Tag Archives: marijuana
Cannabinoids in health and disease
Abstract
“Cannabis sativa L. preparations have been used in medicine for millenia. However, concern over the dangers of abuse led to the banning of the medicinal use of marijuana in most countries in the 1930s. Only recently, marijuana and individual natural and synthetic cannabinoid receptor agonists and antagonists, as well as chemically related compounds, whose mechanism of action is still obscure, have come back to being considered of therapeutic value. However, their use is highly restricted. Despite the mild addiction to cannabis and the possible enhancement of addiction to other substances of abuse, when combined with cannabis, the therapeutic value of cannabinoids is too high to be put aside. Numerous diseases, such as anorexia, emesis, pain, inflammation, multiple sclerosis, neurodegenerative disorders (Parkinson’s disease, Huntington’s disease, Tourette’s syndrome, Alzheimer’s disease), epilepsy, glaucoma, osteoporosis, schizophrenia, cardiovascular disorders, cancer, obesity, and metabolic syndrome-related disorders, to name just a few, are being treated or have the potential to be treated by cannabinoid agonists/antagonists/cannabinoid-related compounds. In view of the very low toxicity and the generally benign side effects of this group of compounds, neglecting or denying their clinical potential is unacceptable – instead, we need to work on the development of more selective cannabinoid receptor agonists/antagonists and related compounds, as well as on novel drugs of this family with better selectivity, distribution patterns, and pharmacokinetics, and – in cases where it is impossible to separate the desired clinical action and the psychoactivity – just to monitor these side effects carefully.”
Cancer
“The antiproliferative action of cannabinoids on cancer cells was first noticed in the 1970s. Since then cannabinoids were found to act on various cancer cell lines, through various mechanisms. Cannabinoids were also found to be suppressors of angiogenesis and tumor invasion. Our knowledge on the anticancer activity of cannabinoids is rapidly expanding.”
Conclusion
“Many drugs used today can cause addiction and are misused and abused, for example opiates, cocaine, benzodiazepines, barbiturates, cholinergic agonists, ketamine, dopaminergic agonists, amphetamines, and others. Nevertheless they are still an important part of our pharmacopeia. Marijuana was used for centuries as a medicinal plant, but during the last century, because of its abuse and addictive potential it was taken out of clinical practice. Now, we believe that its constituents and related compounds should be brought back to clinical use. The reasons are: (i) the therapeutic potential of CB1 agonists is huge, as described in this review; (ii) for local action, topical CB1 agonists, or agonists that do not penetrate the blood-brain barrier, can be used; (iii) cannabinoids acting specifically on CB2 receptors, which cause no psychoactivity, may be used on peripheral targets (such as osteoporosis, which is only one of many examples); (iv) there are additional, new cannabinoid targets distinct from the CB1/CB2 receptors which do not cause psychoactivity; (v) there are cannabinoids, such as CBD, which do not cause psychoactivity, but have various therapeutic effects.”
Cannabinoid receptors in brain: pharmacogenetics, neuropharmacology, neurotoxicology, and potential therapeutic applications.
“Much progress has been achieved in cannabinoid research. A major breakthrough in marijuana-cannabinoid research has been the discovery of a previously unknown but elaborate endogenous endocannabinoid system (ECS), complete with endocannabinoids and enzymes for their biosynthesis and degradation with genes encoding two distinct cannabinoid (CB1 and CB2) receptors (CBRs) that are activated by endocannabinoids, cannabinoids, and marijuana use.
