“The endocannabinoid system (ECS) controls a large number of vital functions. Suboptimal tone of the ECS in certain regions of the nervous system may be associated with disorders that are also associated with pain. Pain and inflammation processes can be modulated by the exogenous supply of cannabinoids. Low-to-moderate pain-relieving effects and in individual cases large pain-relieving effects were observed in randomized, controlled studies of various types of chronic pain. People with chronic neuropathic pain and stress symptoms seem to particularly benefit. The therapeutic range of cannabinoids is small; often small doses are sufficient for clinically significant effects. The “Cannabis-als-Medizin-Gesetz” (cannabis as medicine law) allows the prescription of cannabis preparations under certain conditions. Available data indicate good long-term efficacy and tolerability. However, there is little systematic long-term experience from clinical studies.” https://www.ncbi.nlm.nih.gov/pubmed/29881935 https://link.springer.com/article/10.1007%2Fs00482-018-0299-1]]>
Category Archives: Endocannabinoid System
Medicinal cannabis: presenting possible treatment modalities for the future
“Cannabis is the most popular recreational drug used in the world. It is estimated that 178 million people aged 15–64 years used cannabis at least once in 2012. Cannabis or cannabinoids used to manage medical conditions is referred to as medicinal cannabis. There are various formulations of cannabis available on the market. Cannabis can be administered orally, sublingually, or topically; it can be smoked, inhaled, mixed with food, or made into tea. It can be taken in herbal form, extracted naturally from the plant, gained by isomerization of cannabidiol (CBD), or manufactured synthetically. The commercially available prescribed cannabinoids include dronabinol capsules, nabilone capsules, and the oromucosal spray nabiximols. Canada and the Netherlands have government-run programs in which dedicated companies supply quality-controlled herbal cannabis. In the United States, 23 states and Washington, DC (May 2015) have introduced laws permitting the medical use of cannabis; other countries have similar laws.” https://www.ncbi.nlm.nih.gov/pubmed/29870436 https://insights.ovid.com/crossref?an=01787381-201806000-00001]]>
Cannabidiol Induces Rapid and Sustained Antidepressant-Like Effects Through Increased BDNF Signaling and Synaptogenesis in the Prefrontal Cortex.
“Currently available antidepressants have a substantial time lag to induce therapeutic response and a relatively low efficacy. The development of drugs that addresses these limitations is critical to improving public health.
Cannabidiol (CBD), a non-psychotomimetic component of Cannabis sativa, is a promising compound since it shows large-spectrum therapeutic potential in preclinical models and humans.
However, its antidepressant properties have not been completely investigated. Therefore, the aims of this study were to investigate in male rodents (i) whether CBD could induce rapid and sustained antidepressant-like effects after a single administration and (ii) whether such effects could be related to changes in synaptic proteins/function.
These results indicate that CBD induces fast and sustained antidepressant-like effect in distinct animal models relevant for depression. These effects may be related to rapid changes in synaptic plasticity in the mPFC through activation of the BDNF-TrkB signaling pathway.
The data support a promising therapeutic profile for CBD as a new fast-acting antidepressant drug.”
https://www.ncbi.nlm.nih.gov/pubmed/29869197
https://link.springer.com/article/10.1007%2Fs12035-018-1143-4
Cannabinoid Receptor 2-Deficiency Ameliorates Disease Symptoms in a Mouse Model with Alzheimer's Disease-Like Pathology.
“It is widely accepted that the endocannabinoid system (ECS) is a modulator of neuroinflammation associated with neurodegenerative disorders, including Alzheimer’s disease (AD).
Thus, expression of the cannabinoid receptor 2 (CB2) is induced in plaque-associated microglia and astrocytes in brain tissues from AD patients and in genetic mouse models expressing pathogenic variants of the amyloid precursor protein (APP).
However, the exact mechanism of CB2 signaling in this mouse model remains elusive, because the genetic deletion of CB2 and the pharmacological activation of CB2 both reduced neuroinflammation.
Here, we demonstrate that CB2 deletion also improved cognitive and learning deficits in APP/PS1*CB2-/- mice. This was accompanied by reduced neuronal loss and decreased plaque levels and coincided with increased expression of Aβ degrading enzymes. Interestingly, plaque-associated microglia in APP/PS1*CB2-/- mice showed a less activated morphology, while plaques were smaller and more condensed than in APP/PS1 mice.
Taken together, these results indicate a beneficial effect of CB2-deficiency in APP transgenic mice. CB2 appears to be part of a protective system that may be detrimental when engaged continuously.”
https://www.ncbi.nlm.nih.gov/pubmed/29865078
https://content.iospress.com/articles/journal-of-alzheimers-disease/jad180230
“At the beginning of the 21st century, the therapeutic management of neurodegenerative disorders remains a major biomedical challenge, particularly given the worldwide aging of the population over the past 50 years that is expected to continue in the forthcoming years.
This review will focus on the promise of 
“G protein-coupled receptors (GPCRs) interact with multiple intracellular effector proteins such that different ligands may preferentially activate one signal pathway over others, a phenomenon known as signaling bias. Signaling bias can be quantified to optimize drug selection for preclinical research.
Here, we describe moderate-throughput methods to quantify signaling bias of known and novel compounds. In the example provided, we describe a method to define 
“Maintenance of body weight is fundamental to maintain one’s health and to promote longevity. Nevertheless, it appears that the global obesity epidemic is still constantly increasing.
Endocannabinoids (eCBs) are lipid messengers that are involved in overall body weight control by interfering with manifold central and peripheral regulatory circuits that orchestrate energy homeostasis.
Initially, blocking of eCB signaling by first generation 
“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 
“Inflammation as well as glutamate excitotoxicity have been proposed to participate in the propagation of autism. Palmitoylethanolamide (PEA) is an