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Vincenzo Di Marzo - One of the best experts on this subject based on the ideXlab platform.
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Cannabinoids and the expanded Endocannabinoid System in neurological disorders
Nature Reviews Neurology, 2020Co-Authors: Luigia Cristino, Tiziana Bisogno, Vincenzo Di MarzoAbstract:Anecdotal evidence that cannabis preparations have medical benefits together with the discovery of the psychotropic plant cannabinoid Δ^9-tetrahydrocannabinol (THC) initiated efforts to develop cannabinoid-based therapeutics. These efforts have been marked by disappointment, especially in relation to the unwanted central effects that result from activation of cannabinoid receptor 1 (CB1), which have limited the therapeutic use of drugs that activate or inactivate this receptor. The discovery of CB2 and of endogenous cannabinoid receptor ligands (Endocannabinoids) raised new possibilities for safe targeting of this Endocannabinoid System. However, clinical success has been limited, complicated by the discovery of an expanded Endocannabinoid System — known as the Endocannabinoidome — that includes several mediators that are biochemically related to the Endocannabinoids, and their receptors and metabolic enzymes. The approvals of nabiximols, a mixture of THC and the non-psychotropic cannabinoid cannabidiol, for the treatment of spasticity and neuropathic pain in multiple sclerosis, and of purified botanical cannabidiol for the treatment of otherwise untreatable forms of paediatric epilepsy, have brought the therapeutic use of cannabinoids and Endocannabinoids in neurological diseases into the limelight. In this Review, we provide an overview of the Endocannabinoid System and the Endocannabinoidome before discussing their involvement in and clinical relevance to a variety of neurological disorders, including Parkinson disease, Alzheimer disease, Huntington disease, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, stroke, epilepsy and glioblastoma. In this Review, Cristino, Bisogno and Di Marzo outline the biology of cannabinoids, the Endocannabinoid System and the expanded Endocannabinoid System and discuss the involvement of these Systems and the therapeutic potential of cannabinoids across the spectrum of neurological disease. Cannabinoid receptors 1 and 2 (CB1 and CB2), the two Endocannabinoids anandamide and 2-arachidonoylglycerol, and Endocannabinoid anabolic and catabolic enzymes form the Endocannabinoid System. Endocannabinoid signalling is involved in regulation of cell, tissue, organ and organism homeostasis, brain development, neurotransmitter release and synaptic plasticity, and cytokine release from microglia, and hence is implicated in multiple neurological disorders. Endocannabinoid signalling is altered in most neurological disorders; enhancers or inhibitors of Endocannabinoid signalling can have therapeutic effects in preclinical models, depending on disease characteristics and the roles of CB1 and CB2. Endocannabinoids can activate different receptors and their biosynthetic and catabolic pathways are often shared with other mediators. Consequently, the System is considered to be part of an expanded signalling System, the Endocannabinoidome. The Endocannabinoidome hinders therapeutic targeting of Endocannabinoid anabolic or catabolic enzymes but inhibitors of Endocannabinoid inactivation and allosteric modulators of CB1 and CB2 are being actively investigated in neurological disorders. The existence of the Endocannabinoidome explains in part why some non-euphoric cannabinoids, which affect several Endocannabinoidome proteins, are useful for the treatment of neurological disorders, such as multiple sclerosis and epilepsy.
