“Anandamide (arachydonylethanolamide) is a naturally-occurring ligand of the canabinoid receptor. When anandamide binds to its receptor, adenylate cyclase is inhibited…
The conclusions are that the motor nerve terminal has a cannabinoid receptor.
The binding of anandamide to this receptor seems to block adenylate cyclase.”
“Two cannabinoid receptors, designated neuronal (or CB1) and peripheral (or CB2), have recently been cloned. Activation of CB1 receptors leads to inhibition of adenylate cyclase and N-type voltage-dependent Ca2+ channels.
Here we show, using a CB2 transfected Chinese hamster ovary cell line, that this receptor binds a variety of tricyclic cannabinoid ligands as well as the endogenous ligand anandamide.
Activation of the CB2 receptor by various tricyclic cannabinoids inhibits adenylate cyclase activity and this inhibition is pertussis toxin sensitive indicating that this receptor is coupled to the Gi/G(o) GTP-binding proteins…
These results characterize the CB2 receptor as a functional and distinctive member of the cannabinoid receptor family.”
http://www.ncbi.nlm.nih.gov/pubmed/7498464
“Extensive structure-activity relationship studies have demonstrated that specific requirements within the cannabinoid structure are necessary to produce potent analgesia.
A three-point association between the agonist and the receptor mediating analgesia consists of: 1) the C ring hydroxyl, 2) the phenolic A ring hydroxyl, and 3) the A ring alkyl hydrophobic side chain. Potent tricyclic and bicyclic structures were synthesized as “nonclassical” cannabinoid analgetics that conform to this agonist-receptor three-point interaction model.
At the cellular level, centrally active cannabinoid drugs inhibit adenylate cyclase activity in a neuroblastoma cell line. The structure-activity relationship profile for inhibition of adenylate cyclase in vitro was consistent with this same three-point association of agonists with the receptor.
A correlation exists between the potency of drugs to produce analgesia in vivo and to inhibit adenylate cyclase in vitro.
Based on the parallels in structure-activity relationships and the enantioselective effects, it is postulated that the receptor that is associated with the regulation of adenylate cyclase in vitro may be the same receptor as that mediating analgesia in vivo.
A conceptualization of the cannabinoid analgetic receptor is presented.”
“A putative endogenous cannabinoid ligand, arachidonylethanolamide (termed “anandamide”), was isolated recently from porcine brain.
Here we demonstrate that this compound is a specific cannabinoid agonist and exerts its action directly via the cannabinoid receptors.
Anandamide specifically binds to membranes from cells transiently (COS) or stably (Chinese hamster ovary) transfected with an expression plasmid carrying the cannabinoid receptor DNA but not to membranes from control nontransfected cells.
Moreover, anandamide inhibited the forskolin-stimulated adenylate cyclase in the transfected cells and in cells that naturally express cannabinoid receptors (N18TG2 neuroblastoma) but not in control nontransfected cells. As with exogenous cannabinoids…
These data indicate that anandamide is an endogenous agonist that may serve as a genuine neurotransmitter for the cannabinoid receptor.”
“The abilities of lipophilic cannabinoid drugs to regulate adenylate cyclase activity in neuroblastoma cell membranes were analyzed by thermodynamic studies…
These data suggest that, for the entropy-driven hormone-stimulated adenylate cyclase enzyme, less disorder of the system occurs in the presence of regulators that inhibit the enzyme via Gi.
In summary, thermodynamic data suggest that cannabidiol can influence adenylate cyclase by increasing membrane fluidity, but that the inhibition of adenylate cyclase by delta 9-tetrahydrocannabinol is not related to membrane fluidization.”
http://www.ncbi.nlm.nih.gov/pubmed/2554920
“delta 9Tetrahydrocannabinol (THC) has been shown to inhibit the activity of adenylate cyclase in the N18TG2 clone of murine neuroblastoma cells. The concentration of delta 9THC exhibiting half-maximal inhibition was 500 nM. delta 8Tetrahydrocannabinol was less active, and cannabinol was only partially active. Cannabidiol, cannabigerol, cannabichromene, olivetol and compounds having a reduced length of the C3 alkyl side chain were inactive. The metabolites of delta 8THC and delta 9THC hydroxylated at the C11 position were more potent than the parent drugs. However, hydroxylation at the C8 position of the terpenoid ring resulted in loss of activity. Compounds hydroxylated along the C3 alkyl side chain were equally efficacious but less potent than delta 9THC. These findings are compared to the pharmacology of cannabinoids reported for psychological effects in humans and behavioral effects in a variety of animal models.”
