Can THC Help Prevent Transplant Rejection?

Tens of thousands of organ transplants help to save lives every year. However, it’s not always a happy ending. Complications, especially transplant rejections, can prevent the transplant from being a long-term success. Research shows us how THC may help prevent the immune system from rejecting a transplant.

Organ transplants have saved, and continue to save, thousands of lives every day around the world, but ensuring everything goes well isn’t as easy as it sounds. The main problem we must tackle is that our bodies are programmed to use our immune system to protect themselves from any external attacks. That includes transplanted organs.

The immune system can trigger a reaction or transplant rejection, which can have fatal consequences. However, a 2015 study by Nagarkatti and colleagues suggests that tetrahydrocannabinol (THC) can help delay the rejection of transplanted organs or tissues in rodents. THC is one of the best known and best studied cannabinoids, responsible for many, if not most, of the physical and psychoactive effects of cannabis.

The legalisation of medicinal, as well as recreational, cannabis is a prominent issue in many countries around the world. Some have already legalised it while others are in the process of doing so, or starting discussions regarding this issue.

Every day, more studies emerge that demonstrate and publicise the numerous medical and therapeutic benefits of the cannabis plant, and the cannabinoids it contains.

These studies help to dispel the misgivings of those who continue to oppose the legalisation of cannabis. They also highlight the need to make continued progress in scientific research so that such studies may be conducted in a clinical setting, but with human subjects.

Some of the more recent studies concern surgery. In this article, we’ll specifically focus on one of the most interesting ones published in 2015, adding another benefit to an already long list for cannabis and more specifically the cannabinoid THC.

The therapeutic value of THC

In 2015, a group of researchers from the Faculty of Medicine at the University of South Carolina published a study to test the effects of THC on skin grafts. According to this study, tetrahydrocannabinol (THC), one of the main compounds of the cannabis plant, can help delay rejection in incompatible organ transplant patients by activating cannabinoid CB1 receptors in immune cells.

“More and more research is identifying potential beneficial effects of substances contained in marijuana, but a major challenge has been identifying the molecular pathways involved,” said John Wherry, deputy editor of the magazine Journal of Leukocyte Biology, in a statement.

The ability of THC to regulate the immune system was first identified in the 1970s. Following a series of tests conducted in rodents, the research by Nagarkatti and colleagues now suggests that THC may improve the outcome of organ transplants by blocking the immune response that causes the transplanted organs to be rejected.

As a result, more lives could be saved through transplants. Clearly, this provides yet more evidence of the obvious therapeutic potential of cannabis. This is particularly true for THC, which together with CBD, is the most studied natural cannabinoid.

Organ transplantation: what does it involve?

Organ transplants are one of the most significant examples of scientific progress in medicine today. When organs or tissues begin to fail due to illness, it may be necessary to replace the diseased organ or tissue. To do so and in order to prolong lives, there needs to be a donor and subsequently, the recipient’s immune system must not trigger a rejection.

Kidneys, livers, hearts, and bone marrow are among the most commonly transplanted organs and tissues. While some organs (such as the heart) can only be donated when the donor has died, others (such as the kidney, liver and bone marrow) can be donated by living donors.

Worldwide, the figures speak for themselves. Every day, hundreds of thousands of people continue to wait for an organ; thousands die while waiting for the arrival of an organ they need to survive. A single person can potentially save up to eight lives, since one person can donate eight organs. Approximately 10% of potential recipients die while waiting to receive an organ.

Transplant rejection: why does it happen?

Each of us has an individualised immune system, which is affected both by our genetics and our environment. This system recognises foreign bodies and infectious agents, helping to protect us against disease. Agents from outside the body may be infectious (such as bacteria or viruses), but so can cells that come from another person whose immune system and own individualised response are very different from ours.

Nucleated cells have markers on their surface that are recognised as foreign once they are inoculated or transplanted to another subject. These markers are called histocompatibility antigens (Ag) or transplantation antigens and they provide the tissues of every individual with unique characteristics that differentiate them from others.

Our “innate immunity” does an excellent job in protecting us and is characterised by:

  • a rapid response in its first line of defence (such as the skin, our largest organ) against infectious agents
  • its ability to stimulate non-specific immune cells that work to destroy potentially harmful substances that have entered the body

When the intrusion is so severe that the innate immune system can no longer cope, our “adaptive immunity” comes into play. Adaptive immunity is characterised by a more specific, slower, and longer-term response provided by specialised cells (such as T cells and B cells) against agents from outside the body. This is the kind of immunity that comes into play with transplant rejection.

Although organs and tissue transplants currently help to prolong peoples’ lives more than ever before, there are risks involved. There are several types of rejection. One of the main problems is when the recipient’s immune system (specifically, their T cells) recognises the new organ or tissue donor as “foreign” and begins to attack and destroy it.

For this reason, it’s essential that the recipient’s immune system is as similar as possible to the donor’s, which can be very difficult to coordinate given how unique everyone’s immune system is, and the speed with which organ failure can lead to death.

And this is where THC comes in.

The immune system: can rejection be avoided?

To avoid rejection, the tissue must be examined prior to transplantation in order to identify whether or not the antigens it contains are compatible with the recipient. Although tissue examination ensures the transplanted organ or tissue is as similar as possible to the recipient’s, there’s no such thing as 100% compatibility.

No one has antigens that are identical to those of someone else, except in the case of identical twins. For this reason, it’s necessary to use immunosuppressive drugs (which suppress our immune system) so the body doesn’t always trigger an immune response thus causing destruction of the foreign tissue.

