Tag Archives: cannabis

Prolonged oral cannabinoid administration prevents neuroinflammation, lowers β-amyloid levels and improves cognitive performance in Tg APP 2576 mice

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“Background

Alzheimer’s disease (AD) brain shows an ongoing inflammatory condition and non-steroidal anti-inflammatories diminish the risk of suffering the neurologic disease. Cannabinoids are neuroprotective and anti-inflammatory agents with therapeutic potential.”

“… we have shown that chronically administered cannabinoid showed marked beneficial effects concomitant with inflammation reduction and increased Aβ clearance.”

“Cannabinoids, whether plant derived, synthetic or endocannabinoids, interact with two well characterized cannabinoid receptors, CB1 and CB2 . In addition, some cannabinoids may interact with other receptors, such as the TRPV1 receptor or the orphan receptor GPR55. The CB1 receptor is widely distributed, with a particularly high expression in brain, which contrasts with the limited expression of the CB2 receptor, which is characteristic of immune organs and cells. In fact, while CB1 receptors are expressed by all types of cells in the brain (neurons and glial cells), CB2 are mainly localized in microglial cells, the resident immune cell of the brain.”

“We and others have proposed cannabinoids as preventive treatment for AD, based on their neuroprotective and anti-inflammatory effects. Indeed, cannabinoids are able to decrease the release of cytokines and nitric oxide in cultured microglial cells induced by lipopolysacharide and Aβ addition. In several in vitro studies cannabidiol (CBD), the major non-psychotropic constituent of cannabis, has shown to be neuroprotective against β-amyloid (Aβ) addition to cultured cells.”

“Conclusions

In summary, cannabinoid agonists, in particular CB2 selective agonists, interfere with several interconnected events of importance in the pathophysiology of AD. These compounds by directly interacting with cannabinoid receptors, in particular CB2, decrease microglial activation thereby reducing inflammation and its consequences (eg cognitive deficits). At the same time they may indirectly have beneficial effects on microglial activation (eg decrease cytokine release) by lowering brain Aβ levels.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292807/

The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain.

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Abstract

“Cannabidiol, the major psycho-inactive component of cannabis, has substantial anti-inflammatory and immunomodulatory effects. This study investigated its therapeutic potential on neuropathic (sciatic nerve chronic constriction) and inflammatory pain (complete Freund’s adjuvant intraplantar injection) in rats. In both models, daily oral treatment with cannabidiol (2.5-20 mg/kg to neuropathic and 20 mg/kg to adjuvant-injected rats) from day 7 to day 14 after the injury, or intraplantar injection, reduced hyperalgesia to thermal and mechanical stimuli. In the neuropathic animals, the anti-hyperalgesic effect of cannabidiol (20 mg/kg) was prevented by the vanilloid antagonist capsazepine (10 mg/kg, i.p.), but not by cannabinoid receptor antagonists. Cannabidiol’s activity was associated with a reduction in the content of several mediators, such as prostaglandin E(2) (PGE(2)), lipid peroxide and nitric oxide (NO), and in the over-activity of glutathione-related enzymes. Cannabidiol only reduced the over-expression of constitutive endothelial NO synthase (NOS), without significantly affecting the inducible form (iNOS) in inflamed paw tissues. Cannabidiol had no effect on neuronal and iNOS isoforms in injured sciatic nerve. The compound’s efficacy on neuropathic pain was not accompanied by any reduction in nuclear factor-kappaB (NF-kappaB) activation and tumor necrosis factor alpha (TNFalpha) content. The results indicate a potential for therapeutic use of cannabidiol in chronic painful states.”

http://www.ncbi.nlm.nih.gov/pubmed/17157290

Oral anti-inflammatory activity of cannabidiol, a non-psychoactive constituent of cannabis, in acute carrageenan-induced inflammation in the rat paw.

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Abstract

“Cannabidiol, the major non-psychoactive component of marijuana, has various pharmacological actions of clinical interest. It is reportedly effective as an anti-inflammatory and anti-arthritic in murine collagen-induced arthritis.

The present study examined the anti-inflammatory and anti-hyperalgesic effects of cannabidiol, administered orally (5-40 mg/kg) once a day for 3 days after the onset of acute inflammation induced by intraplantar injection of 0.1 ml carrageenan (1% w/v in saline) in the rat. At the end of the treatment prostaglandin E2 (PGE2) was assayed in the plasma, and cyclooxygenase (COX) activity, production of nitric oxide (NO; nitrite/nitrate content), and of other oxygen-derived free radicals (malondialdehyde) in inflamed paw tissues. All these markers were significantly increased following carrageenan. Thermal hyperalgesia, induced by carrageenan and assessed by the plantar test, lasted 7 h. Cannabidiol had a time- and dose-dependent anti-hyperalgesic effect after a single injection. Edema following carrageenan peaked at 3 h and lasted 72 h; a single dose of cannabidiol reduced edema in a dose-dependent fashion and subsequent daily doses caused further time- and dose-related reductions. There were decreases in PGE2 plasma levels, tissue COX activity, production of oxygen-derived free radicals, and NO after three doses of cannabidiol. The effect on NO seemed to depend on a lower expression of the endothelial isoform of NO synthase.

