“The rostral ventromedial medulla (RVM) is a relay in the descending pain modulatory system and an important site of endocannabinoid modulation of pain.
These studies demonstrate that endocannabinoid signaling to CB1- and CB2-receptors in adult RVM is altered in persistent inflammation.
The emergence of CB2 receptor function in the RVM provides additional rationale for the development of CB2 receptor-selective agonists as useful therapeutics for chronic inflammatory pain.”
“Human Gingival Mesenchymal Stem Cells (hGMSCs) are multipotential cells that can expand and differentiate in culture under specific and standardized conditions.
In the present study, we have investigated whether in vitro pre-treatment of hGMSCs with Cannabidiol(CBD) can influence their expression profile, improving the therapeutic potential of this cell culture.
In conclusion, the present study will provide a new simple and reproducible method for preconditioning hGMSCs with CBD, before transplantation, as an interesting strategy for improving the hGMSCs molecular phenotype, reducing the risk of immune or inflammatory reactions in the host, and in parallel, for increasing their survival and thus, their long-term therapeutic efficacy.”
“Chronic pain is a complex, severe and debilitating condition which can lead to a considerable reduction in function and quality of life. Patients may present with different forms of chronic pain resulting from a number of identifiable causes, including pain due to lesion or dysfunction of the nerves, spinal cord or brain (neuropathic pain), or persistent pain caused by other non-malignant conditions, such as low-back pain or pain due to inflammation of various arthritic conditions. The prevalence of chronic non-cancer pain or neuropathic pain among Canadian adults is not well known. However, prevalence estimates using large, population-based questionnaires have shown that 4% to 8% of the general population in the developed world experiences neuropathic pain, suggesting that approximately two million Canadians may be affected by this disabling condition. Chronic pain is of particular concern among Canadians aged 65 years and older; based on cross-sectional data from the 1996/1997 National Population Health Survey and the 2005 Canadian Community Health Survey, chronic pain was estimated to affect 27% and 38% of seniors living in households and health care institutions, respectively. A number of treatments are available for the management of neuropathic pain or chronic non-cancer pain. These include tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors (duloxetine, venlafaxine), anticonvulsants (pregabalin, gabapentin, carbamazepine, phenytoin), topical lidocaine, and opioid analgesics. However, these medications are associated with limited pain relief and numerous adverse effects. The therapeutic use of several synthetic cannabinoid products for the symptomatic relief of chronic pain has also been studied. In particular, a combination of two products, delta-9-tetrahydrocannabinol and cannabidiol (THC:CBD) marketed under the name Sativex® is available for use as a buccal spray. This cannabis-based agent is approved for use in Canada as an add-on therapy for adult patients experiencing muscle spasticity caused by multiple sclerosis (MS), and it has received a Notice of Compliance with conditions for MS-related central neuropathic pain and the treatment of cancer pain unresponsive to opioids. The purpose of this review is to examine the available published literature relating to THC:CBD buccal spray for the treatment of chronic non-cancer or neuropathic pain in adults.”
“Cannabinoid pharmacology has made important advances in recent years after the cannabinoid system was discovered.
Studies in experimental models and in humans have produced promising results using cannabinoid-based drugs for the treatment of obesity and cancer, as well as neuroinflammatory and chronic inflammatory diseases.
Moreover, as we discuss here, additional studies also indicates that these drugs have immunosuppressive and anti-inflammatory properties including modulation of immune cell function.
Thus, manipulation of the endocannabinoid system in vivo may provide novel therapeutic strategies against inflammatory disorders.
At least two types of cannabinoid receptors, cannabinoid 1 and cannabinoid 2 receptors are expressed on immune cells such as dendritic cells (DC). Dendritic cells are recognized for their critical role in initiating and maintaining immune responses.
Therefore, DC are potential targets for cannabinoid-mediated modulation.
Here, we review the effects of cannabinoids on DC and provide some perspective concerning the therapeutic potential of cannabinoids for the treatment of human diseases involving aberrant inflammatory processes.”
“Medical marijuana continues to gain acceptance and become legalized in many states. Various species of the marijuana plant have been cultivated, and this plant can contain up to 100 active compounds known as cannabinoids.
Two cannabinoids seem the most clinically relevant: Δ9-tetrahydrocannabinol (THC), which tends to produce the psychotropic effects commonly associated with marijuana, and cannabidiol (CBD), which may produce therapeutic effects without appreciable psychoactive properties.
Smoking marijuana, or ingesting extracts from the whole plant orally (in baked goods, teas, and so forth), introduces variable amounts of THC, CBD, and other minor cannabinoids into the systemic circulation where they ultimately reach the central and peripheral nervous systems.
