Archive for the ‘Contributing Author: Jahan Marcu’ Category
Tuesday, September 15th, 2009
A recent animal study out of Australia showed for the first time that food deprivation and stress hormones may enhance the release of THC stored in fat, thus increasing the amount of cannabinoids in the blood. The results may provide a mechanism for so called “Cannabis Flashbacks,” explaining instances where ex-cannabis users that were exposed to stress or under went weight loss, tested positive for THC.
THC is a lipophillic, fat loving or fat-like compound, that is rapidly absorbed or stored in fat. Interestingly, some researchers have discovered that THC accumulates in rodent gonadal fat tissue (epididymal) at higher levels than any other fatty tissue including the brain and liver (Ravitch 1979). In, humans it is still somewhat unclear where most of the THC gathers for its stay in the body. The precise mechanism whereby THC is released from fat is unknown but it appears THC is NOT metabolized in fat. THC is degraded by the liver to the excreted product: 11-Hydroxy-THC. Furthermore, THC has been found in fat 28 days since the last exposure. This long term storage of THC is consistent with observations that users can test positive after 77 days at levels >20ng/ml (Ellis et al 1985).
The authors suggest that it could be possible for THC to cause intoxication after being stored and released from fat. However,several things can cause THC release: stress,food deprivation, weight loss, exercise, physical or mental stress. However, MUCH MORE research is need in order to determine if it’s even possible to cause a measurable intoxication. Important questions remain like, “What’s the difference between a ‘perma-high‘ and a ‘cannabis flashback’? Will eating a lot of food and remaining sedentary help you test negative for THC? And if THC intoxication can occur from physical activity, then could Santonio Holmes have caught the winning pass in super bowl 43 while intoxicated?…similar analogies apply to Ricky Williams, Rob Van Dam, Michael Phelps, and other professional athletes.
Eating your way through a drug test is an attractive speculation. However, it would olny work if it was balanced with remaining abstinent from cannabis use.
Posted in Cannabination, Contributing Author: Jahan Marcu | 2 Comments »
Saturday, August 22nd, 2009
On August 20th 2009, researchers from Italy published an article in the Journal of Molecular Medicine on the benefits of cannabidiol (CBD) to treat Inflammatory bowel disease (IBD), in a mouse model of colitis. CBD dramatically reduced tissue damage and inflammation in vivo.
The research team showed, for the first time that CBD reduced radical oxygen species (ROS) and lipid peroxidation in intestinal cells of mice. ROS production is a hallmark of IBD, as oxidative stress is the leading tissue destructive force that contributes to the development of IBD. The article also features pictures of treated and untreated intestinal tissue.
Of additional interest is the pharmacology of CBD. CBD was most effective at 5mg/kg. However, there wasn’t much difference at higher doses, even a dose of 10mg/kg did not exert a further protective effect. Lower doses (1-2.5mg/kg) were not significantly effective.
Also, the researchers found that CBD inhibited Nitric Oxide Synthase, an enzyme with produces Nitric oxide (NO). High levels of NO correlate correlate well with IBD activity, and previous experiments have shown that other Nitric Oxide Synthase Inhibitors can also improve symptoms of IBD.
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Thursday, August 20th, 2009
If you live long enough, you will suffer from a bone disease. So, there is a tremendous need for osteoporosis and bone disease treatments. A short article published in the journal of Cell Metabolism provides insights into how cannabinoid receptors regulate bone formation. Furthermore, the research team is from the UK at the University of Edinburgh and the BBC published a short article on their research, entitled, “Cannabis may prevent Osteoporosis.”
Bone Background
Bone is a very dynamic tissue which is constantly undergoing remodeling. And it is the remodeling of bone that in part, gives it strength. The remodeling of bone is regulated by a balance between two types of cells: Osteoblast and Osteoclasts. Osteoblasts lay down bone and Osteoclasts dissolve bone. The remodeling process allows your body to replace all your bone about every 8 years or so. Disease begins when the remodeling process becomes unbalanced. If your osteoblasts can’t keep up with osteoclasts, then you will begin to lose bone…the net loss or gain of bone is bad.
The cannabinoid receptors are found on bone cells and on nerves that run through bone.
Mice without Cannabinoid receptors
It has been established that mice without CB1 or CB2 receptors develop osteoporosis early in life, among other ailments. The author’s findings provide a much needed, deeper understanding of why cannabinoid receptors are important.