“Air pollution causes lung cancer, World Health Organization confirms” http://www.cbsnews.com/8301-204_162-57607955/air-pollution-causes-lung-cancer-world-health-organization-confirms/
“Marijuana May Fight Lung Tumors… active ingredient in marijuana may help combat lung cancer… In lab and mouse studies, the compound, known as THC, cut lung tumor growth in half and helped prevent the cancer from spreading…” http://www.cbsnews.com/2100-500368_162-2696726.html
“Air Pollution a Leading Cause of Cancer. The United Nation’s World Health Organization (WHO) has classified air pollution as a prime cause of cancer worldwide, especially in the case of lung cancer.” http://www.webmd.com/cancer/news/20131018/air-pollution-cancer
“Marijuana May Fight Lung Tumors… the active ingredient in marijuana may help combat lung cancer…”http://www.webmd.com/lung-cancer/news/20070417/marijuana-may-fight-lung-tumors
“WHO agency: Air pollution causes cancer. What many commuters choking on smog have long suspected has finally been scientifically validated: air pollution causes lung cancer.” http://www.abclocal.go.com/ktrk/story?section=news%2Fhealth&id=9290406
“Marijuana Compound May Fight Lung Cancer… Harvard University researchers have found that, in both laboratory and mouse studies, delta-tetrahydrocannabinol (THC) cuts tumor growth in half in common lung cancer while impeding the cancer’s ability to spread.”
http://abcnews.go.com/Health/Healthday/story?id=4506595&page=1
“Drinking alcohol may boost lung cancer risk” http://www.foodconsumer.org/newsite/Nutrition/Food/drinking_alcohol_and_lung_cancer_risk_1024110625.html
“Groups seek to curb tobacco use in cancer patients… Tobacco use plays a role in 18 different cancers… Patients who use tobacco have worse outcomes and more difficult treatment… tobacco use decreases the effectiveness of chemotherapies and interferes with drug metabolism… data also shows that it decreases survival… we call on the oncology community… to provide cessation support to all cancer patients,” http://www.oncologypractice.com/oncologyreport/news/top-news/single-view/groups-seek-to-curb-tobacco-use-in-cancer-patients/1a87bf57bcccdadf01ae769c48eadce4.html
“Marijuana habit not linked to lung cancer” http://www.oncologypractice.com/oncologyreport/news/top-news/single-view/marijuana-habit-not-linked-to-lung-cancer/73840afd2cca226b9e6a9ddc7cb0d039.html
“Tobacco Smoke Causes Lung Inflammation, Promotes Lung Cancer Growth” http://www.sciencedaily.com/releases/2010/01/100119121206.htm
“Marijuana Cuts Lung Cancer Tumor Growth In Half, Study Shows”
http://www.sciencedaily.com/releases/2007/04/070417193338.htm
“Delta–9 Tetrahydrocannabinol inhibits growth and metastasis of lung cancer” http://www.thctotalhealthcare.com/delta-9-tetrahydrocannabinol-inhibits-growth-and-metastasis-of-lung-cancer-harvard-university/
“Antineoplastic activity of cannabinoids. Lewis lung adenocarcinoma growth was retarded by the oral administration of delta-9-tetrahydrocannabinol, delta-8-tetrahydrocannabinol, and cannabinol (CBN)… Delta-9-THC, delta-8-THC, and cannabinol (CBN) all inhibited primary Lewis lung tumor growth….. All occur naturally in marihuana… these compounds readily cross the blood-brain barrier and do not possess many of the toxic manifestations of presently used cytotoxic agents…” http://www.ukcia.org/research/AntineoplasticActivityOfCannabinoids/index.php
“Antineoplastic activity of cannabinoids.” http://www.ncbi.nlm.nih.gov/pubmed/1159836
“Antineoplastic: A drug used to inhibit the growth and spread of cancerous cells.. a chemotherapeutic agent that controls or kills cancer cells…” http://medical-dictionary.thefreedictionary.com/antineoplastic
“The Inhibition of DNA Synthesis by Cannabinoids. Several of the cannabinoids found in marihuana have been shown to inhibit tumor growth and increase the life-span… our in vitro observations with these cannabinoids are supported by in vivo tumor inhibition studies… Δ9-trans-tetrahydrocannabinol demonstrated the least toxicity of all inhibitory cannabinoids in vivo…” http://cancerres.aacrjournals.org/content/36/1/95.short
“Inhibition: “arrest or restraint of a process… Something that restrains, blocks, or suppresses… (in chemistry) the stopping or slowing of the rate of a chemical reaction.” http://medical-dictionary.thefreedictionary.com/inhibition
“Effects of delta9-tetrahydrocannabinol in Lewis lung adenocarcinoma cells in tissue culture… We found a dose-related decrease in DNA synthesis in transformed cell cultures treated with delta9-tetrahydrocannabinol (delta9-THC)… delta9-THC inhibited DNA synthesis…” http://www.ncbi.nlm.nih.gov/pubmed/943561
