Cannabis research, medicine and use
Posted: Sun Apr 05, 2009 5:20 amOkies here comes the first installment. Ill continue and improve this thread later, but Ill just ram the first ones in without organizing them too well.
Cannabis extract shrinks brain tumours
http://www.medicalnewstoday.com/articles/12088.php
Researchers in Spain have discovered that a cannabis extract makes brain tumors shrink by halting the growth of blood vessels that supply the tumors with life. Cannabis has chemicals called cannabinoids, these are the chemicals that could effectively starve tumors to death, say the researchers.
The study was carried out at the Complutense University, Madrid, Spain.
The team used mice to demonstrate that the cannabinoids block vessel growth.
You can read about this latest research in the journal Cancer Research.
Apparently, the procedure is also effective in humans.
The Spanish team, led by Dr Manuel Guzm�n, wanted to see whether they could prevent glioblastoma multiforme cancer from growing by cutting off its blood supply. Glioblastoma multiforme is one of the most difficult cancers to treat - it seldom responds to any medical intervention, such as radiotherapy, chemotherapy and surgery.
The scientists knew that cannabinoids will block the growth of blood vessels (to tumors) in mice - they wanted to find out whether the same thing would happen with humans.
The mice were given a cancer similar to the human brain cancer (glioblastoma multiforme). The mice were then given cannabinoids and the genes examined.
The genes associated with blood vessel growth in tumors through the production of a chemical called vascular endothelial growth factor (VEGF) had their activity reduced.
Cannabinoids halt VEGF production by producing Ceramide. Ceramide controls cell death.
Dr Guzm�n said: "As far as we know, this is the first report showing that ceramide depresses VEGF pathway by interfering with VEGF production."
They then wanted to see if this would also happen with humans.
They selected two patients who had glioblastoma multiforme and had not responded to chemotherapy, radiotherapy or surgery. The scientists took samples from them before and after treating them with a cannabinoids solution - this was administered directly into the tumor.
Amazingly, both patients experienced reduced VEGF levels in the tumor as a result of treatment with cannabinoids.
The researchers said that the results were encouraging. In order to be sure about their findings they need to carry out a larger study, they said.
Dr Guzm�n said "The present findings provide a novel pharmacological target for cannabinoid-based therapies."
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Cannabis receptor linked to colon cancer
http://www.medicinenet.com/script/main/ ... ekey=91511
Cannabis-Linked Cell Receptor Might Help Prevent Colon Cancer
FRIDAY, Aug. 1 (HealthDay News) — A cannabinoid receptor lying on the surface of cells may help suppress colorectal cancer, say U.S. researchers. When the receptor is turned off, tumor growth is switched on.
Cannabinoids are compounds related to the tetrahydrocannabinol (THC) found in the cannabis plant.
It's already known that the receptor, CB1, plays a role in relieving pain and nausea, elevating mood and stimulating appetite by serving as a docking station for the cannabinoid group of signaling molecules. This study suggests that CB1 may offer a new path for cancer prevention or treatment.
"We've found that CB1 expression is lost in most colorectal cancers, and when that happens, a cancer-promoting protein is free to inhibit cell death," senior author Dr. Raymond Dubois, provost and executive vice president of the University of Texas M.D. Anderson Cancer Center, said in a university news release.
In their study of human colorectal tumor specimens, the researchers also found that the drug decitabine can restore CB1 expression.
In addition, mice that are prone to developing intestinal tumors and also have functioning CB1 receptors developed fewer and smaller tumors when treated with a drug that mimics a cannabinoid receptor ligand, the researchers found. Ligands are molecules that function by binding to specific receptors.
"Potential application of cannabinoids as anti-tumor drugs is an exciting prospect, because cannabinoid agonists (synthetic molecules that mimic the action of natural molecules) are being evaluated now to treat the side effects of chemotherapy and radiation therapy," DuBois said. "Turning CB1 back on and than treating with a cannabinoid agonist could provide a new approach to colorectal cancer treatment or prevention."
The study was published in the Aug. 1 issue of the journal Cancer Research.
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Cannabis compound shows promise in fighting breast cancer
http://www.sciencedaily.com/releases/20 ... 211703.htm
A compound found in cannabis may prove to be effective at helping stop the spread of breast cancer cells throughout the body.
The study, by scientists at the California Pacific Medical Center Research Institute, is raising hope that CBD, a compound found in Cannabis sativa, could be the first non-toxic agent to show promise in treating metastatic forms of breast cancer.
“Right now we have a limited range of options in treating aggressive forms of cancer,” says Sean D. McAllister, Ph.D., a cancer researcher at CPMCRI and the lead author of the study. “Those treatments, such as chemotherapy, can be effective but they can also be extremely toxic and difficult for patients. This compound offers the hope of a non-toxic therapy that could achieve the same results without any of the painful side effects.”
The researchers used CBD to inhibit the activity of a gene called Id-1, which is believed to be responsible for the aggressive spread of cancer cells throughout the body, away from the original tumor site.
“We know that Id-1 is a key regulator of the spread of breast cancer,” says Pierre-Yves Desprez, Ph.D., a cancer researcher at CPMCRI and the senior author of the study. “We also know that Id-1 has also been found at higher levels in other forms of cancer. So what is exciting about this study is that if CBD can inhibit Id-1 in breast cancer cells, then it may also prove effective at stopping the spread of cancer cells in other forms of the disease, such as colon and brain or prostate cancer.”
However, the researchers point out that while their findings are promising they are not a recommendation for people with breast cancer to smoke marijuana. They say it is highly unlikely that effective concentrations of CBD could be reached by smoking cannabis. And while CBD is not psychoactive it is still considered a Schedule 1 drug.
This study was recently published in the journal Molecular Cancer Therapeutics.
The study was primarily funded by the California Breast Cancer Research Program.
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Cannabis compound slows lung cancer
http://www.scienceblog.com/cms/marijuan ... 18538.html
The active ingredient in marijuana cuts tumor growth in common lung cancer in half and significantly reduces the ability of the cancer to spread, say researchers at Harvard University who tested the chemical in both lab and mouse studies.
They say this is the first set of experiments to show that the compound, Delta-tetrahydrocannabinol (THC), inhibits EGF-induced growth and migration in epidermal growth factor receptor (EGFR) expressing non-small cell lung cancer cell lines. Lung cancers that over-express EGFR are usually highly aggressive and resistant to chemotherapy.
THC that targets cannabinoid receptors CB1 and CB2 is similar in function to endocannabinoids, which are cannabinoids that are naturally produced in the body and activate these receptors. The researchers suggest that THC or other designer agents that activate these receptors might be used in a targeted fashion to treat lung cancer.
"The beauty of this study is that we are showing that a substance of abuse, if used prudently, may offer a new road to therapy against lung cancer," said Anju Preet, Ph.D., a researcher in the Division of Experimental Medicine.
Acting through cannabinoid receptors CB1 and CB2, endocannabinoids (as well as THC) are thought to play a role in variety of biological functions, including pain and anxiety control, and inflammation. Although a medical derivative of THC, known as Marinol, has been approved for use as an appetite stimulant for cancer patients, and a small number of U.S. states allow use of medical marijuana to treat the same side effect, few studies have shown that THC might have anti-tumor activity, Preet says. The only clinical trial testing THC as a treatment against cancer growth was a recently completed British pilot study in human glioblastoma.
In the present study, the researchers first demonstrated that two different lung cancer cell lines as well as patient lung tumor samples express CB1 and CB2, and that non-toxic doses of THC inhibited growth and spread in the cell lines. "When the cells are pretreated with THC, they have less EGFR stimulated invasion as measured by various in-vitro assays," Preet said.