Bone stem cells AKA Mesenchymal Stem Cells (MSCs) can become bone cells or other cells such as fat cells AKA adipocytes. Without the CB1 receptor MSCs had an enhanced maturation into adipocytes (fat cells) and less of an ability to become bone cells. Fewer osteoblasts will lead to a loss of bone. Thus way more fat was being made and sintegrated into bone.
The story doesn’t end there. Osteoclasts, the bone dissolving cells, are inhibited as well. So, young mice without cannabinoid receptors have thicker bones during bone growth and development.
However, increasing bone mass is not for everyone, heavier bones are bad too. Don’t let the X-man Wolverine fool you with his indestructible skeleton; thicker bones are not as flexible or as dynamic as healthy bone and can lead to increased breaks and injuries.
The authors conclude that the Cb1 receptor has a “unique role” in bone development and metabolism. Since, it appears that the receptor continues to affect bone through out life, the authors speculate that cannabinoid drugs could be used to:
1) Increase bone mass during growth and development–in theory correcting bone related deficits in children
2) Maintain bone and combat osteoporosis in old age–keeping all of us healthy and strong
However, the authors don’t speculate on a particular treatment or how best to utilize these receptors. Yet, I can’t help to think that the ancient Indian drink Bhang could become a potential home remedy–I mean I wonder what the epidemiological data would say about women, cannabis use, and bone health from places like India. Also, gathering bone data (bone density, etc) from cannabis users,say 45 and older may provide additional insights.
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Thursday, August 13th, 2009
The journal of Experimental Dermatology has published a review, in which the authors point out the therapeutic possibilities of using cannabinoids to treat skin diseases.
Recent evidence has sown that cannabinoid receptors, CB1 and CB2 are expressed in healthy and diseased skin. Therefore, a treatment targeting these receptors could prove very effective.
Where are the receptors in skin?
The CB1 receptor is located on nerves that run through out skin; large nerves fibers and even small nerve fibers associated with hair follicles have the receptors. Furthermore, previous work has demonstrated that human skin cells, epidermal kertinocytes, have the machinery to “synthesize, bind, and metabolize anandamide (AEA).” While the role of the endocannabinoid system in skin is a bit of a mystery, it appears to be important in skin cell maturation.
Cannabinoids and Inflammatory Skin Diseases
Cannabinoids may attenuate allergic responses. Mice lacking cannabinoid receptors experience more swelling and recruitment of immune cells than normal or wild-type mice. Blocking the CB2 receptor may also lead to a decrease in inflammation.
Pruritus
We all hate getting an itch, especially when it leads to intense scratching and pain. While numerous treatments are available for anti-itching regiments, none are very effective as “anti-pruritic” medicines. Thus there is a great need for new and effective medicines.
In regards to pruritus the authors discuss a study which had nearly 2500 people with atopic eczema. The patients used a cream containing the endocannabinoid N-Palmithoylethanolamide or PEA. This cream signifcantly decreased symptoms of eczema and was well tolerated.
Furthermore, another study of patients with uremic pruritus showed that a cream containing AEA and PEA eliminated all symptoms within 3weeks, in 38.1% of patients and more than half experienced significant reductions. A treatment this effective is desperately needed-60% of all dialysis patients will suffer from this potentially disabling disease. On a side note, this is the closest that AEA has EVER come to being ingested for a clinical trial…
Lastly, there is evidence that some cannabinoids may be able to inhibit malignant skin tumors. However, synthetic cannabinoids that are more potent than THC, have proven to be more effective in this regard, especially WIN-55,212-2 and JWH-133.
The authors conclude, “Possibly, in the future, cannabinoids will be widely applied to treat skin pruitus, inflammatory skin disease, and even skin cancers.”
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Tuesday, August 4th, 2009
In the journal of Clincal Pyschopharmacology, a research team reports on the improvement of schizophrenic symptoms in a small group of patients who were treated with pure Delta9-THC (Marinol AKA Dronabinol). The doctors sought out patients who had chronic refractory schizophrenia and had a documented history of cannabis use. After going through about 200 patients, the doctors found a total of 6 that met the criteria.
Generally, cannabinoids are associated with the worsening of psychotic symptoms. So, why did Doctors give THC, the main ingredient in cannabis, to a group of patients who had severe cases of mental illness?
