“Low back pain (LBP) occurs in many patients with fibromyalgia (FM). The current study aimed to assess the possible pain and function amelioration associated with medical cannabis therapy (MCT) in this setting.
“Low back pain (LBP) occurs in many patients with fibromyalgia (FM). The current study aimed to assess the possible pain and function amelioration associated with medical cannabis therapy (MCT) in this setting.

“Characterized by chronic widespread pain, generalized hyperalgesia, and psychological stress fibromyalgia (FM) is difficult to diagnose and lacks effective treatments. The endocannabinoids – arachidonoylethanolamide (AEA), 2-arachidonoylglycerol (2-AG), and the related oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA) – are endogenous lipid mediators with analgesic and anti-inflammatory characteristics, in company with psychological modulating properties (e.g., stress and anxiety), and are included in a new emerging “ome”, the endocannabinoidome. This case -control study compared the concentration differences of AEA, OEA, PEA, SEA, and 2-AG in 104 women with FM and 116 healthy controls (CON). All participants OEArated their pain, anxiety, depression, and current health status. The relationships between the lipid concentrations and the clinical assessments were investigated using powerful multivariate data analysis and traditional bivariate statistics. The concentrations of OEA, PEA, SEA, and 2-AG were significantly higher in FM than in CON; significance remained for OEA and SEA after controlling for BMI and age. 2-AG correlated positively with FM duration and BMI, and to some extent negatively with pain, anxiety, depression, and health status. In FM, AEA correlated positively with depression ratings. The elevated circulating levels of endocannabinoidome lipids suggest that these lipids play a role in the complex pathophysiology of FM and might be signs of ongoing low-grade inflammation in FM. Although the investigated lipids are significantly altered in FM their biological roles are uncertain with respect to the clinical manifestations of FM. Thus, plasma lipids alone are not good biomarkers for FM.
“Fibromyalgia is a chronic pain syndrome, characterized by chronic musculoskeletal pain, fatigue, and mood disturbances. There are nearly no data on the effect of medical cannabis (MC) treatment on patients with fibromyalgia.
“Medicine continues to struggle in its approaches to numerous common subjective pain syndromes that lack objective signs and remain treatment resistant. Foremost among these are migraine, fibromyalgia, and irritable bowel syndrome, disorders that may overlap in their affected populations and whose sufferers have all endured the stigma of a psychosomatic label, as well as the failure of endless pharmacotherapeutic interventions with substandard benefit. The commonality in symptomatology in these conditions displaying hyperalgesia and central sensitization with possible common underlying pathophysiology suggests that a clinical endocannabinoid deficiency might characterize their origin. Its base hypothesis is that all humans have an underlying endocannabinoid tone that is a reflection of levels of the endocannabinoids, anandamide (arachidonylethanolamide), and 2-arachidonoylglycerol, their production, metabolism, and the relative abundance and state of cannabinoid receptors. Its theory is that in certain conditions, whether congenital or acquired, endocannabinoid tone becomes deficient and productive of pathophysiological syndromes. When first proposed in 2001 and subsequently, this theory was based on genetic overlap and comorbidity, patterns of symptomatology that could be mediated by the endocannabinoid system (ECS), and the fact that exogenous cannabinoid treatment frequently provided symptomatic benefit. However, objective proof and formal clinical trial data were lacking. Currently, however, statistically significant differences in cerebrospinal fluid anandamide levels have been documented in migraineurs, and advanced imaging studies have demonstrated ECS hypofunction in post-traumatic stress disorder. Additional studies have provided a firmer foundation for the theory, while clinical data have also produced evidence for decreased pain, improved sleep, and other benefits to cannabinoid treatment and adjunctive lifestyle approaches affecting the ECS. Various strategies to treat CED conditions are possible. A direct approach with CB1 agonists must recognize the fact that the ECS operates as a homeostatic regulator that sometimes requires a gentle pharmacological nudge, rather than a forceful shove, by synthetic full agonists. Thus, small doses of a weak partial agonist (e.g., THC) should be considered, which would not induce tolerance and may jump-start the ECS. Even THC alone is poorly tolerated or appreciated by patients,98 and standardized whole cannabis extracts that contain additional synergistic and buffering components, such as CBD and cannabis terpenoids, are certainly preferable.93 Alternatively, FAAH inhibitors will also raise AEA levels, but only CBD among them has achieved current legal commercial market availability. Pharmaceutical approaches affecting endocannabinoid transport or its genetic regulation would also hold promise. Beyond drug interventions, a growing body of knowledge supports the realistic goal that lifestyle approaches should be integral to the treatment of CED; specifically, low-impact aerobic regimens have demonstrated beneficial effects on endocannabinoid function,99 and as discussed above, dietary manipulations with probiotics and prebiotics may ameliorate not only IBS symptoms but also the entire spectrum of CED conditions. Ultimately, multimodality approaches are most likely to be fruitful in treatment of these common yet difficult clinical challenges. http://online.liebertpub.com/doi/pdf/10.1089/can.2016.0009]]>

“Legalization of cannabis’ medicinal use is rapidly increasing worldwide, raising the need to evaluate medical implications of cannabis. Currently evidence supports cannabis and its active ingredients as an immune-modulating agents, affecting T-cells, B-cells, Monocytes and Microglia-cells, causing an overall reduction in pro-inflammatory cytokine expression and an increase in anti-inflammatory cytokines. Due to the supporting evidence of cannabinoids as an immune-modulating agent, research focusing on cannabinoids and autoimmunity has emerged. Several clinical trials in multiple sclerosis, inflammatory bowel disease and fibromyalgia suggest cannabis’ effectiveness as an immune-modulator. However, contradicting results and lack of large scale clinical trials obscure these results. Though lacking clinical research, in-vitro and in-vivo experiments in rheumatoid arthritis, diabetes type 1 and systemic sclerosis, demonstrate a correlation between disease activity and cannabinoids.”

