Tag Archives: anti-inflammatory

Efficacy and Tolerability of Phytomedicines in Multiple Sclerosis Patients: A Review.

Posted on by
Reply

 CNS Drugs

“Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disorder of the central nervous system (CNS) that can cause cognition, mobility, and sensory impairments. It is considered one of the most common non-traumatic causes of disability in the world.

The aim of the present article was to review the clinical evidence related to medicinal plants in the management of MS symptoms.

Electronic databases, including the Cochrane Library, Pubmed, and Scopus, were searched for entries from 1966 to February 2017. Only clinical studies were included in this review. Different medicinal plants have positive effects on MS, including Andrographis paniculata, Boswellia papyrifera, Ruta graveolens, Vaccinium spp., Camellia sinensis, Panax ginseng, Aloysia citrodora, Ginkgo biloba, Oenothera biennis, and Cannabis sativa.

C. sativa had the highest level of clinical evidence, supporting its efficacy in MS symptoms.

Proanthocyanidins, ginkgo flavone glycosides, ginsenosides, epigallocatechin-3-gallate, cannabinoids (including delta-9-tetrahydrocannabinol and cannabidiol), boswellic acid, and andrographolide were presented as the main bioactive components of medicinal plants with therapeutic benefits in MS.

The main complications of MS in which natural drugs were effective include spasticity, fatigue, scotoma, incontinence, urinary urgency, nocturia, memory performance, functional performance, and tremor. Herbal medicines were mostly well tolerated, and the adverse effects were limited to mild to moderate. Further well-designed human studies with a large sample size and longer follow-up period are recommended to confirm the role of medicinal plants and their metabolites in the management of MS.”

https://www.ncbi.nlm.nih.gov/pubmed/28948486

https://link.springer.com/article/10.1007%2Fs40263-017-0466-4

Targeting the Endocannabinoid System to Treat Sepsis

Posted on by
Reply

Image result for Signa Vitae

“Sepsis is a complex immune disorder that can affect the function of almost all organ systems in the body. This disorder is characterised by a malfunctioning immune response to an infection that involves both pro-inflammatory and immunosuppressive mediators. This leads to severe damage and failure of vital organs, resulting in patient death. Sepsis, septic shock, and systemic inflammatory response syndrome are the leading causes of mortality in surgical intensive care unit patients internationally.

The current lack of viable therapeutic treatment options for sepsis underscores our insufficient understanding of this complex disease. The endocannabinoid system, a key regulator of essential physiological functions including the immune system, has recently emerged as a potential therapeutic target for sepsis treatment. The endocannabinoid system acquires its name from the plant Cannabis Sativa, which has been used medically to treat a variety of ailments, as well as recreationally for centuries. Cannabis Sativa contains more than 60 active phytocannabinoids with the primary phytocannabinoid Δ9-tetrahydrocannabinol (THC), (6) activating both endogenous endocannabinoid receptors.

The endocannabinoid system represents a potential therapeutic target in sepsis due to the presence of cannabinoid receptors (CB2) on immune cells. In this review we discuss how various targets within the endocannabinoid system can be manipulated to treat the immune consequences of sepsis. One of the targets outlined are the endocannabinoid receptors and modulation of their activity through pharmacological agonists and antagonists. Another therapeutic target covered in this review is the modulation of the endocannabinoid degradative enzyme’s activity. Modulation of degradative enzyme activity can change the levels of endogenous cannabinoids thereby altering immune activity. Overall, activation of the CB2 receptors causes immunosuppression and can be beneficial during the hyperactivated immune state of sepsis, while suppression of the CB2 receptors may be beneficial during a hypoimmune septic state.

