nervous system (CNS), which has limited the therapeutic use of drugs that bind this receptor. The discovery of the functional neuronal CB2R raised new possibilities for the potential and safe...

Please use this link to access this publication: https://www.sciencedirect.com/science/article/abs/pii/S0165178123005930 Abstract Prenatal infections and cannabis use during adolescence are well-recognized risk factors for schizophrenia. As inflammation and oxidative stress (OS) contribute to this disorder, anti-inflammatory drugs have been proposed as potential therapies. This study aimed to evaluate the association between delta-9-tetrahydrocannabinol (THC) and schizophrenia-like abnormalities in a maternal immune activation (MIA) model. Additionally, we assessed the preventive effect of cannabidiol (CBD), a non-psychotropic/anti-inflammatory cannabinoid. THC and/or CBD were administered to Saline- and MIA-offspring during periadolescence. At adulthood, THC-exposed MIA-offspring showed significant improvements in sensorimotor gating deficits. Structural and metabolic brain changes were evaluated by magnetic resonance...

Please use this link to access this publication: https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(23)00143-8/fulltext Summary Background The relationship between psychotic disorders and cannabis use is heavily debated. Shared underlying genetic risk is one potential explanation. We investigated the genetic association between psychotic disorders (schizophrenia and bipolar disorder) and cannabis phenotypes (lifetime cannabis use and cannabis use disorder). Methods We used genome-wide association summary statistics from individuals with European ancestry from the Psychiatric Genomics Consortium, UK Biobank, and International Cannabis Consortium. We estimated heritability, polygenicity, and discoverability of each phenotype. We performed genome-wide and local genetic correlations. Shared loci were identified and mapped to genes, which were tested for functional enrichment....

Abstract Background Natural Cannabis (NC) and Synthetic Cannabinoids (SCs) use can increase the risk of developing psychotic disorders and exacerbate their course. Aims To examine the differences between psychoses not associated with cannabis use and those associated with NC and SCs use, evaluating psychotic symptoms, global functioning, dissociative symptoms and suicidal ideation. Methods The sample of 61 patients with First Episode Psychosis (FEP) was divided into 3 groups: non-Cannabis users (non-users, N = 20); NC users (THC-users, N = 21); SCs users (SPICE-users, N = 20). Each group was assessed at FEP and after 3 and 9 months through specific psychopathological scales. Results THC-users, and even more SPICE-users, displayed much...

Abstract Cannabis use is consistently associated with both increased incidence of frank psychotic disorders and acute exacerbations of psychotic symptoms in healthy individuals and people with psychosis spectrum disorders. Although there is uncertainty around causality, cannabis use may be one of a few modifiable risk factors for conversion to psychotic disorders in individuals with Clinical High Risk for Psychosis (CHR-P) syndromes, characterized by functionally impairing and distressing subthreshold psychotic symptoms. To date, few recommendations beyond abstinence to reduce adverse psychiatric events associated with cannabis use have been made. This narrative review synthesizes existing scientific literature on cannabis' acute psychotomimetic effects and epidemiological associations with...

Abstract BackgroundPrevious research suggests an increase in schizophrenia population attributable risk fraction (PARF) for cannabis use disorder (CUD). However, sex and age variations in CUD and schizophrenia suggest the importance of examining differences in PARFs in sex and age subgroups. MethodsWe conducted a nationwide Danish register-based cohort study including all individuals aged 16–49 at some point during 1972–2021. CUD and schizophrenia status was obtained from the registers. Hazard ratios (HR), incidence risk ratios (IRR), and PARFs were estimated. Joinpoint analyses were applied to sex-specific PARFs. ResultsWe examined 6 907 859 individuals with 45 327 cases of incident schizophrenia during follow-up across 129 521 260...

Please use this link to access this publication: https://www.sciencedirect.com/science/article/abs/pii/S0149763423003780 Abstract Schizophrenia (SCZ) is a multifactorial neurodevelopmental disorder caused by genetic and environmental alterations, especially during prenatal stages. On the other hand, cannabis consumption in adolescence has been also linked to an increased risk of developing SCZ. The combination of both hits has been proposed as the dual hit hypothesis of SCZ. We systematically reviewed prenatal environmental alterations and cannabis consumption during adolescence that are associated with an increased risk of SCZ, following the PRISMA model. The analysis focused on dual animal models where the first hit is prenatal environmental exposure and the second hit consists of postnatal cannabis...

Abstract Preclinical and clinical data indicate that cannabidiol (CBD), a non-psychotomimetic compound from the Cannabis sativa plant, can induce antipsychotic-like effects. In an animal model of schizophrenia based on the antagonism of NMDA receptors, the behavioral and molecular changes induced by repeated treatment with the NMDA receptor antagonist MK-801 were prevented when CBD was co-administered with MK-801. It is unknown, however, if CBD would reverse these changes once they have been established. Thus, in the present study we used male C57BL/6J mice, 6 weeks old, to evaluate whether daily CBD injection for seven days, starting after the end of the repeated treatment with MK-801...

Abstract: The potential therapeutic use of some Cannabis sativa plant compounds has been attracting great interest, especially for managing neuropsychiatric disorders due to the relative lack of efficacy of the current treatments. Numerous studies have been carried out using the main phytocannabinoids, tetrahydrocannabinol (THC) and cannabidiol (CBD). CBD displays an interesting pharmacological profile without the potential for becoming a drug of abuse, unlike THC. In this review, we focused on the anxiolytic, antidepressant, and antipsychotic effects of CBD found in animal and human studies. In rodents, results suggest that the effects of CBD depend on the dose, the strain, the administration time course (acute...

Neuropsychiatric disorders such as schizophrenia are associated with cognitive impairment, including learning, memory and attention deficits. Antipsychotic drugs are limited in their efficacy to improve cognition; therefore, new therapeutic agents are required. Cannabidiol (CBD), the non-intoxicating component of cannabis, has anti-inflammatory, neuroprotective and antipsychotic-like properties; however, its ability to improve the cognitive deficits of schizophrenia remains unclear. Using a prenatal infection model, we examined the effect of chronic CBD treatment on cognition and social interaction. Time-mated pregnant Sprague-Dawley rats (n=16) were administered polyinosinic-polycytidilic acid (poly I:C) (POLY; 4 mg/kg) or saline (CONT) at gestation day 15. Male offspring (PN56) were injected twice daily with...