Then, for three weeks, researchers injected standard doses of THC into mice that had been implanted with human lung cancer cells, and found that tumors were reduced in size and weight by about 50 percent in treated animals compared to a control group. There was also about a 60 percent reduction in cancer lesions on the lungs in these mice as well as a significant reduction in protein markers associated with cancer progression, Preet says.
Although the researchers do not know why THC inhibits tumor growth, they say the substance could be activating molecules that arrest the cell cycle. They speculate that THC may also interfere with angiogenesis and vascularization, which promotes cancer growth.
Preet says much work is needed to clarify the pathway by which THC functions, and cautions that some animal studies have shown that THC can stimulate some cancers. "THC offers some promise, but we have a long way to go before we know what its potential is," she said.
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Marijuana Use and the Risk of Lung and Upper Aerodigestive Tract Cancers: Results of a Population-Based Case-Control Study
http://cebp.aacrjournals.org/cgi/conten ... type=HWCIT
Abstract:
Background: Despite several lines of evidence suggesting the biological plausibility of marijuana being carcinogenic, epidemiologic findings are inconsistent. We conducted a population-based case-control study of the association between marijuana use and the risk of lung and upper aerodigestive tract cancers in Los Angeles.
Methods: Our study included 1,212 incident cancer cases and 1,040 cancer-free controls matched to cases on age, gender, and neighborhood. Subjects were interviewed with a standardized questionnaire. The cumulative use of marijuana was expressed in joint-years, where 1 joint-year is equivalent to smoking one joint per day for 1 year.
Results: Although using marijuana for 30 joint-years was positively associated in the crude analyses with each cancer type (except pharyngeal cancer), no positive associations were observed when adjusting for several confounders including cigarette smoking. The adjusted odds ratio estimate (and 95% confidence limits) for 60 versus 0 joint-years was 1.1 (0.56, 2.1) for oral cancer, 0.84 (0.28, 2.5) for laryngeal cancer, and 0.62 (0.32, 1.2) for lung cancer; the adjusted odds ratio estimate for 30 versus 0 joint-years was 0.57 (0.20, 1.6) for pharyngeal cancer, and 0.53 (0.22, 1.3) for esophageal cancer. No association was consistently monotonic across exposure categories, and restriction to subjects who never smoked cigarettes yielded similar findings.
Conclusions: Our results may have been affected by selection bias or error in measuring lifetime exposure and confounder histories; but they suggest that the association of these cancers with marijuana, even long-term or heavy use, is not strong and may be below practically detectable limits. (Cancer Epidemiol Biomarkers Prev 2006;15(10):1829–34)
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Cannabis May Help Combat Cancer-causing Herpes Viruses
http://www.sciencedaily.com/releases/20 ... 092627.htm
ScienceDaily (Sep. 24, 2004) — Tampa, FL (Sept. 22, 2004) -- The compound in marijuana that produces a high, delta-9 tetrahydrocannbinol or THC, may block the spread of several forms of cancer causing herpes viruses, University of South Florida College of Medicine scientists report.
The findings, published Sept. 15 in the online journal BMC Medicine, could lead to the creation of antiviral drugs based on nonpsychoactive derivatives of THC.
The gamma herpes viruses include Kaposi's Sarcoma Associated Herpes virus, which is associated with an increased risk of cancer that is particularly prevalent in AIDS sufferers. Another is Epstein-Barr virus, which predisposes infected individuals to cancers such as Burkitt's lymphoma and Hodgkin's disease.
Once a person is infected, these viruses can remain dormant for long periods within white blood cells before they burst out and begin replicating. This reactivation of the virus boosts the number of cells infected thereby increasing the chances that the cells will become cancerous.
The USF team, led by virologist Peter Medveczky, MD, found that this sudden reactivation was prevented if infected cells were grown in the presence of THC. While cells infected with a mouse gamma herpes virus normally died when the virus was reactivated, these same cells survived when cultured in the laboratory along with the cannabinoid compound – further evidence that THC prevents viral reactivation.
Furthermore, the researchers showed that THC acts specifically on gamma herpes viruses. The chemical had no effect on another related virus, herpes simplex-1, which causes cold sores and genital herpes.
Small concentrations of THC were more potent and selective against gamma herpes viruses than the commonly used antiviral drugs acyclovir, gancicyclovir and foscamet, said Dr. Medveczky, a professor in the Department of Medical Microbiology and Immunology.
The USF researchers suggest that THC selectively inhibits the spread of gamma herpes viruses by targeting a gene these viruses all share called ORF50.
Dr. Medveczky emphasized that more studies are needed. "We have not evaluated the effect of THC in an animal model yet so we do not recommend people start using pot to prevent or treat cancers."
In fact, Dr. Meveczky said, THC has also been shown to suppress the immune system so smoking marijuana could "do more harm than good" to patients whose immune systems are often already weakened.
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Cannabis Use, Effect And Potential Therapy For Alzheimer's, MS and Parkinson's
http://www.sciencedaily.com/releases/20 ... 163644.htm
Cannabis (marijuana) is the most widely produced plant-based illicit drug worldwide and the illegal drug most frequently used in Europe. Its use increased in almost all EU countries during the 1990s, in particular among young people, including school students. Cannabis use is highest among 15- to 24-year-olds, with lifetime prevalence ranging for most countries from 20--40% (EMCDDA 2006).
Recently there has been a new surge in the level of concern about potential social and health outcomes of cannabis use, although the available evidence still does not provide a clear-cut understanding of the issues. Intensive cannabis use is correlated with non-drug-specific mental problems, but the question of co-morbidity is intertwined with the questions of cause and effect (EMCDDA 2006). Prevention is of importance in adolescents, which is underlined by evidence that early-onset cannabis-users (pre- to mid-adolescence) have a significantly higher risk of developing drug problems, including dependence (Von Sydow et al., 2002; Chen et al., 2005).
The illegal status and wide-spread use of cannabis made basic and clinical cannabis research difficult in the past decades; on the other hand, it has stimulated efforts to identify the psychoactive constituents of cannabis. As a consequence, the endocannabinoid system was discovered, which was shown to be involved in most physiological systems -- the nervous, the cardiovascular, the reproductive, the immune system, to mention a few.
One of the main roles of endocannabinoids is neuroprotection, but over the last decade they have been found to affect a long list of processes, from anxiety, depression, cancer development, vasodilatation to bone formation and even pregnancy (Panikashvili et al., 2001; Pachter et al., 2006).
Cannabinoids and endocannabinoids are supposed to represent a medicinal treasure trove which waits to be discovered.
Raphael Mechoulam will tell the discovery story of the endocannabinoid system. His research has not only helped us to advance our understanding of cannabis use and its effects, but has also made key contributions with regard to understanding "neuroprotection," and has opened the door for the development of new drugs.
Endocannabinoid system
In the 1960s the constituent of the cannabis plant was discovered -- named tetrahydrocannabinol, or THC -- which causes the 'high' produced by it (Gaoni & Mechoulam, 1964). Thousands of publications have since appeared on THC. Today it is even used as a therapeutic drug against nausea and for enhancing appetite, and, surprisingly, has not become an illicit drug -- apparently cannabis users prefer the plant-based marijuana and hashish.
Two decades later it was found that THC binds to specific receptors in the brain and the periphery and this interaction initiates a cascade of biological processes leading to the well known marijuana effects. It was assumed that a cannabinoid receptor is not formed for the sake of a plant constituent (that by a strange quirk of nature binds to it), but for endogenous brain constituents and that these putative 'signaling' constituents together with the cannabinoid receptors are part of a new biochemical system in the human body, which may affect various physiological actions.