 In conclusion, oral cannabidiol has a beneficial action on two symptoms of established inflammation: edema and hyperalgesia.”

http://www.ncbi.nlm.nih.gov/pubmed/14963641

Cannabinoids as novel anti-inflammatory drugs

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Figure 1

“Cannabinoids are a group of compounds that mediate their effects through cannabinoid receptors. The discovery of Δ9-tetrahydrocannabinol (THC) as the major psychoactive principle in marijuana, as well as the identification of cannabinoid receptors and their endogenous ligands, has led to a significant growth in research aimed at understanding the physiological functions of cannabinoids. Cannabinoid receptors include CB1, which is predominantly expressed in the brain, and CB2, which is primarily found on the cells of the immune system. The fact that both CB1 and CB2 receptors have been found on immune cells suggests that cannabinoids play an important role in the regulation of the immune system. Recent studies demonstrated that administration of THC into mice triggered marked apoptosis in T cells and dendritic cells, resulting in immunosuppression. In addition, several studies showed that cannabinoids downregulate cytokine and chemokine production and, in some models, upregulate T-regulatory cells (Tregs) as a mechanism to suppress inflammatory responses. The endocannabinoid system is also involved in immunoregulation. For example, administration of endocannabinoids or use of inhibitors of enzymes that break down the endocannabinoids, led to immunosuppression and recovery from immune-mediated injury to organs such as the liver. Manipulation of endocannabinoids and/or use of exogenous cannabinoids in vivo can constitute a potent treatment modality against inflammatory disorders. This review will focus on the potential use of cannabinoids as a new class of anti-inflammatory agents against a number of inflammatory and autoimmune diseases that are primarily triggered by activated T cells or other cellular immune components.”

“Cannabis, commonly known as marijuana, is a product of the Cannabis sativa plant and the active compounds from this plant are collectively referred to as cannabinoids. For several centuries, marijuana has been used as an alternative medicine in many cultures and, recently, its beneficial effects have been shown in: the treatment of nausea and vomiting associated with cancer chemotherapy; anorexia and cachexia seen in HIV/AIDS patients; and in neuropathic pain and spasticity in multiple sclerosis. Cannabinoid pharmacology has made important advances in recent years after the discovery of the cannabinoid receptors (CB1 and CB2). Cannabinoid receptors and their endogenous ligands have provided an excellent platform for the investigation of the therapeutic effects of cannabinoids. It is well known that CB1 and CB2 are heterotrimeric Gi/o-protein-coupled receptors and that they are both expressed in the periphery and the CNS. However, CB1 expression is predominant in the CNS, especially on presynaptic nerves, and CB2 is primarily expressed on immune cells.”

“Cannabinoids are potent anti-inflammatory agents and they exert their effects through induction of apoptosis, inhibition of cell proliferation, suppression of cytokine production and induction of T-regulatory cells (Tregs).”

“Executive summary

  • Cannabinoids, the active components of Cannabis sativa, and endogenous cannabinoids mediate their effects through activation of specific cannabinoid receptors known as cannabinoid receptor 1 and 2 (CB1 and CB2).
  • The cannabinoid system has been shown both in vivo and in vitro to be involved in regulating the immune system through its immunomodulatory properties.
  • Cannabinoids suppress inflammatory response and subsequently attenuate disease symptoms. This property of cannabinoids is mediated through multiple pathways such as induction of apoptosis in activated immune cells, suppression of cytokines and chemokines at inflammatory sites and upregulation of FoxP3+ regulatory T cells.
  • Cannabinoids have been tested in several experimental models of autoimmune disorders such as multiple sclerosis, rheumatoid arthritis, colitis and hepatitis and have been shown to protect the host from the pathogenesis through induction of multiple anti-inflammatory pathways.
  • Cannabinoids may also be beneficial in certain types of cancers that are triggered by chronic inflammation. In such instances, cannabinoids can either directly inhibit tumor growth or suppress inflammation and tumor angiogenesis.”                      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828614/

The cannabinergic system as a target for anti-inflammatory therapies.

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“Habitual cannabis use has been shown to affect the human immune system, and recent advances in endocannabinoid research provide a basis for understanding these immunomodulatory effects. Cell-based experiments or in vivo animal testing suggest that regulation of the endocannabinoid circuitry can impact almost every major function associated with the immune system.

 These studies were assisted by the development of numerous novel molecules that exert their biological effects through the endocannabinoid system. Several of these compounds were tested for their effects on immune function, and the results suggest therapeutic opportunities for a variety of inflammatory diseases such as multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, atherosclerosis, allergic asthma, and autoimmune diabetes through modulation of the endocannabinoid system.”

http://www.ncbi.nlm.nih.gov/pubmed/16918457

Toward drugs derived from cannabis.

