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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Disclaimer: These views are strictly the views of the author and not those of Temple University or its units.
This blog is not intended to diagnose or treat any disease.

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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Thanks,
Jahan