Medical Marijuana-Is it Safe? Does it Help?

Presenter:  Cindy O’Bryant PharmD, BCOP, Skaggs School of Pharmacy and Pharmaceutical Sciences/University of Colorado Cancer Center

This is a video of a workshop presented at the 2019 Celebrating a Second Chance at Life Survivorship Symposium

Presentation time:  42 minutes

Summary: Medical marijuana use by stem cell transplant recipients is common, but there are concerns about its purity, potential interactions with other transplant drugs and other side effects.  

Highlights:

• There is great variability in the quality and concentration of cannabis in marijuana products
• If using marijuana, start with a low dose until you figure out how and when it affects your body
• Before taking a marijuana product, talk with your doctor or pharmacist about whether it will interact badly with other medications you are taking
• Use a reputable source for marijuana products. Contamination in the processing of marijuana could be a problem for people with weak immune systems.

Transcript of Presentation

00:00  Overview of presentation: We're going to get started today. As you'll learn throughout this lecture, or this presentation, that what we're learning about medical marijuana, or marijuana in general, and the role of the treatment of cancer, or for supportive care in cancer, is really a burgeoning field. It's something that is progressing quite quickly as we're starting to see more and more use and legalization of marijuana, and so it's a very interesting topic and there's a lot of research that really is left to be done for us to really understand what's going on.

Here are kind of the things that I want you to get as we are done with this presentation today. Knowing the mechanism by which medical marijuana affects mood and physical discomfort. We'll talk about that, and that is still an area of research. The evidence by which medical marijuana in cancer patients and transplant patients, and what kind of the evidence there for its use. Then looking at the common adverse effects, and drug-drug interactions associated with that.

01:06  It is hard to determine which of the 400 compounds in marijuana are responsible for various effects: What is medical marijuana, or marijuana in general? We know it comes from the plant, the cannabis sativa. That plant contains over 400 compounds, and this is a big issue that we have with natural substances. I do other natural substance research and cancer, with a group at our school, and the difficulty we have with these natural substances is that they have so many compounds. It's very hard to begin to whittle down and narrow down which of those compounds is really having the therapeutic or medical effect that we want it to have. We know that it has over 400 compounds. We know it has over 60 cannabinoids, and cannabinoids are those parts of the marijuana plant that affect receptors within our body, and release chemicals that produce its effect.

Medical marijuana really is just using the whole plant, or the unprocessed plant, or its extracts for the treatment of symptoms of illness or other conditions. That's the federal or legal name of medical marijuana.

02:13  Medical marijuana works on the endocannabinoid system in the body that regulates many functions: When you look at marijuana, and how it works in the body, your body has its own system called the endocannabinoid system. This endocannabinoid system regulates many of our just normal systems within our body. It works within our brain. It works within our immune system, and it works within our hormone system as well. This is a natural kind of process that we have.

02:37  Two types of cannabinoids in our body: When we look at cannabinoids within our body there's two types. There are endogenous cannabinoids, and these are the cannabinoids that are own body produces. The most commonly known is anandamide, so you can see a picture here. It's the brain's chemical, and then we also produce a second cannabinoid called two acylglycerol, or 2AG. Those are kind of our own cannabinoids our body produces.

There are also phytocannabinoids, and these are cannabinoids that come from plant sources. These are the ones that we're most familiar with related to marijuana.
We have our THC, our delta-9-tetrahydrocannabinol, our cannabinol or CBD. These are the two parts, or the two cannabinoids from the natural substances that get the most press out there. Even within these, especially the cannabidiols, there are many, many different types of cannabidiols. You can see here between THC and anandamide that they're very similar and so they're going to be able to bind to those receptors within our body in a very similar way.

03:50  How cannabinoids affect the nervous system: When we talk about the cannabinoid receptors there's primarily two receptors that have probably the most research that we know the most about. The first is the cannabidiol 1, or cannabinoid receptor 1. This is the one that's found primarily in our nervous system. In our brain and other parts of our nervous system within our body. This is where when people use marijuana and they feel the high, this is where the THC is binding to the CB1 receptors and resulting in this kind of high feeling.