“In vivo effects of cannabinoids on macromolecular biosynthesis in Lewis lung carcinomas. Cannabinoids represent a novel class of drugs active in increasing the life span mice carrying Lewis lung tumors and decreasing primary tumor size…” http://www.ncbi.nlm.nih.gov/pubmed/616322
“Anti-emetic efficacy and toxicity of nabilone, a synthetic cannabinoid, in lung cancer chemotherapy… Symptom scores were significantly better for patients on nabilone for nausea, retching and vomiting. Fewer subjects vomited with nabilone and the number of vomiting episodes was lower; no patients on nabilone required additional parenteral anti-emetic. More patients preferred nabilone for anti-emetic control… Nabilone is an effective oral anti-emetic drug for moderately toxic chemotherapy, but the range and unpredictability of its side-effects warrant caution in its use.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2011510/
“Apoptosis: programmed cell death at a molecular level.” http://www.ncbi.nlm.nih.gov/pubmed/12833244
“WHO agency says air pollution causes lung cancer” http://www.foxnews.com/health/2013/10/17/who-agency-says-air-pollution-causes-lung-cancer/
“Marijuana May Fight Lung Tumors… marijuana may help combat lung cancer… In lab and mouse studies, the compound, known as THC, cut lung tumor growth in half and helped prevent the cancer from spreading, says Anju Preet, PhD, a Harvard University researcher in Boston…”http://www.foxnews.com/story/2007/04/18/marijuana-may-fight-lung-tumors/
“Air pollution causes lung cancer, WHO agency announces. Experts at the International Agency for Research on Cancer, an agency of the World Health Organization, have concluded that exposure to outdoor air pollution.causes lung cancer and increases the risk for bladder cancer.” http://www.nbcnews.com/video/nightly-news/53309399/#53309399
“Marijuana Compound Fights Cancer; Human Trials Next.
Research shows component in medical cannabis fights cancer.” http://www.nbcbayarea.com/news/local/Marijuana-Compound-Fights-Cancer-Human-Trials-Next-170406116.html
“The endocannabinoid system and cancer: therapeutic implication… Identification of safe and effective treatments to manage and improve cancer therapy is critical to improve quality of life and reduce unnecessary suffering in cancer patients. In this regard, cannabis-like compounds offer therapeutic potential for the treatment of… cancer… anti-cancer properties of cannabinoids…” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165955/
“The endocannabinoid system and its therapeutic exploitation… since the discovery of cannabinoid receptors, the endocannabinoid system seems to hold even more promise for the future development of therapeutic drugs.” http://www.ncbi.nlm.nih.gov/pubmed/15340387
“The endocannabinoid system as a target for the development of new drugs for cancer therapy… evidence has accumulated indicating that stimulation of cannabinoid receptors by either THC or the endocannabinoids influence the intracellular events controlling the proliferation and apoptosis of numerous types of cancer cells, thereby leading to anti-tumour effects both in vitro and in vivo. This evidence is reviewed here and suggests that future anti-cancer therapy might be developed from our knowledge of how the endocannabinoid system controls the growth and metastasis of malignant cells.”
http://www.ncbi.nlm.nih.gov/pubmed/12723496
“Cannabinoid receptor systems: therapeutic targets for tumour intervention… there is now a genuine expectation that the manipulation of cannabinoid receptor systems may have therapeutic potential for a diverse range of human diseases… demonstrated antitumour actions of cannabinoids indicates possible avenues for the future development of cannabinoids as antitumour agents.”
http://www.ncbi.nlm.nih.gov/pubmed/14640910
“Cannabinoid-associated cell death mechanisms in tumor models… cannabinoids (the active components of Cannabis sativa)… in addition to their inhibitory effects on tumor growth and migration, angiogenesis and metastasis… these compounds induce different pathways of cell death… death mechanisms induced by cannabinoids… we analyze the pathways triggered by cannabinoids to induce apoptosis or autophagy… the results reported here suggest that the exploration of molecular mechanisms induced by cannabinoids in cancer cells can contribute to the development of safe and effective treatments in cancer therapy.” http://www.ncbi.nlm.nih.gov/pubmed/22614735
“Towards the use of cannabinoids as antitumour agents.. cannabinoids (the active components of marijuana and their derivatives) can reduce tumour growth and progression in animal models of cancer, in addition to their well-known palliative effects on some cancer-associated symptoms.”
