Tag Archives: therapeutic

Hepatic Cannabinoid Receptor Type 1 Mediates Alcohol-Induced Regulation of Bile Acid Enzyme Genes Expression Via CREBH.

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“In this study, we have investigated the effect of alcohol exposure on hepatic bile acid homeostasis and elucidated the mediatory roles of Cb1r and Crebh in this process.

We found that alcohol exposure or Cb1r-agonist 2-AG treatment increases hepatic bile acid synthesis and serum ALT, AST levels in vivo along with significant increase in Crebh gene expression and activation.

 Alcohol exposure activated Cb1r, Crebh, and perturbed bile acid homeostasis…

 Overall, our study demonstrates a novel regulatory mechanism of hepatic bile acid metabolism by alcohol via Cb1r-mediated activation of Crebh, and suggests that targeting Crebh can be of therapeutic potential in ameliorating alcohol-induced perturbation of bile acid homeostasis.”

http://www.ncbi.nlm.nih.gov/pubmed/23894352

Anandamide deficiency and heightened neuropathic pain in aged mice.

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“Damaging of peripheral nerves may result in chronic neuropathic pain for which the likelihood is increased in the elderly. We assessed in mice if age-dependent alterations of endocannabinoids contributed to the heightened vulnerability to neuropathic pain at old age.

We assessed nociception, endocannabinoids and the therapeutic efficacy of R-flurbiprofen in young and aged mice in the spared nerve injury model of neuropathic pain.

 R-flurbiprofen was used because it is able to reduce neuropathic pain in young mice in part by increasing anandamide.

Aged mice developed stronger nociceptive hypersensitivity after sciatic nerve injury than young mice.

This was associated with low anandamide levels in the dorsal root ganglia, spinal cord, thalamus and cortex, which further decreased after nerve injury…”

 More: http://www.ncbi.nlm.nih.gov/pubmed/23597506

Controlling 2-arachidonoylglycerol metabolism as an anti-inflammatory strategy.

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“The endocannabinoid system is implicated in, and regulates, several physiological processes, ranging from food intake and energy balance to pain and inflammation.

 2-Arachidonoylglycerol (2-AG) is a full agonist at the cannabinoid receptors which classically mediate its effects. The activity of this bioactive lipid is dependent on its endogenous levels, which are tightly controlled by several hydrolases, monoacylglycerol lipase and α/β-hydrolase domain 6 and 12.

 Moreover, 2-AG is also a substrate of cyclooxygenase-2, and this reaction leads to the formation of prostaglandin glycerol esters, the effects of which remain to be fully elucidated.

 In this review we discuss the multiple mechanisms by which 2-AG controls inflammation and the therapeutic potential of 2-AG metabolism inhibitors.”

http://www.ncbi.nlm.nih.gov/pubmed/23891880

From here to eternity – the secret of Pharaohs: Therapeutic potential of black cumin seeds and beyond

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“From here to eternity – the secret of Pharaohs: Therapeutic potential of black cumin seeds and beyond” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2583426/

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“Anticarcinogenic effects of some Indian plant products.” http://www.ncbi.nlm.nih.gov/pubmed/1473788

“Plant products as protective agents against cancer.” http://www.ncbi.nlm.nih.gov/pubmed/2283166

“Potential of spice-derived phytochemicals for cancer prevention.” http://www.ncbi.nlm.nih.gov/pubmed/18612945

“Antimicrobial and chemopreventive properties of herbs and spices.” http://www.ncbi.nlm.nih.gov/pubmed/15180577

“Antioxidant activity and protecting health effects of common medicinal plants.” http://www.ncbi.nlm.nih.gov/pubmed/23034115

“Chemopreventive effects of Cuminum cyminum in chemically induced forestomach and uterine cervix tumors in murine model systems.” http://www.ncbi.nlm.nih.gov/pubmed/15087270

“Cancer cell signaling pathways targeted by spice-derived nutraceuticals.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3645308/

