2+, Na+, and various type of K+ channels), ligand-gated ion channels (i.e., GABA, glycine), and ion-transporting membranes proteins such as transient potential receptor class (TRP) channels. The first direct, cannabinoid receptor-independent interaction was reported on the function of serotonin 5-HT3 receptor-ion channel complex. Similar effects were reported also on the other above mentioned ion channels. In the early ninety, studies searching for endogenous modulators of L-type Ca2+ channels identified anandamide as ligand for L-type Ca2+ channel. Later investigations indicated that other types of Ca2+ currents are also affected by endocannabinoids, and, in the late ninety, it was discovered that endocannabinoids activate the vanilloid receptor subtype 1 (TRPV1), and nowadays, it is known that (endo)cannabinoids gate at least five distinct TRP channels. This chapter focuses on cannabinoid regulation of ion channels and lays special emphasis on their action at transient receptor channels.” https://www.ncbi.nlm.nih.gov/pubmed/28826537]]>
Tag Archives: endocannabinoid system
Endocannabinoid Analytical Methodologies: Techniques That Drive Discoveries That Drive Techniques.
“Identification of the two major endogenous cannabinoid ligands, known as endocannabinoids, N-arachidonoyl-ethanolamine (anandamide, AEA) and 2-arachidonoyl-glycerol (2-AG), opened the way for the identification and isolation of other lipid congeners, all derivatives of fatty acids and related to the Endocannabinoid System. The nomenclature of this anandamide-type class of lipids is evolving as new species are discovered all the time. However, they each fall under the larger umbrella of lipids that are a conjugation of a fatty acid with an amine through and amide bond, which we will refer to as lipoamines. Specific subspecies of lipoamines that have been discovered are the N-acyl-ethanolamides (including AEA), N-acyl-dopamines, N-acyl-serotonins, N-acyl-GABA, N-acyl-taurines, and a growing number of N-acyl amino acids. Emerging data from multiple labs also show that monoacylglycerols (including 2-AG), COX-2 metabolites, and fatty acid esters of hydroxyl fatty acids are interconnected with these lipoamines at both the biosynthetic and metabolic levels. Understanding the molecular relatedness of these lipids is important for studying how they act as signaling molecules; however, a first step in this process hinges on advances in being able to accurately measure them.” https://www.ncbi.nlm.nih.gov/pubmed/28826532]]>
The effects of cannabinoid receptors activation and glucocorticoid receptors deactivation in the amygdala and hippocampus on the consolidation of a traumatic event.
“Ample evidence demonstrates that fear learning contributes significantly to many anxiety pathologies including post-traumatic stress disorder (PTSD). The endocannabinoid (eCB) system may offer therapeutic benefits for PTSD and it is a modulator of the hypothalamic pituitary adrenal (HPA) axis. Here we compared the separated and combined effects of blocking glucocorticoid receptors (GRs) using the GR antagonist RU486 and enhancing CB1r signaling using the CB1/2 receptor agonist WIN55,212-2 in the CA1 and basolateral amygdala (BLA) on the consolidation of traumatic memory. Traumatic memory was formed by exposure to a severe footshock in an inhibitory avoidance apparatus followed by exposure to trauma reminders. Intra-BLA RU486 (10 ng/side) and WIN55,212-2 (5 μg/side) administered immediately after shock exposure dampened the consolidation of the memory about the traumatic event and attenuated the increase in acoustic startle response in rats exposed to shock and reminders. In the CA1, WIN55,212-2 impaired consolidation and attenuated the increase in acoustic startle response whereas RU486 had no effect. The effects of WIN55,212-2 were found to be mediated by CB1 receptors, but not by GRs. Moreover, post-shock systemic WIN55,212-2 (0.5 mg/kg) administration prevented the increase in GRs and CB1 receptor levels in the CA1 and BLA in rats exposed to shock and reminders. The findings suggest that the BLA is a locus of action of cannabinoids and glucocorticoids in modulating consolidation of traumatic memory in a rat model of PTSD. Also, the findings highlight novel targets for the treatment of emotional disorders and PTSD in particular.” https://www.ncbi.nlm.nih.gov/pubmed/28818702 http://www.sciencedirect.com/science/article/pii/S1074742717301284]]>
Anticonvulsant effect of cannabidiol in the pentylenetetrazole model: Pharmacological mechanisms, electroencephalographic profile, and brain cytokine levels.
