Cognitive dysfunction and impaired neuroplasticity following repeated exposure to the synthetic cannabinoid JWH-018 in male mice.

Background And Purpose: Psychotic disorders have been reported in long-term users of synthetic cannabinoids. This study aims at investigating the long-lasting effects of repeated JWH-018 exposure.

Experimental Approach: Male CD-1 mice were injected with vehicle, JWH-018 (6 mg·kg ), the CB -antagonist NESS-0327 (1 mg·kg ) or co-administration of NESS-0327 and JWH-018, every day for 7 days.

Assay of GTPγS Binding in Autoradiography.

Autoradiography of radiolabeled GTPγS ([S]GTPγS) binding is a relevant technique to study the function of G protein-coupled receptors (GPCRs) ex vivo. Here, we describe the protocol for such a method, suitable for investigating CB receptor functionality in tissue slices from rodent brains.

Long-Term Consequences of Adolescent Exposure to THC-Rich/CBD-Poor and CBD-Rich/THC-Poor Combinations: A Comparison with Pure THC Treatment in Female Rats.

Cannabis is the most-used recreational drug worldwide, with a high prevalence of use among adolescents. In animal models, long-term adverse effects were reported following chronic adolescent exposure to the main psychotomimetic component of the plant, delta-9-tetrahydrocannabinol (THC). However, these studies investigated the effects of pure THC, without taking into account other cannabinoids present in the cannabis plant.

Therapeutic potential of cannabidivarin for epilepsy and autism spectrum disorder.

Recent years have seen a renewed interest on the possible therapeutic exploitations of specific cannabinoids derived from the Cannabis sativa plant. Thus far, the most studied non-psychotomimetic cannabinoid is cannabidiol (CBD), which has shown promising therapeutic potential for relieving a variety of neurological diseases. However, also its propyl analogue, cannabidivarin (CBDV), has recently gained much attention as a potential therapeutic agent for the management of disabling neurological conditions.

Neurobiological mechanisms underlying cannabis-induced memory impairment.

A growing body of literature suggests that cannabis intake can induce memory loss in humans and animals. Besides the recreational use, daily cannabis users may also belong to the ever-increasing population of patients who are administered cannabis as a medicine. As such, they also can experience impairments in memory as a negative side effect of their therapy.

Cannabidivarin Treatment Ameliorates Autism-Like Behaviors and Restores Hippocampal Endocannabinoid System and Glia Alterations Induced by Prenatal Valproic Acid Exposure in Rats.

Autism spectrum disorder (ASD) is a developmental condition whose primary features include social communication and interaction impairments with restricted or repetitive motor movements. No approved treatment for the core symptoms is available and considerable research efforts aim at identifying effective therapeutic strategies. Emerging evidence suggests that altered endocannabinoid signaling and immune dysfunction might contribute to ASD pathogenesis.

Cannabidivarin completely rescues cognitive deficits and delays neurological and motor defects in male mutant mice.

Background: Recent evidence suggests that 2-week treatment with the non-psychotomimetic cannabinoid cannabidivarin (CBDV) could be beneficial towards neurological and social deficits in early symptomatic mutant mice, a model of Rett syndrome (RTT).

Aim: The aim of this study was to provide further insights into the efficacy of CBDV in -null mice using a lifelong treatment schedule (from 4 to 9 weeks of age) to evaluate its effect on recognition memory and neurological defects in both early and advanced stages of the phenotype progression.

Methods: CBDV 0.

Adult Cellular Neuroadaptations Induced by Adolescent THC Exposure in Female Rats Are Rescued by Enhancing Anandamide Signaling.

Background: In rodent models, chronic exposure to cannabis' psychoactive ingredient, Δ9-tetrahydrocannabinol, during adolescence leads to abnormal behavior in adulthood. In female rats, this maladaptive behavior is characterized by endophenotypes for depressive-like and psychotic-like disorders as well as cognitive deficits. We recently reported that most depressive-like behaviors triggered by adolescent Δ9-tetrahydrocannabinol exposure can be rescued by manipulating endocannabinoid signaling in adulthood with the anandamide-inactivating enzyme FAAH inhibitor, URB597.

