Tag Archives: anti-inflammatory

Evaluation of oral cannabinoid-containing medications for the management of interferon and ribavirin-induced anorexia, nausea and weight loss in patients treated for chronic hepatitis C virus

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  “The systemic and cognitive side effects of hepatitis C virus (HCV) therapy may be incapacitating, necessitating dose reductions or abandonment of therapy. Oral cannabinoid-containing medications (OCs) ameliorate chemotherapy-induced nausea and vomiting, as well as AIDS wasting syndrome. The efficacy of OCs in managing HCV treatment-related side effects is unknown.”

 

“Although formal studies are lacking, there is anecdotal evidence that cannabis may be beneficial by alleviating common side effects associated with interferon-ribavirin, including anorexia, nausea, weight loss and insomnia. Despite the potential benefits of cannabis, concerns related to the long-term medical complications of inhaled cannabis use and the inability to legally obtain this product limit the use of it as a therapeutic intervention.”

“Oral cannabinoid-containing medications (OCs) have multiple potential therapeutic uses due to their analgesic, antiemetic, anticonvulsant, bronchodilatory and anti-inflammatory effects. They have been shown in clinical trials to ameliorate chemotherapy-induced nausea, to benefit those with AIDS wasting syndrome and to reduce spasticity in multiple sclerosis patients.”

“CONCLUSIONS:

The present retrospective cohort analysis found that OC use is often effective in managing HCV treatment-related symptoms that contribute to weight loss, and may stabilize weight decline once initiated.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2662895/

Therapeutic Potential of Monoacylglycerol Lipase Inhibitors.

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Abstract

 “Marijuana and aspirin have been used for millennia to treat a wide range of maladies including pain and inflammation. Both cannabinoids, like marijuana, that exert anti-inflammatory action through stimulating cannabinoid receptors, and cyclooxygenase (COX) inhibitors, like aspirin, that suppress pro-inflammatory eicosanoid production have shown benefitial outcomes in mouse models of neurodegenerative diseases and cancer. Both cannabinoids and COX inhibitors, however, have untoward effects that discourage their chronic usage, including cognitive deficits and gastrointestinal toxicity, respectively. Recent studies have uncovered that the serine hydrolase monoacylglycerol lipase (MAGL) links the endocannabinoid and eicosanoid systems together through hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG) to provide the major arachidonic acid (AA) precursor pools for pro-inflammatory eicosanoid synthesis in specific tissues. Studies in recent years have shown that MAGL inhibitors elicit anti-nociceptive, anxiolytic, and anti-emetic responses and attenuate precipitated withdrawal symptoms in addiction paradigms through enhancing endocannabinoid signaling. MAGL inhibitors have also been shown to exert anti-inflammatory action in the brain and protect against neurodegeneration through lowering eicosanoid production. In cancer, MAGL inhibitors have been shown to have anti-cancer properties not only through modulating the endocannabinoid-eicosanoid network, but also by controlling fatty acid release for the synthesis of protumorigenic signaling lipids. Thus, MAGL serves as a critical node in simultaneously coordinating multiple lipid signaling pathways in both physiological and disease contexts. This review will discuss the diverse (patho)physiological roles of MAGL and the therapeutic potential of MAGL inhibitors in treating a vast array of complex human diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/23142242

Endogenous cannabinoids and neutrophil chemotaxis.

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Abstract

  “Neutrophils are the earliest inflammatory cell to infiltrate tissue, playing an important role in early phagocytosis. Under pathological conditions, pro-inflammatory actions of neutrophils contribute to the development of various inflammatory diseases. G(i) protein-coupled cell-surface receptors are an essential component of pro-migratory responses in leukocytes; however, few investigations regarding inhibitors of cell migration have been reported. Kurihara et al. (2006) and McHugh et al. (2008) have revealed that certain endogenous cannabinoids and lipids are potent inhibitors of induced human neutrophil migration. McHugh et al. implicate a novel SR141716A-sensitive pharmacological target distinct from cannabinoid CB(1) and CB(2) receptors, which is antagonized by N-arachidonoyl-l-serine; and that the CB(2) receptor exerts negative co-operativity upon this receptor. Kurihara et al. demonstrate that fMLP-induced RhoA activity is decreased following endocannabinoid pretreatment, disrupting the front/rear polarization necessary for neutrophils to engage in chemotaxis.