“Cannabidiol (CBD), the main nonpsychotomimetic compound from Cannabis sativa, inhibits experimental seizures in animal models and alleviates certain types of intractable epilepsies in patients. Here we tested the hypothesis that CBD anticonvulsant mechanisms are prevented by cannabinoid (CB1 and CB2) and vanilloid (TRPV1) receptor blockers. We also investigated its effects on electroencephalographic (EEG) activity and hippocampal cytokines in the pentylenetetrazole (PTZ) model. Pretreatment with CBD (60mg/kg) attenuated seizures induced by intraperitoneal, subcutaneous, and intravenous PTZ administration in mice. The effects were reversed by CB1, CB2, and TRPV1 selective antagonists (AM251, AM630, and SB366791, respectively). Additionally, CBD delayed seizure sensitization resulting from repeated PTZ administration (kindling). This cannabinoid also prevented PTZ-induced EEG activity and interleukin-6 increase in prefrontal cortex. In conclusion, the robust anticonvulsant effects of CBD may result from multiple pharmacological mechanisms, including facilitation of endocannabinoid signaling and TRPV1 mechanisms. These findings advance our understanding on CBD inhibition of seizures, EEG activity, and cytokine actions, with potential implications for the development of new treatments for certain epileptic syndromes.” https://www.ncbi.nlm.nih.gov/pubmed/28821005 http://www.epilepsybehavior.com/article/S1525-5050(17)30322-0/fulltext]]>
GPR55 G protein-coupled receptor 55 [ Homo sapiens (human) ]
“This gene belongs to the G-protein-coupled receptor superfamily. The encoded integral membrane protein is a likely cannabinoid receptor. It may be involved in several physiological and pathological processes by activating a variety of signal transduction pathways. ” https://www.ncbi.nlm.nih.gov/gene/9290
“The orphan receptor GPR55 is a novel cannabinoid receptor” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095107/
]]>A Review of the Therapeutic Antitumor Potential of Cannabinoids.
“The aim of this review is to discuss cannabinoids from a preclinical and clinical oncological perspective and provide the audience with a concise, retrospective overview of the most significant findings concerning the potential use of cannabinoids in cancer treatment.
RESULTS:
Cannabis sativa is a plant rich in more than 100 types of cannabinoids. Besides exogenous plant cannabinoids, mammalian endocannabinoids and synthetic cannabinoid analogues have been identified. Cannabinoid receptors type 1 (CB1) and type 2 (CB2) have been isolated and characterized from mammalian cells. Through cannabinoid receptor and non-receptor signaling pathways, cannabinoids show specific cytotoxicity against tumor cells, while protecting healthy tissue from apoptosis. The dual antiproliferative and proapoptotic effects of cannabinoids and associated signaling pathways have been investigated on a large panel of cancer cell lines. Cannabinoids also display potent anticancer activity against tumor xenografts, including tumors that express high resistance to standard chemotherapeutics. Few studies have investigated the possible synergistic effects of cannabinoids with standard oncology therapies, and are based on the preclinically confirmed concept of “cannabinoid sensitizers.” Also, clinical trials aimed to confirm the antineoplastic activity of cannabinoids have only been evaluated on a small number of subjects, with no consensus conclusions regarding their effectiveness.CONCLUSIONS:
A large number of cannabinoid compounds have been discovered, developed, and used to study the effects of cannabinoids on cancers in model systems. However, few clinical trials have been conducted on the use of cannabinoids in the treatment of cancers in humans. Further studies require extensive monitoring of the effects of cannabinoids alone or in combination with standard anticancer strategies. With such knowledge, cannabinoids could become a therapy of choice in contemporary oncology.”Neuroprotective activity of cannabinoid receptor-2 against oxidative stress and apoptosis in rat pups having experimentally-induced congenital hypothyroidism.