The authors write, “The idea for our use of dronabinol in this population came from the surprisingly good response of 1 patient. He was grossly psychotic, assaultive, disorganized, and highly refractory to multiple medication trials. However, in reviewing his history, we noted that he had a history of several years of calm behavior when he was using marijuana.”
After treatment with pure THC the authors note, ” Remarkably, he became calm, logical, nonviolent, and cooperative within days and was discharged within weeks. This prompted us to try dronabinol on other patients who fit this profile: having a diagnosis of chronic refractory schizophrenia, together with a history of marijuana use during which they reported some improvement.”
In regards to the safety profile of synthetic THC, the author’s comment that it “does not seem to have significant addictive potential or withdrawal in clinical practice.”
These results are remarkable patients with refractory schizophrenia because current interventions and treatments rarely succeed. These patients were also unresponsive to standard dopamine blockers, thus the abnormalities could lay in a non-dopamine system, i.e, the endocannabiod system. Perhaps the abnormalities may be related to the endocannabinoid deficiency theory. Since there is no viable treatment–there us an urgent need to find and develop medications for this patient population.
Additionally, these results go against the current accepted theory that activating the cannabinoid receptors (CB1) should worsen psychotic symptoms and blocking the receptor should improve it. Another piece of supporting evidence against this theory, comes from a clinical trial with Rimonabant, a CB1 Receptor Blocker. CB1 Blockers prevent other compunds from activating the receptor, thus limiting the activity of the receptor. The Cb1 receptor blocker did not improve symptoms.
The Doctors also site current research (1,2,3) which shows that not all cases of schizophrenia become worse after using Cannabis. It is also now being considered that vulnerability to the side effects of cannabis comes from a genetic predisposition.
The take home message is that the main ingredient of cannabis may become an effective treatment for patients with a severe mental illness. And that the Endocannabinoid system might be more important and complex than previously thought.
Posted in Cannabination, Contributing Author: Jahan Marcu | 1 Comment »
Sunday, July 26th, 2009
Two reviews (one & two) published this month highlight the emerging role of the Endocannabinoid system (ECS) as one of the most important mediators of our stress response, and further research into ECS could bring us new antidepressants and anxiolytic drugs—a few drugs are already a success in animal models!
There are two approaches to exploiting the ECS against depression and anxiety. One is developing a cannabis based medicine (pill, spray, etc) that targets the Cannabinoid Type 1 Receptor (CB1R).
The other approach utilizes our bodies own enzymes that degrade the THC-like compounds, synthesized from arachadonic acid, namely Anandamide (AEA) and 2-Arachidonyl glycerol (2-AG). This treatment requires compounds that inhibit the breakdown of AEA and 2-AG, thus raising the levels of AEA and 2-AG for the duration of the drug treatment. Normally, AEA and 2-AG are rapidly made, used, and degraded by our body.
Furthermore, AEA is the only known neurotransmitter that is synthesized on demand and it signals retroactivley or “backwards”—again it’s the first and only. Yet, if you check any recent biochemical pathway charts in medical textbooks, AEA is usually missing from the chart– nearly 20 years after it’s discovery! And AEA has NEVER been used in a clinical trial even though acetominophen, once metabolized inhibits AEA degradation! Since, one of the most widely used OTC drugs in the world works partially through the ECS, why are there no clincal trials with non-toxic AEA?
Most likely the biggest break through in depression and cannabinoid research occurred at the University of Saskatchewan in Canada, when researchers gave a drug, code named “HU-210″ to rats. HU-210 is 100 to 1000x more potent than THC, depending on the experimental assay. After a few weeks of treatment, analysis of the rat brains revealed that HU-210 caused neurogenesis. Meaning the rats grew new brain cells from stem cells, and those brain cells matured into neurons. This occurred specifically in the hippocampus. The Authors speculated that this compound could be a cure for depression and this could also be considered a stem cell based therapy.
As the patents on billion-drugs (like questionably effective drugs such as SSRI’s) are near expiration, cannabinoids stand as a clear beacon of therapeutic promise. Other governments (UK, Israel, the Netherlands, Spain, Germany…) have realized this, eased cannabis research restrictions, and allowed legitimate companies to emerge which focus solely on developing and distributing cannabinoid medicines. If our governemnt waits too much longer and restrictions on cannabis research are not eased, U.S. researchers will miss out on this centuries medical breakthroughs. And that would truly be depressing…
Posted in Cannabination, Contributing Author: Jahan Marcu | 2 Comments »
Friday, July 3rd, 2009
The San Jose Mercury News reported that Marijuana smoke will be added to the ever-growing list of cancer-causing materials covered by prop. 65 in CA.