Physical and genetic localization of the CBR genes CNR1 and CNR2 have been mapped to chromosome 6 and 1, respectively. A number of variations in CBR genes have been associated with human disorders including osteoporosis, attention deficit hyperactivity disorder (ADHD), posttraumatic stress disorder (PTSD), drug dependency, obesity, and depression. Other family of lipid receptors including vanilloid (VR1) and lysophosphatidic acid (LPA) receptors appear to be related to the CBRs at the phylogenetic level. The ubiquitous abundance and differential distribution of the ECS in the human body and brain along with the coupling to many signal transduction pathways may explain the effects in most biological system and the myriad behavioral effects associated with smoking marijuana. The neuropharmacological and neuroprotective features of phytocannabinoids and endocannabinoid associated neurogenesis have revealed roles for the use of cannabinoids in neurodegenerative pathologies with less neurotoxicity. The remarkable progress in understanding the biological actions of marijuana and cannabinoids have provided much richer results than previously appreciated cannabinoid genomics and raised a number of critical issues on the molecular mechanisms of cannabinoid induced behavioral and biochemical alterations. These advances will allow specific therapeutic targeting of the different components of the ECS in health and disease.
This review focuses on these recent advances in cannabinoid genomics and the surprising new fundamental roles that the ECS plays in the retrograde signaling associated with cannabinoid inhibition of neurotransmitter release to the genetic basis of the effects of marijuana use and pharmacotherpeutic applications and limitations. Much evidence is provided for the complex CNR1 and CNR2 gene structures and their associated regulatory elements. Thus, understanding the ECS in the human body and brain will contribute to elucidating this natural regulatory mechanism in health and disease.”
Endocannabinoids and cannabinoid receptor genetics.
“This review presents the remarkable advances that have been achieved in marijuana (cannabinoid) research, with the discovery of specific receptors and the existence of naturally occurring cannabis-like substances in the human body and brain.
The last decade has seen more rapid progress in marijuana research than any time in the thousands of years that marijuana has been used by humans, particularly in cannabinoid genomics. The cDNA and genomic sequences encoding G protein-coupled cannabinoid receptors (Cnrs) from several species have now been cloned. Endogenous cannabinoids (endocannabinoids), synthetic and hydrolyzing enzymes and transporters that define neurochemically-specific cannabinoid brain pathways have been identified. Endocannabinoid lipid signaling molecules alter activity at G protein-coupled receptors (GPCR) and possibly at anandamide-gated ion channels, such as vanilloid receptors. Availability of increasingly-specific CB1 and CB2 Cnr antagonists and of CB1 and CB2 Cnr knockout mice have increased our understanding of these cannabinoid systems and provides tantalizing evidence for even more G protein-coupled Cnrs. Initial studies of the Cnr gene structure, regulation and polymorphisms whet our appetite for more information about these interesting genes, their variants and roles in vulnerabilities to addictions and other neuropsychiatric disorders. Behavioral studies of cannabinoids document the complex interactions between rewarding and aversive effects of these drugs.
Pursuing cannabinoid-related molecular, pharmacological and behavioral leads will add greatly to our understanding of endogenous brain neuromodulator systems, abused substances and potential therapeutics. This review of CB1 and CB2 Cnr genes in human and animal brain and their neurobiological effects provide a basis for many of these studies.
Therefore, understanding the physiological cannabinoid control system in the human body and brain will contribute to elucidating this natural regulatory mechanism in health and disease.”
Established and potential therapeutic applications of cannabinoids in oncology.
Abstract
“Cannabis occurs naturally in the dried flowering or fruiting tops of the Cannabis sativa plant. Cannabis is most often consumed by smoking marihuana. Cannabinoids are the active compounds extracted from cannabis. Recently, there has been renewed interest in cannabinoids for medicinal purposes. The two proven indications for the use of the synthetic cannabinoid (dronabinol) are chemotherapy-induced nausea and vomiting and AIDS-related anorexia. Other possible effects that may prove beneficial in the oncology population include analgesia, antitumor effect, mood elevation, muscle relaxation, and relief of insomnia. Two types of cannabinoid receptors, CB1 and CB2, have been detected. CB1 receptors are expressed mainly in the central and peripheral nervous system. CB2 receptors are found in certain nonneuronal tissues, particularly in the immune cells. Recent discovery of both the cannabinoid receptors and endocannabinoids has opened a new era in research on the pharmaceutical applications of cannabinoids. The use of cannabinoids should be continued in the areas indicated, and further studies are needed to evaluate other potential uses in clinical oncology.”
