“A 47‐year‐old man, affected by Schwannomatosis, presented a very severe pain (10/10, NRS) with paroxysmal shooting episodes, allodynia, paresthesia, and dysesthesia; in parallel, the patient had lost weight (from 70 to 49 kg) and experienced fatigue and deep depression. The previous pain prescription, including opioids and antineutopathic drugs, was fully ineffective. We progressively substituted this therapy with 15 drops, 3 times/daily, of THC/CBD in a concentration ratio 5:1, equal to 15 mg of active substance each time, reaching improvement in pain intensity (6/10) and in several other aspects as mood and quality of life” https://www.ncbi.nlm.nih.gov/pubmed/29845778 https://onlinelibrary.wiley.com/doi/abs/10.1002/brb3.1011 “Schwannomatosis is a rare genetic disorder that results in tumors (called schwannomas) that grow on the peripheral nerves throughout the body. It is recognized most often in people over the age of 30. Schwannomatosis can cause severe, debilitating pain and neurological dysfunction.” https://www.hopkinsmedicine.org/neurology_neurosurgery/centers_clinics/neurofibromatosis/schwannomatosis/index.html]]>
Monthly Archives: May 2018
Mechanistic Potential and Therapeutic Implications of Cannabinoids in Nonalcoholic Fatty Liver Disease.
“Nonalcoholic fatty liver disease (NAFLD) is comprised of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). It is defined by histologic or radiographic evidence of steatosis in the absence of alternative etiologies, including significant alcohol consumption, steatogenic medication use, or hereditary disorders.
NAFLD is now the most common liver disease, and when NASH is present it can progress to fibrosis and hepatocellular carcinoma. Different mechanisms have been identified as contributors to the physiology of NAFLD; insulin resistance and related metabolic derangements have been the hallmark of physiology associated with NAFLD.
The mainstay of treatment has classically involved lifestyle modifications focused on the reduction of insulin resistance. However, emerging evidence suggests that the endocannabinoid system and its associated cannabinoid receptors and ligands have mechanistic and therapeutic implications in metabolic derangements and specifically in NAFLD.
Cannabinoid receptor 1 antagonism has demonstrated promising effects with increased resistance to hepatic steatosis, reversal of hepatic steatosis, and improvements in glycemic control, insulin resistance, and dyslipidemia. Literature regarding the role of cannabinoid receptor 2 in NAFLD is controversial.
Exocannabinoids and endocannabinoids have demonstrated some therapeutic impact on metabolic derangements associated with NAFLD, although literature regarding direct therapeutic use in NAFLD is limited. Nonetheless, the properties of the endocannabinoid system, its receptors, substrates, and ligands remain a significant arena warranting further research, with potential for a pharmacologic intervention for a disease with an anticipated increase in economic and clinical burden.”
https://www.ncbi.nlm.nih.gov/pubmed/29843404
http://www.mdpi.com/2305-6320/5/2/47
Investigational cannabinoids in seizure disorders, what have we learned thus far?
“The anticonvulsant activity of cannabinoids attracted much attention in the last decade. Cannabinoids that are currently investigated with the intention of making them drugs for the treatment of epilepsy are cannabidiol, cannabidivarin, Δ9-tetrahydrocannabivarin and Δ9-tetrahydrocannabinolic acid.
Areas covered. In this review, the authors look at the results of pre-clinical and clinical studies with investigational cannabinoids. Relevant literature was searched for in MEDLINE, SCOPUS, EBSCO, GOOGLE SCHOLAR and SCINDEX databases.
