“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]]>
Category Archives: THC (Delta-9-Tetrahydrocannabinol)
Targeting cannabinoid receptors in gastrointestinal cancers for therapeutic uses: current status and future perspectives
“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]]>
Endocannabinoid system and anticancer properties of cannabinoids
“Cannabinoids impact human body by binding to cannabinoids receptors (CB1 and CB2). The two main phytocannabinoids are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC interacts with CB1 receptors occurring in central nervous system and is responsible for psychoactive properties of marijuana. CBD has low affinity to CB1 receptor, has no psychoactive characteristics and its medical applications can be wider. CB receptors are part of a complex machinery involved in regulation of many physiological processes – endocannabinoid system. Cannabinoids have found some applications in palliative medicine, but there are many reports concerning their anticancer affects. Agonists of CB1 receptors stimulate accumulation of ceramides in cancer cells, stress of endoplasmic reticulum (ER stress) and, in turn, apoptosis. Effects of cannabinoids showing low affinity to CB receptors is mediated probably by induction of reactive oxygen species production. Knowledge of antitumor activity of cannabinoids is still based only on preclinical studies and there is a necessity to conduct more experiments to assess the real potential of these compounds.” https://content.sciendo.com/view/journals/fobio/12/1/article-p11.xml]]>
Repeated social defeat-induced neuroinflammation, anxiety-like behavior and resistance to fear extinction were attenuated by the cannabinoid receptor agonist WIN55,212-2.
“Psychosocial stress contributes to the development of psychiatric disorders. Repeated social defeat (RSD) is a murine stressor that causes a release of inflammatory monocytes into circulation. Moreover, RSD-induced anxiety-like behavior is dependent on the recruitment of these monocytes to the brain.
Activation of the endocannabinoid (ECB) system may modulate both neuroendocrine and inflammatory responses mediated by stress. Therefore, we hypothesized that a cannabinoid receptor agonist would attenuate RSD-induced inflammation, anxiety, and stress sensitization.
In conclusion, activation of cannabinoid receptors limited the immune and neuroinflammatory responses to RSD and reversed the short-term and long-term behavioral deficits associated with RSD.”
https://www.ncbi.nlm.nih.gov/pubmed/29786066
https://www.nature.com/articles/s41386-018-0064-2
Cannabinoid WIN-55,212-2 mesylate inhibits tumor necrosis factor-α-induced expression of nitric oxide synthase in dorsal root ganglion neurons.
“Tumor necrosis factor-α (TNF-α) is an established pain modulator in the peripheral nervous system. Elevated levels of TNF-α in dorsal root ganglion (DRG) neurons reportedly is critical for neuropathic pain processing. It has been shown that the production of nitric oxide, a key player in the development and maintenance of nociception, depends on the expression of nitric oxide synthases (NOSs) and their activities.
Accumulating evidence also supports an important role of cannabinoids in modulating neuropathic pain.
In this study, we explored the effects and the underlying mechanisms of crosstalk between TNF-α and cannabinoid on the expression/activity of NOS in DRG neurons.
Our findings suggest that TNF-α induces the expression/activity of nNOS in DRG neurons by increasing its mRNA stability by a p38 MAPK-dependent mechanism; WIN-55 inhibits this effect of TNF-α by inhibiting p38 MAPK via CB2.
By linking the functions of TNF-α, NOS and cannabinoid in DRG neurons, this study adds new insights into the molecular mechanisms underlying the pharmacologic effects of cannabinoids on neuropathic pain as well as into the pathophysiology of neuropathic pain.”
https://www.ncbi.nlm.nih.gov/pubmed/29786105
https://www.spandidos-publications.com/10.3892/ijmm.2018.3687
“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.”
“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.”
“Structural imaging studies of