“Corticotropin-releasing factor (CRF) mediates anxiogenic responses by activating CRF type 1 (CRF1) receptors in limbic brain regions. Anxiety is further modulated by the endogenous cannabinoid (eCB) system that attenuates the synaptic effects of stress. In the amygdala, acute stress activates the enzymatic clearance of the eCB N-arachidonoylethanolamine via fatty acid amide hydrolase (FAAH), although it is unclear whether chronic dysregulation of CRF systems induces maladaptive changes in amygdalar eCB signaling. Here, we used genetically selected Marchigian Sardinian P (msP) rats carrying an innate overexpression of CRF1receptors to study the role of constitutive upregulation in CRF systems on amygdalar eCB function and persistent anxiety-like effects.
Treatment with an FAAH inhibitor relieves sensitized glutamatergic responses in msPs and attenuates the anxiety-like phenotype. Pathological anxiety and stress hypersensitivity are driven by constitutive increases in CRF1 signaling that dysregulate N-arachidonoylethanolamine signaling mechanisms and reduce neuronal inhibitory control of CeA glutamatergic synapses.” https://www.ncbi.nlm.nih.gov/pubmed/28209423]]>Tag Archives: endocannabinoid system
Can cannabinoids be a potential therapeutic tool in amyotrophic lateral sclerosis?
“Amyotrophic lateral sclerosis (ALS) is the most common degenerative disease of the motor neuron system. Over the last years, a growing interest was aimed to discovery new innovative and safer therapeutic approaches in the ALS treatment. In this context, the bioactive compounds of Cannabis sativa have shown antioxidant, anti-inflammatory and neuroprotective effects in preclinical models of central nervous system disease. However, most of the studies proving the ability of cannabinoids in delay disease progression and prolong survival in ALS were performed in animal model, whereas the few clinical trials that investigated cannabinoids-based medicines were focused only on the alleviation of ALS-related symptoms, not on the control of disease progression. The aim of this report was to provide a short but important overview of evidences that are useful to better characterize the efficacy as well as the molecular pathways modulated by cannabinoids.” https://www.ncbi.nlm.nih.gov/pubmed/28197175
“The endocannabinoid system in amyotrophic lateral sclerosis. There is increasing evidence that cannabinoids and manipulation of the endocannabinoid system may have therapeutic value in ALS. Cannabinoids exert anti-glutamatergic and anti-inflammatory actions through activation of the CB(1) and CB(2) receptors. The ability of cannabinoids to target multiple neurotoxic pathways in different cell populations may increase their therapeutic potential in the treatment of ALS.” http://www.ncbi.nlm.nih.gov/pubmed/18781981
“Abnormal sensitivity of cannabinoid CB1 receptors in the striatum of mice with experimental amyotrophic lateral sclerosis (ALS). Our data suggest that cannabinoid CB1 receptors might be potential therapeutic targets for this dramatic disease.” http://www.ncbi.nlm.nih.gov/pubmed/19452308
“Cannabinoid CB2 receptor selective compound, delays disease progression in a mouse model of amyotrophic lateral sclerosis. Cannabinoid CB2 receptor-selective compounds may be the basis for developing new drugs for the treatment of ALS and other chronic neurodegenerative diseases.” http://www.ncbi.nlm.nih.gov/pubmed/16781706
“Amyotrophic lateral sclerosis: delayed disease progression in mice by treatment with a cannabinoid. The cannabinoid receptor system has the potential to reduce both excitotoxic and oxidative cell damage. Here we report that treatment with Delta(9)-tetrahydrocannabinol (Delta(9)-THC) was effective. As Delta(9)-THC is well tolerated, it and other cannabinoids may prove to be novel therapeutic targets for the treatment of ALS.” http://www.ncbi.nlm.nih.gov/pubmed/15204022
“Δ9-Tetrahydrocannabinol (Δ9-THC) is the main psychoactive constituent in the plant Cannabis sativa (marijuana) and produces its effects by activation of cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) cannabinoid receptors. Administration of the non-selective partial cannabinoid agonists Δ9-THC or cannabinol are successful in delaying motor impairment and prolonging survival in mice after the onset of symptoms. Collectively, these studies suggest that cannabinoid receptors might serve as novel therapeutic targets for ALS drug development. CB2 agonists may slow motor neuron degeneration and preserve motor function, and represent a novel therapeutic modality for treatment of ALS.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819701/
“Cannabinoids exert neuroprotective and symptomatic effects in amyotrophic lateral sclerosis (ALS)” http://www.ncbi.nlm.nih.gov/pubmed/22594565
“Therapeutic options for amyotrophic lateral sclerosis (ALS) remain limited. Evidence suggests that cannabinoids, the bioactive ingredients of marijuana (Cannabis sativa) might have some therapeutic benefit in this disease. We found that this treatment significantly delays disease onset. Cannabinoids might be useful in ameliorating symptoms in ALS.” http://www.ncbi.nlm.nih.gov/pubmed/16183560
