Archive for the ‘Cannabination’ Category
Saturday, January 2nd, 2010
The Journal of Molecular Psychiatry recently published an LTE from a group of researchers who demonstrated that chronic low doses of the cannabinoid WIN55212, resulted in new brain cells or neurons in the hippocampus of old rats. As we age, our ability to make new cells decreases, this may be the cause of many age related disorders. A class of drugs that can restore neurons may be a potential cure for diseases such as Parkinson’s, depression, etc.
The data was simply amazing–3 weeks of treatment resulted in noticeable effects! So this blog includes the figures from the publication, see below. On the left hand side, Figure A shows brain cells stained with red and green. Green, spindle like, staining indicates neuron growth. Pictures A and B show the typical neuron growth in developing brains. As you can see in pictures E and F, chronic administration of a non-psychotropic dose of WIN55212 restores neuron production in older rats, indicated by the green wisps. Note that this green stain is very low in old rats that did not receive the cannabinoid, pictures C and D.
The authors speculate, “Cannabinoid receptor stimulation therapy may thus provide clinical benefit for humans with age-associated memory impairment.”
Lots of molecules can activate cannabinoid receptors, so take your pick. More research is needed to determine which cannabinoids are the best option. None of the plant cannabinoids have not been explored for this effect. This not the first time cannabinoids have been linked to neurogenesis; HU-210 has also demonstrated similar effects.
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Thursday, November 12th, 2009
Scientists think the most abundant ingredients in tea may mediate activity of cannabinoid receptors. Polyphenols are the most abundant ingredient found in tea leaves. The average western diet usually includes at least 50mg of these polyphenols, the “mediterranean” diet contains at least twice this amount. Polyphenols such as catechins are known for their numerous health benefits including nueroprotection, anti-inflammatory properties, and appetite modulation. These health benefits manifest as reducing the chance of a stroke, slowing cognitive decline, and protecting against obesity. However, there is considerable disagreement on how these polyphenols cause these effects, for instance these researchers hypothesize that these compounds interact with cannabinoid receptor signalling.
Upon analysis the authors found that the compounds in tea actually bind both types of cannabinoid receptors, with notable higher affinity for the CB1 receptor. However, the receptor binding affinity of these polyphenols was relatively weak compared to a synthetic cannabinoid, CP55,940.
The authors speculate, “Signal strength may be amplified in vivo by non-receptor related mechanisms, i.e. Fatty acid amide hydrolase(FAAH)…” Meaning, the combination of polyphenols may activate many things at once in humans. FAAH would be an interesting target because the inhibition of this enzyme makes the levels of endocannabinoids rise.
Will Tea drinking or tea extracts be prohibited because of cannabinoid receptor activity? Does this mean Tea will become a schedule I drug like cannabis? Will 4:20 become the new tea time? Probably not. This is not the first evidence for cannabinoids as part of the human diet. Beta-caryophyllene can activate the CB2 receptor, and it is FDA approved.
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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 olny 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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