Alternatively, products containing THC, CBD, or a combination of both compounds, can also be ingested as oral tablets, or via sprays applied to the oral mucosal membranes. These products may provide a more predictable method for delivering a known amount of specific cannabinoids into the body.
Although there is still a need for randomized controlled clinical trials, preliminary studies have suggested that medical marijuana and related cannabinoids may be beneficial in treating chronic pain, inflammation, spasticity, and other conditions seen commonly in physical therapist practice.
Physical therapists should therefore be aware of the options that are available for patients considering medical marijuana, and be ready to provide information for these patients.”
“A randomized, placebo-controlled crossover trial utilizing vaporized cannabis containing placebo and 6.7% and 2.9% delta-9-tetrahydrocannabinol (THC) was performed in 42 subjects with central neuropathic pain related to spinal cord injury and disease.
Dose-dependent improvement in pain score was evident across all pain scale elements.
Plans for future work are outlined to explore the relationship of plasma concentrations with the analgesic response to different cannabinoids.
Such an appraisal of descriptors might contribute to the identification of distinct pathophysiologic mechanisms and, ultimately, the development of mechanism-based treatment approaches for neuropathic pain, a condition that remains difficult to treat.”
“Endocannabinoids and cannabinoid receptors are expressed in various central pain modulation regions. They maintain in dynamic changes in the expression level and distribution under different pathological and physiological conditions. These changes possess advantage as well as disadvantage. Exogenous administration of endocannabinoids exerts analgesic effect in different pain models, which is mainly mediated by the cannabinoid CB1 and CB2 receptors. Inhibition of enzymes for degrading endocannabinoids in different pain models also shows analgesic effect due to the increased local levels of endocannabinoids.”
“Compared with acute pain that arises suddenly in response to a specific injury and is usually treatable, chronic pain persists over time, and is often resistant to medical treatment.
Because of the heterogeneity of chronic pain origins, satisfactory therapies for its treatment are lacking, leading to an urgent need for the development of new treatments.
The leading approach in drug design is selective compounds, though they are often less effective and require chronic dosing with many side effects.
Herein, we review novel approaches to drug design for the treatment of chronic pain represented by dual-acting compounds, which operate at more than one biological target.
A number of studies suggest the involvement of the cannabinoid and vanilloid receptors in pain.
Interestingly cannabinoid system is in interrelation with other systems that comprise lipid mediators: prostaglandins, produced by COX enzyme.
Therefore, in the present review, we summarize the role of dual-acting molecules (FAAH/TRPV1 and FAAH/COX-2 inhibitors) that interact with endocannabinoid and endovanillinoid systems and act as analgesics by elevating the endogenously produced endocannabinoids and dampening the production of pro-inflammatory prostaglandins.
The plasticity of the endocannabinoid system (ECS) and the ability of a single chemical entity to exert an activity on two receptor systems has been developed and extensively investigated.
Here, we review up-to-date pharmacological studies on compounds interacting with FAAH enzyme together with TRPV1 receptor or COX-2 enzyme respectively.
Multi-target pharmacological intervention for treating pain may lead to the development of original and efficient treatments.”
“Neurogenic inflammation is a local inflammatory response that is driven by the peripheral release of neuropeptides from small diameter afferents which occurs in many organs including joints.
The knee joint has a rich endocannabinoid system which has been shown to decrease acute synovitis.
The aim of this study was to investigate the influence of joint afferents on leukocyte-endothelial interactions within the synovial microcirculation of mice and determine the role of endocannabinoids on this inflammatory response.
These results provide evidence that antidromic stimulation of the mouse saphenous nerve promotes leukocyte rolling within the synovial microcirculation, and that endocannabinoids can attenuate this neurogenic inflammatory response.”
“Alleviation of neuropathic pain by cannabinoids is limited by their central nervous system (CNS) side effects. Indole and indene compounds were engineered for high hCB1R affinity, peripheral selectivity, metabolic stability, and in vivo efficacy. An epithelial cell line assay identified candidates with <1% blood-brain barrier penetration for testing in a rat neuropathy induced by unilateral sciatic nerve entrapment (SNE). The SNE-induced mechanical allodynia was reversibly suppressed, partially or completely, after intraperitoneal or oral administration of several indenes. At doses that relieve neuropathy symptoms, the indenes completely lacked, while the brain-permeant CB1R agonist HU-210 (1) exhibited strong CNS side effects, in catalepsy, hypothermia, and motor incoordination assays. Pharmacokinetic findings of ~0.001 cerebrospinal fluid:plasma ratio further supported limited CNS penetration. Pretreatment with selective CB1R or CB2R blockers suggested mainly CB1R contribution to an indene’s anti-allodynic effects. Therefore, this class of CB1R agonists holds promise as a viable treatment for neuropathic pain.”