The endocannabinoid system modulates the immune response in experimental sepsis. Manipulating the endocannabinoid system may have potential therapeutic benefit in clinical sepsis where immune and inflammatory dysfunction can be detrimental. Multiple targets exist within the endocannabinoid system, e.g. the system can be targeted at the level of receptors by administration of synthetic compounds, similar to the endocannabinoids, which either increase or inhibit receptor activation to provide the desired therapeutic effect. Alternatively, the endogenous enzymes that degrade endocannabinoids or cannabinoid-like lipids can also be targeted in order to manipulate the levels of endocannabinoids. Proper identification of the septic stage is crucial to determine the adequate therapeutic response that will be most beneficial. Due to the biphasic nature of sepsis immunopathology, immune suppression through endocannabinoid modulation can help mitigate the hyper-immune response during the early septic state, while immune activation may be beneficial in later stages.” http://www.signavitae.com/2013/05/targeting-the-endocannabinoid-system-to-treat-sepsis/

Targeting the Endocannabinoid System to Treat Sepsis

Treatment with cannabidiol reverses oxidative stress parameters, cognitive impairment and mortality in rats submitted to sepsis by cecal ligation and puncture.

Posted on by
Reply

Brain Research

“Oxidative stress plays an important role in the development of cognitive impairment in sepsis. Here we assess the effects of acute and extended administration of cannabidiol (CBD) on oxidative stress parameters in peripheral organs and in the brain, cognitive impairment, and mortality in rats submitted to sepsis by cecal ligation and perforation (CLP).

Our data provide the first experimental demonstration that CBD reduces the consequences of sepsis induced by CLP in rats, by decreasing oxidative stress in peripheral organs and in the brain, improving impaired cognitive function, and decreasing mortality.”

https://www.ncbi.nlm.nih.gov/pubmed/20561509

http://www.sciencedirect.com/science/article/pii/S0006899310013582?via%3Dihub

“Antioxidant treatment reverses mitochondrial dysfunction in a sepsis animal model.” https://www.ncbi.nlm.nih.gov/pubmed/18417427

Preferences for Medical Marijuana over Prescription Medications Among Persons Living with Chronic Conditions: Alternative, Complementary, and Tapering Uses.

Posted on by
Reply

Mary Ann Liebert, Inc. publishers

“Despite expanded legalization and utilization of medical cannabis (MC) internationally, there is a lack of patient-centered data on how MC is used by persons living with chronic conditions in tandem with or instead of prescription medications. This study describes approaches to use of MC vis-à-vis prescription medications in the treatment of selected chronic conditions.

RESULTS:

Participants described a range of approaches to using MC, including (1) as alternatives to using prescription or over-the-counter medications; (2) complementary use with prescription medications; and (3) as a means for tapering off prescription medications. Motives reported for reducing or eliminating prescription medications included concerns regarding toxicity, dependence, and tolerance, and perceptions that MC improves management of certain symptoms and has quicker action and longer lasting effects.

CONCLUSIONS:

MC appears to serve as both a complementary method for symptom management and treatment of medication side-effects associated with certain chronic conditions, and as an alternative method for treatment of pain, seizures, and inflammation in this population. Additional patient-centered research is needed to identify specific dosing patterns of MC products associated with symptom alleviation and produce longitudinal data assessing chronic disease outcomes with MC use.”

 https://www.ncbi.nlm.nih.gov/pubmed/28945457
http://online.liebertpub.com/doi/10.1089/acm.2017.0184

Cannabidiol attenuates alcohol-induced liver steatosis, metabolic dysregulation, inflammation and neutrophil-mediated injury.

Posted on by
Reply

“Cannabidiol (CBD) is a non-psychoactive component of marijuana, which has anti-inflammatory effects. It has also been approved by FDA for various orphan diseases for exploratory trials. Herein, we investigated the effects of CBD on liver injury induced by chronic plus binge alcohol feeding in mice. CBD may have therapeutic potential in the treatment of alcoholic liver diseases associated with inflammation, oxidative stress and steatosis, which deserves exploration in human trials.”  https://www.ncbi.nlm.nih.gov/pubmed/28935932

“Cannabidiol (CBD) is the most abundant non-psychoactive constituent of marijuana plant (Cannabis Sativa) with excellent safety profile in humans even after chronic use. In conclusion, we demonstrate that CBD treatment significantly attenuates liver injury induced by chronic plus binge alcohol in a mouse model and oxidative burst in human neutrophils. CBD ameliorates alcohol-induced liver injury by attenuating inflammatory response involving E-selectin expression and neutrophil recruitment, and consequent oxidative/nitrative stress, in addition to attenuation of the alcohol-induced hepatic metabolic dysregulation and steatosis. These beneficial effects, coupled with the proven safety of CBD in human clinical trials and its current orphan drug approval by FDA for various indications suggest that it may have therapeutic potential in liver disease associated with inflammation, oxidative stress, metabolic dysregulation and steatosis.” https://www.nature.com/articles/s41598-017-10924-8

Targeting fatty acid amide hydrolase as a therapeutic strategy for antitussive therapy.

