Friday, June 11th, 2010
The original version of this article first appeared in the Lab Bench Science Column of the West Coast Leaf NewsPaper on June 4th 2010.
The Lab Bench
By Jahan Marcu
A research team from the School of Medicine at Temple University, Philadelphia, presented their preliminary cannabinoid and bone data at a scientific meeting in Anaheim, CA in April. Our results add to a growing body of scientific evidence, suggesting a prominent role for the endocannabinoid system in bone development. For the last year, researchers have been trying to reproduce and build upon previous work on cannabinoids and bone, specifically, by characterizing the effects of removing the CB1 and CB2 receptors from mice.
Few labs have published new discoveries regarding cannabis and bone. However, those that have are surprising so far. Some findings are so profound that the upcoming International Cannabinoid Research Society (ICRS) meeting will have a special symposium to discuss the bone data produced by just a few laboratories.
Research shows that bone cells have cannabinoid receptors and produce endocannabinoids. Bone cells express a lot of CB2 receptors and nerves that traverse our bones produce CB1 receptors. The `anti-cannabinoid’ receptor, GPR55, is also expressed in bone.
These receptors appear to work together to regulate bone health. Some clinical evidence supports the role of cannabinoids in various diseases. The Clinical Endocannabinoid Deficiency (Russo 2004) is thought to underlie many treatment- resistant conditions such as irritable bowel syndrome, fibromyalgia, and chronic pain. Recently, CB1 receptor mutations were linked to migraines, bi-polar disorder, and major depression (Monteleone 2010).
Now CB2 receptor mutations may be linked to lower human bone density and hand-bone strength. Research from Japan and France shows that mutations correlate to osteoporosis in post-menopausal women. The two studies looked at 2,626 elderly adults with and without osteoporosis. A study out in Russia analyzed the hand-bone strength of 574 adults and found that those with CB2 receptor muta- tions had weaker hand-bone strength (Yamada 2007, Karsak 2005, 2009). These all suggest that a less functional receptor is related to poor bone health.
Researchers have been studying how the body responds to traumatic brain injuries (TBI). When TBI occurs in a mouse, endocannabinoids are made and new bone is formed. Thus, cannabinoids may enhance the healing of bones in some instances such as fractures.
Genetically modified mice without the cannabinoid receptors have a deregulated skeleton. Depending on genetic makeup, the animals make too much or too little bone. So, research has shown that cannabinoids can both increase and decrease bone mass. However, all mice without cannabinoid receptors eventually develop severe osteoporosis (Bab 2008).
Plant cannabinoids such as CBDV, CBG, CBN, THC, and THCV may increase the number of bone stem cells in rats (Scutt 2007). Conversely, Anandamide has been shown to increase bone turnover by acti- vating osteoclasts, the cells that remodel or dissolve bone. CBD can inhibit osteoclasts. The infamous diet drug Rimonabandt, or SR141716A, is thought to prevent bone loss in mice by activating GPR55, not the CB1 receptor. Additionally, derivatives like WIN55,212 and some JWH compounds appear to severely inhibit osteoclasts from remodeling bone. Researchers have already speculated that cannabinoids represent a new generation of drugs that could treat a variety of bone diseases. For more information check out this recent review of the scientific literature, which discusses the role of the endocannabinoid system in bone disease and pathology.
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Saturday, February 6th, 2010
A growing body of scientific research suggests that cannabinoid receptors or the endocannabinoid system may have a therapeutic role in major depression (MD) and/or bipolar disorder (BD). A paper published in “Pharmaceutic Research” demonstrated that certain variations or mutations associated with the Endocannabinoid system may make humans more susceptible to MD or BD. The current study found that specific mutations in both the CB1 receptor and FAAH enzyme, were found in human subjects suffering from MD and BP. Interestingly, only the CB1 receptor mutations were linked to Major Depression, while both CB1 receptor and FAAH mutations were found patients suffering from bipolar disorders
What is the Endocannabinoid system (ECS)? And why is it linked to emotion?
The ECS is comprised of two receptors, the CB1 and CB2 receptor. The CB1 receptor is perhaps one of the most abundant receptors in the human brain. It is found in high amounts in many areas of the human brain, including parts of the brain important for emotion. It is fairly common knowledge that THC, from the cannabis plant, can activate CB1 receptors. However, humans and many other animals also make a “natural THC” called Anandamide. Anandamide is synthesized by cells in our body, and can impact a variety of natural processes such as eating, sleeping, memory, energy, and mood. Once Anandamide is synthesized it will be degraded or destroyed by another protein FAAH. The enzyme activity or the rate at which FAAH destroys Anandamide will indirectly affect the level of CB1 activity.
So, if FAAH is over active there will be fewer signals in the brain telling you to eat and sleep, among other things. If there is not enough FAAH, it will make a person hungry.
Mutations in FAAH or cannabinoid receptors may underlie many diseases; in fact a “Clinical Endocannabinoid Deficiency” has already been proposed to explain some chronic diseases such as “migraines, fibromyalgia, irritable bowel syndrome, and other functional conditions alleviated by clinical cannabis“. A previous study has also linked variations in FAAH and CB1 rceptors to anorexia nervosa and bulimia nervosa.
Posted in Cannabination, Contributing Author: Jahan Marcu | 2 Comments »
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 »
