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Endogenous Cannabinoid Receptors and Medical Cannabis
Published in Sahar Swidan, Matthew Bennett, Advanced Therapeutics in Pain Medicine, 2020
Physiologically, pain processing is mediated through the central, autonomic, and peripheral nervous systems, all of which are potential targets for cannabinoids. Cannabinoids act on pain through mechanisms that are distinct from opioids, and it appears that these overlapping pathways may explain their synergistic and opioid-sparing effects. Cannabinoid receptors have been identified in peripheral, spinal, and supra-spinal sites and play a clear role in CNS pain signaling. Brain sites involved in cannabinoid analgesia reflect the role of descending pathways of neural connections from the brain to the spinal cord. Research indicates that both CB1 and CB2 receptors play independent roles in controlling peripheral pain.
Traumatic Brain Injury and Neurocognitive Disorders
Published in Gail S. Anderson, Biological Influences on Criminal Behavior, 2019
Cannabis, or marijuana, is very commonly used by adolescents and may adversely affect the endocannabinoid system, which plays a vital role in neural maturation during adolescence. The endocannabinoid system includes endocannabinoids or types of neurotransmitters that bind to cannabinoid receptors and cannabinoid receptor proteins. The system is important in many processes, including memory, learning, and cognition, but in adolescence is particularly important in neural development and maturation.4 Cannabis use during this time can disrupt this system. Animal studies have shown that cannabis use can impact emotional reaction, anxiety, and depression and can have long-term effects on learning and memory.4 A review of human studies indicated long-term effects of both chronic and acute cannabis use, including psychotic disorders, cognitive malfunction, mood disorders, and increased substance abuse.4 Cannabis use has been shown to impact many parts of the brain, including prefrontal, medial, temporal, and striatal regions, and chronic use can double the risk for developing schizophrenia.53
Recent Cannabinoid Delivery Systems
Published in Betty Wedman-St Louis, Cannabis as Medicine, 2019
Natascia Bruni, Carlo Della Pepa, Simonetta Oliaro-Bosso, Daniela Gastaldi, Franco Dosio, Enrica Pessione
CB2 is principally expressed in immune cells, but can also be found in various other cell types, including chondrocytes, osteocytes, and fibroblasts, meaning that it can be considered the peripheral cannabinoid receptor. It is also present in some nervous tissues, such as dorsal root ganglia and microglial cells. CB2 shows 44% amino acid similarity with CB1, and similarly inhibits adenylate cyclase as well as activating mitogen-activated protein kinase. Moreover, CB2 activation can increase intracellular calcium levels via phospholipase C. While both CB1 and CB2 are coupled to G-proteins, the transduction pathways that they activate can be different, for example, in their interactions with ion channels [10]. The association of a particular variant of CB2, known as Q63R, with celiac disease, immune thrombocytopenic purpura, and juvenile idiopathic arthritis is particularly interesting for the field of autoimmune and rheumatic diseases [11].
Palmitoylethanolamide: A Potential Alternative to Cannabidiol
Published in Journal of Dietary Supplements, 2023
Paul Clayton, Silma Subah, Ruchitha Venkatesh, Mariko Hill, Nathasha Bogoda
A few studies suggest that lower doses of 10 mg/kg may have greater anxiolytic effects than 100 mg/kg in rats (61). The anxiolytic effect may contribute to CBD’s role in sleep modulation. For example, a crossover study compared nitrazepam with CBD and reported that a high dose of 160 mg/kg CBD increased the duration of sleep for patients with insomnia (62). Previously, CBD (600 mg) was shown to induce sedative effects in healthy volunteers with six hours of sleep (58). Conversely more recent studies have reported that injecting CBD directly into the lateral hypothalamus and brain ventricles increased waking and decreased REM sleep (63, 64). Notably, along with the contradictory dose ranges and efficacy outcomes of CBD on anxiety and sleep, these studies failed to elucidate CBD’s direct mechanism of action through cannabinoid receptors.
A primer on sleeping, dreaming, and psychoactive agents
Published in Journal of Social Work Practice in the Addictions, 2023
The endocannabinoid system is a complicated biological system involved in regulating movement, mood, memory, appetite, fertility, pain, and physiological homeostasis. It consists of cannabinoid receptors and cannabinoid receptor proteins that are active throughout both the central and peripheral nervous systems. Two endogenous molecules that activate the endocannabinoid system have been found. The first, 2-arachidonoyl glycerol (2-AG), occurs in peripheral tissues, while anandamide (Sanskrit for ‘supreme joy’) is a neurotransmitter. The psychoactive component of cannabis, Δ9-tetrahydrocannabinol (THC), mimics the actions of anandamide, whereas the main therapeutic component of cannabis, cannabidiol (CBD), mimics 2-AG (Mechoulan & Parker, 2013). Data from the past 20 years indicates that the endocannabinoid system plays a role in modulating the human sleep-wake cycle and can play a part in the decrease in sleep disturbance or insomnia through the restoration of sleeping and dreaming through the regulation of how this occurs is not yet fully understood (Kesner & Lovinger, 2020; Prospéro-García et al., 2016).
Monoacylglycerol lipase deficiency in the tumor microenvironment slows tumor growth in non-small cell lung cancer
Published in OncoImmunology, 2021
Melanie Kienzl, Carina Hasenoehrl, Kathrin Maitz, Arailym Sarsembayeva, Ulrike Taschler, Paulina Valadez-Cosmes, Oliver Kindler, Dusica Ristic, Sofia Raftopoulou, Ana Santiso, Thomas Bärnthaler, Luka Brcic, Lisa Hahnefeld, Robert Gurke, Dominique Thomas, Gerd Geisslinger, Julia Kargl, Rudolf Schicho
In contrast to our knowledge of the role of MGL in tumor cells, not much is known about the presence and function of MGL in the immune and stromal cells of the tumor microenvironment (TME), in particular, as to how TME-derived MGL influences tumorigenesis. Immune cells express cannabinoid receptors, and they generate/degrade and respond to endocannabinoids, virtually forming an “immune-endocannabinoid system” (rev. in31,32). MGL has been detected in macrophages/monocytes and eosinophils (rev. in32), and a recent study suggests that MGL is present in tumor-associated macrophages (TAMs) that regulate tumor progression in mouse models of CRC.33 Using RNAScope® in situ hybridization (ISH), we recently showed that T cells (CD3+) and macrophages of mouse intestines express MGL.34