In trying to identify these unknown putative signaling molecules, our research group in the 1990s was successful in isolating 2 such endogenous 'cannabinoid' components -- one from the brain, named anandamide (from the word ´ananda, meaning ´supreme joy´ in Sanscrit), and another one from the intestines named 2-arachidonoyl glycerol (2-AG) (Devane et al., 1992; Mechoulam et al., 1995).
Neuroprotection
The major endocannabinoid (2-AG) has been identified both in the central nervous system and in the periphery. Stressful stimuli -- traumatic brain injury (TBI) for example -- enhance brain 2-AG levels in mice. 2-AG, both of endogenous and exogenous origin, has been shown to be neuroprotective in closed head injury, ischemia and excitotoxicity in mice. These effects may derive from the ability of cannabinoids to act through a variety of biochemical mechanisms. 2-AG also helps repair the blood brain barrier after TBI.
The endocannabinoids act via specific cannabinoid receptors, of which the CB1 receptors are most abundant in the central nervous system. Mice whose CB1 receptors are knocked out display slower functional recovery after TBI and do not respond to treatment with 2-AG. Over the last few years several groups have noted that CB2 receptors are also formed in the brain, particularly as a reaction to numerous neurological diseases, and are apparently activated by the endocannabinoids as a protective mechanism.
Through evolution the mammalian body has developed various systems to guard against damage that may be caused by external attacks. Thus, it has an immune system, whose main role is to protect against protein attacks (microbes, parasites for example) and to reduce the damage caused by them. Analogous biological protective systems have also been developed against non-protein attacks, although they are much less well known than the immune system. Over the last few years the research group of Esther Shohami in collaboration with our group showed that the endocannabinoid system, through various biological routes, lowers the damage caused by brain trauma. Thus, it helps to attenuate the brain edema and the neurological injuries caused by it (Panikashvili et al., 2001; Panikashvili et al., 2006).
Clinical importance
Furthermore it is assumed that the endocannabinoid system may be involved in the pathogenesis of hepatic encephalopathy, a neuropsychiatric syndrome induced by fulminant hepatic failure. Indeed in an animal model the brain levels of 2-AG were found to be elevated. Administration of 2-AG improved a neurological score, activity and cognitive function (Avraham et al., 2006). Activation of the CB2 receptor by a selective agonist also improved the neurological score. The authors concluded that the endocannabinoid system may play an important role in the pathogenesis of hepatic encephalopathy.
Modulation of this system either by exogenous agonists specific for the CB2 receptors or possibly also by antagonists to the CB1 receptors may have therapeutic potential. The endocannabinoid system generally is involved in the protective reaction of the mammalian body to a long list of neurological diseases such as multiple sclerosis, Alzheimer's and Parkinson's disease. Thus, there is hope for novel therapeutic opportunities.
Numerous additional endocannabinoids -- especially various fatty acid ethanolamides and glycerol esters -- are known today and regarded as members of a large ´endocannabinoid family´. Endogenous cannabinoids, the cannabinoid receptors and various enzymes that are involved in their syntheses and degradations comprise the endocannabinoid system.
The endocannabinoid system acts as a guardian against various attacks on the mammalian body.
Conclusion
The above described research concerning the endocannabinoid-system is of importance in both basic science and in therapeutics:
The discovery of the cannabis plant active constituent has helped advance our understanding of cannabis use and its effects.
The discovery of the endocannabinoids has been of central importance in establishing the existence of a new biochemical system and its physiological roles -- in particular in neuroprotection.
These discoveries have opened the door for the development of novel types of drugs, such as THC for the treatment of nausea and for enhancing appetite in cachectic patients.
The endocannabinoid system is involved in the protective reaction of the mammalian body to a long list of neurological diseases such as multiple sclerosis, Alzheimer's and Parkinson's disease which raises hope for novel therapeutic opportunities for these diseases.
References
Avraham Y, Israeli E, Gabbay E, et al. Endocannabinoids affect neurological and cognitive function in thioacetamide-induced hepatic encephalopathy in mice. Neurobiology of Disease 2006;21:237-245
Chen CY, O´Brien MS, Anthony JC. Who becomes cannabis dependent soon after onset of use" Epidemiological evidence from the United States: 2000-2001. Drug and alcohol dependence 2005;79:11-22
Devane WA, Hanus L, Breuer A, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 1992;258:1946-1949
[EMCDDA 2006] European Monitoring Centre for Drugs and Drug Addiction. The state of the drugs problem in Europe. Annual Report 2006 (http://www.emcdda.europa.eu)
Gaoni Y, Mechoulam R. Isolation, structure and partial synthesis of an active constituent of hashish. J Amer Chem Soc 1964;86:1646-1647
Journal Interview 85: Conversation with Raphael Mechoulam. Addiction 2007;102:887-893
Mechoulam R, Ben-Shabat S, Hanus L, et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 1995;50:83-90
Mechoulam R, Panikashvili D, Shohami E. Cannabinoids and brain injury. Trends Mol Med 2002;8:58-61
Pachter P, Batkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 2006;58:389-462
Panikashvili D, Simeonidou C, Ben-Shabat S, et al. An endogenous cannabinoid (2-AG) is neuroprotective after brain injury. Nature 2001;413:527-531
Panikashvili D, Shein NA, Mechoulam R, et al. The endocannabinoid 2-AG protects the blood brain barrier after closed head injury and inhibits mRNA expression of proinflammatory cytokines. Neurobiol Disease 2006;22:257-264
Von Sydow K, Lieb R, Pfister H, et al. What predicts incident use of cannabis and progression to abuse and dependence" A 4-year prospective examination of risk factors in a community sample of adolescents and young adults. Drug and alcohol dependence 2002;68:49-64
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http://www.guardian.co.uk/uk/2005/feb/2 ... on.science
Scientists at one of Spain's leading research centres claimed yesterday to have found evidence that cannabis helps prevent the memory loss experienced by people suffering from Alzheimer's.
The potential breakthrough in understanding a disease that affects nearly half a million people in Britain, and around nine million worldwide, was made by a team led by María de Ceballos at the Cajal Institute in Madrid.
Their study seems to show that THC, the main active ingredient in cannabis, inhibits the activity of cells that cause damage to neurons in the brain.
Although the study is preliminary, it was welcomed by patient groups.
"Right now, there are no good drugs for Alzheimer's. There are some that treat symptoms but nothing that halts the disease," said Susanne Sorensen, head of research at the Alzheimer's Society.
While the beneficial effects of cannabis looked promising, Dr Sorensen cautioned that people with Alzheimer's should not start using the drug to help their memories, because of side effects.
Memory loss in Alzheimer's patients is not fully understood, but part of the problem is thought to lie with cells called microglia that surround neurons in the brain. In Alzheimer's, the activity of microglia gets out of control, damaging neurons and killing off parts of the brain. Dr de Ceballos's team conducted two separate experiments using human brain tissue and rats which showed that THC inhibits the activity of microglia, thus reducing memory loss.
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A review of studies done on cannabidiole, CBD
http://blog.norml.org/tag/zuardi/
While the prohibition of cannabis is absurd, the ban on the plant’s non-psychoactive components is even more mind-boggling — particularly when it’s apparent that these compounds possess amazing therapeutic properties. Case in point: cannabidiol (CBD).
A just published scientific review by Sao Paulo University (Brazil) researcher Antonio Zuardi reports that there’s been an “explosive increase” of interest in CBD over the past five years. It’s apparent why.
“Studies have suggested a wide range of possible therapeutic effects of cannabidiol on several conditions, including Parkinson’s disease, Alzheimer’s disease, cerebral ischemia, diabetes, rheumatoid arthritis, other inflammatory diseases, nausea and cancer,” Zuardi writes. Let’s look at a few of these in detail, shall we?
1. Antiepileptic action
“In 1973, a Brazilian group reported that CBD was active in … blocking convulsions produced in experimental animals.”
