“This narrative review summarizes recent insights into the role of the cannabinoid type 2 (CB2) receptor as potential therapeutic target in neuropathic pain and neurodegenerative conditions.
“The landscape of medical cannabis is rapidly expanding. Cannabis preparations have been used in medicine for millennia, and now there is a strong renaissance in the study of their therapeutic properties. The vast majority of controlled clinical trials that support the medical use of what is commonly known as “cannabis” or “marijuana” have actually been conducted with purified cannabinoids or a single extract of Cannabis sativa that contains an equimolecular proportion of Δ9-THC and CBD. Based on these studies, THC/dronabinol (Marinol) and its synthetic analogue nabilone (Cesamet), as well as nabiximols (Sativex), are already approved by several regulatory agencies, including FDA, Health Canada, and EMA, as antiemetic, anticachexic, analgesic, or antispastic medicines. This study provides a precious piece of information on the use of medical cannabis for the management of cancer symptoms.” https://www.liebertpub.com/doi/10.1089/can.2018.0009]]>
“The present review shows that cannabinoids exert their anti-cancer effects in a number of ways and in a variety of tissues. The endocannabinoid system is an almost ubiquitous signalling system involved in the control of cell fate. Recent studies have investigated the possibility that drugs targeting the endocannabinoid system might be used to retard or block cancer growth. The endocannabinoids have been shown to inhibit the growth of tumour cells in culture and animal models by modulating key cell signalling pathways. Therefore, the present review indicated that cannabinoids exert their anti-cancer effects in a number of ways and in a variety of tissues.
“A number of studies have consistently shown that cannabinoids are able to prevent or reduce carcinogenesis in different animal models of colon cancer. Cannabinoids, via CB1 and possibly CB2 receptors, suppress proliferation and migration and stimulate apoptosis in colorectal cancer cells. Convincing scientific evidence suggests that cannabinoids, in addition to their well-known use in palliative care in oncology (e.g. improvement of appetite, attenuation of nausea associated to antitumoral medicines, alleviation of moderate neuropathic pain) can reduce, via antiproliferative and proapoptotic as well as by inhibiting angiogenesis, invasion and metastasis or by attenuating inflammation, the growth of cancer cells and hinder the development of experimental colon carcinogenesis in vivo.” https://www.tandfonline.com/doi/full/10.1080/17474124.2017.1367663?src=recsys]]>
“Gliobalstoma multiforme (GBM) or grade 4 astrocytoma is the most malignant form of primary brain tumor. Treatment of glioblastoma is difficult despite of surgery, radiotherapy and chemotherapy. Patients with glioblastoma survive for less than 12 months. Considering to biology function of glioblastoma, researchers have recently offered new therapeutic approaches such as cannabinoid therapy for glioblastoma. Cannabinoids are active compounds of Cannabis sativa that operate in the body similar to endogenous canabinoids –the endocannabinoids- through cell surface receptors. It is interesting that cannabinoids could exert a wide spectrum from antiproliferative effects in condition of the cell culture, animal models of glioblastoma and clinical trials. As a result, Cannabinoids seem to modulate intracellular signaling pathways and the endoplasmic reticulum stress response in glioma cells. Those play antitumoral effects through apoptosis induction and inhibition of glioblastoma angiogenesis. The goal of this study was to discuss cannabinoid therapy and also what cellular mechanisms are involved in the tumoricidal effect of the cannabinoids. In this review article, we will focus on cannabinoids, their receptor dependent functional roles against glioblastoma acccording to growth, angiogenesis, metastasis, and future purposes in exploring new possible therapeutic opportunities.” http://journals.sbmu.ac.ir/Neuroscience/article/view/13655]]>
“Glioblastoma (GBM) is the most malignant brain tumor and one of the deadliest types of solid cancer overall. Despite aggressive therapeutic approaches consisting of maximum safe surgical resection and radio-chemotherapy, more than 95% of GBM patients die within 5 years after diagnosis. Thus, there is still an urgent need to develop novel therapeutic strategies against this disease. Accumulating evidence indicates that cannabinoids have potent anti-tumor functions and might be used successfully in the treatment of GBM. This review article summarizes the latest findings on the molecular effects of cannabinoids on GBM, both in vitro and in (pre-) clinical studies in animal models and patients. The therapeutic effect of cannabinoids is based on reduction of tumor growth via inhibition of tumor proliferation and angiogenesis but also via induction of tumor cell death. Additionally, cannabinoids were shown to inhibit the invasiveness and the stem cell-like properties of GBM tumors. Recent phase II clinical trials indicated positive results regarding the survival of GBM patients upon cannabinoid treatment. Apart from a direct killing effect on tumor cells, cannabinoids can also induce cell cycle arrest thereby inhibiting tumor cell proliferation. In conclusion, cannabinoids show promising anti-neoplastic functions in GBM by targeting multiple cancer hallmarks such as resistance to programmed cell death, neoangiogenesis, tissue invasion or stem cell-induced replicative immortality. The effects of cannabinoids can be potentially enhanced by combination of different cannabinoids with each other or with chemotherapeutic agents. This requires, however, a detailed understanding of cannabinoid-induced molecular mechanisms and pharmacological effects. Ultimately, these findings might foster the development of improved therapeutic strategies against GBM and, perhaps, other diseases of the nervous system as well.” https://www.frontiersin.org/articles/10.3389/fnmol.2018.00159/full “Accumulating evidence indicates that cannabinoids have potent anti-tumor functions and might be used successfully in the treatment of GBM.” https://www.ncbi.nlm.nih.gov/pubmed/29867351]]>
“Nearly half a century has passed since the demonstration that cannabis and its chief psychoactive component Δ⁸-THC lowers intraocular pressure (IOP).
