“The objective of this prospective, open-label study was to determine the long-term effect of medicinal cannabis treatment on pain and functional outcomes in subjects with treatment-resistant chronic pain.
The treatment of chronic pain with medicinal cannabis in this open-label, prospective cohort resulted in improved pain and functional outcomes, and significant reduction in opioid use.
The results suggest long-term benefit of cannabis treatment in this group of patients…”
“We report the discovery of compound 4a, a potent β-lactam-based monoacylglycerol lipase (MGL) inhibitor characterized by an irreversible and stereoselective mechanism of action, high membrane permeability, high brain penetration evaluated using a human in vitro blood brain barrier model, high selectivity in binding and affinity-based proteomic profiling assays, and low in vitro toxicity.
Mode-of-action studies demonstrate that 4a, by blocking MGL, increases 2-arachidonoylglycerol, and behaves as cannabinoid (CB1/CB2) receptor indirect agonist.
Administration of 4a in mice suffering from experimental autoimmune encephalitis ameliorates the severity of the clinical symptoms in a CB1/CB2-dependent manner. Moreover, 4a produced analgesic effects in a rodent model of acute inflammatory pain, which was antagonized by CB1 and CB2 receptor antagonists/inverse agonists. 4a also relieves the neuropathic hypersensitivity induced by oxaliplatin.
Given these evidences, 4a, as MGL selective inhibitor, could represent a valuable lead for the future development of therapeutic options for multiple sclerosis and chronic pain.”
“Chronic pain is commonly and closely correlated with inflammation.
Both cannabinoid signaling and mesenchymal stem cells (MSCs) have been demonstrated to reduce inflammatory pain.
Although cannabinoid signaling is essential for mesenchymal stem cell survival and differentiation, little is known about its role in modulatory effect of MSCs on inflammation and pain sensitivity. Here we showed that mouse bone-marrow derived MSCs (BM-MSCs) expressed both cannabinoid receptor type 1 and 2 (CB1 and CB2). CB2 expression level in BM-MSCs increased with their maturation.
In addition, we found that tetrahydrocannabinol (THC) activated CB2 receptor and ERK signaling, consequently enhancing the modulation of MSCs on inflammation-associated cytokine release from lipopolysaccharides-stimulated microglia.
Consistent with in vitro data, THC pretreatment enhanced the immunomodulatory effects of BM-MSC on thermal hyperalgesia and mechanical allodynia in chronic constriction injury model, by decreasing the release of pro-inflammation cytokines.
Our study revealed the crucial role of THC in promoting the immunomodulatory effects of MSCs and proposed a new strategy to alleviate pain based on stem cells therapy.”
“Chronic pain is an escalating public health problem. Currently available treatments are inadequate to control chronic pain conditions, and there is a critical need for novel treatments.
Over a half century of elegant preclinical research has identified the presence of a sophisticated endocannabinoid system that is part of our natural pain and immune defense network.
Convergent work has supported the significant potential to exploit this system to decrease pain and inflammation.
Although the clinical research remains in its infancy, recent systematic reviews have found that 25 of 30 randomized controlled trials have demonstrated a significant analgesic effect.
The authors concluded that cannabinoids currently available for clinical use demonstrate a modest analgesic effect and are safe for the management of chronic pain.
There is a critical need for more translational research so that the excellent work of Dr. Itai Bab and our basic science colleagues around the world can move forward in providing novel cannabinoid-based medicines.
This should include more potent analgesics that are limited in side effects with several routes of delivery. Our patients deserve additional agents for pain control with a novel mechanism of action, and cannabinoids are the new frontier.”
“According to this study:
* Moderate-quality evidence supports the use of cannabinoids for the treatment of chronic pain and for the spasticity related to multiple sclerosis.
* Low-quality evidence suggests that cannabinoids may be effective for chemotherapy-induced nausea and vomiting and other indications.”
“Medical Cannabis Effective for Chronic Pain, Other Indications. According to this study.” http://www.ncbi.nlm.nih.gov/pubmed/26402288
“Cannabinoid compounds include phytocannabinoids, endocannabinoids, and synthetics.
The two primary phytocannabinoids are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), with CB1 receptors in the brain and peripheral tissue and CB2 receptors in the immune and hematopoietic systems.
The route of delivery of cannabis is important as the bioavailability and metabolism are very different for smoking versus oral/sublingual routes.
Gold standard clinical trials are limited; however, some studies have thus far shown evidence to support the use of cannabinoids for some cancer, neuropathic, spasticity, acute pain, and chronic pain conditions.”
“In Switzerland, medical cannabinoids can be prescribed under compassionate use after special authorization in justified indications such as refractory pain. Evidence of efficacy in pain is limited and the clinical benefit seems to be modest. Their drug-drug interactions (DDI) profile is poorly documented. Cytochromes P450 (CYP) 2C9 and 3A4 are involved in the metabolism of tetrahydrocannabinol and cannabidiol, which implies possible DDI with CYP450 inhibitor and inducer, such as anticonvulsivants and HIV protease inhibitors, which may be prescribed in patients with neuropathic pain.”
“Sustained administration of cannabinoid agonists acting on neuronal CB1 receptors (CB1Rs) are proposed for treating spasticity and chronic pain…
Our data suggest that CB1Rs may control the circuit gateway regulating the inflow of sensory afferent inputs into the locomotor circuits, indicating a potential site of action for restricting peripheral signals disruptive for locomotor activity.”
“Use of marijuana for chronic pain, neuropathic pain, and spasticity due to multiple sclerosis is supported by high-quality evidence.
Several of these trials had positive results, suggesting that marijuana or cannabinoids may be efficacious for these indications.
Medical marijuana is used to treat a host of indications, a few of which have evidence to support treatment with marijuana and many that do not. Physicians should educate patients about medical marijuana to ensure that it is used appropriately and that patients will benefit from its use.”
“Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear.
To conduct a systematic review of the benefits and adverse events (AEs) of cannabinoids.
There was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome.
Cannabinoids were associated with an increased risk of short-term AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination.”