“Modulation of apoptosis in human hepatocellular carcinoma (HepG2 cells) by a standardized herbal decoction of Nigella sativa seeds, Hemidesmus indicus roots and Smilax glabra rhizomes with anti- hepatocarcinogenic effects.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3364896/

“A long-term investigation of the anti-hepatocarcinogenic potential of an indigenous medicine comprised of Nigella sativa, Hemidesmus indicus and Smilax glabra” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1475831/

“[Anti-metastasis effect of thymoquinone on human pancreatic cancer]… thymoquinone (TQ), a component derived from the medicinal spice Nigella sativa (also called black cumin)” http://www.ncbi.nlm.nih.gov/pubmed/22007514

“Thymoquinone suppresses metastasis of melanoma cells by inhibition of NLRP3 inflammasome… our results indicate that thymoquinone can be a potential immunotherapeutic agent not only as an adjuvant therapy for melanoma, but also, in the control and prevention of metastatic melanoma.” http://www.ncbi.nlm.nih.gov/pubmed/23583630

“Anti-inflammatory effects of the Nigella sativa seed extract, thymoquinone, in pancreatic cancer cells” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2742606/

“Thymoquinone extracted from black seed triggers apoptotic cell death in human colorectal cancer cells via a p53-dependent mechanism.” http://www.ncbi.nlm.nih.gov/pubmed/15375533

“Structure-Activity Studies on Therapeutic Potential of Thymoquinone Analogs in Pancreatic Cancer” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093961/

“Thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing AKT and ERK signaling pathways” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2587125/

“Thymoquinone and cisplatin as a therapeutic combination in lung cancer: In vitro and in vivo” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2909169/

“Comparison of potential chemotherapeutic agents, 5-fluoruracil, green tea, and thymoquinone on colon cancer cells.”  http://www.ncbi.nlm.nih.gov/pubmed/16817633

“Thymoquinone from Nigella sativa was more potent than cisplatin in eliminating of SiHa cells via apoptosis with down-regulation of Bcl-2 protein.” http://www.ncbi.nlm.nih.gov/pubmed/21609759

“Thymoquinone: potential cure for inflammatory disorders and cancer.” http://www.ncbi.nlm.nih.gov/pubmed/22005518

“Thymoquinone suppresses growth and induces apoptosis via generation of reactive oxygen species in primary effusion lymphoma.” http://www.ncbi.nlm.nih.gov/pubmed/21215312

“Anti-cancer effects of thymoquinone in mouse neuroblastoma (Neuro-2a) cells through caspase-3 activation with down-regulation of XIAP.” http://www.ncbi.nlm.nih.gov/pubmed/22732633

“Anticancer activity of thymoquinone in breast cancer cells: possible involvement of PPAR-γ pathway.” http://www.ncbi.nlm.nih.gov/pubmed/21679698

“Antineoplastic and apoptotic potential of traditional medicines thymoquinone and diosgenin in squamous cell carcinoma.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471895/

“Antineoplastic effects of bee honey and Nigella sativa on hepatocellular carcinoma cells.” http://www.ncbi.nlm.nih.gov/pubmed/21147814

“Antitumor and anti-angiogenesis effects of thymoquinone on osteosarcoma through the NF-κB pathway.” http://www.ncbi.nlm.nih.gov/pubmed/23232982

“Antiproliferative properties of methanolic extract of Nigella sativa against the MDA-MB-231 cancer cell line.” http://www.ncbi.nlm.nih.gov/pubmed/23317266

“Methanolic extract of Nigella sativa seed inhibits SiHa human cervical cancer cell proliferation through apoptosis… could potentially be an alternative source of medicine for cervical cancer therapy.”  http://www.ncbi.nlm.nih.gov/pubmed/23513732

“Plant crude extracts could be the solution: extracts showing in vivo antitumorigenic activity.” http://www.ncbi.nlm.nih.gov/pubmed/18390447

