Please use this link to access publication Abstract Introduction: Low voltage-activated T-type calcium channels (T-type ICa), CaV3.1, CaV3.2, and CaV3.3, are opened by small depolarizations from the resting membrane potential in many cells and have been associated with neurological disorders, including absence epilepsy and pain. Δ9-tetrahydrocannabinol (THC) is the principal psychoactive compound in Cannabis and also directly modulates T-type ICa; however, there is no information about functional activity of most phytocannabinoids on T-type calcium channels, including Δ9-tetrahydrocannabinolic acid (THCA), the natural nonpsychoactive precursor of THC. The aim of this work was to characterize THCA effects on T-type calcium channels. Materials and Methods: We used HEK293 Flp-In-TREx cells stably expressing CaV3.1,...

Abstract Background: The main biological activities of cannabis are due to the presence of several compounds known as cannabinoids. Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are two of the main cannabinoids. Studies have shown that the efects of THC can be modulated by CBD. Objective: This study aims to look at the efect of diferent concentrations of THC and CBD separately and in combination, on blood viscosity, elasticity and membrane integrity. Methods: Blood samples were collected from twenty-four healthy adult non-smokers. Blood viscosity and elasticity were determined using the Vilastic Scientifc Bioprofler for diferent concentrations (0, 2.5, 25, 50 and 100ng/ml) of CBD and THC...

Background: Cannabis use is a component risk factor for the manifestation of schizophrenia. The biological effects of cannabis include effects on epigenetic systems, immunological parameters, in addition to changes in cannabinoid receptors 1 and 2, that may be associated with this risk. However, there has been limited study of the effects of smoked cannabis on these biological effects in human peripheral blood cells. We analyzed the effects of two concentrations of tetrahydrocannabinol (THC) vs. placebo in lymphocytes of a subset of participants who enrolled in a double-blind study of the effects of cannabis on driving performance (outcome not the focus of this study). Methods: Twenty four...

Please use this link to access publication Abstract Mitochondria have the main roles in myocardial tissue homeostasis, through providing ATP for the vital enzymes in intermediate metabolism, contractile apparatus and maintaining ion homeostasis. Mitochondria-related cardiotoxicity results from the exposure with illicit drugs have previously reported. These illicit drugs interference with processes of normal mitochondrial homeostasis and lead to mitochondrial dysfunction and mitochondrial-related oxidative stress. Cannabis consumption has been shown to cause ventricular tachycardia, to increase the risk of myocardial infarction (MI) and potentially sudden death. Here, we investigated this hypothesis that delta-9-tetrahydrocannabinol (Delta-9-THC) as a main cannabinoid found in cannabis could directly cause mitochondrial...

Please use this link to access publication Abstract Previous studies have demonstrated that phosphine gas (PH3) released from aluminium phosphide (AlP) can inhibit cytochrome oxidase in cardiac mitochondria and induce generation of free radicals, oxidative stress, alteration in antioxidant defense system and cardiotoxicity. Available evidence suggests that cannabinoids have protective effects in the reduction of oxidative stress, mitochondrial and cardiovascular damages. The objective of this study was to evaluate the effect of trans-Δ-9-tetrahydrocannabinol (THC) on AlP-induced toxicity in isolated cardiomyocytes and cardiac mitochondria. Rat heart isolated cardiomyocytes and mitochondria were cotreated with different concentrations of THC (10, 50 and 100 μM) and IC50 of AlP, then cellular and mitochondrial toxicity parameters were assayed. Treatment with AlP alone...

Abstract Cannabis usage has steadily increased as acceptance is growing for both medical and recreational reasons. Medical cannabis is administered for treatment of chronic pain based on the premise that the endocannabinoid system signals desensitize pain sensor neurons and produce anti-inflammatory effects. The major psychoactive ingredient of cannabis is D9-tetrahydrocannabinol (THC) that signals mainly through cannabinoid receptor-1 (CBr), which is also present on nonneuron cells including blood platelets of the circulatory system. In vitro, CBr-mediated signaling has been shown to acutely inhibit platelet activation downstream of the platelet collagen receptor glycoprotein (GP)VI. The systemic effects of chronic THC administration on platelet activity and function...

Abstract The PINK1/Parkin pathway plays an important role in maintaining a healthy pool of mitochondria. Activation of this pathway can lead to apoptosis, mitophagy, or mitochondrial-derived vesicle formation, depending on the nature of mitochondrial damage. The signaling by which PINK/Parkin activation leads to these different mitochondrial outcomes remains understudied. Here we present evidence that cannabidiol (CBD) activates the PINK1-Parkin pathway in a unique manner. CBD stimulates PINK1-dependent Parkin mitochondrial recruitment similarly to other well-studied Parkin activators but with a distinctive shift in the temporal dynamics and mitochondrial fates. The mitochondrial permeability transition pore inhibitor cyclosporine A exclusively diminished the CBD-induced PINK1/Parkin activation and its associated mitochondrial effects. Unexpectedly, CBD treatment also...

Abstract Intraocular pressure (IOP) is regulated primarily through aqueous humor production by ciliary body and drainage through uveoscleral and trabecular meshwork (TM) tissues. The goal of this study was to measure the effect of non-psychotropic cannabidiol (CBD) on aqueous humor outflow through TM and assess the effect of CBD on the TM cell signaling pathways that are important for regulating outflow. Perfused porcine eye anterior segment explants were used to investigate the effects of CBD on aqueous humor outflow. Cultured porcine TM cells were used to study the effects of CBD on TM cell contractility, myosin light chain (MLC) and myosin phosphatase targeting subunit...

Abstract Background: Recent studies suggested that individuals with metabolic disorders have altered function of adipocytes and adipose stem cell subpopulations, which impairs tissue homeostasis, promoting insulin resistance and diabetes development. The non-psychoactive phytocannabinoid CBD was found to modulate adipose tissue metabolism, however, its exact role in controlling ASCs’ fate is still poorly understood. Objectives: This investigation aimed to elucidate whether pretreatment of ASCs with CBD can protect against ER stress development and maintain the cytophysiological properties of cells. Methods: Human ASCs were cultured under control and adipogenic conditions. Prior to the experiments, cells in the experimental group were pretreated with CBD following the addition...

Please use this link to access this publication: Abstract The oxytosis/ferroptosis regulated cell death pathway recapitulates many features of mitochondrial dysfunction associated with the aging brain and has emerged as a potential key mediator of neurodegeneration. It has thus been proposed that the oxytosis/ferroptosis pathway can be used to identify novel drug candidates for the treatment of age-associated neurodegenerative diseases that act by preserving mitochondrial function. Previously, we identified cannabinol (CBN) as a potent neuroprotector. Here, we demonstrate that not only does CBN protect nerve cells from oxytosis/ferroptosis in a manner that is dependent on mitochondria and it does so independently of cannabinoid receptors. Specifically, CBN directly targets mitochondria and preserves key mitochondrial functions including redox regulation, calcium...