“Cannabinoid-2 receptor agonists may be useful in treating intestinal motility disorders.”
“Cannabinoid-2 receptor agonists may be useful in treating intestinal motility disorders.”
“Cannabinoid compounds are potential analgesics. Users of medicinal Cannabis report efficacy for pain control, clinical studies show that cannabis can be effective and opioid sparing in chronic pain, and some constituent cannabinoids have been shown to target nociceptive ion channels. Here, we explore and compare a suite of cannabinoids for their impact upon the physiology of TRPV1. The cannabinoids tested evoke differential responses in terms of kinetics of activation and inactivation. Cannabinoid activation of TRPV1 displays significant dependence on internal and external calcium levels. Cannabinoid activation of TRPV1 does not appear to induce the highly permeant, pore-dilated channel state seen with Capsaicin, even at high current amplitudes. Finally, we analyzed cannabinoid responses at nocioceptive channels other than TRPV1 (TRPV2, TRPM8 and TRPA1), and report that cannabinoids differentially activate these channels. On the basis of response activation and kinetics, state-selectivity and receptor selectivity, it may be possible to rationally design approaches to pain using single or multiple cannabinoids.”
“Recent evidence suggests that 2-week treatment with the non-psychotomimetic cannabinoid cannabidivarin (CBDV) could be beneficial towards neurological and social deficits in early symptomatic Mecp2 mutant mice, a model of Rett syndrome (RTT). The aim of this study was to provide further insights into the efficacy of CBDV in Mecp2-null mice using a lifelong treatment schedule to evaluate its effect on recognition memory and neurological defects in both early and advanced stages of the phenotype progression. CBDV rescues recognition memory deficits in Mecp2 mutant mice and delays the appearance of neurological defects. CBDV administration exerts an enduring rescue of memory deficits in Mecp2 mutant mice. CBDV delays neurological defects but this effect is only transient.” https://www.ncbi.nlm.nih.gov/pubmed/31084246
“Chronic treatment with the phytocannabinoid Cannabidivarin (CBDV) rescues behavioural alterations and brain atrophy in a mouse model of Rett syndrome.” https://www.ncbi.nlm.nih.gov/pubmed/30056123
“Cannabis sativa (cannabis) produces a resin that is valued for its psychoactive and medicinal properties. Despite being the foundation of a multi-billion dollar global industry, scientific knowledge and research on cannabis is lagging behind compared to other high-value crops. This is largely due to legal restrictions that have prevented many researchers from studying cannabis, its products, and their effects in humans. Cannabis resin contains hundreds of different terpene and cannabinoid metabolites. Our understanding of the genomic and biosynthetic systems of these metabolites in cannabis, and the factors that affect their variability, is rudimentary. As a consequence, there is concern about lack of consistency with regard to the terpene and cannabinoid composition of different cannabis ‘strains’. Likewise, claims of some of the medicinal properties attributed to cannabis metabolites would benefit from thorough scientific validation.”
“Medicinal properties of terpenes found in Cannabis sativa” https://www.ncbi.nlm.nih.gov/pubmed/30096653
“Terpene synthases from Cannabis sativa” https://www.ncbi.nlm.nih.gov/pubmed/28355238
“Cannabinoid receptor activation is involved in homeostatic regulation of the body. These receptors are activated by cannabinoids, that include the active constituents of Cannabis sativa as well as endocannabinoids (eCBs). The eCBs are endogenously synthesized from the omega-6 and omega-3 polyunsaturated fatty acids (PUFAs). In summary, we outline the novel findings regarding a growing class of signaling molecules, omega-3 eCBs, that can control the physiological and pathophysiological processes in the body.” https://www.ncbi.nlm.nih.gov/pubmed/31085370
“Anti-inflammatory ω-3 endocannabinoid epoxides.” https://www.ncbi.nlm.nih.gov/pubmed/28687674
“Antitumorigenic Properties of Omega-3 Endocannabinoid Epoxides.” https://www.ncbi.nlm.nih.gov/pubmed/29856219
“Cannabidiol (CBD), the non-psychoactive component of Cannabis sativa, acts on a diverse selection of membrane proteins with promising therapeutic potential in epilepsy and chronic pain. In this review, we will outline the studies that report reproducible results of CBD and other cannabinoids changing membrane channel function, with particular interest on Nav. Nav are implicated in fatal forms of epilepsy and are also associated with chronic pain. This makes Nav potential targets for CBD interaction since it has been reported to reduce pain and seizures. This discovery will not only prompt further research towards CBD’s characterization, but also promotes the application of cannabinoids as potentially therapeutic compounds for diseases like epilepsy and pain.” https://www.ncbi.nlm.nih.gov/pubmed/31088312
“Vulvodynia is a remarkably prevalent chronic pain condition of unknown etiology.
