A Guide to Targeting the Endocannabinoid System in Drug Design

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(8), P. 2778 - 2778

Published: April 16, 2020

The endocannabinoid system (ECS) is one of the most crucial systems in human organism, exhibiting multi-purpose regulatory character. It engaged a vast array physiological processes, including nociception, mood regulation, cognitive functions, neurogenesis and neuroprotection, appetite, lipid metabolism, as well cell growth proliferation. Thus, ECS proteins, cannabinoid receptors their endogenous ligands’ synthesizing degrading enzymes, are promising therapeutic targets. Their modulation has been employed or extensively studied treatment multiple diseases. However, due to complex nature its crosstalk with other biological systems, development novel drugs turned out be challenging task. In this review, we summarize potential applications for ECS-targeting drugs, especially focusing on synthetic compounds preclinical studies. We put emphasis specific proteins different pathophysiological areas. addition, stress possible difficulties risks highlight proposed solutions. By presenting point information pivotal spotlight drug design, provide an overview current state knowledge ECS-related pharmacodynamics show directions needed research.

Language: Английский

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Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2018, Volume and Issue: 86, P. 255 - 261

Published: June 6, 2018

Cannabidiol (CBD) is a compound of Cannabis sativa with relevant therapeutic potential in several neuropsychiatric disorders including depression. CBD treatment has shown significant antidepressant-like effects different rodent preclinical models. However, the mechanisms involved CBD-induced antidepressant are still poorly understood. Therefore, this work aimed at investigating participation serotonin (5-HT) and/or noradrenaline (NA) forced swimming test (FST) by: 1) testing if co-administration serotonergic (fluoxetine, FLX) or noradrenergic (desipramine, DES) antidepressants would have synergistic effects; and 2) 5-HT NA depletion impair behavioral effects. Results showed that (10 mg/kg), FLX mg/kg) DES (5 induced mice submitted to FST. Ineffective doses (7 when co-administered ineffective (2.5 resulted effects, thus implicating additive mechanisms. Pretreatment PCPA (an inhibitor synthesis: 150 mg/kg, i.p., once per day for 4 days), but not DSP-4 (a neurotoxin: 1 μg/μl, i.c.v., 24 h before test), reduced monoamine levels brain. only abolished FST, indicating None treatments locomotor Our results suggest effect by FST dependent on central nervous system (CNS).

Language: Английский

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Cannabidiol Regulates the Expression of Keratinocyte Proteins Involved in the Inflammation Process through Transcriptional Regulation

Cells, Journal Year: 2019, Volume and Issue: 8(8), P. 827 - 827

Published: Aug. 3, 2019

Cannabidiol (CBD), a natural phytocannabinoid without psychoactive effect, is well-known anti-inflammatory and antioxidant compound. The possibility of its use in cytoprotection cells from harmful factors, including ultraviolet (UV) radiation, an area ongoing investigation. Therefore, the aim this study was to evaluate effect CBD on regulatory mechanisms associated with redox balance inflammation keratinocytes irradiated UVA [30 J/cm2] UVB [60 mJ/cm2]. Spectrophotometric results show that significantly enhances activity enzymes such as superoxide dismutase thioredoxin reductase UV keratinocytes. Furthermore, despite decreased glutathione peroxidase activities, prevents lipid peroxidation, which observed level 4-HNE 15d-PGJ2 (measured using GC/MS LC/MS). Moreover, Western blot analysis protein levels shows that, under stress conditions, influences interactions transcription factors Nrf2- NFκB by inhibiting pathway, increasing expression Nrf2 activators stimulating Nrf2. In conclusion, through activation well properties inhibitor should be considered during design new protective treatments for skin.

Language: Английский

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Neuroprotection in Oxidative Stress-Related Neurodegenerative Diseases: Role of Endocannabinoid System Modulation

Antioxidants and Redox Signaling, Journal Year: 2017, Volume and Issue: 29(1), P. 75 - 108

Published: May 12, 2017

Significance: Redox imbalance may lead to overproduction of reactive oxygen and nitrogen species (ROS/RNS) subsequent oxidative tissue damage, which is a critical event in the course neurodegenerative diseases. It still not fully elucidated, however, whether stress primary trigger or consequence process neurodegeneration. Recent Advances: Increasing evidence suggests that involved propagation neuronal injury consequent inflammatory response, concert promote development pathological alterations characteristic most common Critical Issues: Accumulating recent also there an important interplay between lipid endocannabinoid system [ECS; comprising main cannabinoid 1 2 receptors (CB1 CB2), endocannabinoids, their synthetic metabolizing enzymes] various key redox-dependent processes. Future Directions: Targeting ECS modulate redox state-dependent cell death decrease preceding response holds therapeutic potential multitude stress-related acute chronic disorders from stroke traumatic brain Alzheimer's Parkinson's diseases multiple sclerosis, just name few, will be discussed this overview. Antioxid. Signal. 29, 75–108.

Language: Английский

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Cannabidiol as a Potential Treatment for Anxiety and Mood Disorders: Molecular Targets and Epigenetic Insights from Preclinical Research

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(4), P. 1863 - 1863

Published: Feb. 13, 2021

Cannabidiol (CBD) is the most abundant non-psychoactive component of cannabis; it displays a very low affinity for cannabinoid receptors, facilitates endocannabinoid signaling by inhibiting hydrolysis anandamide, and stimulates both transient receptor potential vanilloid 1 2 serotonin type 1A receptors. Since CBD interacts with wide variety molecular targets in brain, its therapeutic has been investigated number neuropsychiatric diseases, including anxiety mood disorders. Specifically, received growing attention due to anxiolytic antidepressant properties. As consequence, given safety profile, considered promising new agent treatment However, exact mechanism action still remains unknown. In present preclinical review, we provide summary animal-based studies that support use as an anxiolytic- antidepressant-like compound. Next, describe neuropharmacological evidence links pharmacology behavioral effects. Finally, taking into consideration effects on DNA methylation, histone modifications, microRNAs, elaborate putative role epigenetic mechanisms mediating CBD’s outcomes.

Language: Английский

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