Search: Study says marijuana fights cancer
“Researchers in Madrid say the main psychoactive ingredient in marijuana (what is it?) and other “cannabinoids” (what are those?) could help slow cancer growth, as well as manage many cancer symptoms (like what?). Scientists studied cancer cells (which type?) that grow faster than normal cells, and discovered that the cancer cells died whenever they were exposed to the pot ingredient.”
http://specials.msn.com/a-list/healthyliving/marijuana-fights-cancer-popular-pages
Marijuana compound could help fight breast cancer – ABC News
“There may be a new weapon in the fight against aggressive forms of breast cancer in the future, and it comes from an unlikely source: Marijuana. Researchers at California Pacific Medical Center in San Francisco believe a compound in marijuana may help.
The research funded by the California Breast Cancer Research Program builds on more than a decade of studies involving the genes responsible for the spread of cancer. Now scientists have found at the cellular level, a compound in cannabis inhibits the gene that controls the spread of cancer.
“The problem is not the cancer itself, the problem is the spread of the cancer,” said cancer researcher Yvez Desprez, Ph.D.
Cancer researcher Pierre Desprez points to the gene ID-1 as the trigger.
“When this type of gene is expressed, the cells basically go crazy and they’re very aggressive and they metastasize everywhere in the body,” said Desprez.
“We could expect that if we create really effective inhibitors against it, we could potentially treat many types of aggressive cancers,” said cancer researcher Sean McAllister, Ph.D.
Their research in breast cancer cell lines focused on using a non-toxic compound in cannabis to target the ID-1 gene.
“What we found was cannabidiol is a particularly good inhibitor of this gene that’s responsible for the ability of cancer cells to become very aggressive,” said McAllister.”
http://abclocal.go.com/kgo/story?section=news/health&id=5771385
Scientists believe marijuana compound could fight cancer
“Scientists in California believe they may have discovered a compound in marijuana that can reduce the aggressiveness of some forms of cancer.
The San Francisco Gate reports on the data that has been years in the making. While marijuana has been shown to help reduce nausea and pain in cancer patients, scientists believe that a compound in marijuana has the ability to “turn off” the activity of a gene responsible for metastasis in breast and other types of cancers.
The research team is working out of San Francisco’s California Pacific Medical Center Research Institute and have been working for years on the study. The compound they’re focused on, called cannabidiol, does not produce the psychotropic high associated with marijuana.
Last year, the team published a small study showing the positive effects of cannabidiol on mice. New data is about to be released that expands upon the previous results that the researchers hope will help propel the study even further.
“The preclinical trial data is very strong, and there’s no toxicity. There’s really a lot of research to move ahead with and to get people excited,” said Sean McAllister, who is working alongside scientist Pierre Desprez in the study.
Desprez and McAllister believe that their merging of separate areas of study was serendipitous.
Desprez had been studying the protein ID-1, which he found to play an important role in how cancer could spread. McAllister, on the other hand, was focused on studying anabolic steroids in drug abuse. He soon became focused on with the role non-psychotropic cannabidiol, or CBD, interacts with cancer.
McAllister, after hearing an internal seminar from Desprez on his studies of ID-1, came up with the question “How effective would cannabidiol be on targeting metastatic cancer cells?”
The two then teamed up, with Desprez armed with ID-1 cancer-causing protein, and McAllister with CBD, his cancer-fighting compound.
For their experimentation, the doctors exposed ID-1 to CBD in a petri dish. In a shocking result, the ID-1, the cancer-causing protein, reverted to a normal state and stopped acting “crazy.”
“We thought we did the experiment the wrong way,” McAllister said of the overwhelming results.
However, their results proved to be consisted.
“I told Sean, ‘Maybe your drug is working through my gene,’ ” Desprez said.
What the researchers have discovered thus far in their research is that CBD turns off the overexpression of ID-1, which prevents it from traveling to foreign tissues. Thus, the metastasization – cancer’s fatal ability – is blocked.
