Abstract Although apoptosis of keratinocytes has been relatively well studied, there is a lack of information comparing potentially proapoptotic treatments for healthy and diseased skin cells. Psoriasis is a chronic autoimmune-mediated skin disease manifested by patches of hyperproliferative keratinocytes that do not undergo apoptosis. UVB phototherapy is commonly used to treat psoriasis, although this has undesirable side effects, and is often combined with anti-inflammatory compounds. The aim of this study was to analyze if cannabidiol (CBD), a phytocannabinoid that has anti-inflammatory and antioxidant properties, may modify the proapoptotic effects of UVB irradiation in vitro by influencing apoptotic signaling pathways in donor psoriatic and healthy...

Abstract Background Use of cannabidiol (CBD), the primary non-psychoactive compound found in cannabis, has recently risen dramatically, while relatively little is known about the underlying molecular mechanisms of its effects. Previous work indicates that direct CBD exposure strongly impacts the brain, with anxiolytic, antidepressant, antipsychotic, and other effects being observed in animal and human studies. The epigenome, particularly DNA methylation, is responsive to environmental input and can direct persistent patterns of gene regulation impacting phenotype. Epigenetic perturbation is particularly impactful during embryogenesis, when exogenous exposures can disrupt critical resetting of epigenetic marks and impart phenotypic effects lasting into adulthood. The impact of prenatal CBD...

Abstract Current treatments for stroke, which account for 6.5 million global deaths annually, remain insufficient for treatment of disability and mortality. One targetable hallmark of stroke is the inflammatory response following infarct, which leads to significant damage post-infarct. Cannabinoids and their endogenous targets within the CNS have emerged as potential treatments for neuroinflammatory indications. We and others have previously shown that synthetic agonists of the cannabinoid CB2 receptor reduce infarct size and microglial activation in rodent models of stroke. The non-cannabinoid receptor mediated effects of the phytocannabinoid cannabidiol (CBD) have also shown effectiveness in these models. The present aim was to determine the single...

Abstract Systems pharmacology employs computational and mathematical methods to study the network of interactions a drug may have within complex biological pathways. These tools are well suited for research on multitarget drugs, such as natural compounds, in diseases with complex etiologies, such as osteoarthritis (OA). The present study focuses on cannabidiol (CBD), a non-psychoactive constituent of cannabis, targeting over 60 distinct molecular targets as a potential treatment for OA, a degenerative joint disease leading to chronic pain with a neuropathic component. We successfully identified molecular targets of CBD that were relevant in the context of OA treatment with both beneficial and detrimental effects. Our...

Abstract The liver is a key metabolic organ that is particularly sensitive to environmental factors, including UV radiation. As UV radiation induces oxidative stress and inflammation, natural compounds are under investigation as one method to counteract these consequences. The aim of this study was to assess the effect of topical application of phytocannabinoid-cannabidiol (CBD) on the skin of nude rats chronically irradiated with UVA/UVB, paying particular attention to its impact on the liver antioxidants and phospholipid metabolism. The results of this study indicate that CBD reaches the rat liver where it is then metabolized into decarbonylated cannabidiol, 7-hydroxy-cannabidiol and cannabidiol-glucuronide. CBD increased the levels...

Abstract Cannabidiol (CBD) is a phytocannabinoid with a broad-range of therapeutic potential in several conditions, including neurological (epilepsy, neurodegenerative diseases, traumatic and ischemic brain injuries) and psychiatric disorders (schizophrenia, addiction, major depressive disorder, and anxiety). The pharmacological mechanisms responsible for these effects are still unclear, and more than 60 potential molecular targets have been described. Regarding neuropsychiatric disorders, most studies investigating these mechanisms have focused on neuronal cells. However, glial cells (astrocytes, oligodendrocytes, microglia) also play a crucial role in keeping the homeostasis of the central nervous system. Changes in glial functions have been associated with neuropathological conditions, including those for which CBD is...

Abstract This study evaluated the effects of cannabidiol (CBD) and/or sertraline (STR) on behavioral and gene expression alterations induced by a new chronic animal model of post-traumatic stress disorder (PTSD). C57BL/6J male mice were repeatedly exposed to physical and psychogenic alternate stressful stimuli. Fear-related memory and anxiety-like behaviors were evaluated. The effects of the administration of CBD (20 mg/kg, i.p.) and/or STR (10 mg/kg, p.o.) were analyzed on behavioral and gene expression changes induced by the model of PTSD. Gene expression alterations of targets related with stress regulation, endocannabinoid and serotonergic systems were analyzed by real-time PCR. The results revealed an increased and long-lasting...

Abstract Tardive dyskinesia (TD) is a movement disorder that appears after chronic use of drugs that block dopaminergic receptors such as antipsychotics. Besides the motor symptoms, patients with TD also present cognitive deficits. Neuroinflammatory mechanisms could be involved in the development of these symptoms. A previous study showed that cannabidiol (CBD), the major non-psychotomimetic compound of Cannabis sativa plant, prevents orofacial dyskinesia induced by typical antipsychotics by activating peroxisome proliferator-activated receptors gamma (PPARγ). Here, we investigated if CBD would also reverse haloperidol-induced orofacial dyskinesia and associated cognitive deficits. We also verified if these effects depend on PPARγ receptor activation. Daily treatment with haloperidol (3 mg/kg, 21 days) increased the frequency of vacuous chewing movements (VCM) and decreased the discrimination index in the novel object...

Abstract Cocaine use disorder (CUD) is a major public health issue associated with physical, social, and psychological problems. Excessive and repeated cocaine use induces oxidative stress leading to a systemic inflammatory response. Cannabidiol (CBD) has gained substantial interest for its anti-inflammatory properties, safety, and tolerability profile. However, CBD anti-inflammatory properties have yet to be confirmed in humans. This exploratory study is based on a single-site randomized controlled trial that enrolled participants with CUD between 18 and 65 years, randomized (1:1) to daily receive either CBD (800 mg) or placebo for 92 days. The trial was divided into a 10-day detoxification (phase I) followed by a...

Abstract The potential, multifaceted therapeutic profile of cannabidiol (CBD), a major constituent derived from the Cannabis sativa plant, covers a wide range of neurological and psychiatric disorders, ranging from anxiety to pediatric epilepsy and drug addiction. However, the molecular targets responsible for these effects have been only partially identified. In this view, the involvement of the orexin system, the key regulator in arousal and the sleep/wake cycle, and in motivation and reward processes, including drug addiction, prompted us to explore, using computational and experimental approaches, the possibility that CBD could act as a ligand of orexin receptors, orexin 1 receptor of type 1 (OX1R)...