Expert opinion. Pre-clinical studies confirmed anticonvulsant activity of cannabidiol and cannabidivarin in a variety of epilepsy models. While the results of clinical trials with cannabidivarin are still awaited, cannabidiol showed clear therapeutic benefit and good safety in patients with therapy resistant seizures associated with Dravet syndrome and in patients with Lennox-Gastaut syndrome who have drop seizures. However, the full therapeutic potential of cannabinoids in treatment-resistant epilepsy needs to be investigated in the near future.”
https://www.ncbi.nlm.nih.gov/pubmed/29842819
https://www.tandfonline.com/doi/abs/10.1080/13543784.2018.1482275
“Although almost every state medical marijuana (MM) law identifies cancer as a qualifying condition, little research supports MM’s use in oncology. We hypothesized that the discrepancy between these laws and the scientific evidence base poses clinical challenges for oncologists. Oncologists’ beliefs, knowledge, and practices regarding MM were examined in this study.
“Inflammation as well as glutamate excitotoxicity have been proposed to participate in the propagation of autism. Palmitoylethanolamide (PEA) is an 
“In the past decades, a vast amount of data accumulated on the role of lipid signaling pathways in the progression of malignant melanoma, the most metastatic/aggressive human cancer type. Genomic studies identified that PTEN loss is the leading factor behind the activation of the PI3K-signaling pathway in melanoma, mutations of which are one of the main resistance mechanisms behind target therapy failures. On the other hand, illegitimate expressions of megakaryocytic genes p12-lipoxyganse, cyclooxygenase-2, and phosphodiestherase-2/autotaxin (ATX) are mostly involved in the regulation of motility signaling in melanoma through various G-protein-coupled bioactive lipid receptors. Furthermore, endocannabinoid signaling can also be a novel paracrine survival factor in melanoma. Last but not least, prenylation inhibitors acting even on mutated small GTP-ases, such as NRAS of melanoma may offer novel therapeutic opportunities. As regards melanoma, the most effective therapy nowadays is immunotherapy, with the resistance mechanisms also possibly involving the lipid signaling activities of melanoma cells, which further supports the idea of their being therapeutic targets.”
“Cell fate events are regulated by different endogenous developmental factors such as cell microenvironment, external or remote signals and epigenetic regulation. Among the many regulatory factors, endocannabinoid associated signalling pathways are known to lead several of these events in the developing nervous system and in the adult brain. Interestingly, endocannabinoids exert its modulatory actions in health and pathological conditions. Endocannabinoid signalling can promote cell survival acting on non-transformed brain cells (neurons, astrocytes or oligodendrocytes) while can either have a protumoural or antitumoural effect on transformed cells. Moreover, endocannabinoids are able to attenuate detrimental effects on neurogenesis and neuroinflammation associated with ageing. Thus, the endocannabinoid system emerges as an important regulator of cell fate to control cell survival/cell death decisions depending on the cell type and its environment.”
“Prepulse inhibition (PPI) of acoustic startle reflex is a well-established behavior paradigm to measure sensorimotor gating deficits. PPI is disrupted in several neuropsychiatric disorders, including schizophrenia. PPI tests can be used to screen new drugs for treatment of such disorders.
In this review, we discuss how PPI paradigm can help in screening the therapeutic effects of 
“Limited therapeutic interventions are clinically available for treating aggressive endometrial cancer (EC). Therefore, effective therapies are urgently required.
Therefore, the present study investigated the role of ∆9-tetrahydrocannabinol (THC), which is reported to impact proliferative and migratory activities during impairment of cancer progression.
In the present study, cell migration in response to THC was measured using transwell assays. Using western blot analysis, the levels of cannabinoid receptors in EC tissues were detected and pathways leading to the inhibition of cell migration by THC on human EC cells were determined.
Results suggested that cannabinoid receptors were highly expressed in EC tissues.
Furthermore, THC inhibited EC cell viability and motility by inhibiting epithelial-mesenchymal transition (EMT) and downregulating matrix metalloproteinase-9 (MMP-9) gene expression in aggressive human EC cells.
The results have the potential to promote the development of novel compounds for the treatment of EC metastasis. The present findings suggest that THC may inhibit human EC cell migration through regulating EMT and MMP-9 pathways.”