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Plant-Derived Compounds as New Therapeutics for Substance Use Disorders
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Kevin S. Murnane, Mary Frances Vest
Cannabinoid systems are one of the most promising targets for plant-derived medicines. The endocannabinoid system (ECS) has been implicated in the abuse-related effects of cannabinoids, nicotine, opioids and alcohol (Maldonado et al., 2006). Evidence for the involvement of the ECS in drug dependence has been derived from randomized controlled trials, as well as animal studies of alcohol-seeking behavior, including voluntary alcohol consumption, operant ethanol SA, ethanol preference and ethanol-induced place conditioning (de Fonseca et al., 1999; Houchi et al., 2005; Hungund et al., 2003; Maldonado et al., 2006; Sloan et al., 2017; Wang et al., 2003). The ECS is composed of two different G protein-coupled receptors (GPCRs), the CB1 and CB2 receptors (Matsuda et al., 1990). These receptors are activated by endogenous endocannabinoids such as 2-arachidonoyl ethanolamine (also known as anandamide) and 2-arachidonoylglycerol (2-AG), as was recently reviewed (Devane et al., 1992; Oppong-Damoah et al., 2021; Sugiura et al., 1995).
Endogenous Cannabinoid Receptors and Medical Cannabis
Published in Sahar Swidan, Matthew Bennett, Advanced Therapeutics in Pain Medicine, 2020
Endogenous ligands: 2-arachidonylglycerol (2-AG)N-arachidonylethanolamine (AEA or anandamide)
Cannabis
Published in Ilana B. Crome, Richard Williams, Roger Bloor, Xenofon Sgouros, 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).
Decreased melanoma CSF-1 secretion by Cannabigerol treatment reprograms regulatory myeloid cells and reduces tumor progression
Published in OncoImmunology, 2023
Iris Wyrobnik, Miryam Steinberg, Anat Gelfand, Ronen Rosenblum, Yara Eid Mutlak, Liron Sulimani, Shiri Procaccia, Yishai Ofran, Hila Novak-Kotzer, David Meiri
Although the connection between the endocannabinoid system and the immune system is well established, only a few studies focused on investigating its involvement in TME modulation. Because of the immunoregulatory properties of cannabinoids, the endocannabinoid system was previously suggested to play a fundamental role in shaping the TME and influencing tumor progression42. One study has shown the endocannabinoid 2-arachidonoylglycerol (2-AG) exhibits direct antitumor effects but also promotes an immunosuppressive microenvironment by increasing the suppressive immune cell population of MDSCs43. Another study focused on the effect of CBD on cytokine secretion in triple-negative breast cancer44. These studies, together with our results, support the potential of cannabinoids in modulating the TME in a variety of cancers. Moreover, we bring support for the utility of minor cannabinoids such as CBG in therapeutic settings.
Emerging drugs for the treatment of bladder storage dysfunction
Published in Expert Opinion on Emerging Drugs, 2022
The cannabinoid (CB) receptors, their endogenous ligands and related enzymes for biosynthesis and degradation constitutes the endocannabinoid system [22,83,84]. From the cannabis plant cannabinoids (phytocannabinoids) can be extracted. The main compounds in such extracts are THC, cannabidiol, and cannabinol. Two G-protein-coupled CB receptors have been defined: type 1 (CB1) and type 2 (CB2). The G-protein-coupled receptor 55 (GPR55), has been described as a third CB receptor, but its pharmacology is incompletely known. Endocannabinoids and ‘exocannabinoids,’ such as phyto-cannabinoids and synthetic cannabinoids, interact with these receptors and some associated endogenous fatty acid amides (FAA). Within the endocannabinoid system at least two major arachidonate-derived ligands, anandamide, and 2-arachidonoylglycerol (2-AG), mediate their effects by binding to CB1 and CB2 receptors. Both anandamide and 2-AG act extensively in the central and peripheral nervous system. They affect not only LUT function but may influence pain, mood, feeding behavior, motivation, and inflammation [85–87].
Medical marijuana for inflammatory bowel disease: the highs and lows
Published in Scandinavian Journal of Gastroenterology, 2022
The endocannabinoid system is composed primarily of the G protein coupled cannabinoid receptors CB1 and CB2 (also known as CNR1 and CNR2 respectively); endogenous cannabinoids targeting these and other receptors; and enzymes catalyzing the biosynthesis and metabolism of endocannabinoids [13]. Other cannabinoid receptors include transient receptor potential vanilloid type 1 (TRPV1), peroxisome proliferator activated receptor-α, and orphan G protein coupled receptors GPR55 and GPR119 [15], but this review article will be focusing on the CB1 and CB2 receptors. The two endocannabinoids that have been most studied are N-arachidonoylethanolamine (anandamine) and 2-arachidonoylglycerol (2-AG), both of which exert most of their functions by binding to and activating CB1 and CB2 receptors [16]. CB1 receptors are found predominantly at central and peripheral nerve terminals and mediate the inhibition of neurotransmitter release. CB2 receptors are found mainly on immune cells and one of their key roles appears to be in the modulation of cytokine release [17]. Atypical endocannabinoids include 2-arachidonoylglycerol ether (noladin ether), N-arachidonoyl dopamine (NADA), virodhamine, N-homo-γ-linolenoyl-ethanolamine (HEA), N-docosatetraenoyl-ethanolamine (DEA), palmitoylethanolamide (PEA), and oleoylethanolamide; these endocannabinoids bind to non CB1 and CB2 receptors and their roles in the endocannabinoid system are less clearly defined [18].