Cannabidiol Administered During Peri-Adolescence Prevents Behavioral Abnormalities in an Animal Model of Schizophrenia

Abstract

Schizophrenia is considered a debilitating neurodevelopmental psychiatric disorder and its pharmacotherapy remains problematic without recent major advances. The development of interventions able to prevent the emergence of schizophrenia would therefore represent an enormous progress. Here, we investigated whether treatment with cannabidiol (CBD – a compound of Cannabis sativa that presents an antipsychotic profile in animals and humans) during peri-adolescence would prevent schizophrenia-like behavioral abnormalities in an animal model of schizophrenia: the spontaneously hypertensive rat (SHR) strain. Wistar rats and SHRs were treated with vehicle or CBD from 30 to 60 post-natal days. In experiment 1, schizophrenia-like behaviors (locomotor activity, social interaction, prepulse inhibition of startle and contextual fear conditioning) were assessed on post-natal day 90. Side effects commonly associated with antipsychotic treatment were also evaluated: body weight gain and catalepsy throughout the treatment, and oral dyskinesia 48 h after treatment interruption and on post-natal day 90. In experiment 2, serum levels of triglycerides and glycemia were assessed on post-natal day 61. In experiment 3, levels of BDNF, monoamines, and their metabolites were evaluated on post-natal days 61 and 90 in the prefrontal cortex and striatum. Treatment with CBD prevented the emergence of SHRs’ hyperlocomotor activity (a model for the positive symptoms of schizophrenia) and deficits in prepulse inhibition of startle and contextual fear conditioning (cognitive impairments). CBD did not induce any of the potential motor or metabolic side effects evaluated. Treatment with CBD increased the prefrontal cortex 5-HIAA/serotonin ratio and the levels of 5-HIAA on post-natal days 61 and 90, respectively. Our data provide pre-clinical evidence for a safe and beneficial effect of peripubertal and treatment with CBD on preventing positive and cognitive symptoms of schizophrenia, and suggest the involvement of the serotoninergic system on this effect.

Developmental exposure to cannabidiol (CBD) alters longevity and health span of zebrafish (Danio rerio)

“…Dietary restriction due to litter crowding in early life leads to increased life span (Sun et al 2009). CBD has shown potential benefits long after its consumption as peri-adolescent exposure prevented the onset of behavioral abnormalities in a rat model of schizophrenia many months later (Peres et al 2018). The effects of CBD on life span and health span, however, are currently unknown.…”

Schizophrenia and drug addiction comorbidity: recent advances in our understanding of behavioural susceptibility and neural mechanisms

“…However, chronic low dose (i.e. 0.5 -5 mg/kg) CBD treatment during adolescence dosedependently reverses locomotor hyperactivity, sensorimotor gating deficits and fear-associated cognitive impairment in SHR [153]. Chronic adolescent CBD treatment also increases the ratio of 5-HIAA/serotonin tissue levels in the PFC in adulthood in both SHR and controls, but CBD has no effect on serotonin levels in the dorsal striatum or BDNF levels in the PFC or dorsal striatum [153], suggesting that CBD ameliorates schizophreniarelevant behaviours in SHR by a different mechanism (e.g.…”

Cannabis et neurodéveloppement

“…Des études sont en cours pour étudier plus précisément les effets du CBD. Certains travaux réalisés chez des modèles animaux pour la schizophrénie [52,53] ou exposés au THC [54,55] ont montré que l'injection de CBD pendant l'adolescence peut prévenir l'apparition de certaines anomalies neurobiologiques et comportementales à court ou long terme telles que l'hyperactivité locomotrice, la baisse des performances mnésiques, la réduction des interactions sociales ou l'augmentation de l'anxiété des animaux. Cependant, ces résultats n'ont pas toujours été répliqués et il convient de rester prudent car certaines études ont mis en évidence des conséquences délétères telles qu'une aggravation des anomalies dans le groupe modèle, voire la diminution des interactions sociales dans le groupe contrôle exposé au CBD [55,56]…”