Therapeutic intra-vaginal administration of Δ9-tetrahydrocannabinol (THC) reduced mast cell accumulation and tactile sensitivity.
Mast cell-targeted therapeutic strategies may therefore provide new ways to manage and treat vulvar pain potentially instigated by repeated allergenic exposures.”
“Diabetes mellitus is a complex, multifactorial disorder that is attributed to pancreatic β cell dysfunction. Pancreatic β cell dysfunction results in declining utilization of glucose by peripheral tissues as kidney and it leads to nephropathy. Excessive production and accumulation of free radicals and incapable antioxidant defense system lead to impaired redox status. Macromolecular damage may occur due to impaired redox status and also immune imbalance.
Δ9-Tetrahydrocannabinol (THC) is the main active ingredient in cannabis. THC acts as an immunomodulator and an antioxidant agent.
Our aim was to evaluate the effects of THC in the diabetic kidney.
According to our data, THC has ameliorative effects on the impaired redox status of diabetic kidney and also it acts as an immunomodulator. Therefore, THC might be used as a therapeutic agent for diabetic kidneys but its usage in the healthy kidney may show adverse effects.”
“Pot Won’t Harm Healthy Young People’s Kidneys, Study Suggests” https://www.medicinenet.com/script/main/art.asp?articlekey=206375
“Glioma is a devastating primary tumor of the central nervous system with difficult-to-manage symptoms.
Cannabis products have been postulated to potentially benefit glioma patients. Recent state legalization allowed investigators an opportunity to study glioma patients’ adoption of medical marijuana (MM).
Objective: Our goals were to: (1) determine the prevalence of marijuana use, both through physician recommendation and self-medication, and (2) evaluate its perceived risks and benefits in glioma patients.
Results: A total of 73 patients were surveyed. The majority of participants were aware that MM was legal in the state, and most reported learning of this through the media. Over 70% of participants reported having considered using MM, and a third reported using marijuana products after their diagnosis. Most received recommendations from friends/family rather than a medical provider, and only half of the users had obtained a physician’s recommendation. Users generally reported benefits.
Conclusions: With the increasing national conversation that accompanies legalization, glioma patients are pursuing marijuana for the treatment for their symptoms. More research and education is needed to bring health care providers into the conversation.”
“The orphan G-protein coupled receptor (GPCR), GPR18, has been recently proposed as a potential member of the cannabinoid family as it recognizes several endogenous, phytogenic, and synthetic cannabinoids. Potential therapeutic applications for GPR18 include intraocular pressure, metabolic disorders, and cancer. GPR18 has been reported to have high constitutive activity, i.e., activation/signaling occurs in the absence of an agonist. This activity can be reduced significantly by the A3.39N mutation. At the intracellular (IC) ends of (transmembrane helices) TMH3 and TMH6 in GPCRs, typically, a pair of oppositely charged amino acids form a salt bridge called the “ionic lock”. Breaking of this salt bridge creates an IC opening for coupling with G protein. The GPR18 “ionic lock” residues (R3.50/S6.33) can form only a hydrogen bond. In this paper, we test the hypothesis that the high constitutive activity of GPR18 is due to the weakness of its “ionic lock” and that the A3.39N mutation strengthens this lock. To this end, we report molecular dynamics simulations of wild-type (WT) GPR18 and the A3.39N mutant in fully hydrated (POPC) phophatidylcholine lipid bilayers. Results suggest that in the A3.39N mutant, TMH6 rotates and brings R3.50 and S6.33 closer together, thus strengthening the GPR18 “ionic lock”.”