2. Sedative action
“In humans with insomnia, high doses of CBD increased sleep duration compared to placebo.”
3. Anxiolytic action
“CBD induce[s] a clear anxiolytic effect and a pattern of cerebral activity compatible with an anxiolytic activity.”
4. Antipsychcotic action
“[C]linical studies suggest that CBD is an effective, safe and well-tolerated alternative treatment for schizophrenic patients.”
5. Antidystonic action
“CBD … had antidystonic effects in humans when administered along with standard medication to five patients with dystonia, in an open study.”
6. Antioxidative action
“[I]t was demonstrated that CBD can reduce hydroperoxide-induced oxidative damage as well as or better than other antioxidants. CBD was more protective against glutamate neurotoxicity than either ascorbate or a-tocopherol, indicating that this drug is a potent antioxidant.”
7. Neuroprotective action
“A marked reduction in the cell survival was observed following exposure of cultured rat pheochromocytoma PC12 cells to beta-A peptide. Treatment of the cells with CBD prior to beta-A exposure significantly elevated the cell survival.”
8. Antiinflammatory action
“CBD, administered i.p. or orally, has blocked the progression of arthritis.”
9. Cardioprotective action
“CBD induces a substantial cardioprotective effect.”
10. Action on diabetes
“CBD treatment of NOD (non-obese diabetic) mice before the development of the disease reduced its incidence from 86% in the non-treated control mice to 30% in CBD-treated mice. … It was also observed that administration of CBD to 11-14 week old female NOD mice, which were either in a latent diabetes stage or had initial symptoms of diabetes, ameliorated the manifestations of the disease.”
11. Antiemetic action
“The expression of this conditioned retching reaction was completely suppressed by CBD and delta9-THC, but not by ondansetron, [an] antagonist that interferes with acute vomiting.”
12. Anticancer action
“A study of the effect of different cannabinoids on eight tumor cell lines, in vitro, has clearly indicated that, of the five natural compounds tested, CBD was the most potent inhibitor of cancer cell growth.”
In sum, the past 45 years of scientific study on CBD has revealed the compound to be non-toxic, non-psychoactive, and to possess a multitude of therapeutic properties. Yet, to this day it remains illegal to possess or use (and nearly impossible to study in US clinical trials) simply because it is associated with marijuana.
What possible advancements in medical treatment may have been achieved over the past decades had US government officials chosen to advance — rather than inhibit — clinical research into CBD (which, under federal law, remains a Schedule I drug defined as having “no currently accepted medical use”)? Perhaps it’s time someone asks John Walters or the DEA?
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Cannabis and schizophrenia - is there a link?
Arch Gen Psychiatry. 2008 Nov;65(11):1269-74.
Familial predisposition for psychiatric disorder: comparison of subjects treated for cannabis-induced psychosis and schizophrenia.
Arendt M, Mortensen PB, Rosenberg R, Pedersen CB, Waltoft BL.
Centre for Psychiatric Research, Aarhus University Hospital, Skovagervej 2, Risskov, 8240 Risskov, Denmark. mca@psykiatri.aaa.dk
CONTEXT: Cannabis-induced psychosis is considered a distinct clinical entity in the existing psychiatric diagnostic systems. However, the validity of the diagnosis is uncertain. OBJECTIVES: To establish rate ratios of developing cannabis-induced psychosis associated with predisposition to psychosis and other psychiatric disorders in a first-degree relative and to compare them with the corresponding rate ratios for developing schizophrenia spectrum disorders. DESIGN: A population-based cohort was retrieved from the Danish Psychiatric Central Register and linked with the Danish Civil Registration System. History of treatment of psychiatric disorder in family members was used as an indicator of predisposition to psychiatric disorder. Rate ratios of cannabis-induced psychosis and schizophrenia associated with predisposition to psychiatric disorders were compared using competing risk analyses. SETTING: Nationwide population-based sample of all individuals born in Denmark between January 1,1955, and July 1, 1990 (N = 2,276,309). Patients During the 21.9 million person-years of follow-up between 1994 and 2005, 609 individuals received treatment of a cannabis-induced psychosis and 6476 received treatment of a schizophrenia spectrum disorder. RESULTS: In general, the rate ratios of developing cannabis-induced psychosis and schizophrenia spectrum disorder associated with predisposition to schizophrenia spectrum disorder, other psychoses, and other psychiatric disorders in first-degree relatives were of similar magnitude. However, children with a mother with schizophrenia were at a 5-fold increased risk of developing schizophrenia and a 2.5-fold increased risk of developing cannabis-induced psychosis. The risk of a schizophrenia spectrum disorder following a cannabis-induced psychosis and the timing of onset were unrelated to familial predisposition. CONCLUSIONS: Predisposition to both psychiatric disorders in general and psychotic disorders specifically contributes equally to the risk of later treatment because of schizophrenia and cannabis-induced psychoses. Cannabis-induced psychosis could be an early sign of schizophrenia rather than a distinct clinical entity.
PMID: 18981338 [PubMed - indexed for MEDLINE]
http://stash.norml.org/new-study-casts- ... zophrenia/
NEW YORK (Reuters Health) - People who have long-lasting psychotic episodes after smoking marijuana may be exhibiting early signs of schizophrenia, researchers reported Monday in the Archives of General Psychiatry.
“Cannabis-induced psychosis,” in which a person loses touch with reality and the symptoms persist for at least 48 hours, is an established psychiatric diagnosis, but it is controversial, Dr. Mikkel Arendt of Aarhus University in Risskov, Denmark, and colleagues note in their report.
In a previous study, Arendt and colleagues found that nearly half of people who had an episode of cannabis-induced psychosis went on to develop schizophrenia within the next six years. In the current study, the researchers looked at the genetic roots of both conditions by comparing the family histories of 609 people treated for cannabis-induced psychosis and 6,476 who had been treated for schizophrenia or a related psychiatric condition.
They found that individuals treated for post-pot smoking psychotic episodes had the same likelihood of having a mother, sister or other “first-degree” relative with schizophrenia as did the individuals who had actually been treated for schizophrenia themselves. This suggests that cannabis-induced psychosis and schizophrenia are one and the same, the researchers note. “These people would have developed schizophrenia whether or not they used cannabis,” Arendt explained in comments to Reuters Health.
Based on the findings, the researcher says, “cannabis-induced psychosis is probably not a valid diagnosis. It should be considered schizophrenia.”
Even as we’ve complained that no data show that cannabis use causes schizophrenia, we’ve been told that for those who are genetically predisposed to schizophrenia, there seems to be a correlation between cannabis use and onset of psychotic symptoms. So while it may not be psychologically dangerous for most of us, there is that 1% minority that would be harmed, so we have to ban it for everyone.
But this report counteracts even that claim. In the conclusion of the report, the study authors note, “The degree of hereditary predisposition in individuals who receive treatment of cannabis-induced psychosis closely mirrors that in those who develop schizophrenia with no history of cannabis induced psychosis.” This seems to tell us that when you take a look at a group of schizophrenics, whether they smoked pot of not, they still had the same genetic chances of becoming schizophrenics - the pot use didn’t matter!
Schizophrenia is rare and it comes on slowly for some. This “cannabis-induced psychosis” is really just people in the beginning stages of schizophrenia who happen to smoke pot, and the pot is getting blamed. It would be as valid to say the schizophrenic having an episode in a Krispy Kreme shop was suffering from “donut-induced psychosis”.
Cannabis extract shrinks brain tumours
http://www.medicalnewstoday.com/articles/12088.php
Researchers in Spain have discovered that a cannabis extract makes brain tumors shrink by halting the growth of blood vessels that supply the tumors with life. Cannabis has chemicals called cannabinoids, these are the chemicals that could effectively starve tumors to death, say the researchers.
