At Cornerstone we feel an obligation to our members to be on the leading edge of medical cannabis information. As a result, we are constantly on the lookout for new roles medical cannabis could serve in society. Recently, we noticed a paper by the University of South Carolina that argued that cannabinoids could have a therapeutic role in organ transplantation. Although we are cautious of taking in new information, after digging through the medical literature currently available, we have reason to believe that these researchers are onto something. Below we’ll outline the reasoning behind exploring cannabis or cannabinoids as therapeutic agents during organ transplants, as well as discuss the current debate surrounding organ transplants for medical cannabis patients.

The idea of transplanting organs has existed for thousands of years. Without knowledge of biology, it seems strikingly unjust that some will die of faulty organs when so many other healthy organs exist that will only be thrown into a grave. However, the essential problem with organ transplantation is not a lack of physical similarity or identical function. The problem is the immune system. In normal functioning, the immune system has a variety of watchdog mechanisms that activate upon finding biological “intruders”. Cell networks work together to attack and dismantle various threats, from cancer cells, to bacteria, to viruses. However, what makes the immune system so effective on a day-to-day basis is exactly what makes transplants so hard; the immune system identifies transplanted cells as foreign and proceeds to reject the transplant. The transplant then essentially rots inside the host, introducing more complications than the original organ. In fact, in the 1930’s the first transplant from a non-living host to a living one ended in failure from organ rejection. A major turning point, therefore, in organ transplantation, arrived upon the discovery of immunosuppressant drugs. Doctors realized that if they could lower the guard of the immune system long enough for the new organ to “take”, the organ would not be rejected. Although this idea had existed since the 50’s, it was not until 1970 that the first sufficiently powerful immunosuppressant was discovered. New drugs followed and as a result, transplants are common and are nowhere near as risky as before.

Unfortunately, managing these drugs is difficult for an obvious reason: without the immune system functioning at full steam, infections and other complications have a higher rate of occurring. Doctors are often playing a game of adjusting the amount of suppressant given to lower the immune reaction as far as is safe, but no further. Ideally, at some point in human history, we will have the knowledge to selectively turn off certain areas of the immune system.

Where cannabis pops into this equation is the communication between the endocannabinoid system and the immune system. For one, cannabinoid receptors (specifically CB2 receptors) are prevalent among immune cells, hinting a role at immune regulation. Secondly, as we’ve reported in various instances, cannabidiol (CBD) has helped reduce inflammation and swelling in countless situations. Although we don’t usually put the two in the same category, inflammation is actually part of the body’s immune response. In fact, endocannabinoids have formally been proven to suppress the production of inflammatory molecules that originate from the immune system, which is why cannabidiol is effective.

Yet researchers from the University of South Carolina have another theory of how the two might interact. Endothelial cells are cells that line blood vessels and “regulate interactions between blood and tissues.” These cells are intrinsically involved in transplant rejection because they allow immune cells to infiltrate the transplant tissue and begin destroying it. For metaphor, think of these cells as gatekeepers. A recent study showed that cannabinoids could inhibit migration of molecules from one side to another of these cells, which means that potentially cannabinoids could prevent the immune system from getting through to attack a transplant. The best part is that, unlike other immuno-suppressants, cannabinoids are safe and non-toxic to the human body. This means that fewer life-ending complications could result from transplant as doctors could increase dose without fear of harmful side-effects.

Beyond the theory, one experiment has shown physical promise that cannabinoids might aid organ transplantation. Roughly a year ago, researchers at the Temple University School of Medicine harvested mice cells and added foreign cells to observe a reaction known as Mixed Lymphocyte Reaction or MLR. This reaction is generally thought of as an in vitro correlate of graft rejection following skin and organ transplantation, which simply means that the way the cells react in solution is very similar to the way they would react within mouse bodies. Some cells were untreated to serve as comparisons or controls, while others were given solutions of THC, JWH-015, and O-1966. JWH-015 and O-1966 are synthetic cannabinoids. Researchers found that all three suppressed the reaction significantly, with THC suppressing by 54%, JWH-015 by 62%, and O-1966 by 90.4%! Researchers speculated that the immuno-suppressant effects were occurring as a result of CB2 cannabinoid receptor activation and they went on to prove this by administering receptor antagonists that would selectively block CB1 receptors during one round and CB2 receptors during another. Although blocking CB1 receptors made no difference, blocking CB2 receptors eliminated the reduction in reaction, proving that the effects were indeed occurring via CB2 receptor signaling.

Unfortunately, this is the end of the road for this area of cannabis research at the time being. We’re still waiting to see in-vivo experiments (in actual organisms rather than cell dishes). Many effects are observed in cell experiments that do not occur in actual organisms and even those effects do not always duplicate in humans. In other words, the book is not closed on organ transplant. We can pull two major ideas out of this research: 1) Organ transplant accommodation will likely be a future avenue of cannabis research 2) The immune system and the endocannabinoid system have a complex relationship, and we’re only seeing the tip of the iceberg.

This is not the only area where cannabis research and the practice of providing organ transplants intersect. As the Huffington Post and various other news sources have reported, medical cannabis patients, specifically in California, are being denied organ transplants. These are patients who in some cases were legally prescribed cannabis at the same hospitals that are currently denying them transplants. Federal law gives hospitals the legal grounds to deny patients for cannabis use. Since being added to an organ transplant list requires a subjective evaluation by a group of healthcare professionals, it is difficult to force hospitals to admit that this was the sole reason for excluding the patient from the list. After several deaths from failures to receive transplants and much lobbying, political wheels are finally turning to correct the issue. Last year the California Medical Association adopted a non-binding resolution that cannabis patients should be allowed to receive transplants. This year, California State Assembly Member Marc Levine (D) sponsored a bill that would specifically protect medical cannabis patients from being kicked off donor lists.

(You can support this bill, AB258, by following on the link below)

http://org.salsalabs.com/o/182/p/dia/action3/common/public/?action_KEY=14961

In the meantime, what exists is an incredibly ironic situation: cannabis likely aids transplants, and yet transplant recipients are being kicked off donor lists for using it.

 

 

Works Cited

Rebecca Robinson, Joseph Meissler, Jessica Breslow-Deckman, John Gaughan, Martin Adler, et. al. (2013) “Cannabinoids Inhibit T-cells via Cannabinoid Receptor 2 in an In-Vitro Assay for Graft Rejection, the Mixed Lymphocyte Reaction.” Journal of Neuroimmune Pharmacology (December 2013); 8(5).

Mitzi Nagarkatti, Sadiye Rieder, Venkatesh Hegde, Shunsuke Kanada, and Prakash Nagarkatti. (2010) “Do Cannabinoids have a therapeutic role in transplantation?” Trends of Pharmacological Science (2010) 31(8):345-350.