Elevated IOP remains the chief hallmark and therapeutic target for glaucoma, a condition that places millions at risk of blindness. It is likely that Δ⁸-THC exerts much of its IOP-lowering effects via the activation of CB1 cannabinoid receptors.
However, the initial promise of CB1 as a target for treating glaucoma has not thus far translated into a credible therapeutic strategy. We have recently shown that blocking monoacylglycerol lipase (MAGL), an enzyme that breaks the endocannabinoid 2-arachidonoyl glycerol (2-AG), substantially lowers IOP.
Another strategy is to develop cannabinoid CB1 receptor agonists that are optimized for topical application to the eye. Recently we have reported on a controlled-deactivation approach where the “soft” drug concept of enzymatic deactivation was combined with a “depot effect” that is commonly observed with Δ⁸-THC and other lipophilic cannabinoids.
This approach allowed us to develop novel cannabinoids with a predictable duration of action and is particularly attractive for the design of CB1 activators for ophthalmic use with limited or no psychoactive effects.
We have tested a novel class of compounds using a combination of electrophysiology in autaptic hippocampal neurons, a well-characterized model of endogenous cannabinoid signaling, and measurements of IOP in a mouse model.
We now report that AM7410 is a reasonably potent and efficacious agonist at CB1 in neurons and that it substantially (30%) lowers IOP for as long as 5 h after a single topical treatment. This effect is absent in CB1 knockout mice.
Our results indicate that the direct targeting of CB1 receptors with controlled-deactivation ligands is a viable approach to lower IOP in a murine model and merits further study in other model systems.”
https://www.ncbi.nlm.nih.gov/pubmed/29786643
http://www.mdpi.com/1424-8247/11/2/50
“Many malignant cancers, including breast cancer, have a propensity to invade bones, leading to excruciating bone pain.
Opioids are the primary analgesics used to alleviate this cancer-induced bone pain (CIBP) but are associated with numerous severe side effects, including enhanced bone degradation, which significantly impairs patients’ quality of life.
In contrast, agonists activating only peripheral CB1 receptors (CB1Rs) have been shown to effectively alleviate multiple chronic pain conditions with limited side effects, yet no studies have evaluated their role(s) in CIBP.
Here, we demonstrate for the first time that a peripherally selective CB1R agonist can effectively suppress CIBP.
Overall, our studies demonstrate that CIBP can be effectively managed by using a peripherally restricted CB1R agonist, PrNMI, without inducing dose-limiting central side effects.
Thus, targeting peripheral CB1Rs could be an alternative therapeutic strategy for the treatment of CIBP.”
“The pharmacological importance of cannabidiol (CBD) has been in study for several years.
CBD is the major nonpsychoactive constituent of plant Cannabis sativa and its administration is associated with reduced side effects.
Currently, CBD is undergoing a lot of research which suggests that it has no addictive effects, good safety profile and has exhibited powerful therapeutic potential in several vital areas.
It has wide spectrum of action because it acts through endocannabinoid receptors; CB1 and CB2 and it also acts on other receptors, such as GPR18, GPR55, GPR 119, 5HT1A, and TRPV2.
This indicates its therapeutic value for numerous medical conditions because of its neuroprotective and immunomodulatory properties.
Potential therapeutic applications of CBD include, analgesic, anti-inflammatory, anxiolytic, anti-arthritic, anti-depressant, anti-Alzheimer disease, anti-ischemic, neuroprotective, and anti-fibrotic.
More promising areas appear to include diabetes and cancer where CBD exhibits lesser side effects and more therapeutic benefits as compared to recent available medical therapies.
Hence, CBD is a promising substance for the development of new drug. However further research and clinical studies are required to explore its complete potential.”