Development of palliative medicine in the United Kingdom and Ireland
Eduardo Bruera, Irene Higginson, Charles F von Gunten, Tatsuya Morita in Textbook of Palliative Medicine and Supportive Care, 2015
The cannabinoid receptor 2 (CB2 receptor) is found in the peripheral nervous system; in contrast, the cannabinoid receptor 1 (CB1 receptor) is found in central nervous system and can induce psychotropic effects. CB2 is normally expressed in osteoblasts, osteoclasts, and their precursors, and is also found in the system associated with immune responses, such as the spleen, tonsils, monocytes, B-cells, and T-cell [31]. CB2 agonists have been shown to not only produce antinociceptive and anti-inflammatory effects, but also increase bone density by increasing the number of osteoblasts and inhibiting the production of osteoclasts [32]. In a murine bone cancer model, the systemic administration of a selective CB2 agonist significantly attenuated spontaneous and evoked pain, while reducing bone loss and decreasing the incidence of cancer-induced bone fractures [31].
Recent Cannabinoid Delivery Systems
Betty Wedman-St Louis in Cannabis as Medicine, 2019
Although phytocannabinoids have similar chemical structures, they can elicit different pharmacological action. The identification of THC paved the way for the discovery, in 1988, of cannabinoid receptor type 1 (CB1) [4], and, later, of cannabinoid receptor type 2 (CB2) [5]. CB1 and CB2, belong to a family of seven transmembrane guanosine binding protein-coupled receptors, are widely expressed and distinguished by their specific functions, localization, and signaling mechanisms. They are one of the important endogenous lipid signaling pathways, named the “endocannabinoid system,” which consists of cannabinoid receptors, the endogenous ligands of cannabinoid receptors (endocannabinoids), and the enzymes that regulate the biosynthesis and inactivation of endocannabinoids. This lipid signaling system is involved in many important physiological functions in the central and peripheral nervous system and in the endocrine and immune systems [6,7].
Cannabis
Ilana B. Crome, Richard Williams, Roger Bloor, Xenofon Sgouros in Substance Misuse and Young People, 2019
It was not until the end of the twentieth century that the specific mechanism of action of Δ9-THC was studied at the neuronal level. It was confirmed that Δ9-THC affects the brain mainly by binding to a specific cannabinoid receptor type 1 (CB1) that is expressed at high levels in many central nervous system regions, but also to a lesser degree in the peripheral nervous system and spine and other organs (Elphick, and Egertova, 2001; Wilson and Nicoll, 2002; Pagotto et al., 2006). The effects of two endocannabinoid neurotransmitter groups, anandamide and 2-arachidonoylglycerol (2-AG) (Devane et al, 1992; Stella et al., 1997) are also mediated primarily by CB1 receptors. Anandamide has been shown to impair working memory in rats (Mallet, 1996) and is important in the implantation of early stage embryos into the uterus in blastocyst form (Piomelli, 2004). It also plays a role in regulating feeding behaviour and the neural generation of motivation and pleasure (Mahler et al., 2007). 2-AG is the principal endogenous ligand for the CB2 receptors, mainly found in the peripheral tissues of the immune system that primarily mediate cytokine release (Munro et al., 1993; Cabral and Griffin-Thomas, 2009; Basu et al., 2011). CB2 receptors are also found throughout the gastrointestinal system where they modulate intestinal inflammatory response (Izzo, 2004; Wright et al., 2008).
Allosteric modulators of cannabinoid receptor 1: developing compounds for improved specificity
Published in Drug Metabolism Reviews, 2018
Rachel Dopart, Dai Lu, Aron H. Lichtman, Debra A. Kendall
The cannabinoid receptor 1 (CB1) is an attractive drug target for the management of pain (Donvito et al. 2018; Woodhams et al. 2017), neurodegenerative disorders (Fernández-Ruiz et al. 2015), obesity (Silvestri and Di Marzo 2013; Simon and Cota 2017), and substance abuse (Maldonado et al. 2006; Smith et al. 2010). Traditional approaches to designing therapeutics for targeting CB1 have focused on the orthosteric site of the receptor; the site where the endogenous cannabinoids such as anandamide (AEA) and 2-arachidonylglycerol (2-AG) bind, and where the phytocannabinoid Δ9-tetrahydrocannabinol (Δ9-THC) binds (Pertwee 2008). However, ligands targeting the orthosteric site on CB1 can cause unwanted psychoactive effects, tolerance and dependence. Allosteric ligands, which bind to site(s) topographically distinct on CB1 have been identified. These novel CB1 ligands exhibit new mechanisms of action and hold promise for discovery of CB1-targeting drugs which may have less side effects than the drugs developed by targeting the CB1 orthosteric site (Nguyen et al. 2016).
Cannabis withdrawal induced brief psychotic disorder: a case study during the national lockdown secondary to the COVID-19 pandemic
Published in Journal of Addictive Diseases, 2021
Julen Marín, Xabier Pérez de Mendiola, Sergio Fernández, Juan Pablo Chart
There is extensive evidence supporting that CUD leads to important physical, cognitive, and psychosocial problems.3–7 The association between CUD and increased risk of psychosis is consistent, although the exact biological connection is unknown.4,8 Cannabis use can contribute to the onset of an acute psychotic episode or precipitate a relapse in patients with established psychosis.4,8–10 However, it is not clear whether cannabis misuse is a cause of psychosis or a consequence of subclinical stages (self-medication).9 There is also data suggesting the existence of a shared genetic vulnerability for the development of both pathologies.9 In any case, the risk of developing psychosis is dose-dependent: it is higher in individuals with severe CUD and in those who use cannabis with a high concentration of delta-9-tetrahydrocannabinol (THC).4,8,9 THC, a partial agonist of the cannabinoid receptor 1 (CB1), is the main psychoactive component of cannabis. In the last decades, THC concentration in marijuana plants has increased remarkably,1,2,6 from 3% in the '60s to 20% nowadays.4 This is the primary reason why cannabis today has a greater addictive and psychotic potential.
Cannabinoid receptors modulate LPS-induced increase of class-II transactivator expression levels in a microglial cell line
Published in Journal of Receptors and Signal Transduction, 2021
Fatma Nihan Cankara, Zülfinaz Betül Çelik, Caner Günaydın
The effects of cannabinoids have been studied by researchers for the past two decades. Besides endocannabinoids, several synthetic compounds have been synthesized and extensively investigated for experimental and clinical studies [1]. It is becoming clear that modulation of endocannabinoids or exogenous administration of synthetic analogs offers novel treatment options for neurodegenerative diseases [2]. Cannabinoids mainly exert their effects through cannabinoid receptor-1 (CB1) and cannabinoid receptor-2 (CB2). Recent studies have revealed that the transient receptor potential vanilloid-1 (TRPV1), the transient receptor potential vanilloid-2 (TRPV2), the G protein-coupled receptor-18 (GPR18), the G protein-coupled receptor-55 (GPR55) and, the G protein-coupled receptor-155 (GPR155) are acting as possible cannabinoid receptors, and research into understanding the role of these signaling pathways on the effects of cannabinoids is increasing day by day [3–5].
Related Knowledge Centers
- Anandamide
- Cannabinoid Receptor
- Central Nervous System
- Gene Expression
- Peripheral Nervous System
- Cannabinoid
- G Protein-Coupled Receptor
- Gene
- Retrograde Signaling
- 2-Arachidonoylglycerol