We also know that when these cannabinoids will bind to the nervous system, it also can produce a depressant effect. People have slower cognition. They move slower because of that slower cognition. It could have a depressant effect as well as having a high feeling.

04:42  Cannabinoids may also affect the immune system: The other receptor that we know most about is our cannabinoid 2 receptor. This cannabinoid 2 receptor is a very interesting receptor because it has a function in the immune system. It's found primarily throughout our body in the immune system. It has been associated, and we'll talk about this a little bit later in our presentation, but it's been associated with some immunosuppressive activity, which in some cases can be good. It's also related to a decrease of what we call pro inflammatory substances, which is why we see this immunosuppressive activity. These two receptors cannabinoid 1 and cannabinoid 2 are the ones that we have the most information about.

05:25  Different forms of cannabis - bud, resin and oil: When we think about the different cannabis formulations patients may use we can think about the bud, and the bud really is just the whole unprocessed flower. We can see that, and most people when we think about buds we think about it being smoked. This type of formulation being smoked.

There's a resin, which is essentially a powder from the dried buds and leaves of the plant, and so this resin can be used, and you can see a picture of the resin here. It can be smoked, as well, or it can be utilized to develop edibles or to create edible products.

Then lastly there's an oil and you can see the oil here. The oil can be used either as a topical agent, it  can also be smoked, or it can be incorporated into edibles. There's a lot of different ways in which our patients will utilize marijuana. We typically will refer them to using something other than smoked products, and we'll talk about why that is important as we go through this presentation.

06:27  Assessing the CBD to THC ratio can be difficult: We think about the products that you may use, or patients may use, and think about the whole product versus those extracted products. The resins and those oils. When we think about the whole product we really, it can be difficult to assess what that ratio of THC, which is the compound that causes the high, and the CBD which is the compound we think probably has the most medicinal effect. That ratio can be difficult to assess because there's many things that can impact that in the whole plant. The ground, the water, the sun, the temperature, things that we may or may not have control over. The variety of the strain.

The extraction products, though, as we're pulling these chemicals out of the plants to develop these products is something we do have a little bit more control over. When you look at these products and you're researching them you may find that they will categorize them based on their CBD to THC ratio. There may be THC dominant products, there may be more balanced products where it's a one to one ratio, or there may be CBD more dominant products.

07:40  Dronabinol (Marinol) and Nabilone have been approved by the FDA for nausea, vomiting and anorexia: When we're looking at those drugs that have been FDA approved, we have several drugs that are synthetic cannabinoids that have been approved for use. We have Dronabinol, which is Marinol. I don't know if you guys know brand and generic, but we call it Dronabinol. Dronabinol has been FDA approved for the use of chemotherapy induced nausea and vomiting, as well as anorexia. These patients will typically use this for nausea and vomiting. Cancer patients will usually use it for nausea and vomiting as what we call an adjunctive agent, which means we added onto standard antiemetics. We don't use it alone by itself. Nabilone is also approved for chemotherapy induced nausea and vomiting. Again, it's an adjunctive agent that we add into therapy.

08:29  Ajulemic acid is being studied for use in chronic inflammation disorders: Ajulemic acid is being studied in phase 2 clinical trials right now. It's being studied looking at its use for chronic inflammation disorders. Primarily looking at its use in systemic lupus. It's also been looked at in Cystic Fibrosis and several other chronic inflammation disorders. There's been some phase 2 trials that have shown promise and they're moving onto phase 3 trials, so we probably should hear something from that drug probably within the next two to three years, depending on how fast those trials enroll.

