ABSTRACT Enhancing the therapeutic efficacy of anti-tumor drugs is essential for cancer management. Although cannabinoid receptor 2 (CB2R) stimulation exerts anti-tumor action in glioma cells by regulating cellular proliferation, differentiation, or apoptosis, selective CB2R agonist alone does not achieve a satisfactory therapeutic outcome. Herein, we aimed to evaluate the possible strategy for enhancing the anti-glioma efficacy of JWH133, a selective CB2R agonist. In this study, immunofluorescence and qRT-PCR were used to investigate microglia polarization. Tumor growth was monitored via bioluminescent imaging using the IVIS Spectrum System. The angiogenesis of human brain microvascular endothelial cells (HBMECs) was detected by the tube formation assay. qRT-PCR was used to...

Please use this link to access this publication. Abstract Uncontrolled infection and increased inflammatory mediators might cause systemic inflammatory response. It is already known that Cannabinoid Type 2 (CB2) receptors, which are commonly expressed in immune cells and in many other tissues, have an effect on the regulation of immune response. In the present study of ours, the effects of CB2 receptor agonist JWH-133 was investigated on cecal ligation and puncture (CLP)-induced polymicrobial sepsis model in rats. In the present study, Sprague-Dawley rats were divided into 5 groups (i.e. the Sham, CLP, JWH-133 0.2 mg/kg, JWH-133 1 mg/kg, and JWH-133 5 mg/kg Groups). Except for the Sham Group, the CLP-induced sepsis...

Abstract The anti-cancer effects of cannabinoids including CBD (Cannabidiol) and THC ((−)-trans-∆9-tetrahydrocannabinol) have been reported in the case of pancreatic cancer (PC). The connection of these cannabinoids to KRas oncogenes that mutate in more than 90% of PC, and their effects on PD-L1, a key target of immune checkpoint blockade, have not been thoroughly investigated. Using cell lines and mouse models of PC, the effects of CBD and THC on cancer growth, the interaction between PC cells and a stromal cell, namely pancreatic stellate cells (PSCs), and the mechanism(s) involved were determined by cell-based assays and mouse study in vivo. CBD and THC inhibited the proliferation...

Abstract Endo-, phyto- and synthetic cannabinoids have been proposed as promising anti-cancer agents able to impair cancer cells’ behavior without affecting their non-transformed counterparts. However, cancer outcome depends not only on cancer cells’ activity, but also on the stromal cells, which coevolve with cancer cells to sustain tumor progression. Here, we show for the first time that cannabinoid treatment impairs the activation and the reactivity of cancer-associated fibroblasts (CAFs), the most represented stromal component of prostate tumor microenvironment. Using prostate cancer-derived CAFs, we demonstrated that WIN 55-212.2 mesylate, a synthetic full agonist of cannabinoid receptors (CBs) 1 and 2, downregulates α-smooth muscle actin and...

Abstract Although a lot of information can be found on the specific dual role of the endocannabinoid system in the emotional-related responses, little is known whether stimulation or inhibition of the cannabinoid (CB) receptors may affect the activity of the frequently prescribed antidepressant drugs. Our interests have been particularly focused on the potential influence of the CB2 receptors, as the ones whose central effects are relatively poorly documented when compared to the central effects of the CB1 receptors. Therefore, we evaluated the potential interaction between the CB2 receptor ligands (i.e., JWH133 – CB2 receptor agonist and AM630 – CB2 receptor inverse agonist) and several common antidepressant drugs that influence...

Please use this link to access this publication. Abstract Purpose of review To evaluate the impact of flavonoids and cannabinoids as anti-inflammatory and antiallergic treatments on the anterior surface of the eye. Recent findings Allergic conjunctivitis and dry eye syndrome are common ocular surface diseases that have been treated with traditional pharmacological measures, e.g. corticosteroids, antihistamines. Given the side-effect profiles of these medications and the growing interest in complementary treatment modalities as part of integrative medical interventions, well known flavonoids, such as quercetin and catechin, are under investigation for topical and systemic application methods for relief. As flavonoid derivatives, pycnogenol and epigallocatechin gallate have...

Abstract In this proof-of-concept study, the antioxidant activity of phytocannabinoids, namely cannabidiol (CBD) and Δ9- tetrahydrocannabinol (THC), were investigated using an in vitro system of differentiated human neuronal SY-SH5Y cells. The oxidative stress was induced by hydrogen peroxide, as reactive oxygen species (ROS). Alzheimer’s disease (AD)-like pathological conditions were mimicked in vitro by treating the differentiated neuronal cells with amyloid-β1–42 (Aβ1–42) in the presence of Cu(II). We showed that THC had a high potency to combat oxidative stress in both in vitro models, while CBD did not show a remarkable antioxidant activity. The cannabis extracts also exhibited a significant antioxidant activity, which depended on the...

Please use this link to access this publication. Abstract Glutamatergic plasticity in the nucleus accumbens core (NAcore) is a key neuronal process in appetitive learning and contributes to pathologies such as drug addiction. Understanding how this plasticity factors into cannabis addiction and relapse has been hampered by the lack of a rodent model of cannabis self-administration. We used intravenous self-administration of two constituents of cannabis, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) to examine how contingent cannabis use and cue-induced cannabinoid-seeking alters glutamatergic neurotransmission and synaptic plasticity in NAcore. NMDA receptor (NMDAR)–dependent long-term depression (LTD) in the NAcore was lost after cannabinoid, but not sucrose self-administration....

Please use this link to access this publication. Abstract There is growing interest in using cannabinoids for chronic pain. We performed a systematic review and meta-analysis of randomized controlled trials to evaluate the analgesic efficacy and adverse effects of cannabinoids for chronic non-cancer pain. PubMed, EMBASE, Web of Science, Cochrane CENTRAL and clinicaltrials.gov were searched up to December 2018. Information on the type, dosage, route of administration, pain conditions, pain scores, and adverse events were extracted for qualitative analysis. Meta-analysis of analgesic efficacy was performed. Meta-regression was performed to compare the analgesic efficacy for different pain conditions (neuropathic versus non-neuropathic pain). Risk of bias was assessed...

ABSTRACT Cannabis is commonly used among people who drink alcohol, but findings are mixed regarding the direction of this relationship. The type of cannabis used [high-cannabidiol (CBD) vs. high-delta-9tetrahydrocannabinol (THC)] and motives for use (i.e., whether cannabis is used to treat a medical condition) may influence the relationship between cannabis and drinking. Specifically, CBD has shown preclinical promise in reducing alcohol consumption, and medical cannabis users report using cannabis to reduce drinking. This study leverages survey data from cannabis users who drink alcohol (N = 533). Respondents were categorized as using cannabis to treat (CTT) a medical condition or as individuals whose cannabis use is...