“Cannabinoids have analgesic, immunomodulatory and anti-inflammatory properties and attenuate joint damage in animal models of arthritis.
Chondrocytes appeared to constitutively express cannabinoid receptors CB1 and CB2.
It is concluded that biologically stable synthetic cannabinoids protect cartilage matrix from degradation induced by cytokines and this effect is possibly CB-receptor mediated and involves effects on prostaglandin and nitric oxide metabolism.”
“Cannabinoids exhibit medicinal properties including analgesic, anti-inflammatory and immunosuppressive properties. This paper reviews some of the recent findings in the study of cannabinoids in pain and inflammation. Some of the effects of cannabinoids are receptor mediated and others are receptor independent. Endocannabinoids naturally reduce pain and are cerebroprotective. Natural and synthetic cannabinoids have the potential to reduce nociception, reverse the development of allodynia and hyperalgesia, reduce inflammation and inflammatory pain and protect from secondary tissue damage in traumatic head injury.”
“For thousands of years, physicians and their patients employed cannabis as a therapeutic agent.
Despite this extensive historical usage, in the Western world, cannabis fell into disfavor among medical professionals because the technology available in the 1800s and early 1900s did not permit reliable, standardized preparations to be developed.
However, since the discovery and cloning of cannabinoid receptors (CB1 and CB2) in the 1990s, scientific interest in the area has burgeoned, and the complexities of this fascinating receptor system, and its endogenous ligands, have been actively explored.
Recent studies reveal that cannabinoids have a rich pharmacology and may interact with a number of other receptor systems-as well as with other cannabinoids-to produce potential synergies.
Cannabinoids-endocannabinoids, phytocannabinoids, and synthetic cannabinoids-affect numerous bodily functions and have indicated efficacy of varying degrees in a number of serious medical conditions.
Cannabinoid receptor agonists and/or molecules that affect the modulation of endocannabinoid synthesis, metabolism, and transport may, in the future, offer extremely valuable tools for the treatment of a number of currently intractable disorders.”
“A review of the therapeutic potentials of the cannabinoids is presented. With respect to the antifertility aspects of cannabinoids, 2 mg delta 9-THC suppressed luteinizing hormone secretion in rats and 2 and 3 mg/kg resulted in a deterioation of male sexual performance. A new chapter in marijuana research was opened in 1964 with the identification of delta 9-tetrahydrocannabinol as the active ingredient. Antiedema, analgesic, antipyretic, antiinflammatory, antifertility, antiepileptic, anticonvulsant, antihypertensive, cardiotonic, pulmonary, and antidepressant effects along with potentiation of barbiturates and analgesics are reviewed leading one to the conclusion that marijuana is “a drug for all reasons”. During the past decade many investigators have pursued the possibility of modification of the delta 9 structure to delineate activities. 1 compound, Abbott 40656, SP106, a water-soluble benzopyran derivative is presently under Phase 1 clinical evaluation as a sedative-hypnotic.”
“Research has suggested that cannabis may be a promising treatment option for a number of different physical and mental health conditions, from post-traumatic stress disorder to chronic pain. A study released this week suggests that depression , anxiety and migraine can be added to that list.
Neuroscientists from the University of Buffalo’s Research Institute on Addictions found that endocannabinoids — chemical compounds in the brain that activate the same receptors as THC, an active compound in marijuana — may be helpful in treating depression, anxiety and migraine that results from chronic stress.
In studies on rats, the researchers found that chronic stress reduced the production of endocannabinoids, which affect our cognition, emotion and behavior, and have been linked to reduced feelings of pain and anxiety, increases in appetite and overall feelings of well-being. The body naturally produces these compounds, which are similar to the chemicals in cannabis. Reduction of endocannabinoid production may be one reason that chronic stress is a major risk factor in the development of depression.
Then, the research team administered marijuana cannabinoids to the rats, finding it to be an effective way to restore endocannabinoid levels in their brains — possibly, thereby, alleviating some symptoms of depression.
“Using compounds derived from cannabis — marijuana — to restore normal endocannabinoid function could potentially help stabilize moods and ease depression,” lead researcher Dr. Samir Haj-Dahmane said in a university press release.
Recent research around marijuana’s effect on symptoms of post-traumatic stress disorder further bolsters the Buffalo neuroscientists’ findings, since both disorders involve the way the brain responds to stress. A study published last year in the journal Neuropsychopharmacology, for instance, found synthetic cannabinoids triggered changes in brain centers associated with traumatic memories in rats, preventing some of the behavioral and physiological symptoms of PTSD. Another study published last year found that patients who smoked cannabis experienced a 75 percent reduction in PTSD symptoms.
However, it’s important to note that the relationship between marijuana and depression is complex. Some research has suggested that regular and heavy marijuana smokers are at a higher risk for depression, although a causal link between cannabis use and depression has not been established. More studies are needed in order to determine whether, and how, marijuana might be used in a clinical context for patients with depression.” http://painphysicianjournal.co/2016/06/30/new-study-finds-marijuana-to-be-effective-against-depression-migraine-and-anxiety/
New Study Finds Marijuana To Be Effective Against Depression, Migraine and Anxiety
“Previous studies have demonstrated that locally administered cannabinoids attenuate allodynia and hyperalgesia through activation of peripheral cannabinoid receptors (CB1 and CB2).