Posted on by
Reply

European Respiratory Society

“Cough is the most common reason to visit a primary care physician, yet it remains an unmet medical need. Fatty acid amide hydrolase (FAAH) is an enzyme that breaks down endocannabinoids, and inhibition of FAAH produces analgesic and anti-inflammatory effects. Cannabinoids inhibit vagal sensory nerve activation and the cough reflex, so it was hypothesised that FAAH inhibition would produce antitussive activity via elevation of endocannabinoids.

Primary vagal ganglia neurons, tissue bioassay, in vivoelectrophysiology and a conscious guinea pig cough model were utilised to investigate a role for fatty acid amides in modulating sensory nerve activation in vagal afferents. FAAH inhibition produced antitussive activity in guinea pigs with concomitant plasma elevation of the fatty acid amides N-arachidonoylethanolamide (anandamide), palmitoylethanolamide, N-oleoylethanolamide and linoleoylethanolamide. Palmitoylethanolamide inhibited tussive stimulus-induced activation of guinea pig airway innervating vagal ganglia neurons, depolarisation of guinea pig and human vagus, and firing of C-fibre afferents. These effects were mediated via a cannabinoid CB2/Gi/o-coupled pathway and activation of protein phosphatase 2A, resulting in increased calcium sensitivity of calcium-activated potassium channels.

These findings identify FAAH inhibition as a target for the development of novel, antitussive agents without the undesirable side-effects of direct cannabinoid receptor agonists.”

https://www.ncbi.nlm.nih.gov/pubmed/28931663

http://erj.ersjournals.com/content/50/3/1700782

Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis.

Posted on by
Reply

logo

“Osteoarthritis (OA) is a multifactorial joint disease, which includes joint degeneration, intermittent inflammation, and peripheral neuropathy. Cannabidiol (CBD) is a non-euphoria producing constituent of cannabis that has the potential to relieve pain.

The aim of this study was to determine if CBD is anti-nociceptive in OA, and whether inhibition of inflammation by CBD could prevent the development of OA pain and joint neuropathy.

The therapeutic and prophylactic effects of peripheral CBD (100-300μg) were assessed. In end stage OA, CBD dose-dependently decreased joint afferent firing rate, and increased withdrawal threshold and weight bearing (p<0.0001; n=8). Acute, transient joint inflammation was reduced by local CBD treatment (p<0.0001; n=6). Prophylactic administration of CBD prevented the development of MIA-induced joint pain at later time points (p<0.0001; n=8), and was also found to be neuroprotective (p<0.05; n=6-8).

The data presented here indicate that local administration of CBD blocked OA pain. Prophylactic CBD treatment prevented the later development of pain and nerve damage in these OA joints.

These findings suggest that CBD may be a safe, useful therapeutic for treating OA joint neuropathic pain.”

https://www.ncbi.nlm.nih.gov/pubmed/28885454             https://insights.ovid.com/crossref?an=00006396-900000000-99152

Anti-nociceptive interactions between opioids and a cannabinoid receptor 2 agonist in inflammatory pain.

