“Colorectal cancer (CRC) is a major health problem in Western countries. The endocannabinoid 2-arachidonoyl-glycerol (2-AG) exerts antiproliferative actions in a number of tumoral cell lines, including CRC cells. Monoacylglycerol lipase (MAGL), a serine hydrolase that inactivates 2-AG, is highly expressed in aggressive human cancer cells. Here, we investigated the role of MAGL in experimental colon carcinogenesis. MAGL, possibly through modulation of angiogenesis, plays a pivotal role in experimental colon carcinogenesis. Pharmacological inhibition of MAGL could represent an innovative therapeutic approach to reduce colorectal tumor progression.” https://www.ncbi.nlm.nih.gov/pubmed/28193521]]>
Author Archives: David Worrell
Adolescent exposure to chronic delta-9-tetrahydrocannabinol blocks opiate dependence in maternally deprived rats.
“Maternal deprivation in rats specifically leads to a vulnerability to opiate dependence. However, the impact of cannabis exposure during adolescence on this opiate vulnerability has not been investigated. Chronic dronabinol (natural delta-9 tetrahydrocannabinol, THC) exposure during postnatal days 35-49 was made in maternal deprived (D) or non-deprived rats. These findings point to the self-medication use of cannabis in subgroups of individuals subjected to adverse postnatal environment.” https://www.ncbi.nlm.nih.gov/pubmed/19553915 “The surprising effect of cannabis on morphine dependence. Injections of THC, the active principle of cannabis, eliminate dependence on opiates (morphine, heroin) in rats deprived of their mothers at birth.” https://medicalxpress.com/news/2009-07-effect-cannabis-morphine.html
“THC HELPS LAB RATS KICK THE MORPHINE HABIT” http://hightimes.com/medicinal/thc-helps-lab-rats-kick-the-morphine-habit/
]]>Accelerated Burn Wound Closure in Mice with a New Formula Based on Traditional Medicine.
CONCLUSIONS:
A new therapeutic remedy was introduced for the treatment of burn wounds. Further clinical and molecular studies are suggested to determine the exact mechanism(s) involved in the burn wound healing effect of NF.” https://www.ncbi.nlm.nih.gov/pubmed/28191338Therapeutic effects of cannabinoids in animal models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection.
“The isolation and identification of the discrete plant cannabinoids in marijuana revived interest in analyzing historical therapeutic claims made for cannabis in clinical case studies and anecdotes. In particular, sources as old as the 11th and 15th centuries claimed efficacy for crude marijuana extracts in the treatment of convulsive disorders, prompting a particularly active area of preclinical research into the therapeutic potential of plant cannabinoids in epilepsy. Since that time, a large body of literature has accumulated describing the effects of several of the >100 individual plant cannabinoids in preclinical models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection. We surveyed the literature for relevant reports of such plant cannabinoid effects and critically reviewed their findings. We found that acute CB1R agonism in simple models of acute seizures in rodents typically produces anti-convulsant effects whereas CB1R antagonists exert converse effects in the same models. However, when the effects of such ligands are examined in more complex models of epilepsy, epileptogenesis and neuroprotection, a less simplistic narrative emerges. Here, the complex interactions between (i) brain regions involved in a given model, (ii) relative contributions of endocannabinoid signaling to modulation of synaptic transmission in such areas, (iii) multi-target effects, (iv) cannabinoid type 1 and type 2 receptor signaling interactions and, (v) timing, (vi) duration and (vii) localization of ligand administration suggest that there is both anti-epileptic therapeutic potential and a pro-epileptic risk in up- and down-regulation of endocannabinoid signaling in the central nervous system. Factors such receptor desensitization and specific pharmacology of ligands used (e.g. full vs partial agonists and neutral antagonists vs inverse agonists) also appear to play an important role in the effects reported. Furthermore, the effects of several plant cannabinoids, most notably cannabidiol (CBD) and cannabidavarin (CBDV), in models of seizures, epilepsy, epileptogenesis, and neuroprotection are less ambiguous, and consistent with reports of therapeutically beneficial effects of these compounds in clinical studies. However, continued paucity of firm information regarding the therapeutic molecular mechanism of CBD/CBDV highlights the continued need for research in this area in order to identify as yet under-exploited targets for drug development and raise our understanding of treatment-resistant epilepsies. The recent reporting of positive results for cannabidiol treatment in two Phase III clinical trials in treatment-resistant epilepsies provides pivotal evidence of clinical efficacy for one plant cannabinoid in epilepsy. Moreover, risks and/or benefits associated with the use of unlicensed Δ9-THC containing marijuana extracts in pediatric epilepsies remain poorly understood. Therefore, in light of these paradigm-changing clinical events, the present review’s findings aim to drive future drug development for newly-identified targets and indications, identify important limitations of animal models in the investigation of plant cannabinoid effects in the epilepsies, and focuses future research in this area on specific, unanswered questions regarding the complexities of endocannabinoid signaling in epilepsy.” https://www.ncbi.nlm.nih.gov/pubmed/28190698]]>
Cannabidiol: an alternative therapeutic agent for oral mucositis?
