Official Blog of the American Journal of Kidney Diseases
#NephMadness 2020: Mary Jane’s Big Dance – Marijuana is OK (When Used Responsibly and Safely) in Kidney Transplantation
Posted on April 20, 2020 by AJKDblog in NephMadness // 0 Comments
Joshua Rein is an Instructor of Medicine at the Icahn School of Medicine at Mount Sinai in New York City. His clinical and research interests include the kidney endocannabinoid system and the effects of cannabis and cannabinoids on kidney function.
Competitors for the Transplantation Region
Biomarkers in Rejection vs Biopsy in Rejection
Marijuana is OK vs Marijuana is Not OK in Transplantation
Michael Jordan may have won March Madness in 1982 but in 2020, a different MJ flies high and takes to the court. Marijuana (cannabis) for recreational and medicinal uses has exploded in popularity and social acceptance across the world. This is particularly true for older adults and the elderly , whose usage has increased by 200% over the last 3 years.
Many patients are already using cannabis, sometimes without our knowledge. More than ever before, we need to be aware of the risks and benefits of cannabis use in our patients . Physicians remain poorly educated with respect to cannabis and the endocannabinoid system . The federal prohibition on cannabis as a Schedule I drug in the US has strongly limited research and has prevented teaching about the drug in medical education.
Lighting it up in the Transplantation Region, Team Marijuana is OK faces off against Team Marijuana is Not OK in a fiery battle to hash out a winner. There are several arguments supporting both teams, so let’s hit it.
First, the distinction needs to be made between recreational cannabis and medical cannabis. Recreational cannabis is most commonly smoked and contains high levels of Δ-9 tetrahydrocannabinol (THC), responsible for the euphoric intoxicating “high” but which can cause anxiety and panic attacks at high doses. Medical cannabis, which generally contains higher concentrations of cannabidiol (CBD), a nonintoxicating cannabinoid, is taken by mouth, avoiding the cardiovascular and pulmonary harms of smoke inhalation. Medical cannabis may achieve symptom relief with subpsychoactive doses of THC, avoiding the acute neuropsychiatric side effects that are of significant concern for transplant adherence.
Cannabis and cannabinoids may have immunomodulatory effects among kidney transplant recipients but the actual effects are currently unknown. Preclinical models demonstrate a protective effect against graft rejection. We do not know enough regarding the pharmacokinetics and pharmacodynamics of cannabinoids in those with renal insufficiency. Additionally, we do not know enough regarding cannabinoid effects on immunosuppressive regimens including concerns of regimen adherence and the unpredictability of drug interactions. Notably, CBD can inhibit p450 liver enzymes and potentially raise tacrolimus and cyclosporine levels.
We should be mindful that the legal cannabinoid market is still fairly young and early in development but expanding rapidly, possibly even too fast, before regulatory agencies are able to develop appropriate guidance, safety evaluation, quality standards, and consumer protections . It is reasonable to be hesitant regarding cannabis use in transplant recipients until we know more about its effects on transplant recipients. However, this will not be possible as long as cannabis remains a Schedule I controlled substance. As health care providers, we want to do what is best for our patients while keeping them safe.
Symptom management for people living with advanced chronic kidney disease (CKD) and end-stage kidney disease (ESKD) is very important for quality of life. Unfortunately, many symptoms remain uncontrolled and inadequately treated. People may seek alternative treatment options, which may include cannabis and cannabinoid-based preparations as access becomes easier.
Cannabis may be efficacious for several symptoms frequently experienced by people with advanced CKD and ESKD, including pain. Last year’s NephMadness featured the Pain Region , with Team Opioids making it to the final four but losing to the eventual champion, US HTN Guidelines. The opioid epidemic has been devastating. It seems like opioids are the only effective treatment option for pain but as described in last year’s post , opioids have their own issues and short-term and chronic use are associated with increased mortality in people with CKD , ESKD , and kidney transplant recipients .
Despite these adverse effects, 20% of all patients on dialysis take prescription opioids chronically. Access to medical cannabis has been associated with decreased opioid prescriptions and dose reductions . The current opioid epidemic requires approaches to treat pain effectively while decreasing opioid prescriptions in this patient population. Cannabis could have a therapeutic role in pain management that deserves clinical consideration and further clinical trial investigation. Substantial evidence exists for the use of cannabis and cannabinoids to treat chronic pain.