“In this study, it was aimed to show the cannabinoid receptor-2 (CB2) role, which is a part of neuroprotective endocannabinoidal system, against increasing nitric oxide synthetase (iNOS, eNOS) levels and the apoptotic activity (caspase-3, caspase-9 and DNA in situ fragmentation) within the postnatal critical period in pups of pregnant rats with artificially induced maternal thyroid hormone (TH) deficiency. In conclusion, apoptosis was triggered via oxidative stress in hypothyroid pups. Accordingly, neuroprotective activity of CB2 receptors were motivated spontaneously to resist to CNS lesions during the first 3 weeks of postnatal period.” https://www.ncbi.nlm.nih.gov/pubmed/28799288]]>
Modulation of Astrocyte Activity by Cannabidiol, a Nonpsychoactive Cannabinoid.
“The astrocytes have gained in recent decades an enormous interest as a potential target for neurotherapies, due to their essential and pleiotropic roles in brain physiology and pathology. Their precise regulation is still far from understood, although several candidate molecules/systems arise as promising targets for astrocyte-mediated neuroregulation and/or neuroprotection. The cannabinoid system and its ligands have been shown to interact and affect activities of astrocytes. Cannabidiol (CBD) is the main non-psychotomimetic cannabinoid derived from Cannabis. CBD is devoid of direct CB1 and CB2 receptor activity, but exerts a number of important effects in the brain. Here, we attempt to sum up the current findings on the effects of CBD on astrocyte activity, and in this way on central nervous system (CNS) functions, across various tested models and neuropathologies. The collected data shows that increased astrocyte activity is suppressed in the presence of CBD in models of ischemia, Alzheimer-like and Multiple-Sclerosis-like neurodegenerations, sciatic nerve injury, epilepsy, and schizophrenia. Moreover, CBD has been shown to decrease proinflammatory functions and signaling in astrocytes.” https://www.ncbi.nlm.nih.gov/pubmed/28788104 http://www.mdpi.com/1422-0067/18/8/1669]]>
Role of Endocannabinoids on Neuroinflammation in Autism Spectrum Disorder Prevention
Autism Spectrum Disorder (ASD) disease has become a mounting socio-economical alarm around the world. Neuroinflammtion had been shown in postmortem brain specimens from ASD patients.
The Endocannabinoids System (ES) consists of a family of locally produced, short-lived, endogenous, phospholipid-derived agonists (endocannabinoids) that control energy balance and body composition. The growing number of medical benefits of ES, such as their ability to regulate processes like neuroinflammation, neurogenesis and memory, raise the question of their potential role as a preventive treatment of ASD.
The complex nature of ASD advocates a multimodal drug approach that could protect from the various processes underlying neurodegeneration and thus, at minimum, delay the pathological process. The expected benefit from a chronic treatment aimed at stimulating the endocannabinoid system is a delayed progression of ASD: i.e., reduced inflammation, sustained potential for neurogenesis, and delayed memory impairment. Such results could lead to new therapeutic strategies that target the inflammation and the decline in neurogenesis associated ASD.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535348/ ]]>Cannabinoid system of dorsomedial telencephalon modulates behavioral responses to noxious stimulation in the fish Leporinus macrocephalus.
“Fish dorsomedial telencephalon has been considered a pallial region homologous to mammals amygdala, being considered a possible substrate for nociception modulation in this animal group. The present study aimed to evaluate the participation of the cannabinoid system of Dm telencephalon on nociception modulation in the fish Leporinus macrocephalus. We demonstrated that cannabidiol microinjection in Dm telecephalon inhibits the behavioral nociceptive response to the subcutaneous injection of 3% formaldehyde, and this antinociception is blocked by previous treatment with AM251 microinjection. Furthermore, AM251 microinjection in Dm prior to restraint stress also blockades the stress-induced antinociception. These results reinforce the hypothesis that this pallial telencephalic structure has a pivotal role in nociception modulation in fish.” https://www.ncbi.nlm.nih.gov/pubmed/28754268 http://www.sciencedirect.com/science/article/pii/S0031938417302299?via%3Dihub]]>