Adolescent THC exposure in female rats leads to cognitive deficits through a mechanism involving chromatin modifications in the prefrontal cortex.

Background: Increasing cannabis consumption among adolescents, studies that link its early use with mental illnesses, and the political debate on cannabis legalization together call for an urgent need to study molecular underpinnings of adolescent brain vulnerability. The emerging role of epigenetic mechanisms in psychiatric diseases led us to hypothesize that epigenetic alterations could play a role in causes and subsequent development of the depressive/psychotic-like phenotype induced by adolescent, but not adult, Δ9-tetrahydrocannabinol (THC) exposure in female rats.

Methods: We performed a time-course analysis of histone modifications, chromatin remodelling enzymes and gene expression in the prefrontal cortex of female rats after adolescent and adult THC exposure.

The Endocannabinoid System and Autism Spectrum Disorders: Insights from Animal Models.

Autism spectrum disorder (ASD) defines a group of neurodevelopmental disorders whose symptoms include impaired communication and social interaction with restricted or repetitive motor movements, frequently associated with general cognitive deficits. Although it is among the most severe chronic childhood disorders in terms of prevalence, morbidity, and impact to the society, no effective treatment for ASD is yet available, possibly because its neurobiological basis is not clearly understood hence specific drugs have not yet been developed. The endocannabinoid (EC) system represents a major neuromodulatory system involved in the regulation of emotional responses, behavioral reactivity to context, and social interaction.

Remote memories are enhanced by COMT activity through dysregulation of the endocannabinoid system in the prefrontal cortex.

The prefrontal cortex (PFC) is a crucial hub for the flexible modulation of recent memories (executive functions) as well as for the stable organization of remote memories. Dopamine in the PFC is implicated in both these processes and genetic variants affecting its neurotransmission might control the unique balance between cognitive stability and flexibility present in each individual. Functional genetic variants in the catechol-O-methyltransferase (COMT) gene result in a different catabolism of dopamine in the PFC.

New vistas on cannabis use disorder.

Cannabis sativa preparations are the most consumed illicit drugs for recreational purposes worldwide, and the number of people seeking treatment for cannabis use disorder has dramatically increased in the last decades. Due to the recent decriminalization or legalization of cannabis use in the Western Countries, we may predict that the number of people suffering from cannabis use disorder will increase. Despite the increasing number of cannabis studies over the past two decades, we have gaps of scientific knowledge pertaining to the neurobiological consequences of long-term cannabis use.

Lifelong imbalanced LA/ALA intake impairs emotional and cognitive behavior via changes in brain endocannabinoid system.

Imbalanced dietary n-3 and n-6 PUFA content has been associated with a number of neurological conditions. Endocannabinoids are n-6 PUFA derivatives, whose brain concentrations are sensitive to modifications of fatty acid composition of the diet and play a central role in the regulation of mood and cognition. As such, the endocannabinoid system appears to be an ideal candidate for mediating the effects of dietary fatty acids on mood and cognition.

The anabolic steroid nandrolone alters cannabinoid self-administration and brain CB receptor density and function.

Clinical and pre-clinical observations indicate that anabolic-androgenic steroids can induce neurobiological changes that alter the rewarding effects of drugs of abuse. In this study, we investigated the effect of the anabolic steroid nandrolone on the rewarding properties of the cannabinoid CB receptor agonist WIN55,212-2 (WIN) in rats. Lister Hooded male rats were treated intramuscularly with nandrolone (15mg/kg) or vehicle for 14 consecutive days, and then allowed to self-administer WIN (12.

Long-term hippocampal glutamate synapse and astrocyte dysfunctions underlying the altered phenotype induced by adolescent THC treatment in male rats.

Cannabis use has been frequently associated with sex-dependent effects on brain and behavior. We previously demonstrated that adult female rats exposed to delta-9-tetrahydrocannabinol (THC) during adolescence develop long-term alterations in cognitive performances and emotional reactivity, whereas preliminary evidence suggests the presence of a different phenotype in male rats. To thoroughly depict the behavioral phenotype induced by adolescent THC exposure in male rats, we treated adolescent animals with increasing doses of THC twice a day (PND 35-45) and, at adulthood, we performed a battery of behavioral tests to measure affective- and psychotic-like symptoms as well as cognition.