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cannabinoids and the expanded Endocannabinoid System in neurological disorders
Nature Reviews Neurology, 2020Co-Authors: Luigia Cristino, Tiziana Bisogno, Vincenzo Di MarzoAbstract:Anecdotal evidence that cannabis preparations have medical benefits together with the discovery of the psychotropic plant cannabinoid Δ9-tetrahydrocannabinol (THC) initiated efforts to develop cannabinoid-based therapeutics. These efforts have been marked by disappointment, especially in relation to the unwanted central effects that result from activation of cannabinoid receptor 1 (CB1), which have limited the therapeutic use of drugs that activate or inactivate this receptor. The discovery of CB2 and of endogenous cannabinoid receptor ligands (Endocannabinoids) raised new possibilities for safe targeting of this Endocannabinoid System. However, clinical success has been limited, complicated by the discovery of an expanded Endocannabinoid System — known as the Endocannabinoidome — that includes several mediators that are biochemically related to the Endocannabinoids, and their receptors and metabolic enzymes. The approvals of nabiximols, a mixture of THC and the non-psychotropic cannabinoid cannabidiol, for the treatment of spasticity and neuropathic pain in multiple sclerosis, and of purified botanical cannabidiol for the treatment of otherwise untreatable forms of paediatric epilepsy, have brought the therapeutic use of cannabinoids and Endocannabinoids in neurological diseases into the limelight. In this Review, we provide an overview of the Endocannabinoid System and the Endocannabinoidome before discussing their involvement in and clinical relevance to a variety of neurological disorders, including Parkinson disease, Alzheimer disease, Huntington disease, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, stroke, epilepsy and glioblastoma. In this Review, Cristino, Bisogno and Di Marzo outline the biology of cannabinoids, the Endocannabinoid System and the expanded Endocannabinoid System and discuss the involvement of these Systems and the therapeutic potential of cannabinoids across the spectrum of neurological disease.
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Abdominal obesity and the Endocannabinoid System
2014Co-Authors: Jean-pierre Després, Vincenzo Di MarzoAbstract:Abdominal obesity and the Endocannabinoid System : , Abdominal obesity and the Endocannabinoid System : , کتابخانه دیجیتال جندی شاپور اهواز
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the Endocannabinoid System and its therapeutic exploitation
Nature Reviews Drug Discovery, 2004Co-Authors: Vincenzo Di Marzo, Maurizio Bifulco, Luciano De PetrocellisAbstract:The term 'Endocannabinoid' - originally coined in the mid-1990s after the discovery of membrane receptors for the psychoactive principle in Cannabis, Delta9-tetrahydrocannabinol and their endogenous ligands - now indicates a whole signalling System that comprises cannabinoid receptors, endogenous ligands and enzymes for ligand biosynthesis and inactivation. This System seems to be involved in an ever-increasing number of pathological conditions. With novel products already being aimed at the pharmaceutical market little more than a decade since the discovery of cannabinoid receptors, the Endocannabinoid System seems to hold even more promise for the future development of therapeutic drugs. We explore the conditions under which the potential of targeting the Endocannabinoid System might be realized in the years to come.
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Acute neuronal injury, excitotoxicity, and the Endocannabinoid System.
Molecular Neurobiology, 2002Co-Authors: Mario Van Der Stelt, Mauro Maccarrone, Vincenzo Di Marzo, Wouter B. Veldhuis, Peter R. Bär, Klaas Nicolay, Gerrit A. Veldink, Johannes F.g. VliegenthartAbstract:The Endocannabinoid System is a valuable target for drug discovery, because it is involved in the regulation of many cellular and physiological functions. The Endocannabinoid System constitutes the endogenous lipids anandamide, 2-arachidonoylglycerol and noladin ether, and the cannabinoid CB1 and CB2 receptors as well as the proteins for their inactivation. It is thought that (endo)cannabinoid-based drugs may potentially be useful to reduce the effects of neurodegeneration. This paper reviews recent developments in the Endocannabinoid System and its involvement in neuroprotection.
Inés Díaz-laviada - One of the best experts on this subject based on the ideXlab platform.
