Organ transplants have saved, and continue to save, thousands of lives every day around the world, but ensuring everything goes well is not as easy as it sounds. The main problem we have to tackle is that our bodies are programmed to use our immune system to protect themselves from any external attacks, which includes transplanted organs. Our immune system can trigger a reaction or transplant rejection, which can have fatal consequences. However, the results of a recent study published in the September 2015 issue of the Journal of Leukocyte Biology, suggest that tetrahydrocannabinol or Δ9-THC – one of the best known and best studied cannabinoids, responsible for many, if not most, of the physical and psychoactive effects of cannabis – can help delay the rejection of transplanted organs or tissues in rodents.
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 discussions regarding this issue are starting. Every day, more studies and scientific research emerges that demonstrate and publicise the numerous benefits, and the undeniable 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, and 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 and in this article, we will specifically focus on one of the most interesting ones published last year, adding another benefit to an already long list for cannabis and more specifically the cannabinoid THC.
The therapeutic value of THC
According to a study titled “Δ9-Tetrahydrocannabinol attenuates allogeneic host-versus-graft response and delays skin graft rejection through activation of cannabinoid receptor 1 and induction of myeloid-derived suppressor cells” published in 2015 by a group of researchers from the Faculty of Medicine at the University of South Carolina, tetrahydrocannabinol , or 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.
Although the ability of THC to regulate the immune system was first identified in the 1970s, today, following a series of tests conducted in rodents, research 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. Without a doubt, this provides yet even more evidence of the obvious therapeutic potential of cannabis, specifically of 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 an individual’s organs or tissues begin to fail due to illness, it may be necessary to replace the diseased organ or tissue with another one that functions properly. To do so and in order to prolong lives, there needs to be a donor and then 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 and thousands die while waiting for the arrival of an organ they need to survive. An organ from a donor can save up to 8 lives. Approximately 10% of recipients die while waiting to receive an organ. Each day, more and more people require a transplant to survive.
Transplant rejection: Why does it happen?
Each of us has an individualised immune system, which is affected both by our genetics and the type of environment in which we live throughout our lives. 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 can also be cells that come from another person whose immune system and own individualised response are very different from ours.
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, and its ability to stimulate non-specific immune cells that work to destroy potentially harmful substances that have entered the body. We now know that 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.
But when the failure is so severe that the innate immune system can no longer cope, our “adaptive immunity” comes into play, which 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, as we already mentioned, organs and tissue transplants currently help to prolong peoples’ lives more than ever before, there are risks involved in the process of receiving organs from the body of another individual. There are several types of rejection, but one of the main problems is that 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 is 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 each individual’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 is 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, and once again in order to prevent rejection, it is necessary to use immunosuppressive drugs (which suppress our immune system) so that the body does not always trigger an immune response, thus causing the destruction of the foreign tissue.
Following transplantation, depending on the organ involved, rejection can vary between 30 and 60%, but rejection episodes do not necessarily mean the loss of the organ. However, although more than 90% of acute rejections can be treated successfully with modern immunosuppression treatment, it is important to note that the immunosuppressive drugs currently available to prevent transplant rejection can have harmful side effects themselves, such as diarrhoea, hypertension, acne, weight gain, high cholesterol, high levels of blood sugar, and susceptibility to infection. In addition, they can also increase the risk of dental problems. It is clearly important to find safe alternative treatments.
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 often lead to death.
“According to the United States Department of Health and Human Services, among those who receive a transplant, about 25% of kidney recipients and 40% of heart recipients experience an episode of acute rejection during the first year following transplantation.”(Stanford Medicine).
Organ Transplant rejection: Can THC help prevent it?
To conduct the study in question, researchers administered a placebo and THC to mice that had undergone skin transplant surgery, transplanting the skin of a group of mice to another group of genetically different mice. As already mentioned, 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 CB1receptors, 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 is worth remembering another, previous study published in 2013 in the online magazine Journal of Pharmacology Neuroimmune, which already 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 other many 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 that conducted the study 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, co-author of the Faculty of Medicine of the University of South Carolina, in a statement.
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 to treat a large number of diseases, or relieve their symptoms, may, however, be denied an organ transplant if they test positive for cannabis. This is hugely 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 the doctors at the Cedards-Sinai Medical Centre who informed a 64-year old patient named Norman Smith that they would be taking him off the list of transplant patients until he stops consuming cannabis for at least six months, following his positive test result. 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 included again in the waiting list for a transplant.
The doctors argued that “they had to seriously take into consideration the issue of substance abuse, since it often plays a role in the progression of diseases that may require transplantation, and it may adversely affect a new organ following a transplant.” (Dr. Colquhoun). Again, it is 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 are based purely on stigma and ignorance. Unfortunately, such prejudice from some doctors may have fatal effects on the lives of innocent people; people who are ill and require a transplant as much as other patients in the same situation.
Undoubtedly, there is 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.
No doubt this study, like many others before it, demonstrates the need for further and more in-depth research into the usefulness of THC in preventing the rejection process in humans. The potential of THC in this field should be explored in order to prolong and save many more lives worldwide – lives that are given a second chance thanks to donations made altruistically by thousands of caring people. Lives which, thanks to THC, could overcome the awful prospect of rejection after receiving a much needed transplant. If only laws did not stand in the way.
Author: Miranda @ Sensiseeds