The study was carried out at the Complutense University, Madrid, Spain.
The team used mice to demonstrate that the cannabinoids block vessel growth.
You can read about this latest research in the journal Cancer Research.
Apparently, the procedure is also effective in humans.
The Spanish team, led by Dr Manuel Guzm�n, wanted to see whether they could prevent glioblastoma multiforme cancer from growing by cutting off its blood supply. Glioblastoma multiforme is one of the most difficult cancers to treat - it seldom responds to any medical intervention, such as radiotherapy, chemotherapy and surgery.
The scientists knew that cannabinoids will block the growth of blood vessels (to tumors) in mice - they wanted to find out whether the same thing would happen with humans.
The mice were given a cancer similar to the human brain cancer (glioblastoma multiforme). The mice were then given cannabinoids and the genes examined.
The genes associated with blood vessel growth in tumors through the production of a chemical called vascular endothelial growth factor (VEGF) had their activity reduced.
Cannabinoids halt VEGF production by producing Ceramide. Ceramide controls cell death.
Dr Guzm�n said: "As far as we know, this is the first report showing that ceramide depresses VEGF pathway by interfering with VEGF production."
They then wanted to see if this would also happen with humans.
They selected two patients who had glioblastoma multiforme and had not responded to chemotherapy, radiotherapy or surgery. The scientists took samples from them before and after treating them with a cannabinoids solution - this was administered directly into the tumor.
Amazingly, both patients experienced reduced VEGF levels in the tumor as a result of treatment with cannabinoids.
The researchers said that the results were encouraging. In order to be sure about their findings they need to carry out a larger study, they said.
Dr Guzm�n said "The present findings provide a novel pharmacological target for cannabinoid-based therapies."
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Cannabis receptor linked to colon cancer
http://www.medicinenet.com/script/main/ ... ekey=91511
Cannabis-Linked Cell Receptor Might Help Prevent Colon Cancer
FRIDAY, Aug. 1 (HealthDay News) — A cannabinoid receptor lying on the surface of cells may help suppress colorectal cancer, say U.S. researchers. When the receptor is turned off, tumor growth is switched on.
Cannabinoids are compounds related to the tetrahydrocannabinol (THC) found in the cannabis plant.
It's already known that the receptor, CB1, plays a role in relieving pain and nausea, elevating mood and stimulating appetite by serving as a docking station for the cannabinoid group of signaling molecules. This study suggests that CB1 may offer a new path for cancer prevention or treatment.
"We've found that CB1 expression is lost in most colorectal cancers, and when that happens, a cancer-promoting protein is free to inhibit cell death," senior author Dr. Raymond Dubois, provost and executive vice president of the University of Texas M.D. Anderson Cancer Center, said in a university news release.
In their study of human colorectal tumor specimens, the researchers also found that the drug decitabine can restore CB1 expression.
In addition, mice that are prone to developing intestinal tumors and also have functioning CB1 receptors developed fewer and smaller tumors when treated with a drug that mimics a cannabinoid receptor ligand, the researchers found. Ligands are molecules that function by binding to specific receptors.
"Potential application of cannabinoids as anti-tumor drugs is an exciting prospect, because cannabinoid agonists (synthetic molecules that mimic the action of natural molecules) are being evaluated now to treat the side effects of chemotherapy and radiation therapy," DuBois said. "Turning CB1 back on and than treating with a cannabinoid agonist could provide a new approach to colorectal cancer treatment or prevention."
The study was published in the Aug. 1 issue of the journal Cancer Research.
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Cannabis compound shows promise in fighting breast cancer
http://www.sciencedaily.com/releases/20 ... 211703.htm
A compound found in cannabis may prove to be effective at helping stop the spread of breast cancer cells throughout the body.
The study, by scientists at the California Pacific Medical Center Research Institute, is raising hope that CBD, a compound found in Cannabis sativa, could be the first non-toxic agent to show promise in treating metastatic forms of breast cancer.
“Right now we have a limited range of options in treating aggressive forms of cancer,” says Sean D. McAllister, Ph.D., a cancer researcher at CPMCRI and the lead author of the study. “Those treatments, such as chemotherapy, can be effective but they can also be extremely toxic and difficult for patients. This compound offers the hope of a non-toxic therapy that could achieve the same results without any of the painful side effects.”
The researchers used CBD to inhibit the activity of a gene called Id-1, which is believed to be responsible for the aggressive spread of cancer cells throughout the body, away from the original tumor site.
“We know that Id-1 is a key regulator of the spread of breast cancer,” says Pierre-Yves Desprez, Ph.D., a cancer researcher at CPMCRI and the senior author of the study. “We also know that Id-1 has also been found at higher levels in other forms of cancer. So what is exciting about this study is that if CBD can inhibit Id-1 in breast cancer cells, then it may also prove effective at stopping the spread of cancer cells in other forms of the disease, such as colon and brain or prostate cancer.”
However, the researchers point out that while their findings are promising they are not a recommendation for people with breast cancer to smoke marijuana. They say it is highly unlikely that effective concentrations of CBD could be reached by smoking cannabis. And while CBD is not psychoactive it is still considered a Schedule 1 drug.
This study was recently published in the journal Molecular Cancer Therapeutics.
The study was primarily funded by the California Breast Cancer Research Program.
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Cannabis compound slows lung cancer
http://www.scienceblog.com/cms/marijuan ... 18538.html
The active ingredient in marijuana cuts tumor growth in common lung cancer in half and significantly reduces the ability of the cancer to spread, say researchers at Harvard University who tested the chemical in both lab and mouse studies.
They say this is the first set of experiments to show that the compound, Delta-tetrahydrocannabinol (THC), inhibits EGF-induced growth and migration in epidermal growth factor receptor (EGFR) expressing non-small cell lung cancer cell lines. Lung cancers that over-express EGFR are usually highly aggressive and resistant to chemotherapy.
THC that targets cannabinoid receptors CB1 and CB2 is similar in function to endocannabinoids, which are cannabinoids that are naturally produced in the body and activate these receptors. The researchers suggest that THC or other designer agents that activate these receptors might be used in a targeted fashion to treat lung cancer.
"The beauty of this study is that we are showing that a substance of abuse, if used prudently, may offer a new road to therapy against lung cancer," said Anju Preet, Ph.D., a researcher in the Division of Experimental Medicine.
Acting through cannabinoid receptors CB1 and CB2, endocannabinoids (as well as THC) are thought to play a role in variety of biological functions, including pain and anxiety control, and inflammation. Although a medical derivative of THC, known as Marinol, has been approved for use as an appetite stimulant for cancer patients, and a small number of U.S. states allow use of medical marijuana to treat the same side effect, few studies have shown that THC might have anti-tumor activity, Preet says. The only clinical trial testing THC as a treatment against cancer growth was a recently completed British pilot study in human glioblastoma.
In the present study, the researchers first demonstrated that two different lung cancer cell lines as well as patient lung tumor samples express CB1 and CB2, and that non-toxic doses of THC inhibited growth and spread in the cell lines. "When the cells are pretreated with THC, they have less EGFR stimulated invasion as measured by various in-vitro assays," Preet said.
Then, for three weeks, researchers injected standard doses of THC into mice that had been implanted with human lung cancer cells, and found that tumors were reduced in size and weight by about 50 percent in treated animals compared to a control group. There was also about a 60 percent reduction in cancer lesions on the lungs in these mice as well as a significant reduction in protein markers associated with cancer progression, Preet says.
Although the researchers do not know why THC inhibits tumor growth, they say the substance could be activating molecules that arrest the cell cycle. They speculate that THC may also interfere with angiogenesis and vascularization, which promotes cancer growth.