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The Endocannabinoid System in prostate cancer
Nature Reviews Urology, 2011Co-Authors: Inés Díaz-laviadaAbstract:The prostate gland expresses several components of the Endocannabinoid System, including the CB_1 receptor, TRPV1 receptor and the hydrolyzing enzyme fatty acid amide hydrolase Many of the components of the Endocannabinoid System are dysregulated in prostate cancer, and their levels correlate with malignant grade, suggesting that they could be novel prognostic markers Several cannabinoids, including WIN-55,212-2, THC, methanandamide and the CB_2 agonist JWH-015, exert antitumoral effects against prostate cancer in vivo and in cultured prostate cancer cell lines Cannabinoids induce cell cycle arrest and apoptosis through ceramide generation and Akt inhibition in cells in vitro Studies have suggested a role for the cannabinoid receptor CB_2 in the antiproliferative effect of cannabinoids on prostate cancer cells Cannabinoids, their receptors and their metabolizing enzymes are emerging as a new regulatory System, which is involved in multiple physiological functions. Normal prostate tissue expresses several constituents of the Endocannabinoid System including the CB_1 receptor, receptors belonging to the transient receptor potential family and fatty acid amide hydrolase, a hydrolyzing enzyme, all of which have been localized in the glandular epithelia. Accumulating evidence indicate that the Endocannabinoid System is dysregulated in prostate cancer, suggesting that it has a role in prostate homeostasis. Overexpression of several components of the Endocannabinoid System correlate with prostate cancer grade and progression, potentially providing a new therapeutic target for prostate cancer. Moreover, several cannabinoids exert antitumoral properties against prostate cancer, reducing xenograft prostate tumor growth, prostate cancer cell proliferation and cell migration. Although the therapeutic potential of cannabinoids against prostate cancer is very promising, future research using animal models is needed to evaluate the influence of Systemic networks in their antitumoral action. The prostate gland expresses several components of the Endocannabinoid System. In this Review, Díaz-Laviada outlines the anti-proliferative effect of cannabinoids on prostate cancer cells and the signaling pathways underlying cannabinoid action, before discussing the molecular targets and signaling pathways modulated by cannabinoids in prostate cancer cells.
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The Endocannabinoid System in prostate cancer
Nature reviews. Urology, 2011Co-Authors: Inés Díaz-laviadaAbstract:Cannabinoids, their receptors and their metabolizing enzymes are emerging as a new regulatory System, which is involved in multiple physiological functions. Normal prostate tissue expresses several constituents of the Endocannabinoid System including the CB(1) receptor, receptors belonging to the transient receptor potential family and fatty acid amide hydrolase, a hydrolyzing enzyme, all of which have been localized in the glandular epithelia. Accumulating evidence indicate that the Endocannabinoid System is dysregulated in prostate cancer, suggesting that it has a role in prostate homeostasis. Overexpression of several components of the Endocannabinoid System correlate with prostate cancer grade and progression, potentially providing a new therapeutic target for prostate cancer. Moreover, several cannabinoids exert antitumoral properties against prostate cancer, reducing xenograft prostate tumor growth, prostate cancer cell proliferation and cell migration. Although the therapeutic potential of cannabinoids against prostate cancer is very promising, future research using animal models is needed to evaluate the influence of Systemic networks in their antitumoral action.
Rafael Maldonado - One of the best experts on this subject based on the ideXlab platform.
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The Endocannabinoid System in modulating fear, anxiety, and stress .
Dialogues in clinical neuroscience, 2020Co-Authors: Rafael Maldonado, David Cabañero, Elena Martín-garcíaAbstract:The Endocannabinoid System is widely expressed in the limbic System, prefrontal cortical areas, and brain structures regulating neuroendocrine stress responses, which explains the key role of this System in the control of emotions. In this review, we update recent advances on the function of the Endocannabinoid System in determining the value of fear-evoking stimuli and promoting appropriate behavioral responses for stress resilience. We also review the alterations in the activity of the Endocannabinoid System during fear, stress, and anxiety, and the pathophysiological role of each component of this System in the control of these protective emotional responses that also trigger pathological emotional disorders. In spite of all the evidence, we have not yet taken advantage of the therapeutic implications of this important role of the Endocannabinoid System, and possible future strategies to improve the treatment of these emotional disorders are discussed. .
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Involvement of the Endocannabinoid System in osteoarthritis pain.