09:10  Cannabidiol or Epidiolex has been FDA approved for seizure disorders: From a natural product standpoint I think this was a big kind of news blast that went across the country is that we do have an FDA-approved natural product which is our cannabidiol or Epidiolex, which is an oral solution that was FDA approved for seizure disorders in children. There's very specific Dravet and Lennox-Gastaut Syndrome which causes seizures in children that this FDA drug was approved for.

09:40  Nabiximol or Sativex has been fast-tracked by the FDA for treatment of cancer-related pain: The FDA also has fast tracked Sativex or Nabiximols, which are currently already approved in Europe, but the FDA here is looking at this substance for the treatment of cancer pain. There are some current cancer pain studies ongoing that we hope to see some results of over the next couple of years. There was a smaller Sativex trial done earlier in the 2006 that did not show major benefit, but we're hoping that these bigger, larger trials will show something.

I'm a pharmacist. I love to talk about drug-drug interactions. That's kind of what I do. Anytime any of our patients come in and ask about using a product no matter what it is, whether it's an approved drug, a non-approved drug, an over the counter drug, a natural herbal substance. One thing that I always think about is what is the safety of this drug as well as the efficacy. I really focused in on the safety of the drug. We know that marijuana is metabolized like any other substance in our body. It's metabolized primarily through our liver. Our liver really does, is the work horse of drug metabolism. That's where we see our drugs metabolized.

10:59  Marijuana can affect how the liver processes other drugs you are taking, and cause unwanted side effects: Because of this, it goes, marijuana is metabolized through two main systems in our liver. One is called the Cytochrome P450 System. I don't know if any of you guys have ever heard of that, but it's a very major system in our liver that metabolizes drugs. The other is the UGT system. That's another system that will take drugs, add substances to them to inactivate them and get them out of the body. Marijuana is metabolized through this. We know that as it's metabolized through these two systems, it also can induce the systems, which means it can speed them up and increase the metabolism of other drugs. It makes those drugs go through your body faster. Or, it can inhibit them, it can slow them down, it can decrease the ability for those drugs to get through your body. When that happens, we worry about increased side effects.

When we induce these systems, we worry about decreased efficacy. We know marijuana, what we do know, we don't have a lot of information about this, but we do know that marijuana goes through these systems to be metabolized and it does have some inhibitory effects on these systems, as well as inducing effects on these systems. This really is a burgeoning area of research that we're really trying to look at so that we understand better how to utilize these agents and with patient’s current medication list regardless if its cancer, hypertension, diabetes.

12:29  Medical marijuana may affect the effectiveness of medications taken to control GVHD (tacrolimus, cyclosporine, steroids) as well as anti-depressants and potentially antibiotics and antifungals: What we do know from our knowledge is that it does have some effect on post-transplant medications so there is some effect on mycophenolate, tacrolimus, cyclosporine or steroids so many of the medications a patient might receive post-transplant, these agents may inhibit them and cause increased levels of the drug which may result in toxicity. Also, it can inhibit our antidepressants which would again increase our level of toxicity with those drugs. We can see some potential drug-drug interactions with our antibiotics, as well as our antifungals which many transplant patients will receive. We do worry about these because things like Voriconazole, Posaconazole, any of our azoles. Many of our mycins, erythromycin, clarithromycin, antibiotics may be affected by these.

13:28  Medical marijuana may intensify side effects of other medications: We also worry about overlapping side effects from other medications. Sometimes we can see that when patients are on drugs like antihistamine we see increased kind of effects from what we call the anticholinergic effects. People can get increased urinary retention, they can get blurry vision, they can get dry mouth because medical marijuana, or marijuana products can also cause these types of anticholinergic symptoms. We can also see when we combine them with CNS depressants such as pain medications we can see some side effects there from patients being drowsy. Having CNS alterations. Lastly, we can see some effect on what we call our sympathomimetic drugs. Sympathomimetic drugs are drugs that increase the heart rate and increase the blood pressure. We know that marijuana can also do that. Again, we look very carefully if our patients are utilizing these drugs and have questions about using marijuana to make sure we're not causing any kind of issues with the metabolism of their drugs, and not causing any kind of issues with their side effects.