These results suggest that attenuation of mechanically evoked responses of Aδ nociceptors contributes to the behavioral antinociception produced by activation of peripheral CB1 receptors during inflammation.
Several studies have demonstrated that locally administered cannabinoids produce antinociception in animal models of both acute and persistent pain through peripheral mechanisms.
Taken together, our data suggest that peripherally acting cannabinoids could be a potential therapeutic treatment for chronic inflammatory pain.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2585399/
“Cannabinoids, components of the Cannabis sativa (marijuana) plant, are known to exert potent anti-inflammatory, immunomodulatory and analgesic effects through activation of cannabinoid-1 and -2 (CB1 and CB2) receptors located in the central nervous system and immune cells.
The limitation of the therapeutic utility of the major cannabinoid, Δ9-tetrahydrocannabinol, is the development of psychoactive effects through central nervous system CB1 receptor. In contrast, cannabidiol (CBD), one of the most abundant cannabinoids of Cannabis sativa with reported antioxidant, anti-inflammatory, and immunomodulatory effects is well tolerated without side effects when chronically administered to humans and is devoid of psychoactive properties due to a low affinity for the CB1 and CB2 receptors.
A nonpsychoactive cannabinoid cannabidiol (CBD) has been shown to exert potent anti-inflammatory and antioxidant effects and has recently been reported to lower the incidence of diabetes in nonobese diabetic mice and to preserve the blood-retinal barrier in experimental diabetes.
In this study we have investigated the effects of CBD on high glucose (HG)-induced, mitochondrial superoxide generation, NF-κB activation, nitrotyrosine formation, inducible nitric oxide synthase (iNOS) and adhesion molecules ICAM-1 and VCAM-1 expression, monocyte-endothelial adhesion, transendothelial migration of monocytes, and disruption of endothelial barrier function in human coronary artery endothelial cells (HCAECs).
HG markedly increased mitochondrial superoxide generation (measured by flow cytometry using MitoSOX), NF-κB activation, nitrotyrosine formation, upregulation of iNOS and adhesion molecules ICAM-1 and VCAM-1, transendothelial migration of monocytes, and monocyte-endothelial adhesion in HCAECs. HG also decreased endothelial barrier function measured by increased permeability and diminished expression of vascular endothelial cadherin in HCAECs.
Remarkably, all the above mentioned effects of HG were attenuated by CBD pretreatment.
Since a disruption of the endothelial function and integrity by HG is a crucial early event underlying the development of various diabetic complications, our results suggest that CBD, which has recently been approved for the treatment of inflammation, pain, and spasticity associated with multiple sclerosis in humans, may have significant therapeutic benefits against diabetic complications and atherosclerosis.
Collectively, our results suggest that the nonpsychoactive cannabinoid CBD have significant therapeutic benefits against diabetic complications and atherosclerosis by attenuating HG-induced mitochondrial superoxide generation, increased NF-κB activation, upregulation of iNOS and adhesion molecules, 3-NT formation, monocyte-endothelial adhesion, TEM of monocytes, and disruption of the endothelial barrier function.
This is particularly encouraging in light of the excellent safety and tolerability profile of CBD in humans.”
“Myrcene, a monoterpene… The results suggest that myrcene is capable of inducing antinociception in mice, probably mediated by alpha 2-adrenoceptor stimulated release of endogenous opioids.” http://www.ncbi.nlm.nih.gov/pubmed/1983154
“Three different medicinal cannabis varieties were investigated Bedrocan, Bedrobinol and Bediol. The top five major compounds in Bedrocan extracts were Delta(9)-THC, cannabigerol (CBG), terpinolene, myrcene, and cis-ocimene in Bedrobinol Delta(9)-THC, myrcene, CBG, cannabichromene (CBC), and camphene in Bediol cannabidiol (CBD), Delta(9)-THC, myrcene, CBC, and CBG. The major components in Bedrocan smoke were Delta(9)-THC, cannabinol (CBN), terpinolene, CBG, myrcene and cis-ocimene in Bedrobinol Delta(9)-THC, CBN and myrcene in Bediol CBD, Delta(9)-THC, CBN, myrcene, CBC and terpinolene. The major components in Bedrocan vapor were Delta(9)-THC, terpinolene, myrcene, CBG, cis-ocimene and CBD in Bedrobinol Delta(9)-THC, myrcene and CBD in Bediol CBD, Delta(9)-THC, myrcene, CBC and terpinolene. ” http://www.ncbi.nlm.nih.gov/pubmed/20118579
“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.”
“Cannabinoids and related drugs generate profound behavioral effects (such as analgesic effects) through activating CNR1 (cannabinoid receptor 1 [brain]). However, repeated cannabinoid administration triggers lysosomal degradation of the receptor and rapid development of drug tolerance, limiting the medical use of marijuana in chronic diseases.
Here we show that a protein involved in macroautophagy/autophagy (a conserved lysosomal degradation pathway), BECN2 (beclin 2), mediates cannabinoid tolerance by preventing CNR1 recycling and resensitization after prolonged agonist exposure, and deletion of Becn2 rescues CNR1 activity in mouse brain and conveys resistance to analgesic tolerance to chronic cannabinoids.
Overall, our findings demonstrate the functional link among autophagy, receptor signaling and animal behavior regulated by psychoactive drugs, and develop a new strategy to prevent tolerance and improve medical efficacy of cannabinoids by modulating the BECN2 interactome and autophagy activity.”