The European journal of neuroscience, 2014Co-Authors: Carmen La Porta, S.a. Bura, Roger Negrete, Rafael MaldonadoAbstract:Osteoarthritis is a degenerative joint disease associated with articular cartilage degradation. The major clinical outcome of osteoarthritis is a complex pain state that includes both nociceptive and neuropathic mechanisms. Currently, the therapeutic approaches for osteoarthritis are limited as no drugs are available to control the disease progression and the analgesic treatment has restricted efficacy. Increasing evidence from preclinical studies supports the interest of the Endocannabinoid System as an emerging therapeutic target for osteoarthritis pain. Indeed, pharmacological studies have shown the anti-nociceptive effects of cannabinoids in different rodent models of osteoarthritis, and compelling evidence suggests an active participation of the Endocannabinoid System in the pathophysiology of this disease. The ubiquitous distribution of cannabinoid receptors, together with the physiological role of the Endocannabinoid System in the regulation of pain, inflammation and even joint function further support the therapeutic interest of cannabinoids for osteoarthritis. However, limited clinical evidence has been provided to support this therapeutic use of cannabinoids, despite the promising preclinical data. This review summarizes the promising results that have been recently obtained in support of the therapeutic value of cannabinoids for osteoarthritis management.
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involvement of the Endocannabinoid System in drug addiction
Trends in Neurosciences, 2006Co-Authors: Rafael Maldonado, Olga Valverde, Fernando BerrenderoAbstract:Recent studies have shown that the Endocannabinoid System is involved in the common neurobiological mechanism underlying drug addiction. This System participates in the primary rewarding effects of cannabinoids, nicotine, alcohol and opioids, through the release of Endocannabinoids in the ventral tegmental area. Endocannabinoids are also involved in the motivation to seek drugs by a dopamine-independent mechanism, demonstrated for psychostimulants and opioids. The Endocannabinoid System also participates in the common mechanisms underlying relapse to drug-seeking behaviour by mediating the motivational effects of drug-related environmental stimuli and drug re-exposure. In agreement, clinical trials have suggested that the CB 1 cannabinoid antagonist rimonabant can cause smoking cessation. Thus, CB 1 cannabinoid antagonists could represent a new generation of compounds to treat drug addiction.
Josée Guindon - One of the best experts on this subject based on the ideXlab platform.
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Sex differences and the Endocannabinoid System in pain.
Pharmacology biochemistry and behavior, 2021Co-Authors: Henry L. Blanton, Robert C. Barnes, Melissa C. Mchann, Joshua A. Bilbrey, Jenny L. Wilkerson, Josée GuindonAbstract:Cannabis use has been increasing in recent years, particularly among women, and one of the most common uses of cannabis for medical purposes is pain relief. Pain conditions and response to analgesics have been demonstrated to be influenced by sex, and evidence is emerging that this is also true with cannabinoid-mediated analgesia. In this review we evaluate the preclinical evidence supporting sex differences in cannabinoid pharmacology, as well as emerging evidence from human studies, both clinical and observational. Numerous animal studies have reported sex differences in the antinociceptive response to natural and synthetic cannabinoids that may correlate to sex differences in expression, and function, of Endocannabinoid System components. Female rodents have generally been found to be more sensitive to the effects of Δ9-THC. This finding is likely a function of both pharmacokinetic and pharmacodynamics factors including differences in metabolism, differences in cannabinoid receptor expression, and influence of ovarian hormones including estradiol and progesterone. Preclinical evidence supporting direct interactions between sex hormones and the Endocannabinoid System may translate to sex differences in response to cannabis and cannabinoid use in men and women. Further research into the role of sex in Endocannabinoid System function is critical as we gain a deeper understanding of the impact of the Endocannabinoid System in various disease states, including chronic pain.
