“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]]>
Category Archives: Endocannabinoid System
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 – a putative "type 3" cannabinoid receptor in inflammation.
“G protein-coupled receptor 55 (GPR55) shares numerous cannabinoid ligands with CB1 and CB2 receptors despite low homology with those classical cannabinoid receptors. The pharmacology of GPR55 is not yet fully elucidated; however, GPR55 utilizes a different signaling system and downstream cascade associated with the receptor. Therefore, GPR55 has emerged as a putative “type 3” cannabinoid receptor, establishing a novel class of cannabinoid receptor. Furthermore, the recent evidence of GPR55-CB1 and GPR55-CB2 heteromerization along with its broad distribution from central nervous system to peripheries suggests the importance of GPR55 in various cellular processes and pathologies and as a potential therapeutic target in inflammation.”
GPR55 – a putative “type 3” cannabinoid receptor in inflammation.
“G protein-coupled receptor 55 (GPR55) shares numerous cannabinoid ligands with CB1 and CB2 receptors despite low homology with those classical cannabinoid receptors. The pharmacology of GPR55 is not yet fully elucidated; however, GPR55 utilizes a different signaling system and downstream cascade associated with the receptor. Therefore, GPR55 has emerged as a putative “type 3” cannabinoid receptor, establishing a novel class of cannabinoid receptor. Furthermore, the recent evidence of GPR55-CB1 and GPR55-CB2 heteromerization along with its broad distribution from central nervous system to peripheries suggests the importance of GPR55 in various cellular processes and pathologies and as a potential therapeutic target in inflammation.”
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/
]]>The orphan receptor GPR55 is a novel cannabinoid receptor
“Preparations of Cannabis sativa have been used for medicinal and recreational purposes for at least 4000 years and extracts of C. sativa contain over 60 different pharmacologically active components the most prominent being Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol Ligands such as cannabidiol and abnormal cannabidiol which exhibit no CB1or CB2 activity and are believed to function at a novel cannabinoid receptor, also showed activity at GPR55.
These data suggest that GPR55 is a novel cannabinoid receptor, and its ligand profile with respect to CB1and CB2 described here will permit delineation of its physiological function(s).”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095107/
GPR55: A therapeutic target for Parkinson's disease?
“The GPR55 receptor is expressed abundantly in the brain, especially in the striatum, suggesting it might fulfill a role in motor function. Indeed, motor behavior is impaired in mice lacking GPR55, which also display dampened inflammatory responses. Abnormal-cannabidiol (Abn-CBD), a synthetic cannabidiol (CBD) isomer, is a GPR55 agonist that may serve as a therapeutic agent in the treatment of inflammatory diseases. In this study, we explored whether modulating GPR55 could also represent a therapeutic approach for the treatment of Parkinson’s disease (PD). These results demonstrate for the first time that activation of GPR55 might be beneficial in combating PD.” https://www.ncbi.nlm.nih.gov/pubmed/28807673 http://www.sciencedirect.com/science/article/pii/S0028390817303842
“The orphan receptor GPR55 is a novel cannabinoid receptor” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095107/
]]>GPR55: A therapeutic target for Parkinson’s disease?
“The GPR55 receptor is expressed abundantly in the brain, especially in the striatum, suggesting it might fulfill a role in motor function. Indeed, motor behavior is impaired in mice lacking GPR55, which also display dampened inflammatory responses.
Abnormal-cannabidiol (Abn-CBD), a synthetic cannabidiol (CBD) isomer, is a GPR55 agonist that may serve as a therapeutic agent in the treatment of inflammatory diseases.
In this study, we explored whether modulating GPR55 could also represent a therapeutic approach for the treatment of Parkinson’s disease (PD).
These results demonstrate for the first time that activation of GPR55 might be beneficial in combating PD.”
https://www.ncbi.nlm.nih.gov/pubmed/28807673
http://www.sciencedirect.com/science/article/pii/S0028390817303842
“The orphan receptor GPR55 is a novel cannabinoid receptor” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095107/
The novel cannabinoid receptor GPR55 mediates anxiolytic-like effects in the medial orbital cortex of mice with acute stress.
“The G protein-coupled receptor 55 (GPR55) is a novel cannabinoid receptor, whose exact role in anxiety remains unknown. The present study was conducted to explore the possible mechanisms by which GPR55 regulates anxiety and to evaluate the effectiveness of O-1602 in the treatment of anxiety-like symptoms. Mice were exposed to two types of acute stressors: restraint and forced swimming. Anxiety behavior was evaluated using the elevated plus maze and the open field test. We found that O-1602 alleviated anxiety-like behavior in acutely stressed mice. We used lentiviral shRNA to selective ly knockdown GPR55 in the medial orbital cortex and found that knockdown of GPR55 abolished the anxiolytic effect of O-1602. We also used Y-27632, a specific inhibitor of ROCK, and U73122, an inhibitor of PLC, and found that both inhibitors attenuated the effectiveness of O-1602. Western blot analysis revealed that O-1602 downregulated the expression of GluA1 and GluN2A in mice. Taken together, these results suggest that GPR55 plays an important role in anxiety and O-1602 may have therapeutic potential in treating anxiety-like symptoms.”