“Chemo- and radiotherapy are therapeutic modalities often used in patients with malignant neoplasms. They kill tumour cells but act on healthy tissues as well, resulting in adverse effects. Oral mucositis is especially of concern, due to the morbidity that it causes.
We reviewed the literature on the etiopathogenesis of oral mucositis and the activity of cannabidiol, to consider the possibility of its use for the prevention and treatment of oral mucositis.
The control of oxidative stress may prevent and alleviate oral mucositis. Studies have demonstrated that cannabidiol is safe to use and possesses antioxidant, anti-inflammatory and analgesic properties. The literature on the use of cannabidiol in dentistry is still scarce. Studies investigating the use of cannabidiol in oral mucositis and other oxidative stress-mediated side effects of chemotherapy and radiotherapy on the oral mucosa should be encouraged.” https://www.ncbi.nlm.nih.gov/pubmed/28191662“Review: cannabidiol may be beneficial for oral mucositis. The researchers found evidence that oxidative stress control could prevent and relieve oral mucositis. Cannabidiol was found to be safe to use and demonstrated antioxidant, anti-inflammatory, and analgesic properties,” https://medicalxpress.com/news/2017-02-cannabidiol-beneficial-oral-mucositis.html
“Cannabidiol could be beneficial for the treatment of oral mucositis, according to a review published online Feb. 12 in the Journal of Clinical Pharmacy and Therapeutics.” http://www.bioportfolio.com/news/article/3029295/Review-cannabidiol-may-be-beneficial-for-oral-mucositis.html
Bladder cancer cell growth and motility implicate cannabinoid 2 receptor-mediated modifications of sphingolipids metabolism.
“The inhibitory effects demonstrated by activation of cannabinoid receptors (CB) on cancer proliferation and migration may also play critical roles in controlling bladder cancer (BC).
CB expression on human normal and BC specimens was tested by immunohistochemistry.
Human BC cells RT4 and RT112 were challenged with CB agonists and assessed for proliferation, apoptosis, and motility. Cellular sphingolipids (SL) constitution and metabolism were evaluated after metabolic labelling.
CB1-2 were detected in BC specimens, but only CB2 was more expressed in the tumour.
Both cell lines expressed similar CB2. Exposure to CB2 agonists inhibited BC growth, down-modulated Akt, induced caspase 3-activation and modified SL metabolism.
Baseline SL analysis in cell lines showed differences linked to unique migratory behaviours and cytoskeletal re-arrangements.
CB2 activation changed the SL composition of more aggressive RT112 cells by reducing (p < 0.01) Gb3 ganglioside (-50 ± 3%) and sphingosine 1-phosphate (S1P, -40 ± 4%), which ended up to reduction in cell motility (-46 ± 5%) with inhibition of p-SRC.
CB2-selective antagonists, gene silencing and an inhibitor of SL biosynthesis partially prevented CB2 agonist-induced effects on cell viability and motility.
CB2 activation led to ceramide-mediated BC cell apoptosis independently of SL constitutive composition, which instead was modulated by CB2 agonists to reduce cell motility.”
https://www.ncbi.nlm.nih.gov/pubmed/28191815