In the wake of their positive results, the doctors were forced to emphasize that the CBD will only work in the presence of high levels of ID-1 and these do not include all cancerous tumors but, rather, aggressive, metastatic cells. High levels have been found in leukemia, colorectal, pancreatic, lung, ovarian, brain and other cancers.”
Read more: http://www.irishcentral.com/news/Scientists-believe-marijuana-compound-could-fight-cancer-170689736.html#ixzz29rQbc2oS
Marijuana May Fight Lung Tumors WebMD
“Cannabis Compound Slows Cancer Spread in Mice, Researchers Say.
… the active ingredient in marijuana may help combat lung cancer, new research suggests. 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 who tested the chemical.While a lot more work needs to be done, “the results suggest THC has therapeutic potential,” she tells WebMD.Moreover, other early research suggests the cannabis compound could help fight brain, prostate, and skin cancers as well, Preet says.
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The findings were presented at the annual meeting of the American Association for Cancer Research.
The finding builds on the recent discovery of the body’s own cannabinoid system, Preet says. Known as endocannabinoids, the natural cannabinoids stimulate appetite and control pain and inflammation.
THC seeks out, attaches to, and activates two specific endocannabinoids that are present in high amounts on lung cancer cells, Preet says. This revs up their natural anti-inflammatory properties. Inflammation can promote the growth and spread of cancer.
In the new study, the researchers first demonstrated that THC inhibited the growth and spread of cells from two different lung cancer cell lines and from patient lung tumors. Then, they injected THC into mice that had been implanted with human lung cancer cells. After three weeks, tumors shrank by about 50%, compared with tumors in untreated mice.
Paul B. Fisher, PhD, a professor of clinical pathology at Columbia University, says that though the work is “interesting,” it’s still very early.
“The issue with using a drug of this type becomes the window of concentration that will be effective. Can you physiologically achieve what you want without causing unwanted effects?” he tells WebMD.”
More:http://www.webmd.com/lung-cancer/news/20070417/marijuana-may-fight-lung-tumors
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-9 Tetrahydrocannabinol inhibits growth and metastasis of lung cancer.” http://www.aacrmeetingabstracts.org/cgi/content/meeting_abstract/2007/1_Annual_Meeting/4749%20?maxtoshow&hits=80&RESULTFORMAT&fulltext=cannabinoid&searchid=1&FIRSTINDEX=1760&resourcetype=HWCIT
“Delta9-Tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis in vivo.” http://www.ncbi.nlm.nih.gov/pubmed/17621270
Marijuana Chemical May Fight Brain Cancer – WebMD
“Active Component In Marijuana Targets Aggressive Brain Cancer Cells, Study Says
The active chemical in marijuana promotes the death of brain cancer cells by essentially helping them feed upon themselves, researchers in Spain report.Guillermo Velasco and colleagues at Complutense University in Spain have found that the active ingredient in marijuana, THC, causes brain cancer cells to undergo a process called autophagy. Autophagy is the breakdown of a cell that occurs when the cell essentially self-digests.The team discovered that cannabinoids such as THC had anticancer effects in mice with human brain cancer cells and people with brain tumors. When mice with the human brain cancer cells received the THC, the tumor growth shrank.Two patients enrolled in a clinical trial received THC directly to the brain as an experimental treatment for recurrent glioblastoma multiforme, a highly aggressive brain tumor. Biopsies taken before and after treatment helped track their progress. After receiving the THC, there was evidence of increased autophagy activity.
The findings appear in the April 1 issue of the Journal of Clinical Investigation.
The patients did not have any toxic effects from the treatment. Previous studies of THC for the treatment of cancer have also found the therapy to be well tolerated, according to background information in journal article.
Study authors say their findings could lead to new strategies for preventing tumor growth.”
http://www.webmd.com/cancer/brain-cancer/news/20090401/marijuana-chemical-may-fight-brain-cancer