14:44  Example of adverse interaction of marijuana with other drugs in allogeneic transplant patient: This is a case report looking at drug-drug interactions. This is a case report that looked at a patient that had a matched related allogeneic hematopoietic stem cell transplant. This patient came in, received their transplant. Afterwards, they started the typical kind of post-transplant meds. Getting antibiotics, antifungals and immunosuppressants. They were, in the hospital this time they were drawing levels on the immunosuppressant treatment trying to get the levels just right because they converted the patient from IV to PO to send them home.

They were noticing they were having a hard time kind of getting target levels. They kept having to decrease the immunosuppressant drug. What they found out was the patient was using some edible gummies that their family had brought in for them. Because of this potential drug-drug interaction with the post-transplant medications we were seeing higher levels than we had wanted, so this group is decreasing the level of the post-transplant meds. Especially the tacrolimus.

They finally got it to a normal level, they converted the patient over to PO, they sent the patient home. Within six days the patient came back with a toxic tacrolimus level. We normally want levels between eight and 12, this patient had almost 50 as the level. Was experiencing diarrhea, altered mental status, muscle spasticity and all sorts of kind of blurred vision, things that we would see with tacrolimus toxicity.

What they looked at and realized was that the patient was continuing to use marijuana products at home. Not just the gummies, but other products. What they did is they had the patient stop those products, they also stopped their antifungal treatments. The patient's drug level came back down. They restarted the antifungal and asked the patient to no longer to use the medical marijuana product.

What was happening, here, is they think they didn't do a lot of blood testing to look at this, but they think that there was altered metabolism due to those drug-drug interactions with the antifungal, and the tacrolimus, and the marijuana. Again, as a pharmacist this is my job to really pay attention to those types of things to try to minimize this kind of impact upon a patient.

17:14  Small study of 20 patients found positive effect of marijuana in controlling pain and no adverse interaction with other pain medications: Look at another drug-drug interaction study. This study was done in patients who were receiving pain medication, so either morphine or oxycodone. These patients had to have been receiving these pain medications for greater than five days. They were given vaporized cannabis. On the first day they took one dose, days two through four they took three doses a day and on the last day they took one dose. This study did look at drug levels of those pain medications and found that there no difference in the pain medication levels so that we didn't have to worry about inhibition or induction. Patients were getting adequate pain medication.

What they did see is they saw a 27% reduction in pain in this patient population. Potentially some benefit with pain while not affecting the levels of the other drugs. This was a very small study, only 20 patients, but does show promise that we can give these drugs in addition to marijuana in our patients safely.

18:18  Short term side-effects of using marijuana: Again, thinking about our short-term side effects that we see from marijuana. Typically, we can have those cardiovascular affects as I mentioned earlier. Increased heart rate, increased blood pressure. We can see some respiratory symptoms. So, coughing, wheezing, sputum production. This most commonly comes when patients are smoking marijuana. We do see our nervous systems side effects, so we can see psychological side effects. Like I mentioned, patients sometimes may get hallucinations, they may feel paranoid. We can have our cognitive side effects where patients may feel a little slower, may not be able to think and process as quickly.

The one thing that we've seen a lot in Colorado with our legalization of medical marijuana, or marijuana in general, is we've seen this cannabinoid hyperemesis syndrome where patients come in and just are having continuous nausea and vomiting and can't stop until they can get the drug out of their system.

Long-term side effectives of marijuana. Again, there's a cardiovascular risk. The more we put pressure on our heart with increased blood pressure and increased heart rate we can see increased risk of heart attack and strokes.

There is concerns of altered brain development with the use of these agents, with medical marijuana. We think about the risk of addiction, especially with long term use. There is a potential for risk of addiction. Then, there is some data out there that shows that the use of marijuana in addition to patients who already are predisposed to mental health issues that there may be some exacerbation of mental health diagnosis in this patient population. Again, being very careful.

