“The CB1 and CB2 cannabinoid receptors (CB1R, CB2R) are members of the G protein-coupled receptor (GPCR) family that were identified over 20 years ago. CB1Rs and CB2Rs mediate the effects of Δ9-tetrahydrocannabinol (Δ9-THC), the principal psychoactive constituent of marijuana, and subsequently identified endogenous cannabinoids (endocannabinoids) anandamide and 2-arachidonoyl glycerol. CB1Rs and CB2Rs have both similarities and differences in their pharmacology. Both receptors recognize multiple classes of agonist and antagonist compounds and produce an array of distinct downstream effects. Natural polymorphisms and alternative splice variants may also contribute to their pharmacological diversity. As our knowledge of the distinct differences grows, we may be able to target select receptor conformations and their corresponding pharmacological responses. This chapter will discuss their pharmacological characterization, distribution, phylogeny, and signaling pathways. In addition, the effects of extended agonist exposure and how that affects signaling and expression patterns of the receptors are considered.” https://www.ncbi.nlm.nih.gov/pubmed/28826534 http://www.sciencedirect.com/science/article/pii/S1054358917300340?via%3Dihub]]>
Category Archives: Uncategorized
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]]>
Rationale for cannabis-based interventions in the opioid overdose crisis.
“North America is currently in the grips of a crisis rooted in the use of licit and illicit opioid-based analgesics. Drug overdose is the leading cause of accidental death in Canada and the US, and the growing toll of opioid-related morbidity and mortality requires a diversity of novel therapeutic and harm reduction-based interventions.
Research suggests that increasing adult access to both medical and recreational cannabis has significant positive impacts on public health and safety as a result of substitution effect. Observational and epidemiological studies have found that medical cannabis programs are associated with a reduction in the use of opioids and associated morbidity and mortality.
The growing body of research supporting the medical use of cannabis as an adjunct or substitute for opioids creates an evidence-based rationale for governments, health care providers, and academic researchers to consider the implementation and assessment of cannabis-based interventions in the opioid crisis.”
https://www.ncbi.nlm.nih.gov/pubmed/28821296Effects of Legal Access to Cannabis on Scheduled II-V Drug Prescriptions
“Legal access to cannabis may reduce the use of multiple classes of dangerous prescription medications in certain patient populations.”“Medical Cannabis and Reduced Prescription Use. Breakthrough Study Indicates Strong Association Between Medical Cannabis and Reduced Prescription Use.” http://www.prnewswire.com/news-releases/medical-cannabis-and-reduced-prescription-use-300506774.html
“Effects of Legal Access to Cannabis on Scheduled II-V Drug Prescriptions. Legal access to cannabis may reduce the use of multiple classes of dangerous prescription medications in certain patient populations.” https://www.ncbi.nlm.nih.gov/pubmed/28899660
“Legal access to cannabis may reduce the use of multiple classes of dangerous prescription medications in certain patient populations.” http://www.jamda.com/article/S1525-8610(17)30429-2/fulltext]]>Topical Medical Cannabis (TMC): A new treatment for wound pain-Three cases of Pyoderma Gangrenosum.
“Pain associated with integumentary wounds is highly prevalent yet it remains an area of significant unmet need within healthcare. Currently, systemically administered opioids are the mainstay of treatment. However, recent publications are casting opioids in a negative light given their high side effect profile, inhibition of wound healing, and association with accidental overdose, incidents that are frequently fatal. Thus, novel analgesic strategies for wound-related pain need to be investigated. The ideal methods of pain relief for wound patients are modalities that are topical, lack systemic side effects, non-invasive, self-administered, and display rapid onset of analgesia. Extracts derived from the cannabis plant have been applied to wounds for thousands of years. The discovery of the human endocannabinoid system and its dominant presence throughout the integumentary system provides a valid and logical scientific platform to consider the use of topical cannabinoids for wounds. We are reporting a prospective case series of 3 patients with Pyoderma Gangrenosum (PG) that were treated with Topical Medical Cannabis (TMC) compounded in non-genetically modified organic sunflower oil. Clinically significant analgesia that was associated with reduced opioid utilization was noted in all 3 cases. TMC has the potential to improve pain management in patients suffering from wounds of all classes.” https://www.ncbi.nlm.nih.gov/pubmed/28818631 http://www.jpsmjournal.com/article/S0885-3924(17)30351-2/fulltext]]>
How Does Marijuana Effect Outcomes After Trauma in ICU Patients? A Propensity Matched Analysis
“Unlike several studies that focus on the effects of marijuana on the outcomes of diseases, our aim was to assess the relationship between a positive toxicology screen for marijuana and mortality in such patients. A positive marijuana screen is associated with decreased mortality in adult trauma patients admitted to the ICU. This association warrants further investigation of the possible physiological effects of marijuana in trauma patients.” https://insights.ovid.com/pubmed?pmid=28787375]]>
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.”