Assay of GTPγS Binding in Autoradiography.

Autoradiography of radiolabeled GTPγS ([(35)S]GTPγS) binding is a relevant method to study the function of G protein-coupled receptors (GPCRs), in tissue sections. Here, we describe the protocol for such a binding autoradiography, suitable to investigate the functionality of CB1 receptor in tissue slices from rodent brain.

MeCP2 Related Studies Benefit from the Use of CD1 as Genetic Background.

MECP2 mutations cause a number of neurological disorders of which Rett syndrome (RTT) represents the most thoroughly analysed condition. Many Mecp2 mouse models have been generated through the years; their validity is demonstrated by the presence of a broad spectrum of phenotypes largely mimicking those manifested by RTT patients. These mouse models, between which the C57BL/6 Mecp2tm1.

Cortical neuroinflammation contributes to long-term cognitive dysfunctions following adolescent delta-9-tetrahydrocannabinol treatment in female rats.

Over 180 million people consume cannabis globally. Cannabis use peaks during adolescence with a trend for continued consumption by adults. Notably, several studies have shown that long-term and heavy cannabis use during adolescence can impair brain maturation and predispose to neurodevelopmental disorders, although the neurobiological mechanisms underlying this association remain largely unknown.

The Impact of Exposure to Cannabinoids in Adolescence: Insights From Animal Models.

The regular use of cannabis during adolescence is of particular concern because use by this age group seems to be associated with an increased likelihood of deleterious consequences, as reported by several epidemiologic studies. However, despite their unquestionable value, epidemiologic data are inconclusive. Modeling the adolescent phase in animals appears to be a useful approach to investigate the impact of cannabis use on the adolescent brain.

Sex-dependent vulnerability to cannabis abuse in adolescence.

The goal of this review is to summarize current evidence for sex differences in the response to cannabinoid compounds, focusing mainly on a specific age of exposure, i.e., adolescence.

The phytocannabinoid, Δ⁹-tetrahydrocannabivarin, can act through 5-HT₁A receptors to produce antipsychotic effects.

Background And Purpose: This study aimed to address the questions of whether Δ(9)-tetrahydrocannabivarin (THCV) can (i) enhance activation of 5-HT1 A receptors in vitro and (ii) induce any apparent 5-HT₁A receptor-mediated antipsychotic effects in vivo.

Experimental Approach: In vitro studies investigated the effect of THCV on targeting by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) of 5-HT₁A receptors in membranes obtained from rat brainstem or human 5-HT₁A CHO cells, using [(35)S]-GTPγS and 8-[(3)H]-OH-DPAT binding assays. In vivo studies investigated whether THCV induces signs of 5-HT₁A receptor-mediated antipsychotic effects in rats.

Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex.

Current concepts suggest that exposure to THC during adolescence may act as a risk factor for the development of psychiatric disorders later in life. However, the molecular underpinnings of this vulnerability are still poorly understood. To analyze this, we investigated whether and how THC exposure in female rats interferes with different maturational events occurring in the prefrontal cortex during adolescence through biochemical, pharmacological and electrophysiological means.

Cannabidiol, a non-psychoactive cannabinoid compound, inhibits proliferation and invasion in U87-MG and T98G glioma cells through a multitarget effect.

In the present study, we found that CBD inhibited U87-MG and T98G cell proliferation and invasiveness in vitro and caused a decrease in the expression of a set of proteins specifically involved in growth, invasion and angiogenesis. In addition, CBD treatment caused a dose-related down-regulation of ERK and Akt prosurvival signaling pathways in U87-MG and T98G cells and decreased hypoxia inducible factor HIF-1α expression in U87-MG cells. Taken together, these results provide new insights into the antitumor action of CBD, showing that this cannabinoid affects multiple tumoral features and molecular pathways.