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the Endocannabinoid System and cancer therapeutic implication
British Journal of Pharmacology, 2011Co-Authors: Josée Guindon, Andrea G HohmannAbstract:The Endocannabinoid System is implicated in a variety of physiological and pathological conditions (inflammation, immunomodulation, analgesia, cancer and others). The main active ingredient of cannabis, Δ9-tetrahydrocannabinol (Δ9-THC), produces its effects through activation of CB1 and CB2 receptors. CB1 receptors are expressed at high levels in the central nervous System (CNS), whereas CB2 receptors are concentrated predominantly, although not exclusively, in cells of the immune System. Endocannabinoids are endogenous lipid-signalling molecules that are generated in the cell membrane from phospholipid precursors. The two best characterized Endocannabinoids identified to date are anandamide (AEA) and 2-arachidonoylglycerol (2-AG). Here we review the relationship between the Endocannabinoid System and anti-tumour actions (inhibition of cell proliferation and migration, induction of apoptosis, reduction of tumour growth) of the cannabinoids in different types of cancer. This review will focus on examining how activation of the Endocannabinoid System impacts breast, prostate and bone cancers in both in vitro and in vivo Systems. The therapeutic potential of cannabinoids for cancer, as identified in clinical trials, is also discussed. Identification of safe and effective treatments to manage and improve cancer therapy is critical to improve quality of life and reduce unnecessary suffering in cancer patients. In this regard, cannabis-like compounds offer therapeutic potential for the treatment of breast, prostate and bone cancer in patients. Further basic research on anti-cancer properties of cannabinoids as well as clinical trials of cannabinoid therapeutic efficacy in breast, prostate and bone cancer is therefore warranted. LINKED ARTICLES This article is part of a themed issue on Cannabinoids in Biology and Medicine. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue-7
Johannes F.g. Vliegenthart - One of the best experts on this subject based on the ideXlab platform.
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Acute neuronal injury, excitotoxicity, and the Endocannabinoid System.
Molecular Neurobiology, 2002Co-Authors: Mario Van Der Stelt, Mauro Maccarrone, Vincenzo Di Marzo, Wouter B. Veldhuis, Peter R. Bär, Klaas Nicolay, Gerrit A. Veldink, Johannes F.g. VliegenthartAbstract:The Endocannabinoid System is a valuable target for drug discovery, because it is involved in the regulation of many cellular and physiological functions. The Endocannabinoid System constitutes the endogenous lipids anandamide, 2-arachidonoylglycerol and noladin ether, and the cannabinoid CB1 and CB2 receptors as well as the proteins for their inactivation. It is thought that (endo)cannabinoid-based drugs may potentially be useful to reduce the effects of neurodegeneration. This paper reviews recent developments in the Endocannabinoid System and its involvement in neuroprotection.
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Acute neuronal injury, excitotoxicity, and the Endocannabinoid System.
Molecular neurobiology, 2002Co-Authors: Mario Van Der Stelt, Mauro Maccarrone, Vincenzo Di Marzo, Wouter B. Veldhuis, Peter R. Bär, Klaas Nicolay, Gerrit A. Veldink, Johannes F.g. VliegenthartAbstract:The Endocannabinoid System is a valuable target for drug discovery, because it is involved in the regulation of many cellular and physiological functions. The Endocannabinoid System constitutes the endogenous lipids anandamide, 2-arachidonoylglycerol and noladin ether, and the cannabinoid CB1 and CB2 receptors as well as the proteins for their inactivation. It is thought that (endo)cannabinoid-based drugs may potentially be useful to reduce the effects of neurodegeneration. This paper reviews recent developments in the Endocannabinoid System and its involvement in neuroprotection. Exogenous (endo)cannabinoids have been shown to exert neuroprotection in a variety of in vitro and in vivo models of neuronal injury via different mechanisms, such as prevention of excitotoxicity by CB1-mediated inhibition of glutamatergic transmission, reduction of calcium influx, and subsequent inhibition of deleterious cascades, TNF-alpha formation, and anti-oxidant activity. It has been suggested that the release of endogenous Endocannabinoids during neuronal injury might be a protective response. However, several observations indicate that the role of the Endocannabinoid System as a general endogenous protection System is questionable. The data are critically reviewed and possible explanations are given.