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Abstract

“Recent work aimed at the introduction of natural and synthetic cannabinoids as drugs is reviewed. Delta1-Tetrahydrocannabinol (delta1-THC) is mainly investigated as a potential drug against glaucoma and asthma, and as an antiemetic agent in cancer chemotherapy. Cannabidiol is being tried in the clinic against epilepsy and as a hypnotic. Numerous synthetic cannabinoids are currently being investigated as analgetics and as sedative-relaxants.”

http://www.ncbi.nlm.nih.gov/pubmed/351429

News about therapeutic use of cannabis and endocannabinoid system.

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“Growing basic research in recent years led to the discovery of the endocannabinoid system with a central role in neurobiology. New evidence suggests a therapeutic potential of cannabinoids in cancer chemotherapy-induced nausea and vomiting as well as in pain, spasticity and other symptoms in multiple sclerosis and movement disorders. Results of large randomized clinical trials of oral and sublingual Cannabis extracts will be known soon and there will be definitive answers to whether Cannabis has any therapeutic potential. Although the immediate future may lie in plant-based medicines, new targets for cannabinoid therapy focuses on the development of endocannabinoid degradation inhibitors which may offer site selectivity not afforded by cannabinoid receptor agonists.”  http://www.ncbi.nlm.nih.gov/pubmed/15033046

http://www.elsevier.es/es-revista-medicina-clinica-2-linkresolver-novedades-sobre-las-potencialidades-terapeuticas-13059327

[Cannabis and cannabinoids. Possibilities of their therapeutic use].

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Abstract

“Newer aspects of therapeutic potentials of cannabis and cannabinoids are reviewed. The major active constituent of cannabis sativa, delta-9-tetrahydrocannabinol and synthetic cannabinoids are evaluated in several clinical trials on their antiemetic efficacy in cancer chemotherapy induced vomiting. 80% of patients refractory to standard antiemetic treatment could be improved with the synthetic cannabinoid levonantradol. Other therapeutic effects, which are presently investigated in clinical trials are analgesia, antispasticity, anticonvulsion and the reduction of intraocular pressure in glaucoma. The future goal of cannabinoid research is the separation between specific pharmacologic activities and undesirable psychotropic effects.”

http://www.ncbi.nlm.nih.gov/pubmed/7076098

50 years of medicinal plant research – every progress in methodology is a progress in science.

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Abstract

“Many scientific methods of analysis have been developed for the investigation of the constituents and biological activities of medicinal plants during the 50 years since the inaugural meeting of the Gesellschaft für Arzneipflanzenforschung (GA). The chromatographic (e. g., TLC, GLC, HPLC), spectroscopic (e. g., UV, IR, 1H- and 13C-NMR, MS), and biological (e. g., anticancer, anti-inflammatory, immunostimulant, antiprotozoal, CNS) techniques utilized for medicinal plant research are briefly reviewed. The contribution that advances in scientific methodology have made to our understanding of the actions of some herbal medicines (e. g., Echinacea, Ginkgo, St John’s wort, Cannabis), as well as to ethnopharmacology and biotechnology, are briefly summarized. Plants have provided many medicinal drugs in the past and remain as a potential source of novel therapeutic agents. Despite all of the powerful analytical techniques available, the majority of plant species has not been investigated chemically or biologically in any great detail and even well known medicinal plants require further clinical study.”

http://www.ncbi.nlm.nih.gov/pubmed/12865964

Medical use of cannabis. Cannabidiol: A new light for schizophrenia?

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Abstract

“The medical properties of cannabis have been known for many centuries; its first documented use dates back to 2800 BC when it was described for its hallucinogenic and pain-relieving properties. In the first half of the twentieth century, a number of pharmaceutical companies marked cannabis for indications such as asthma and pain, but since then its use has sharply declined, mainly due to its unpredictable effects, but also for socio-political issues. Recently, great attention has been directed to the medical properties of phytocannabinoids present in the cannabis plant alongside the main constituent Δ(9) -Tetrahydrocannabinol (THC); these include cannabinoids such as cannabidiol (CBD), cannabigerol (CBG), and tetrahydrocannabivarin (THCV). Evidence suggests an association between cannabis and schizophrenia: schizophrenics show a higher use of marijuana as compared to the healthy population. Additionally, the use of marijuana can trigger psychotic episodes in schizophrenic patients, and this has been ascribed to THC. Given the need to reduce the side effects of marketed antipsychotics, and their weak efficacy on some schizophrenic symptoms, cannabinoids have been suggested as a possible alternative treatment for schizophrenia. CBD, a non-psychoactive constituent of the Cannabis sativa plant, has been receiving growing attention for its anti-psychotic-like properties. Evidence suggests that CBD can ameliorate positive and negative symptoms of schizophrenia. Behavioural and neurochemical models suggest that CBD has a pharmacological profile similar to that of atypical anti-psychotic drugs and a clinical trial reported that this cannabinoid is a well-tolerated alternative treatment for schizophrenia.”

http://www.ncbi.nlm.nih.gov/pubmed/23109356