Posted on by
Reply

SAGE Journals

“The cannabinoid 1 receptor and cannabinoid 2 receptor can both be targeted in the treatment of pain; yet, they have some important differences. Cannabinoid 1 receptor is expressed at high levels in the central nervous system, whereas cannabinoid 2 receptor is found predominantly, although not exclusively, outside the central nervous system. The objective of this study was to investigate potential interactions between cannabinoid 2 receptor and the mu-opioid receptor in pathological pain. The low level of adverse side effects and lack of tolerance for cannabinoid 2 receptor agonists are attractive pharmacotherapeutic traits. This study assessed the anti-nociceptive effects of a selective cannabinoid 2 receptor agonist (JWH-133) in pathological pain using mice subjected to inflammatory pain using the formalin test. Furthermore, we examined several ways in which JWH-133 may interact with morphine. JWH-133 produces dose-dependent anti-nociception during both the acute and inflammatory phases of the formalin test. This was observed in both male and female mice. However, a maximally efficacious dose of JWH-133 (1 mg/kg) was not associated with somatic withdrawal symptoms, motor impairment, or hypothermia. After eleven once-daily injections of 1 mg/JWH-133, no tolerance was observed in the formalin test. Cross-tolerance for the anti-nociceptive effects of JWH-133 and morphine were assessed to gain insight into physiologically relevant cannabinoid 2 receptor and mu-opioid receptor interaction. Mice made tolerant to the effects of morphine exhibited a lower JWH-133 response in both phases of the formalin test compared to vehicle-treated morphine-naïve animals. However, repeated daily JWH-133 administration did not cause cross-tolerance for morphine, suggesting opioid and cannabinoid 2 receptor cross-tolerance is unidirectional. However, preliminary data suggest co-administration of JWH-133 with morphine modestly attenuates morphine tolerance. Isobolographic analysis revealed that co-administration of JWH-133 and morphine has an additive effect on anti-nociception in the formalin test. Overall these findings show that cannabinoid 2 receptor may functionally interact with mu-opioid receptor to modulate anti-nociception in the formalin test.”

https://www.ncbi.nlm.nih.gov/pubmed/28879802

http://journals.sagepub.com/doi/10.1177/1744806917728227

 

Intra-cerebral cannabidiol infusion-induced neuroprotection is partly associated with the TNF-α/TNFR1/NF-кB pathway in transient focal cerebral ischaemia.

Posted on by
Reply

Publication Cover

“Stroke is a neurological disease, which, in addition to high mortality, imposes many financial and mental burdens on families and the society.

The main objective of this study was to investigate the effect of cannabidiol (CBD) on one of the major inflammatory pathways in cerebral ischaemia.

RESULTS:

Administration of CBD (100 and 200 ng/rat) caused a significant reduction in infarction, brain oedema, and BBB permeability compared with the vehicle-received group. Down-regulation of TNF-α, TNFR1, and NF-кB expression was also observed by CBD.

CONCLUSION:

The results achieved in this study support the idea that CBD has a cerebroprotective effect (partly through suppression of TNF-α, TNFR1, and NF-кB) on ischaemic injury.”

https://www.ncbi.nlm.nih.gov/pubmed/28872345

http://www.tandfonline.com/doi/abs/10.1080/02699052.2017.1358397?journalCode=ibij20

Managing neuropathic pain in multiple sclerosis: Pharmacological interventions.

Posted on by
Reply

Image result for University of New South Wales

“Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Of the plethora of motor and sensory disturbances experienced by sufferers, neuropathic pain is a highly prevalent and debilitating symptom, and at present remains extremely difficult to treat. Common forms of neuropathic pain seen in MS patients include central neuropathic pain, Lhermitte’s phenomenon and trigeminal neuralgia, which are all speculated to arise from specific patterns of lesion formation.

OBJECTIVE:

Efficacious pharmacological interventions for the treatment of neuropathic pain associated with MS are lacking, and have been largely informed by drug trials in peripheral neuropathies and spinal cord injury.

METHOD/RESULTS:

Neuropathic pain in MS is inadequately relieved by conventional analgesics, and first-line therapies are generally comprised of anti-depressive and anti-convulsive drugs. A range of alternatives have been proposed and tested with variable success, including cannabinoids and certain opioid analgesics. Animals with experimental autoimmune encephalomyelitis (EAE), an autoimmune model of MS, also exhibit neuropathic pain symptoms.

CONCLUSION:

Studies aimed at understanding the mechanisms underlying EAE-induced neuropathic pain and investigating the efficacy of novel pharmacological interventions at the animal level offer an exciting area of future research, and may inform future therapeutic options for MS-associated neuropathic pain.”

https://www.ncbi.nlm.nih.gov/pubmed/28875858