We will see more people undergoing kidney transplant evaluation having used or tried cannabis. Additionally, some of these people will have been certified by a physician to use medical cannabis legitimately. Cannabis use in potential transplant recipients may have implications for pre-transplant screening, such as delayed candidate listing or contributing to ineligibility , with implications for post-transplant outcomes. Denying transplant listing solely on the basis of a positive drug screen deprives/blocks numerous patients, some otherwise young and healthy, of increased quality of life and longevity with kidney transplantation. If cannabis is able to treat pain symptoms adequately, and decrease or eliminate the need for opioids, it is reasonable to allow for continued use post-transplant.
Concerns regarding adverse effects on cognition and memory are valid, although medical cannabis tends to be used at doses lower than what causes these cognitive impairments. In all fairness, opioids are associated with these adverse effects on cognition and memory as well.
Anxiety can occur post-transplant due to concerns of health, finances, or concerns of kidney rejection/failure. Anxiety increases risk of post-transplant readmission. CBD has anti-anxiety effects; pain and anxiety are the top 2 reasons why Americans use it.
Alternatively, little is known regarding the safety of cannabis and long-term clinical outcomes among kidney transplant recipients. A few retrospective single center studies do not show an increased risk of graft dysfunction, acute rejection, or graft loss 1-year post-transplant among recipients who consume cannabis .
However, cannabis dependence or abuse (CDOA) after kidney transplantation appears to have consequences for allograft and patient outcomes . Although post-transplant CDOA is associated with increased graft loss, plenty of people use cannabis responsibly and do not abuse it. There is no denying that substance dependence or abuse of any drug is detrimental to health. We should keep an open mind and allow our patients to be honest and open with their cannabis usage to ensure that dependence or abuse does not develop.
Overall, although strong arguments can be made for both teams, marijuana (cannabis) will only become more popular in the years to come. I predict Team Marijuana is OK smokes past Team Marijuana is Not OK , becomes a chronic winner and blazes to victory, as long as transplant recipients consume it responsibly and safely…paging Dr. Greenthumb.
– Guest Post written by Joshua Rein @ThepHunClub
As with all content on the AJKD Blog, the opinions expressed are those of the author of each post, and are not necessarily shared or endorsed by the AJKD Blog, AJKD, the National Kidney Foundation, Elsevier, or any other entity unless explicitly stated.
Joshua Rein @ThepHunClub Joshua Rein is an Instructor of Medicine at the Icahn School of Medicine at Mount Sinai in New York City. His clinical and research interests include the kidney endocannabinoid system and the effects of cannabis and cannabinoids on kidney function. Competitors for the Transplantation Region Biomarkers in Rejection vs Biopsy in Rejection Marijuana…
CBD & Organ Transplant
With CBD becoming more mainstream, doctors are on the lookout for how this powerful chemical affects human health. But a typical adult in the U.S. takes at least one pharmaceutical, and CBD ’s interaction with other medications can be significant, especially given how easily one can overdose on common drugs. A new potential interaction has been highlighted by scientists at the University of Cincinnati, in Ohio. They report a woman using an extremely high dose of pure CBD for epilepsy — between 2-3 grams per day. She was also taking tacrolimus, a common immunosuppresive drug, to treat a kidney disorder. When combining these two treatments, tacrolimus levels in the blood rose by three-fold — a dangerous result. Because the addition of CBD helped control the seizures, her doctors helped her adjust the dose of these two drugs. This is commonly what happens with drug-drug interactions — there is an important need to monitor drug levels, but the interaction can be managed without ill effect for many patients.
The interaction between CBD and tacrolimus – a drug used in kidney disease and organ transplants – can be managed via dosage adjustment and careful monitoring by a doctor.
Tacrolimus is a mainstay medication for organ transplant, so this possible interaction could be important for patients who need an organ transplant. Moreover, there has been some research on the potential to use CBD in transplant patients. Both THC and CBD tend to tone down immune activity and they have recently been suggested for treating graft-versus host disease, a potentially deadly reaction to organ transplants.
How relevant is a cannabinoid-drug interaction like this to the average person? It depends greatly on the dose of CBD . In this case, there are probably two proteins that CBD interferes with to increase drug exposure — it inhibits CYP3A4 , an enzyme that breaks down more than half of all pharmaceuticals, and it can inhibit P-gp, a protein which pumps chemicals out of certain cells. But this woman was using multiple grams of CBD per day. If she got this from good quality cannabis flower (say, a flower that’s 20% CBD by weight), she would have to eat half an ounce each day. That’s not the normal dose that people take, even those using cannabis for epilepsy. When unpurified cannabis extracts are used, the common doses are 10-100 times lower. THC and other plant compounds appear responsible for this greater potency, and the consequent lesser risk of drug-drug interactions. In other words, THC seems to make CBD a safer more effective medicine.
Very high doses of CBD (2-3 grams) might interact with tacrolimus, an immunosuppressive drug used in organ transplant patients.