“Marijuana is a substance with many properties that may be applicable to the management of amyotrophic lateral sclerosis (ALS). These include analgesia, muscle relaxation, bronchodilation, saliva reduction, appetite stimulation, and sleep induction. In addition, marijuana has now been shown to have strong antioxidative and neuroprotective effects. Marijuana should be considered in the pharmacological management of ALS.” http://www.ncbi.nlm.nih.gov/pubmed/11467101
“Ideally, a multidrug regimen would be required to comprehensively address the known pathophysiology of ALS. REMARKABLY, cannabis appears to have activity in all of those areas. Cannabis has powerful antioxidative, anti-inflammatory, and neuroprotective effects. Cannabis might significantly slow the progression of ALS, potentially extending life expectancy and substantially reducing the overall burden of the disease.” http://www.ncbi.nlm.nih.gov/pubmed/20439484
“In light of the above findings, there is a valid rationale to propose the use of cannabinoid compounds in the pharmacological management of ALS patients. Cannabinoids indeed are able to delay ALS progression and prolong survival.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5270417/
http://www.thctotalhealthcare.com/category/amyotrophic-lateral-sclerosis-als-lou-gehrigs-disease/
Pharmacological inhibition of MAGL lipase attenuates experimental colon carcinogenesis.
“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]]>
Differential Expression of Endocannabinoid System-Related Genes in the Dorsal Hippocampus following Expression and Reinstatement of Morphine Conditioned Place Preference in Mice.
“The endocannabinoid signaling plays a critical role in mediating rewarding effects to morphine. The relative stability for the expression and reinstatement of morphine conditioned place preference (CPP) suggests the involvement of differential neuroadaptations in learned associations between environmental cues and morphine. Changes in gene expression in hippocampus through the endogenous cannabinoid system (eCB) may accompany and mediate the development of such neuroadaptations to repeated morphine stimulation. To test this possibility, we systematically compared the expression of eCB-related genes in the dorsal hippocampus following the expression, extinction, and reinstatement of morphine CPP using quantitative RT-PCR analyses. These results suggest that differential regulation of the synthesis and/or degradation of the eCB system contribute to the expression and reinstatement of morphine CPP.” https://www.ncbi.nlm.nih.gov/pubmed/28192193]]>
Endocannabinoid-dependent protection against kainic acid-induced long-term alteration of brain oscillations in guinea pigs.
“Changes in rhythmic activity can serve as early biomarkers of pathological alterations, but it remains unclear how different types of rhythmic activity are altered during neurodegenerative processes. Glutamatergic neurotoxicity, evoked by kainic acid (KA), causes hyperexcitation and acute seizures that result in delayed brain damage. We employed wide frequency range (0.1-300 Hz) local field potential recordings in guinea pigs to study the oscillatory activity of the hippocampus, entorhinal cortex, medial septum, and amygdala in healthy animals for three months after KA introduction. To clarify whether the activation of endocannabinoid (eCB) system can influence toxic KA action, AM404, an eCB reuptake inhibitor, and URB597, an inhibitor of fatty acid amide hydrolase, were applied. Our results demonstrate the protective potential of the eCB system during excitotoxic influences.” https://www.ncbi.nlm.nih.gov/pubmed/28192082]]>
Cannabinoid Receptors in Regulating the GI Tract: Experimental Evidence and Therapeutic Relevance.
“Cannabinoid receptors are fundamentally involved in all aspects of intestinal physiology, such as motility, secretion, and epithelial barrier function. They are part of a broader entity, the so-called endocannabinoid system which also includes their endocannabinoid ligands and the ligands’ synthesizing/degrading enzymes.
The system has a strong impact on the pathophysiology of the gastrointestinal tract and is believed to maintain homeostasis in the gut by controlling hypercontractility and by promoting regeneration after injury.
For instance, genetic knockout of cannabinoid receptor 1 leads to inflammation and cancer of the intestines. Derivatives of Δ9-tetrahydrocannabinol, such as nabilone and dronabinol, activate cannabinoid receptors and have been introduced into the clinic to treat chemotherapy-induced emesis and loss of appetite; however, they may cause many psychotropic side effects.
New drugs that interfere with endocannabinoid degradation to raise endocannabinoid levels circumvent this obstacle and could be used in the future to treat emesis, intestinal inflammation, and functional disorders associated with visceral hyperalgesia.”
https://www.ncbi.nlm.nih.gov/pubmed/28161834