The Cannabis Papers: A citizen’s guide to cannabinoids (2011)
Go Endo Health Edition
Health is an endo thing. As we learn more about our cannabinoid system (CS), we also learn more about health: in fact, the CS is where health begins. In celebration of CS homeostatic health, or endo-healing, here are four 2015 PubMed science stories discussing: cannabinoids in the treatment of late-onset Alzheimer’s disease (LOAD), an anti-epileptogenic approach based on the endo 2-AG, toll-like receptors mediating immune responses via the CS, and rheumatoid arthritis and the multiple regulatory functions of the CS – the endo 2-AG highlighted.
Go Endo All!
I. Late-Onset Alzheimer’s Disease (LOAD) and the CS
“Given the lack of effective treatments for late-onset Alzheimer's disease (LOAD) and the substantial burden on patients, families, healthcare systems, and economies, finding an effective therapy is one of the highest medical priorities. The past few years have seen a growing interest in the medicinal uses of cannabinoids, the bioactive components of the cannabis plant, including the treatment of LOAD and other physical conditions that are common in older people. Several in vitro and in vivo studies have demonstrated that cannabinoids can reduce oxidative stress, neuroinflammation, and the formation of amyloid plaques and neurofibrillary tangles, the key hallmarks of LOAD. Also, in population-based studies, cannabinoids reduced dementia-related symptoms (e.g., behavioral disturbances). The current article provides an overview of the potential of cannabinoids in the treatment of LOAD and related neuropsychiatric symptoms in older people. We also discuss the efficacy, safety and pharmacokinetics of cannabinoid-based drugs in older people with dementia.”
Cannabinoids in late-onset Alzheimer's disease.
Ahmed AI, van der Marck MA, van den Elsen GA, Olde Rikkert MG.
Clin Pharmacol Ther. 2015 Mar 18. doi: 10.1002/cpt.117. [Epub ahead of print]
PMID: 25788394 [PubMed - as supplied by publisher]
II. Kindling Model of Temporal Lobe Epilepsy and the CS (2-AG)
“Endocannabinoids, including 2-arachidonoylglycerol (2-AG), activate presynaptic cannabinoid type 1 receptors (CB1R) on inhibitory and excitatory neurons, resulting in a decreased release of neurotransmitters. Event-specific activation of the endocannabinoid system by inhibition of the endocannabinoid degrading enzymes may offer a promising strategy to selectively activate CB1Rs at the site of excessive neuronal activation with the overall goal to prevent the development epilepsy. The aim of this study was to investigate the impact of monoacylglycerol lipase (MAGL) inhibition on the development and progression of epileptic seizures in the kindling model of temporal lobe epilepsy. … In conclusion, the data demonstrate that indirect CB1R agonism delays the development of generalized epileptic seizures, but has no relevant acute anticonvulsive effects. Furthermore, we confirmed that the effects of JZL184 on kindling progression are CB1R mediated. Thus, the data indicate that the endocannabinoid 2-AG might be a promising target for an anti-epileptogenic approach."
Inhibition of monoacylglycerol lipase mediates a cannabinoid 1-receptor dependent delay of kindling progression in mice.
von Rüden EL, Bogdanovic RM, Wotjak CT, Potschka H.
Neurobiol Dis. 2015 Mar 18. pii: S0969-9961(15)00088-1. doi: 10.1016/j.nbd.2015.03.016. [Epub ahead of print]
PMID: 25796567 [PubMed - as supplied by publisher]
III. Toll-Like Receptors (TLRs), Immune Responses and the CS
“Toll-like receptors (TLRs) mediate the innate immune response to pathogens and are critical in the host defence, homeostasis and response to injury. However, uncontrolled and aberrant TLR activation can elicit potent effects on neurotransmission and neurodegenerative cascades and has been proposed to trigger the onset of certain neurodegenerative disorders and elicit detrimental effects on the progression and outcome of established disease. Over the past decade, there has been increasing evidence demonstrating that the endocannabinoid system can elicit potent modulatory effects on inflammatory processes, with clinical and preclinical evidence demonstrating beneficial effects on disease severity and symptoms in several inflammatory conditions. This review examines the evidence supporting a modulatory effect of endocannabinoids on TLR-mediated immune responses both peripherally and centrally, and the implications for psychiatric disorders such as depression and schizophrenia.”
For whom the endocannabinoid tolls: Modulation of innate immune function and implications for psychiatric disorders.
Henry RJ, Kerr DM, Finn DP, Roche M.
Prog Neuropsychopharmacol Biol Psychiatry. 2015 Mar 17. pii: S0278-5846(15)00055-X. doi: 10.1016/j.pnpbp.2015.03.006. [Epub ahead of print]
PMID: 25794989 [PubMed - as supplied by publisher]
IV. Rheumatoid Arthritis and the CS
“Since the discovery of the endogenous receptor for Δ9-tetrahydrocannabinol, a main constituent of marijuana, the endocannabinoid system (comprising cannabinoid receptors and their endogenous ligands, as well as the enzymes involved in their metabolic processes) has been implicated as having multiple regulatory functions in many central and peripheral conditions, including rheumatoid arthritis (RA). RA is an immune-mediated inflammatory disease that is associated with the involvement of many kinds of cells (such as fibroblastlike synoviocytes [FLSs], osteoclasts, T cells, B cells, and macrophages) and molecules (such as interleukin-1β, tumor necrosis factor-α, interleukin-6, matrix metalloproteinases [MMPs], and chemokines). Increasing evidence suggests that the endocannabinoid system, especially cannabinoid receptor 2 (CB2), has an important role in the pathophysiology of RA. Many members of the endocannabinoid system are reported to inhibit synovial inflammation, hyperplasia, and cartilage destruction in RA. In particular, specific activation of CB2 may relieve RA by inhibiting not only the production of autoantibodies, proinflammatory cytokines, and MMPs, but also bone erosion, immune response mediated by T cells, and the proliferation of FLSs. In this review, we will discuss the possible functions of the endocannabinoid system in the modulation of RA, which may be a potential target for treatment.”
The endocannabinoid system and its therapeutic implications in rheumatoid arthritis.
Gui H, Tong Q, Qu W, Mao CM, Dai SM.
Int Immunopharmacol. 2015 Mar 16. pii: S1567-5769(15)00100-9. doi: 10.1016/j.intimp.2015.03.006. [Epub ahead of print] Review.
PMID: 25791728 [PubMed - as supplied by publisher]
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