Preet says much work is needed to clarify the pathway by which THC functions, and cautions that some animal studies have shown that THC can stimulate some cancers. "THC offers some promise, but we have a long way to go before we know what its potential is," she said.
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Marijuana Use and the Risk of Lung and Upper Aerodigestive Tract Cancers: Results of a Population-Based Case-Control Study
http://cebp.aacrjournals.org/cgi/conten ... type=HWCIT
Abstract:
Background: Despite several lines of evidence suggesting the biological plausibility of marijuana being carcinogenic, epidemiologic findings are inconsistent. We conducted a population-based case-control study of the association between marijuana use and the risk of lung and upper aerodigestive tract cancers in Los Angeles.
Methods: Our study included 1,212 incident cancer cases and 1,040 cancer-free controls matched to cases on age, gender, and neighborhood. Subjects were interviewed with a standardized questionnaire. The cumulative use of marijuana was expressed in joint-years, where 1 joint-year is equivalent to smoking one joint per day for 1 year.
Results: Although using marijuana for 30 joint-years was positively associated in the crude analyses with each cancer type (except pharyngeal cancer), no positive associations were observed when adjusting for several confounders including cigarette smoking. The adjusted odds ratio estimate (and 95% confidence limits) for 60 versus 0 joint-years was 1.1 (0.56, 2.1) for oral cancer, 0.84 (0.28, 2.5) for laryngeal cancer, and 0.62 (0.32, 1.2) for lung cancer; the adjusted odds ratio estimate for 30 versus 0 joint-years was 0.57 (0.20, 1.6) for pharyngeal cancer, and 0.53 (0.22, 1.3) for esophageal cancer. No association was consistently monotonic across exposure categories, and restriction to subjects who never smoked cigarettes yielded similar findings.
Conclusions: Our results may have been affected by selection bias or error in measuring lifetime exposure and confounder histories; but they suggest that the association of these cancers with marijuana, even long-term or heavy use, is not strong and may be below practically detectable limits. (Cancer Epidemiol Biomarkers Prev 2006;15(10):1829–34)
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Cannabis May Help Combat Cancer-causing Herpes Viruses
http://www.sciencedaily.com/releases/20 ... 092627.htm
ScienceDaily (Sep. 24, 2004) — Tampa, FL (Sept. 22, 2004) -- The compound in marijuana that produces a high, delta-9 tetrahydrocannbinol or THC, may block the spread of several forms of cancer causing herpes viruses, University of South Florida College of Medicine scientists report.
The findings, published Sept. 15 in the online journal BMC Medicine, could lead to the creation of antiviral drugs based on nonpsychoactive derivatives of THC.
The gamma herpes viruses include Kaposi's Sarcoma Associated Herpes virus, which is associated with an increased risk of cancer that is particularly prevalent in AIDS sufferers. Another is Epstein-Barr virus, which predisposes infected individuals to cancers such as Burkitt's lymphoma and Hodgkin's disease.
Once a person is infected, these viruses can remain dormant for long periods within white blood cells before they burst out and begin replicating. This reactivation of the virus boosts the number of cells infected thereby increasing the chances that the cells will become cancerous.
The USF team, led by virologist Peter Medveczky, MD, found that this sudden reactivation was prevented if infected cells were grown in the presence of THC. While cells infected with a mouse gamma herpes virus normally died when the virus was reactivated, these same cells survived when cultured in the laboratory along with the cannabinoid compound – further evidence that THC prevents viral reactivation.
Furthermore, the researchers showed that THC acts specifically on gamma herpes viruses. The chemical had no effect on another related virus, herpes simplex-1, which causes cold sores and genital herpes.
Small concentrations of THC were more potent and selective against gamma herpes viruses than the commonly used antiviral drugs acyclovir, gancicyclovir and foscamet, said Dr. Medveczky, a professor in the Department of Medical Microbiology and Immunology.
The USF researchers suggest that THC selectively inhibits the spread of gamma herpes viruses by targeting a gene these viruses all share called ORF50.
Dr. Medveczky emphasized that more studies are needed. "We have not evaluated the effect of THC in an animal model yet so we do not recommend people start using pot to prevent or treat cancers."
In fact, Dr. Meveczky said, THC has also been shown to suppress the immune system so smoking marijuana could "do more harm than good" to patients whose immune systems are often already weakened.
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Cannabis Use, Effect And Potential Therapy For Alzheimer's, MS and Parkinson's
http://www.sciencedaily.com/releases/20 ... 163644.htm
Cannabis (marijuana) is the most widely produced plant-based illicit drug worldwide and the illegal drug most frequently used in Europe. Its use increased in almost all EU countries during the 1990s, in particular among young people, including school students. Cannabis use is highest among 15- to 24-year-olds, with lifetime prevalence ranging for most countries from 20--40% (EMCDDA 2006).
Recently there has been a new surge in the level of concern about potential social and health outcomes of cannabis use, although the available evidence still does not provide a clear-cut understanding of the issues. Intensive cannabis use is correlated with non-drug-specific mental problems, but the question of co-morbidity is intertwined with the questions of cause and effect (EMCDDA 2006). Prevention is of importance in adolescents, which is underlined by evidence that early-onset cannabis-users (pre- to mid-adolescence) have a significantly higher risk of developing drug problems, including dependence (Von Sydow et al., 2002; Chen et al., 2005).
The illegal status and wide-spread use of cannabis made basic and clinical cannabis research difficult in the past decades; on the other hand, it has stimulated efforts to identify the psychoactive constituents of cannabis. As a consequence, the endocannabinoid system was discovered, which was shown to be involved in most physiological systems -- the nervous, the cardiovascular, the reproductive, the immune system, to mention a few.
One of the main roles of endocannabinoids is neuroprotection, but over the last decade they have been found to affect a long list of processes, from anxiety, depression, cancer development, vasodilatation to bone formation and even pregnancy (Panikashvili et al., 2001; Pachter et al., 2006).
Cannabinoids and endocannabinoids are supposed to represent a medicinal treasure trove which waits to be discovered.
Raphael Mechoulam will tell the discovery story of the endocannabinoid system. His research has not only helped us to advance our understanding of cannabis use and its effects, but has also made key contributions with regard to understanding "neuroprotection," and has opened the door for the development of new drugs.
Endocannabinoid system
In the 1960s the constituent of the cannabis plant was discovered -- named tetrahydrocannabinol, or THC -- which causes the 'high' produced by it (Gaoni & Mechoulam, 1964). Thousands of publications have since appeared on THC. Today it is even used as a therapeutic drug against nausea and for enhancing appetite, and, surprisingly, has not become an illicit drug -- apparently cannabis users prefer the plant-based marijuana and hashish.
Two decades later it was found that THC binds to specific receptors in the brain and the periphery and this interaction initiates a cascade of biological processes leading to the well known marijuana effects. It was assumed that a cannabinoid receptor is not formed for the sake of a plant constituent (that by a strange quirk of nature binds to it), but for endogenous brain constituents and that these putative 'signaling' constituents together with the cannabinoid receptors are part of a new biochemical system in the human body, which may affect various physiological actions.
In trying to identify these unknown putative signaling molecules, our research group in the 1990s was successful in isolating 2 such endogenous 'cannabinoid' components -- one from the brain, named anandamide (from the word ´ananda, meaning ´supreme joy´ in Sanscrit), and another one from the intestines named 2-arachidonoyl glycerol (2-AG) (Devane et al., 1992; Mechoulam et al., 1995).
Neuroprotection
The major endocannabinoid (2-AG) has been identified both in the central nervous system and in the periphery. Stressful stimuli -- traumatic brain injury (TBI) for example -- enhance brain 2-AG levels in mice. 2-AG, both of endogenous and exogenous origin, has been shown to be neuroprotective in closed head injury, ischemia and excitotoxicity in mice. These effects may derive from the ability of cannabinoids to act through a variety of biochemical mechanisms. 2-AG also helps repair the blood brain barrier after TBI.