About 25% of kidney recipients and 40% of heart recipients experience an episode of acute rejection during the first year following transplantation. Luckily, rejection episodes don’t necessarily mean the loss of the organ.

However, although more than 90% of acute rejections can be treated successfully with modern immunosuppression treatment, it’s important to note that the immunosuppressive drugs currently available to prevent transplant rejection can have harmful side effects themselves. These side effects can include:

  • Diarrhoea
  • Hypertension
  • Acne
  • Weight gain
  • High cholesterol
  • High levels of blood sugar
  • Susceptibility to infection
  • Dental problems

Taking all these factors into consideration, in addition to the fact that demand for organs is far greater than the available supply and that the majority of patients often only have one chance with a donor organ or tissue, transplant rejection can have devastating consequences, which can lead to death.

Organ transplant rejection: can THC help prevent it?

To conduct the study in question, Nagarkatti used mice that had undergone skin transplant surgery, transplanting the skin of a group of mice to another group of genetically different mice. The incompatible skin was treated with either a placebo or THC, the active cannabis compound.

By injecting donor spleen and skin cells in recipient mice (thus using rodents as models for humans undergoing organ transplant), the researchers found that the recipient mice treated with THC were less likely to reject the new tissue than those that were treated with the placebo. The study showed that by activating CB1 receptors, THC helped prevent rejection through several mechanisms:

  • Preventing an increase in the number of T cell receptors in the recipients’ lymph nodes, thereby reducing the likelihood of a rejection of the donor tissue
  • Effecting a decrease in inflammatory response signals
  • Stimulating myeloid suppressor cells, which act to decrease the response of the T cell receptor and prevent rejection
  • Increasing the duration of the survival of skin cells from donors

It’s worth remembering a previous study published in 2013 in the online magazine Journal of Pharmacology Neuroimmune. This study anticipated how THC could stop the immune reaction that causes the transplanted organs to be rejected, in this case through the CB2 receptors.

Although this study only used cell culture models, the researchers observed a dose-dependent effect: higher doses of THC led to higher levels of immunosuppression. In addition, two synthetic cannabinoids were also included, and it was found that they could work just as well.

Based on these results, the researchers concluded that cannabinoids are promising in terms of improving the success rate of organ transplants.

Study results: THC as a treatment for transplant rejection

This study by the University of South Carolina joins the growing body of evidence that shows that cannabinoids are useful in modulating and reducing inflammatory processes that are involved not only in transplant rejection, but also in autoimmune disorders, cancer, and many other serious debilitating diseases.

“Altogether, our research has shown that for the first time, in our understanding, cannabinoid receptors can provide a new method of treatment for graft versus host disease (GVHD) and prevent allograft rejection through the suppression of the immune response in the recipient,” the research team concluded.

Given the serious side effects associated with current treatments used to prevent transplant rejection, along with the very favourable safety profile of THC, the authors say that more effective treatments with fewer side effects are desperately needed. Unfortunately, advances in cannabis-based medicine appear to be driven by the development of synthetic compounds instead of pure scientific discovery.

“These data support the potential of this class of compounds as useful therapies for prolonging graft survival in transplant patients,” said Mitzi Nagarkatti.

Medicinal cannabis patients awaiting transplant are adversely affected

It seems incredible and paradoxical that although the THC content of medicinal cannabis can help transplant patients in many countries, patients who use medicinal cannabis may be denied an organ transplant. Yes, those who use cannabis to treat a large number of diseases (or relieve their symptoms) and test positive for cannabis may be denied. This is particularly ironic when it occurs in the United States, where medicinal cannabis is legal in many states.

However, various cases have been publicised by the media, such as that of a 64-year old patient named Norman Smith. He was informed his doctors would take him off the list of transplant patients unless he stopped consuming cannabis for at least six months.

They also required him to take part in a treatment program for substance abuse in this period. The irony is that, in that same medical centre, Smith had been given a prescription for medicinal cannabis to help him cope with the adverse effects of chemotherapy treatment for his liver cancer. Unfortunately, Mr. Smith died before being reinstated on the waiting list for a transplant.

Dr Colquhoun argued that they “must consider issues of substance abuse seriously since it does often play a role in the evolution of diseases that may require transplantation, and may adversely impact a new organ after a transplant”. Again, it’s ironic that this statement is not based on scientific evidence, given that cannabis use does not cause organ malfunction or failure.

Moreover, equating the use of a medicinal herb for pain relief in terminal disease with a substance abuse problem seems to be an error in judgment on the part of a healthcare professional. These statements appear to be based on stigma and ignorance.

Unfortunately, such decisions may have fatal effects on the lives of innocent people; people who are ill and require a transplant just as much as other patients in the same situation. Especially since a 2009 study found that cannabis users and non-users had similar survival rates after a liver transplant and that “Current substance abuse policies do not seen [sic] to systematically expose marijuana users to additional risk of mortality.”

Today, there are eight U.S. states that make it illegal to deny an organ transplant based on the use of cannabis. However, this is trickier than it sounds. The fight in Oregon to not discriminate against cannabis users is ongoing. But as Piseth Pich, community relations official for Legacy Health, told AP News: “That being said, it’s difficult to identify a specific number of patients who may be considered less for a transplant based on one factor alone”.

Undoubtedly, there’s a need for a change in existing policies that deny access to healthcare for these people, so that cannabis is recognised as a legitimate medicine. Policy makers would do well to take a page out of California’s book, where a law has been passed to protect such patients.

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