The therapeutic potential of exploiting endocannabinoids as neutrophilic chemorepellants is plain to see.”

http://www.ncbi.nlm.nih.gov/pubmed/19647118

Inhibition of Human Neutrophil Chemotaxis by Endogenous Cannabinoids and Phytocannabinoids: Evidence for a Site Distinct from CB1 and CB2

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   “Here, we show a novel pharmacology for inhibition of human neutrophil migration by endocannabinoids, phytocannabinoids, and related compounds. The endocannabinoids virodhamine and N-arachidonoyl dopamine are potent inhibitors of N-formyl-l-methionyl-l-leucyl-l-phenylalanine-induced migration of human neutrophils…”

   “This study reveals that certain endogenous lipids, phytocannabinoids and related ligands are potent inhibitors of human neutrophil migration, and it implicates a novel pharmacological target distinct from cannabinoid CB1 and CB2 receptors; this target is antagonized by the endogenous compound N-arachidoloyl l-serine. These findings corroborate the emerging clinical and animal model data demonstrating that the nonpsychoactive phytocannabinoid, CBD and its structural analogs are effective in alleviating arthritis. Furthermore, our findings have implications for the potential pharmacological manipulation of elements of the endocannabinoid system for the treatment of various inflammatory conditions.”

http://molpharm.aspetjournals.org/content/73/2/441.long

Fungal biotransformation of cannabinoids: potential for new effective drugs.

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Abstract

“Phytocannabinoids from the plant Cannabis sativa induce a variety of physiological and pharmacological responses in living systems, including anti-inflammatory, antinociceptive, anti-ulcer and antitumor activities. The discovery of the cannabinoid receptors CB1 and CB2 led to the development of agonists and antagonists of these receptors for the treatment of a variety of diseases. Nabilone, a synthetic derivative of Delta9-tetrahydrocannabinol (Delta9-THC), which is the main natural psychotropic constituent of C sativa, was approved by the US FDA for the treatment of nausea and as an anti-emetic for patients undergoing chemotherapy. Delta9-THC and related cannabinoids are involved in a variety of signal transduction pathways; thus, reducing or removing the psychotropic effects of these compounds would enhance their therapeutic spectra. Compound synthesis and qualitative SAR studies are time-consuming activities; however, microbes are effectively the most inventive synthetic chemists because of their metabolic plasticity. This review discusses the potential of C sativa mycoflora, which is pathogenic as well as endophytic, to remove the psychotropic effects of Delta9-THC and related cannabinoids, and describes the development of a model system for the rapid and cost-effective commercial production of cannabinoids through fermentation pathways.”

http://www.ncbi.nlm.nih.gov/pubmed/19333876

Cannabis and cannabinoid receptors.

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Abstract

“Cannabis and cannabinoids exert many of their biological functions through receptor-mediated mechanisms. Two types of cannabinoid receptors have been identified, namely CB(1) and CB(2), both coupled to a G protein. CB(1) receptors have been detected in the central nervous system (where they are responsible for the characteristic effects of Cannabis, including catalepsy, depression of motor activity, analgesia and feelings of relaxation and well being) and in peripheral neurons (where their activation produces a suppression in neurotransmitter release in the heart, bladder, intestine and vas deferens). Cannabinoid CB(2) receptors have only been detected outside the central nervous system, mostly in cells of the immune system, presumably mediating cannabinoid-induced immunosuppression and antinflammatory effects. With the discovery of cannabinoid receptors for exogenous cannabinoids, also endogenous cannabinoids (anandamide, 2-arachidonylglycerol) have been described.”

http://www.ncbi.nlm.nih.gov/pubmed/10930707

Cannabidiol Displays Antiepileptiform and Antiseizure Properties In Vitro and In Vivo

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“CBD is the major nonpsychoactive component of Cannabis sativa whose structure was first described by Mechoulam and Shvo (1963); CBD has recently attracted renewed interest for its therapeutic potential in a number of disease states. CBD has been proposed to possess anticonvulsive, neuroprotective, and anti-inflammatory properties in humans.”