“Chemopreventive potential of volatile oil from black cumin (Nigella sativa L.) seeds against rat colon carcinogenesis.” http://www.ncbi.nlm.nih.gov/pubmed/12881014

“Cancer chemopreventive potential of volatile oil from black cumin seeds, Nigella sativa L., in a rat multi-organ carcinogenesis bioassay.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3436209/

“Effect of Nigella sativa (N. sativa L.) and oxidative stress on the survival pattern of MCF-7 breast cancer cells.” http://www.ncbi.nlm.nih.gov/pubmed/12724920

“The in vitro anti-tumor activity of some crude and purified components of blackseed, Nigella sativa L.” http://www.ncbi.nlm.nih.gov/pubmed/9673365

“Antitumour principles from Nigella sativa seeds.” http://www.ncbi.nlm.nih.gov/pubmed/1555206

“Anti-tumor properties of blackseed (Nigella sativa L.) extracts.” http://www.ncbi.nlm.nih.gov/pubmed/17581684

“Anticancer activity of Nigella sativa (black seed) – a review.” http://www.ncbi.nlm.nih.gov/pubmed/22083982

“Anticancer activities of Nigella sativa (black cumin).” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252704/

“ANTI-CANCER ACTIVITY OF NIGELLA SATIVA” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3336718/

Marijuana for migraines – USAToday

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“Does marijuana have medicinal value for migraine headaches and other maladies?

“There is no question that cannabis is beneficial medicinally,” Bearman says. With migraines, “some people say it makes the pain go completely away or can prevent migraines from coming on. Others say it lessens the pain and allows them to focus on other things to get their work done.”

What cannabis does to alleviate migraines is complicated and not completely understood. “But it works on serotonin and dopamine receptors, and has anti-inflammatory activity,” says Russo, who is just finishing a paper for the Journal of Cannabis Therapeutics.

“Basically, it is a multi-modality agent that works on various aspects of migraine in a way that’s really unique. And it’s not just the THC — tetrahydrocannabinol, the psychoactive chemical — that does it. It appears now that it’s the result of the interaction of a combination of other cannabinoids and also the essential oils in the plant.”

Unlike most headache medications, cannabis is unique in that it works as both a preventive agent and an analgesic. “At any point in the migraine, they could use cannabis by smoking, vaporizer, etc., and about 80% of these people get significant or total relief,” he says. “And, if someone has a chronic migraine, daily use in whatever form will often lead to a complete remission.””

http://usatoday30.usatoday.com/life/health/doctor/lhdoc227.htm

The Use of Marijuana or Synthetic Cannabinoids for the Treatment of Headache – MedScape

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“Pharmacological preparations of cannabinoid compounds have a variety of therapeutic uses in medicine, including different pain syndromes, but have not been previously reported as beneficial for cluster headache.We present a patient with cluster headache who was refractory to multiple acute and preventive medications but successfully aborted his attacks with recreational marijuana use; subsequent use of dronabinol provided equally effective pain relief. The beneficial effect may be related to the high concentration of cannabinoid receptors in the hypothalamus, which has been implicated as a site of dysfunction in neuroimaging studies of patients with cluster headache.

The plant Cannabis sativa has a long history of medical use in the treatment of pain and spasms, the promotion of sleep, and the suppression of nausea and vomiting. However, in the early 1970s cannabis was classified in the Narcotic Acts in countries all over the world as having no therapeutic benefit; therefore, it cannot be prescribed by physicians or dispensed by pharmacists. In the light of this contradictory situation, an increasing number of patients practice a self-prescription with cannabis products for relieving a variety of symptoms.

  The majority of patients used natural cannabis products such as marihuana, hashish, and an alcoholic tincture; in just 5 cases dronabinol (Marinol) was taken by prescription…

 …this survey demonstrates a successful use of cannabis products for the treatment of a multitude of various illnesses and symptoms. This use was usually accompanied only by slight and in general acceptable side effects…”

http://www.medscape.com/viewarticle/738529

Therapeutic Utility of Cannabinoid Receptor Type 2 (CB2) Selective Agonists.