“Several studies in humans have reported that improved pain control is associated with exercise in a variety of painful conditions, including osteoarthritis, fibromyalgia, and neuropathic pain.
Despite the growing amount of experimental data on physical exercise and nociception, the precise mechanisms through which high-intensity exercise reduces pain remain elusive.
Since the glutamatergic system plays a major role in pain transmission, we firstly analyzed if physical exercise could be able to decrease glutamate-induced nociception through G-protein-coupled receptor (G-PCR) activation.
The second purpose of this study was to examine the effect of exercising upon phosphorylation of protein kinase A (PKA) isoforms induced by intraplantar (i.pl.) glutamate injection in mice.
Our results demonstrate that high-intensity swimming exercise decreases nociception induced by glutamate and that i.pl. or intrathecal injections of cannabinoid, opioid, and adenosine receptor antagonists, AM281, naloxone, and 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), respectively, prevent this effect.
Furthermore, the peripheral A1 and opioid receptors, but not CB1, are also involved in exercise’s effect. We also verified that glutamate injection increases levels of phosphorylated PKA (p-PKA). High-intensity swimming exercise significantly prevented p-PKA increase.
The current data show the direct involvement of the glutamatergic system on the hyponociceptive effect of high-intensity swimming exercise as well as demonstrate that physical exercise can activate multiple intracellular pathways through G-PCR activation, which share the same endogenous mechanism, i.e., inhibition of p-PKA.”

“Receptors for the body’s own cannabinoid substances are present in muscle fascia — soft connective tissue surrounding all muscles and involved in several pain states, according to recent research from the University of Padua in Italy.
In addition to casting light on disease processes in fibromyalgia, the findings might lead to better approaches for managing pain and inflammation in the disease, for which current treatments often fail to adequately treat symptoms.
Endocannabinoids are bodily substances chemically resembling the cannabinoid molecules in cannabis. The factors send signals through two receptors that scientists have primarily explored in the brain and in immune cells, and studies show that stimulating the receptors can relieve pain and suppress inflammation.
Research has also demonstrated that patients with fibromyalgia report that marijuana use lowers pain and improves health-related quality of life, making researchers suspect that endocannabinoid receptors, which also mediate the effects of marijuana, might exist in tissues other than the brain and immune cells.
To explore this, the study, “Expression of the endocannabinoid receptors in human fascial tissue,“ published in the European Journal of Histochemistry, turned to muscle fascia, a tissue that has also been linked to other muscle pain conditions.
Extracting the tissue from thigh muscles of 11 volunteers who had orthopedic surgery, researchers isolated the main cell type of the fascia, called fibroblasts. They found both types of receptors, called CB1 and CB2, in the cells. Examining whole tissue levels of the two receptors, researchers noted somewhat higher levels, indicating that the receptors may also be present in other cell types.
A better understanding of how endocannabinoid receptors are involved in fibromyalgia might lead to treatments specifically targeting the receptors in the muscles, avoiding the effects of manipulating cannabinoid receptors in the brain which mediate the psychotropic actions of cannabis.”
“Cannabinoid receptors have been localized in the central and peripheral nervous system as well as on cells of the immune system, but recent studies on animal tissue gave evidence for the presence of cannabinoid receptors in different types of tissues.
Their presence was supposed also in myofascial tissue, suggesting that the endocannabinoid system may help resolve myofascial trigger points and relieve symptoms of fibromyalgia.
However, until now the expression of CB1 (cannabinoid receptor 1) and CB2 (cannabinoid receptor 2) in fasciae has not yet been established.
Small samples of fascia were collected from volunteers patients during orthopedic surgery. For each sample were done a cell isolation, immunohistochemical investigation (CB1 and CB2 antibodies) and real time RT-PCR to detect the expression of CB1 and CB2.
Both cannabinoid receptors are expressed in human fascia and in human fascial fibroblasts culture cells, although to a lesser extent than the control gene. We can assume that the expression of mRNA and protein of CB1 and CB2 receptors in fascial tissue are concentrated into the fibroblasts.
This is the first demonstration that the fibroblasts of the muscular fasciae express CB1 and CB2. The presence of these receptors could help to provide a description of cannabinoid receptors distribution and to better explain the role of fasciae as pain generator and the efficacy of some fascial treatments.
Indeed the endocannabinoid receptors of fascial fibroblasts can contribute to modulate the fascial fibrosis and inflammation.”