 “Plant-derived cannabinoids (phytocannabinoids) are compounds with emerging therapeutic potential. Early studies suggested that cannabidiol (CBD) has anticonvulsant properties in animal models and reduced seizure frequency in limited human trials. Here, we examine the antiepileptiform and antiseizure potential of CBD using in vitro electrophysiology and an in vivo animal seizure model…. These findings suggest that CBD acts, potentially in a CB1 receptor-independent manner, to inhibit epileptiform activity in vitro and seizure severity in vivo. Thus, we demonstrate the potential of CBD as a novel antiepileptic drug in the unmet clinical need associated with generalized seizures.”

“In conclusion, our data in separate in vitro models of epileptiform activity and, in particular, the beneficial reductions in seizure severity caused by CBD in an in vivo animal model of generalized seizures suggests that earlier, small-scale clinical trials for CBD in untreated epilepsy warrant urgent renewed investigation.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819831/

Marijuana-Derived Compound Targets Pain, Inflammation

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   “Researchers are developing a marijuana-derived synthetic compound to relieve pain and inflammation without the mood-altering side effects associated with other marijuana based drugs.

  They say the compound could improve treatment of a variety of conditions, including chronic pain, arthritis and multiple sclerosis. Their findings were presented at the 224th national meeting of the American Chemical Society, the world’s largest scientific society.

   The compound, called ajulemic acid, has produced encouraging results in animal studies of pain and inflammation. It is undergoing tests in a group of people with chronic pain and could be available by prescription within two to three years, the researchers say.

 “We believe that [the compound] will replace aspirin and similar drugs in most applications primarily because of a lack of toxic side effects,” says Sumner Burstein, Ph.D., lead investigator in the study and a professor in the department of biochemistry and molecular pharmacology at the University of Massachusetts Medical School in Worcester. “The indications so far are that it’s safe and effective,” he added.”

Read more: http://www.sciencedaily.com/releases/2002/08/020822071026.htm

The cannabinoid acids: nonpsychoactive derivatives with therapeutic potential.

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Abstract

   “The discovery of carboxylic acid metabolites of the cannabinoids (CBs) dates back more than three decades. Their lack of psychotropic activity was noted early on, and this resulted in a total absence of further research on their possible role in the actions of the CBs. More recent studies have revealed that the acids possess both analgesic and anti-inflammatory properties and may contribute to the actions of the parent drug. A synthetic analog showed similar actions at considerably lower doses. In this review, a brief survey of the extensive literature on metabolism of delta 9-tetrahydrocannabinol to the acids is presented, while more emphasis is given to the recent findings on the biological actions of this class of CBs. A possible mechanism involving effects on eicosanoids for some of these actions is also suggested. Finally, an analogy with a putative metabolite of anandamide, an endogenous CB, is discussed.”

http://www.ncbi.nlm.nih.gov/pubmed/10341359

Ajulemic acid, a synthetic cannabinoid acid, induces an antiinflammatory profile of eicosanoids in human synovial cells.

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“AIMS:

To better understand mechanisms whereby Ajulemic acid (AjA), a synthetic antiinflammatory cannabinoid, promotes resolution of acute and chronic inflammation in animal models, we investigated its influence on cyclooxygenase 2 (COX2) expression and eicosanoid production in human fibroblast-like synovial cells (FLS).”

“KEY FINDINGS:

AjA increased the steady state levels of COX2 mRNA in and arachidonic acid release from FLS. Treatment of FLS with AjA increased 15-deoxy-delta(12,14)-PGJ(2) (15d-PGJ(2)) production in a concentration dependent manner, but did not affect PGE(2) production significantly.”

“SIGNIFICANCE:

The capacity of AjA to increase selectively and markedly 15d-PGJ(2), an eicosanoid which facilitates resolution of inflammation, suggests that AjA may have value as a therapeutic agent for the treatment of rheumatoid arthritis (RA) and other diseases characterized by acute and chronic inflammation.”

http://www.ncbi.nlm.nih.gov/pubmed/18840450