The endocannabinoids act via specific cannabinoid receptors, of which the CB1 receptors are most abundant in the central nervous system. Mice whose CB1 receptors are knocked out display slower functional recovery after TBI and do not respond to treatment with 2-AG. Over the last few years several groups have noted that CB2 receptors are also formed in the brain, particularly as a reaction to numerous neurological diseases, and are apparently activated by the endocannabinoids as a protective mechanism.
Through evolution the mammalian body has developed various systems to guard against damage that may be caused by external attacks. Thus, it has an immune system, whose main role is to protect against protein attacks (microbes, parasites for example) and to reduce the damage caused by them. Analogous biological protective systems have also been developed against non-protein attacks, although they are much less well known than the immune system. Over the last few years the research group of Esther Shohami in collaboration with our group showed that the endocannabinoid system, through various biological routes, lowers the damage caused by brain trauma. Thus, it helps to attenuate the brain edema and the neurological injuries caused by it (Panikashvili et al., 2001; Panikashvili et al., 2006).
Clinical importance
Furthermore it is assumed that the endocannabinoid system may be involved in the pathogenesis of hepatic encephalopathy, a neuropsychiatric syndrome induced by fulminant hepatic failure. Indeed in an animal model the brain levels of 2-AG were found to be elevated. Administration of 2-AG improved a neurological score, activity and cognitive function (Avraham et al., 2006). Activation of the CB2 receptor by a selective agonist also improved the neurological score. The authors concluded that the endocannabinoid system may play an important role in the pathogenesis of hepatic encephalopathy.
Modulation of this system either by exogenous agonists specific for the CB2 receptors or possibly also by antagonists to the CB1 receptors may have therapeutic potential. The endocannabinoid system generally is involved in the protective reaction of the mammalian body to a long list of neurological diseases such as multiple sclerosis, Alzheimer's and Parkinson's disease. Thus, there is hope for novel therapeutic opportunities.
Numerous additional endocannabinoids -- especially various fatty acid ethanolamides and glycerol esters -- are known today and regarded as members of a large ´endocannabinoid family´. Endogenous cannabinoids, the cannabinoid receptors and various enzymes that are involved in their syntheses and degradations comprise the endocannabinoid system.
The endocannabinoid system acts as a guardian against various attacks on the mammalian body.
Conclusion
The above described research concerning the endocannabinoid-system is of importance in both basic science and in therapeutics:
The discovery of the cannabis plant active constituent has helped advance our understanding of cannabis use and its effects.
The discovery of the endocannabinoids has been of central importance in establishing the existence of a new biochemical system and its physiological roles -- in particular in neuroprotection.
These discoveries have opened the door for the development of novel types of drugs, such as THC for the treatment of nausea and for enhancing appetite in cachectic patients.
The endocannabinoid system is involved in the protective reaction of the mammalian body to a long list of neurological diseases such as multiple sclerosis, Alzheimer's and Parkinson's disease which raises hope for novel therapeutic opportunities for these diseases.
References
Avraham Y, Israeli E, Gabbay E, et al. Endocannabinoids affect neurological and cognitive function in thioacetamide-induced hepatic encephalopathy in mice. Neurobiology of Disease 2006;21:237-245
Chen CY, O´Brien MS, Anthony JC. Who becomes cannabis dependent soon after onset of use" Epidemiological evidence from the United States: 2000-2001. Drug and alcohol dependence 2005;79:11-22
Devane WA, Hanus L, Breuer A, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 1992;258:1946-1949
[EMCDDA 2006] European Monitoring Centre for Drugs and Drug Addiction. The state of the drugs problem in Europe. Annual Report 2006 (http://www.emcdda.europa.eu)
Gaoni Y, Mechoulam R. Isolation, structure and partial synthesis of an active constituent of hashish. J Amer Chem Soc 1964;86:1646-1647
Journal Interview 85: Conversation with Raphael Mechoulam. Addiction 2007;102:887-893
Mechoulam R, Ben-Shabat S, Hanus L, et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 1995;50:83-90
Mechoulam R, Panikashvili D, Shohami E. Cannabinoids and brain injury. Trends Mol Med 2002;8:58-61
Pachter P, Batkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 2006;58:389-462
Panikashvili D, Simeonidou C, Ben-Shabat S, et al. An endogenous cannabinoid (2-AG) is neuroprotective after brain injury. Nature 2001;413:527-531
Panikashvili D, Shein NA, Mechoulam R, et al. The endocannabinoid 2-AG protects the blood brain barrier after closed head injury and inhibits mRNA expression of proinflammatory cytokines. Neurobiol Disease 2006;22:257-264
Von Sydow K, Lieb R, Pfister H, et al. What predicts incident use of cannabis and progression to abuse and dependence" A 4-year prospective examination of risk factors in a community sample of adolescents and young adults. Drug and alcohol dependence 2002;68:49-64
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http://www.guardian.co.uk/uk/2005/feb/2 ... on.science
Scientists at one of Spain's leading research centres claimed yesterday to have found evidence that cannabis helps prevent the memory loss experienced by people suffering from Alzheimer's.
The potential breakthrough in understanding a disease that affects nearly half a million people in Britain, and around nine million worldwide, was made by a team led by María de Ceballos at the Cajal Institute in Madrid.
Their study seems to show that THC, the main active ingredient in cannabis, inhibits the activity of cells that cause damage to neurons in the brain.
Although the study is preliminary, it was welcomed by patient groups.
"Right now, there are no good drugs for Alzheimer's. There are some that treat symptoms but nothing that halts the disease," said Susanne Sorensen, head of research at the Alzheimer's Society.
While the beneficial effects of cannabis looked promising, Dr Sorensen cautioned that people with Alzheimer's should not start using the drug to help their memories, because of side effects.
Memory loss in Alzheimer's patients is not fully understood, but part of the problem is thought to lie with cells called microglia that surround neurons in the brain. In Alzheimer's, the activity of microglia gets out of control, damaging neurons and killing off parts of the brain. Dr de Ceballos's team conducted two separate experiments using human brain tissue and rats which showed that THC inhibits the activity of microglia, thus reducing memory loss.
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A review of studies done on cannabidiole, CBD
http://blog.norml.org/tag/zuardi/
While the prohibition of cannabis is absurd, the ban on the plant’s non-psychoactive components is even more mind-boggling — particularly when it’s apparent that these compounds possess amazing therapeutic properties. Case in point: cannabidiol (CBD).
A just published scientific review by Sao Paulo University (Brazil) researcher Antonio Zuardi reports that there’s been an “explosive increase” of interest in CBD over the past five years. It’s apparent why.
“Studies have suggested a wide range of possible therapeutic effects of cannabidiol on several conditions, including Parkinson’s disease, Alzheimer’s disease, cerebral ischemia, diabetes, rheumatoid arthritis, other inflammatory diseases, nausea and cancer,” Zuardi writes. Let’s look at a few of these in detail, shall we?
1. Antiepileptic action
“In 1973, a Brazilian group reported that CBD was active in … blocking convulsions produced in experimental animals.”
2. Sedative action
“In humans with insomnia, high doses of CBD increased sleep duration compared to placebo.”
3. Anxiolytic action
“CBD induce[s] a clear anxiolytic effect and a pattern of cerebral activity compatible with an anxiolytic activity.”
4. Antipsychcotic action
“[C]linical studies suggest that CBD is an effective, safe and well-tolerated alternative treatment for schizophrenic patients.”
5. Antidystonic action
“CBD … had antidystonic effects in humans when administered along with standard medication to five patients with dystonia, in an open study.”
