Archive for August, 2009
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.
Posted in Contributing Author: Jahan Marcu | 1 Comment »
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.
Posted in Cannabination, Contributing Author: Jahan Marcu | No Comments »
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 »