Putting marijuana smoke in this category seems misplaced at best when diet colas, which contain everything from saccharine to questionably FDA-approved Nutrasweet and other chemically engineered sweeteners are not included. (Sorry if Nutrasweet or Diet Coke is on the list, but I couldn’t find it.)
It is particularly ironic that marijuana smoke will be the only smoke on the list, given the level of industrial air pollutants that are not included on the list.
The purpose of prop 65 is to protect our citizens and drinking water, yet toxic molds are not included on prop 65! Further, “businesses are not required to provide OEHHA with any information regarding their Proposition 65 warnings.” The OEHHA (Office of Environmental Health Hazard Assessment) mission is to enhance public health and the environment through scientific evaluation of risks posed by hazardous substances.
It’s too bad the very studies used by OEHHA to make this decision were deeply flawed regarding the methods, leading to artificially high readings of hazardous compounds. Some of the leading cannabis researchers in the world published a three part study on cannabis smoke a few months ago. This study compared the techniques used to analyze cannabis smoke and they found huge flaws with current methods which produced exaggerated levels of side products. In some cases, the authors suggest that previous researchers left out essential information regarding their methods–making it impossible to repeat previous experiments or confirm the results! Despite credible reports which demonstrate that practically all previous research comparing cannabis and tobacco smoke is flawed and inaccurate, OEHHA went ahead and used bad science to support their politics.
A political decision like this, will undoubtedly cause confusion for years to come. After all the two main ingredients on the plant, THC and CBD, have notable anti-cancer properties. In fact, research which demonstrates that combining THC and CBD has synergistic or greater than additive anti-cancer properties, will be presented at the upcoming International Cannabinoid Research Society meeting (July 7th-11th in Chicago).
The leading researcher in this area is Dr. Tashkin, who has been employed by the U.S. government and for the last 30 years has been examining if a link does exist between marijuana smoking and cancer. He did not find a link between cannabis smoke and cancer, unless the smokers also used tobacco.
Prop 65 may cause future inconveniences for any cannabis patients who needs to be able to smoke in a public or private facilities, i.e. trying to ease their glaucoma before their eyes explode from the ocular pressure.
However, there remains two benefits to this decision:
1) Legitimacy
2) Deterrence to non-medical users
1) This is a step towards regulating cannabis. A simple regulatory mechanism such as requiring a warning label, may provide some legal protections for those who follow it. Therefore by listing the potential harms, as on every bottle of a pharmaceutical drug, it provides a bit of legitimacy because the consumer is protected or informed, and because it reinforces the reality that cannabis is a medical treatment.
2) Often I hear criticisms regarding access to medical cannabis, specifically with regard to who has access to it and who gets it. Additionally, some are concerned that people who fake illnesses to get pharmaceutical drugs will also con doctors who recommend medical cannabis. A cancer warning would deter any casual/recreational user from taking advantage of a system intended to serve the state’s seriously afflicted and chronically ill population.
What about the Science?
It has never been conclusively shown that smoking cannabis will cause, prevent, or treat cancer. What science has shown is that:
A) the active ingredients in cannabis, when isolated or in combination have anti-cancer properties.
B) Cannabis smoke contains some of the same cancer causing material as tobacco smoke.
C) People who smoke cannabis have less of a chance of getting lung cancer then non-smokers or cigarette smokers
So, there is no concrete proof that smoking cannabis will cause or fight cancer but the individual compounds in the smoke have anti-cancer and pro-cancer properties. Meaning the side products of cannabis smoke can cause cancer but the most abundant ingredients (cannabinoids) fight cancer. How they work together remains unclear, so it seems unfair to label cannabis smoke as a carcinogen because that’s only half the story.
I know neither politics nor science is about being “fair.” However, science is the pursuit of truth/facts. So in the interest of truth, let’s incorporate what is actually known about cannabis smoke into the Prop 65 warning:
“Cannabis Smoke contains compounds known to the State of California that may cause or treat cancer.”
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