6. Antioxidative action
“[I]t was demonstrated that CBD can reduce hydroperoxide-induced oxidative damage as well as or better than other antioxidants. CBD was more protective against glutamate neurotoxicity than either ascorbate or a-tocopherol, indicating that this drug is a potent antioxidant.”
7. Neuroprotective action
“A marked reduction in the cell survival was observed following exposure of cultured rat pheochromocytoma PC12 cells to beta-A peptide. Treatment of the cells with CBD prior to beta-A exposure significantly elevated the cell survival.”
8. Antiinflammatory action
“CBD, administered i.p. or orally, has blocked the progression of arthritis.”
9. Cardioprotective action
“CBD induces a substantial cardioprotective effect.”
10. Action on diabetes
“CBD treatment of NOD (non-obese diabetic) mice before the development of the disease reduced its incidence from 86% in the non-treated control mice to 30% in CBD-treated mice. … It was also observed that administration of CBD to 11-14 week old female NOD mice, which were either in a latent diabetes stage or had initial symptoms of diabetes, ameliorated the manifestations of the disease.”
11. Antiemetic action
“The expression of this conditioned retching reaction was completely suppressed by CBD and delta9-THC, but not by ondansetron, [an] antagonist that interferes with acute vomiting.”
12. Anticancer action
“A study of the effect of different cannabinoids on eight tumor cell lines, in vitro, has clearly indicated that, of the five natural compounds tested, CBD was the most potent inhibitor of cancer cell growth.”
In sum, the past 45 years of scientific study on CBD has revealed the compound to be non-toxic, non-psychoactive, and to possess a multitude of therapeutic properties. Yet, to this day it remains illegal to possess or use (and nearly impossible to study in US clinical trials) simply because it is associated with marijuana.
What possible advancements in medical treatment may have been achieved over the past decades had US government officials chosen to advance — rather than inhibit — clinical research into CBD (which, under federal law, remains a Schedule I drug defined as having “no currently accepted medical use”)? Perhaps it’s time someone asks John Walters or the DEA?
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Cannabis and schizophrenia - is there a link?
Arch Gen Psychiatry. 2008 Nov;65(11):1269-74.
Familial predisposition for psychiatric disorder: comparison of subjects treated for cannabis-induced psychosis and schizophrenia.
Arendt M, Mortensen PB, Rosenberg R, Pedersen CB, Waltoft BL.
Centre for Psychiatric Research, Aarhus University Hospital, Skovagervej 2, Risskov, 8240 Risskov, Denmark. mca@psykiatri.aaa.dk
CONTEXT: Cannabis-induced psychosis is considered a distinct clinical entity in the existing psychiatric diagnostic systems. However, the validity of the diagnosis is uncertain. OBJECTIVES: To establish rate ratios of developing cannabis-induced psychosis associated with predisposition to psychosis and other psychiatric disorders in a first-degree relative and to compare them with the corresponding rate ratios for developing schizophrenia spectrum disorders. DESIGN: A population-based cohort was retrieved from the Danish Psychiatric Central Register and linked with the Danish Civil Registration System. History of treatment of psychiatric disorder in family members was used as an indicator of predisposition to psychiatric disorder. Rate ratios of cannabis-induced psychosis and schizophrenia associated with predisposition to psychiatric disorders were compared using competing risk analyses. SETTING: Nationwide population-based sample of all individuals born in Denmark between January 1,1955, and July 1, 1990 (N = 2,276,309). Patients During the 21.9 million person-years of follow-up between 1994 and 2005, 609 individuals received treatment of a cannabis-induced psychosis and 6476 received treatment of a schizophrenia spectrum disorder. RESULTS: In general, the rate ratios of developing cannabis-induced psychosis and schizophrenia spectrum disorder associated with predisposition to schizophrenia spectrum disorder, other psychoses, and other psychiatric disorders in first-degree relatives were of similar magnitude. However, children with a mother with schizophrenia were at a 5-fold increased risk of developing schizophrenia and a 2.5-fold increased risk of developing cannabis-induced psychosis. The risk of a schizophrenia spectrum disorder following a cannabis-induced psychosis and the timing of onset were unrelated to familial predisposition. CONCLUSIONS: Predisposition to both psychiatric disorders in general and psychotic disorders specifically contributes equally to the risk of later treatment because of schizophrenia and cannabis-induced psychoses. Cannabis-induced psychosis could be an early sign of schizophrenia rather than a distinct clinical entity.
PMID: 18981338 [PubMed - indexed for MEDLINE]
http://stash.norml.org/new-study-casts- ... zophrenia/
NEW YORK (Reuters Health) - People who have long-lasting psychotic episodes after smoking marijuana may be exhibiting early signs of schizophrenia, researchers reported Monday in the Archives of General Psychiatry.
“Cannabis-induced psychosis,” in which a person loses touch with reality and the symptoms persist for at least 48 hours, is an established psychiatric diagnosis, but it is controversial, Dr. Mikkel Arendt of Aarhus University in Risskov, Denmark, and colleagues note in their report.
In a previous study, Arendt and colleagues found that nearly half of people who had an episode of cannabis-induced psychosis went on to develop schizophrenia within the next six years. In the current study, the researchers looked at the genetic roots of both conditions by comparing the family histories of 609 people treated for cannabis-induced psychosis and 6,476 who had been treated for schizophrenia or a related psychiatric condition.
They found that individuals treated for post-pot smoking psychotic episodes had the same likelihood of having a mother, sister or other “first-degree” relative with schizophrenia as did the individuals who had actually been treated for schizophrenia themselves. This suggests that cannabis-induced psychosis and schizophrenia are one and the same, the researchers note. “These people would have developed schizophrenia whether or not they used cannabis,” Arendt explained in comments to Reuters Health.
Based on the findings, the researcher says, “cannabis-induced psychosis is probably not a valid diagnosis. It should be considered schizophrenia.”
Even as we’ve complained that no data show that cannabis use causes schizophrenia, we’ve been told that for those who are genetically predisposed to schizophrenia, there seems to be a correlation between cannabis use and onset of psychotic symptoms. So while it may not be psychologically dangerous for most of us, there is that 1% minority that would be harmed, so we have to ban it for everyone.
But this report counteracts even that claim. In the conclusion of the report, the study authors note, “The degree of hereditary predisposition in individuals who receive treatment of cannabis-induced psychosis closely mirrors that in those who develop schizophrenia with no history of cannabis induced psychosis.” This seems to tell us that when you take a look at a group of schizophrenics, whether they smoked pot of not, they still had the same genetic chances of becoming schizophrenics - the pot use didn’t matter!
Schizophrenia is rare and it comes on slowly for some. This “cannabis-induced psychosis” is really just people in the beginning stages of schizophrenia who happen to smoke pot, and the pot is getting blamed. It would be as valid to say the schizophrenic having an episode in a Krispy Kreme shop was suffering from “donut-induced psychosis”.
, which can reduce calcium influx through voltage sensitive calcium channels (8, 9). A synthetic cannabinoid (HU-211) also has been demonstrated to be neuroprotective even though it does not activate cannabinoid receptors. This compound is an atypical cannabinoid, however, in that it, unlike other cannabinoids, directly antagonizes NMDAr (10) and possesses some antioxidant properties (11). The present study examines classical cannabinoids as neuroprotectants in vitro but focuses on the nonpsychoactive cannabinoid cannabidiol. Like THC, cannabidiol is a natural component of the marijuana plant, Cannabis sativa, although unlike THC, cannabidiol does not activate cannabinoid receptors and so is devoid of psychoactive effects (12). This study reports that cannabidiol and other cannabinoids such as THC are potent antioxidants that protect neurons from glutamate-induced death without cannabinoid receptor activation.