http://www.ncbi.nlm.nih.gov/pubmed/22555283
“Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide…only limited therapeutic treatments are available. Hence, we investigated the role of cannabinoid receptors, CB1 and CB2, as novel therapeutic targets against NSCLC…. Overall, our results indicate a novel role for cannabinoid receptors CB1 and CB2 in NSCLC growth and metastasis… These results suggest that CB1 and CB2 could be used as novel therapeutic targets against NSCLC.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025486/
“Cannabinoid receptors as therapeutic targets.”
http://www.ncbi.nlm.nih.gov/pubmed/16402900
“Inhibitory effects of cannabinoid CB1 receptor stimulation on tumor growth and metastatic spreading: actions on signals involved in angiogenesis and metastasis… Our findings indicate that CB1 receptor agonists might be used therapeutically to retard tumor growth in vivo by inhibiting at once tumor growth, angiogenesis, and metastasis.” http://www.ncbi.nlm.nih.gov/pubmed/12958205
“Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities. Human tissues express cannabinoid CB(1) and CB(2) receptors that can be activated by endogenously released ‘endocannabinoids’ or exogenously administered compounds in a manner that reduces the symptoms or opposes the underlying causes of several disorders in need of effective therapy. Three medicines that activate cannabinoid CB(1)/CB(2) receptors are now in the clinic: Cesamet (nabilone), Marinol (dronabinol; Δ(9)-tetrahydrocannabinol (Δ(9)-THC)) and Sativex (Δ(9)-THC with cannabidiol)… several possible additional therapeutic targets for cannabinoid receptor agonists. These include other kinds of pain, epilepsy, anxiety, depression, Parkinson’s and Huntington’s diseases, amyotrophic lateral sclerosis, stroke, CANCER, drug dependence, glaucoma, autoimmune uveitis, osteoporosis, sepsis, and hepatic, renal, intestinal and cardiovascular disorders.”
http://www.ncbi.nlm.nih.gov/pubmed/23108552
“Cannabinoid receptor agonists are mitochondrial inhibitors: a unified hypothesis of how cannabinoids modulate mitochondrial function and induce cell death. Time-lapse microscopy of human lung cancer cells showed t…hat the endogenous cannabinoid anandamide (AEA), the phyto-cannabinoid Delta-9-tetrahydrocannabinol (THC) and a synthetic cannabinoid HU 210 all caused morphological changes characteristic of apoptosis.” http://www.ncbi.nlm.nih.gov/pubmed/17931597
“Δ9-Tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis in vivo…Tumor samples from THC-treated animals revealed antiproliferative and antiangiogenic effects of THC. Our study suggests that cannabinoids like THC should be explored as novel therapeutic molecules in controlling the growth and metastasis of certain lung cancers.” http://www.nature.com/onc/journal/v27/n3/abs/1210641a.html
“Use of cannabinoid receptor agonists in cancer therapy as palliative and curative agents. Cannabinoids (the active components of Cannabis sativa)… evidence suggests that agonists of cannabinoid receptors expressed by tumour cells may offer a novel strategy to treat cancer… use of cannabinoid agonists for cancer therapy, not only as palliative but also as curative drugs.” http://www.ncbi.nlm.nih.gov/pubmed/19285265
“Stan and Barb Rutner say cannabis saved their lives from cancer”
“A CULTURE Magazine EXCLUSIVE” : http://ireadculture.com/2013/09/news/flash/convinced-of-the-cure/
“THC and another marijuana-derived compound slow the spread of cervical and lung cancers, test-tube studies suggest.
The new findings add to the fast-growing number of animal and cell-culture studies showing different anticancer effects for cannabinoids, chemical compounds derived from marijuana.
Cannabinoids, and sometimes marijuana itself, are currently used to lessen the nausea and pain experienced by many cancer patients. The new findings — suggest that cannabinoids may have a direct anticancer effect.
“Cannabinoids’ … potential therapeutic benefit in the treatment of highly invasive cancers should be addressed in clinical trials,” conclude Robert Ramer, PhD, and Burkhard Hinz, PhD, of the University of Rostock, Germany…
“Thus the effects of THC on cell invasion occurred at therapeutically relevant concentrations,” Ramer and Hinz note…
Ramer and Hinz report the findings in the Jan. 2, 2008 issue of the Journal of the National Cancer Institute.”
More: http://www.webmd.com/cancer/news/20071226/pot-slows-cancer-in-test-tube
1942-7611/asset/olalertbanner.jpg?v=1&s=4b27d6a6bed6b58a9935efe70e4f95efc39146bd)
“Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines.
The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology.
In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders.”
http://www.ncbi.nlm.nih.gov/pubmed/24006213
http://onlinelibrary.wiley.com/doi/10.1002/dta.1529/abstract