Please use this link to access publication Abstract Rationale Δ9-tetrahydrocannabinol (THC) is the primary psychoactive compound in cannabis and is responsible for cannabis-related neuropsychiatric side effects, including abnormal affective processing, cognitive and sensory filtering deficits and memory impairments. A critical neural region linked to the psychotropic effects of THC is the nucleus accumbens shell (NASh), an integrative mesocorticolimbic structure that sends and receives inputs from multiple brain areas known to be dysregulated in various disorders, including schizophrenia and anxiety-related disorders. Considerable evidence demonstrates functional differences between posterior vs. anterior NASh sub-regions in the processing of affective and cognitive behaviours influenced by THC. Nevertheless, the...

Please use this link to access publication Abstract This review summarizes the most common potential pathways of neurodevelopmental toxicity due to perinatal exposure to Δ9-tetrahydrocannabinol (Δ9-THC) that lead to behavioral and other adverse outcomes (AOs). This is Part III in a set of reviews highlighting the animal-derived data considered by California's Developmental and Reproductive Toxicant Identification Committee (DARTIC) in 2019. The Hazard Identification Document (HID) provided to the DARTIC included a summary of human, whole animal, and mechanistic data on the neurodevelopmental toxicity of cannabis smoke and Δ9-THC. The literature search for mechanistic data has been updated through 2020. We focus on mechanistic pathways...

Abstract Studies on the effective and safe therapeutic dosage of delta-9-tetrahydrocannabinol (THC) for the treatment of Alzheimer’s disease (AD) have been sparse due to the concern about THC’s psychotropic activity. The present study focused on demonstrating the beneficial effect of low-dose THC treatment in preclinical AD models. The effect of THC on amyloid-β (Aβ) production was examined in N2a/AβPPswe cells. An in vivo study was conducted in aged APP/PS1 transgenic mice that received an intraperitoneal injection of THC at 0.02 and 0.2 mg/kg every other day for three months. The in vitro study showed that THC inhibited Aβ aggregation within a safe dose range....

Abstract δ9-Tetrahydrocannabinol (THC) has demonstrated anti-inflammatory effects in animal models of arthritis, but its mechanism of action and cellular targets are still unclear. The purpose of this study is to elucidate the effects of THC (0.1–25 µM) on synovial fibroblasts from patients with rheumatoid arthritis (RASF) and peripheral blood mononuclear cells (PBMC) from healthy donors in respect to proliferation, calcium mobilization, drug uptake, cytokine and immunoglobulin production. Intracellular calcium and drug uptake were determined by fluorescent dyes Cal-520 and PoPo3, respectively. Cytokine and immunoglobulin production were evaluated by ELISA. Cannabinoid receptors 1 and 2 (CB1 and CB2) were detected by flow cytometry. RASF express CB1 and...

Abstract Background: Early invasion of the central nervous system (CNS) by human immunodefciency virus (HIV) (Gray et al. in Brain Pathol 6:1–15, 1996; An et al. in Ann Neurol 40:611–6172, 1996), results in neuroinfammation, potentially through extracellular vesicles (EVs) and their micro RNAs (miRNA) cargoes (Sharma et al. in FASEB J 32:5174–5185, 2018; Hu et al. in Cell Death Dis 3:e381, 2012). Although the basal ganglia (BG) is a major target and reservoir of HIV in the CNS (Chaganti et al. in Aids 33:1843–1852, 2019; Mintzopoulos et al. in Magn Reson Med 81:2896–2904, 2019), whether BG produces EVs and the efect of HIV and/or...

Abstract Background: Ischemia/reperfusion (I/R) is a pivotal mechanism of organ injury during clinical stetting for example for cardiopulmonary bypasses. The generation of reactive oxygen species (ROS) during I/R induces oxidative stress that promotes endothelial dysfunction, DNA dissociation and local inflammation. In turn, those processes induce cytokine release, resulting in damage to cellular structures and cell death. One of the major psychoactive compounds of Cannabis is delta-9-tetrahydrocannabinol (ΔΔ99-THC), which is known as an anti-inflammatory mediator. Our research aimed to test if ΔΔ99-THC may be protective in the treatment of cardiovascular system dysfunction arising from I/R heart injury. Methods: Two experimental models were used: isolated rat hearts perfused with the...

Please use this link to access publication Abstract Introduction Traumatic brain injury (TBI) is a significant source of morbidity and mortality in the United States. Recent shifts in state legislation have increased the use of recreational and medical marijuana. While cannabinoids and tetrahydrocannabinol (THC) have known anti-inflammatory effects, the impact of preinjury THC use on clinical outcomes in the setting of severe TBI is unknown. We hypothesized that preinjury THC use in trauma patients suffering TBI would be associated with decreased thromboembolic events and adverse outcomes. Methods The American College of Surgeons Trauma Quality Improvement Program was used to identify patients aged ≥18 y with TBI and severe injury (Injury Severity Score ≥ 16) in...

Abstract Cannabis derivatives are largely used in the general population for recreational and medical purposes, with the highest prevalence among adolescents, but chronic use and abuse has raised medical concerns. We investigated the prolonged effects of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in organotypic hippocampal slices from P7 rats cultured for 2 weeks. Cell death in the CA1 subregion of slices was quantified by propidium iodide (PI) fluorescence, pre-synaptic and post-synaptic marker proteins were analysed by Western blotting and neurodegeneration and astrocytic alterations by NeuN and GFAP by immunofluorescence and confocal laser microscopy. The statistical significance of differences was analysed using ANOVA with a post...

Abstract Vitamin E acetate, which is used as a diluent of tetrahydrocannabinol (THC), has been reported as the primary causative agent of e-cigarette, or vaping, product use-associated lung injury (EVALI). Here, we employ in vitro assays, docking, and molecular dynamics (MD) computer simulations to investigate the interaction of vitamin E with the membrane-bound cannabinoid 2 receptor (CB2R), and its role in modulating the binding affinity of THC to CB2R. From the MD simulations, we determined that vitamin E interacts with both CB2R and membrane phospholipids. Notably, the synchronized effect of these interactions likely facilitates vitamin E acting as a lipid modulator for the cannabinoid...

Abstract Alzheimer’s disease (AD) is the most common form of dementia, but there is still no available treatment. Δ9-tetrahydrocannabinol (THC) is emerging as a promising therapeutic agent. Using THC in conventional high doses may have deleterious effects. Therefore, we propose to use an ultra-low dose of THC (ULD-THC). We previously published that a single injection of ULD-THC ameliorated cognitive functioning in several models of brain injuries as well as in naturally aging mice. Here, 5xFAD AD model mice received a single treatment of ULD-THC (0.002 mg/kg) after disease onset and were examined in two separate experiments for cognitive functions, neurotropic, and inflammatory factors in...