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“The cannabinoid receptor type 2 (CB2), is a class A GPCR that was cloned in 1993 while looking for an alternate receptor that could explain the pharmacological properties of 9- tetrahydrocannabinol. CB2 was identified among cDNAs based on its similarity in amino-acid sequence to the CB1 receptor and helped provide an explanation for the established effects of cannabinoids on the immune system.

In addition to the immune system, CB2 has widespread tissue expression and has been found in brain, PNS and GI tract. Several “mixed” cannabinoid agonists are currently in clinical use primarily for controlling pain and it is believed that selective CB2 agonism may afford a superior analgesic agent devoid of the centrally mediated CB1 effects.

Thus, selective CB2 receptor agonists represent high value putative therapeutics for treating pain and other disease states. In this perspective, we seek to provide a concise update of progress in the field.”

http://www.ncbi.nlm.nih.gov/pubmed/23865723

CB1 agonists, locally applied to the cortico-thalamic circuit of rats with genetic absence epilepsy, reduce epileptic manifestations.

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“Drugs that modulate the endocannabinoid system and endocannabinoids typically play an anticonvulsant role although some proconvulsant effects have been reported both in humans and animal models.

 This study aims to characterize the role of cannabinoids in specific areas of the cortico-thalamic network involved in oscillations that underlie seizures in a genetic animal model of absence epilepsy, the WAG/Rij rat.

These results, together with previous reports, support therapeutic potential for endocannabinoid system modulators in absence epilepsy and highlight that attenuated endocannabinergic function may contribute to the generation and maintenance of seizures. Furthermore, the entire cortico-thalamic network responds to cannabinoid treatment, indicating that in all areas considered, CB receptor activation inhibits the pathological synchronization that subserves absence seizures.

 In conclusion, our result might be useful for the identification of future drug therapies in absence epilepsy.”

http://www.ncbi.nlm.nih.gov/pubmed/23860329

Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis.

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“Cannabinoids from cannabis (Cannabis sativa) are anti-inflammatory and have inhibitory effects on the proliferation of a number of tumorigenic cell lines, some of which are mediated via cannabinoid receptors.

Cannabinoid (CB) receptors are present in human skin and anandamide, an endogenous CB receptor ligand, inhibits epidermal keratinocyte differentiation.

Psoriasis is an inflammatory disease also characterised in part by epidermal keratinocyte hyper-proliferation.

OBJECTIVE:

We investigated the plant cannabinoids Delta-9 tetrahydrocannabinol, cannabidiol, cannabinol and cannabigerol for their ability to inhibit the proliferation of a hyper-proliferating human keratinocyte cell line and for any involvement of cannabinoid receptors.

CONCLUSION:

The results indicate that while CB receptors may have a circumstantial role in keratinocyte proliferation, they do not contribute significantly to this process.

 Our results show that cannabinoids inhibit keratinocyte proliferation, and therefore support a potential role for cannabinoids in the treatment of psoriasis.”

http://www.ncbi.nlm.nih.gov/pubmed/17157480

Cannabis and Δ9-tetrahydrocannabinol (THC) for weight loss?

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“Obesity is one of the highest preventable causes of morbidity and mortality in the developed world. It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the ‘munchies’). This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome.

This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile. Despite being efficacious, Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market.

We recently discovered that the prevalence of obesity is paradoxically much lower in cannabis users as compared to non-users and that this difference is not accounted for by tobacco smoking status and is still present after adjusting for variables such as sex and age.

Here, we propose that this effect is directly related to exposure to the Δ(9)-tetrahydrocannabinol (THC) present in cannabis smoke.

We therefore propose the seemingly paradoxical hypothesis that THC or a THC/cannabidiol combination drug may produce weight loss and may be a useful therapeutic for the treatment of obesity and its complications.”

http://www.ncbi.nlm.nih.gov/pubmed/23410498