Archive for the ‘Cannabination’ Category
Saturday, October 17th, 2009
Women and men percieve and respond to cannabis differently. Interesting gender differences are begining to be uncovered through animal studies, drug surveys, and clinical trials. Here are a few differences that have been published recently:
- Notably, estrogen can attenuate or inhibit various cannabinoid induced homeostatic changes such as appetite, body temperature, and brain activity.In other words, estrogen may allow women to be less susceptible to effects from cannabis or other cannabinoid medicines. Implying women can handle the effects of the drug better than men. Shel Silverstein‘s “Smoke Off” provides a good analogy.
- In animal studies (Review, Original research Article) on mice without the type 1 cannabinoid receptor (CB1), there appears to be a gender dependent phenotype. Male mice develop “strange” bones earlier, resulting from the removal of the CB1 receptor. In the first few weeks of life ,male mice without this receptor have remarkably higher bone volume. However, both genders develop severe age related osteoporosis later in life. It is also interesting to note, that this gender disparity is not observed in all transgenic mice without cannabinoid receptors–only in mice missing the CB1 receptor. Mice without the CB2 receptor have equally bad bones; gender independent effects.
- The ‘putative’ cannabinoid receptor GPR55, also displays similar gender dependent effects. When knocked out or removed from mice, the males have higher bone mass or volume compared to females.
- Another study completed at Temple Medical School in Philadelphia also showed sex dependent differences in mice without CB1 receptors. These differences were in reward seeking behaviors when it comes to cocaine and food. Basically male mice without CB1 self administer less cocaine and and less sweet food (Ensure). This research suggests that the cannabinoid system modulates appetite differently between genders.
- Drug abuse surveys have shown that women and men endorse different issues when it comes to cannabis use and abuse
As new cannabinid drugs are brought to market, and cannabis is becoming available in pharmacies around the world; more research is needed which tracks potential gender differences in response to cannabinoids.
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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 only work if it was balanced with remaining abstinent from cannabis use.
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Monday, September 7th, 2009
Genetic variations, polymorphisms, or mutations on the gene for the Cannabinoid Type 2 (CB2) Receptor have been linked to osteoporosis, low Bone Mineral Density (BMD), and hand bone strength in case controlled Studies (Yamada 2007, Karsak 2005, and Karsak 2009).
Most cannabinoid research on bone has been conducted in rats and mice. These recent case controlled studies in humans have established a significant association between CB2 gene polymorphisms/mutations to certain bone phenotypes; Mutant CB2 receptors lead to bad bones.
The first study (Karsak 2005) looked at CB1 and CB2 receptor DNA in a sample of French post-menopausal patients and female controls. The authors report that certain changes in CB2 receptor, but not the CB1 receptor, were strongly associated with osteoporosis. The authors claim this is the first study to find a link between the CB2 receptor and a disease in human patients. A study published out of Japan replicated these findings in 2007, in a group of pre and post menopausal women.
Furthermore, it has been speculated that CB2 receptor activation can inhibit atherosclerotic plaques. Atherosclerosis is a late onset disorder, that is inversely correlated to bone mineral density. If your bone density or strength starts decreasing, atherosclerosis progresses. So, CB2 receptor variations could explain the association between the two disorders. THC has already been shown to reduce atherosclerosis in mice by activating the CB2 receptor.
The third study on CB2 genes in humans, examined the role of CB2 DNA or genes on hand bone strength. The author took radio-graphic images and DNA samples from a Chevashian population, an ethnically homogeneous population of people of Bulgaric ancestry that live along the Volga river.
The authors found several recurring, small mutations or SNPs (Small Nucleotide Polymorphisms) were significantly associated certain bone phenotypes. Basically, a less functional form of the CB2 receptor leads to weak hand bone strength.
These studies have showed that the effects of CB2 receptor gene variations have been observed in three different genetic/ethnic backgrounds. Thus supporting a link between the CB2 receptors in humans and bone health. Drugs that activate this receptor are of medical value and importance.
While it appears that cannabinod receptor activation may be positively associated with bone health, no studies have been approved for observing the long term effects of cannabis use/ receptor activation on bone health. An anecdotal answer could be easily derived by comparing different measurements of bone health in long term cannabis users vs. non-users.
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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.
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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 one of the few neurotransmitters that is synthesized on demand and it signals retroactivley or “backwards”. 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…
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Jahan
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