20:04  Factors that may indicate medical marijuana is not safe for a patient: If we think about contraindications, whenever I'm looking at patients and patients are asking me about the use of marijuana, we want to avoid anybody who has a sensitivity to any cannabinoid, which is kind of difficult because we don't really look at that. We know if they have a sensitivity to a synthetic cannabinoid that we prescribe them then we'll pay attention to that.

We look at active or unstable cardiovascular disorders, so again, worried about patients who have cardiovascular issues and those patients with psychiatric issues. Caution should be placed in pregnant or nursing, those women who are pregnant or nursing. Again, we are not sure exactly what those developmental issues would be, and does it affect development? Those who may have a potential for dependence and abuse, as well as people who are operating motor vehicles. If you've watched the news lately that's been an issue in Colorado. Not that the patient was using medical marijuana, but they were operating big large vehicles.

21:06  An increasing number of patients are interested in whether medical marijuana can help with a variety of problems: Thinking about marijuana use in cancer patients what we've really seen in Colorado is now that we've had first time medical marijuana legalized, and then we've had recreational marijuana legalized, there are a lot more questions that are coming out from patients who are looking at ways to treat symptoms in a different way. What we're seeing is that many of our patients come to us asking about how can I improve my sleep? How can I improve my appetite? What can I do for my nausea? Are these products safe? Can I use them? What we're seeing, and many of you may also be seeing, is as medical marijuana legalization increases across the country as well as legalized marijuana that we're seeing more patients who are asking these questions.

21:56  States that currently have legalized marijuana: This is just a schematic of states that currently have legal marijuana as well as medical marijuana. You can see the darker states are those that have both legal recreational, as well as legal medical marijuana. The lighter green are just the medical marijuana states and then those that are gray currently don't have any official legislation or may be in the process of having legislation. Now we have at least 43 states that have some version of medical marijuana laws in the United States.

22:31  Large study showed 47% percent of cancer patients have considered using medical marijuana: With this it's important to understand how medical marijuana can be used in our patient populations, and especially in our cancer patient populations. This was a survey done of stem cell transplant patients. This was done at Fred Hutchinson Cancer Center in Seattle where they have both legalized and medical marijuana. This was a study done in 697 patients. It was a survey where patients answered about 18 questions.

What they saw in the survey is that of these 697 patients, 47% of patients had considered use and 18% had reported use, all right? Whether that's real or not because it was all reported some people may not have felt like reporting their use. This is what we're seeing. Almost a quarter of our patients are starting to report use.

23:31  Reasons cancer patients report for using medical marijuana: You can see here in the graph over here the reasons for use. Of those patients who used, 86% used for physical symptoms. Either for nausea, for pain, for sleep. Some type of physical system. 50% did it for emotional concerns. 45% just did it for recreation, and then 22% used cannabis wanting to treat their cancer. We'll talk a little bit more about this as we go through.
Interestingly, they saw that patients who were between the age of 18 and 40 were three times more likely to be users than those who were older or younger. They also found that the primary reason for many of these predictors for why they wanted to use it were people of Caucasian decent. Also, people who had high educations as well as people who were looking to treat their cancer. It's kind of interesting that those were the promoters of use in this patient population.

24:43  Small studies suggest that marijuana may help in control of graft-versus-host disease: There is some interest in looking at the use of marijuana or cannabinoids in the treatment of what we call graft-versus-host disease. Graft-versus-Host disease is something that can occur post- transplant as our transplants are taking affect. We want those transplants to affect the tumor, which we call graft-versus-tumor disease to keep that cancer from coming back. When the immune system becomes too over-activated then we get graft-versus-host disease.

Really, the transplant or donor cells begin to attack the healthy tissues and organs in the recipient - typically will occur in either an acute or chronic form so that acute, what we call graft-versus-host disease typically will occur within the first 100 days post-transplant where the chronic form will occur any time after that.

Commonly we see effects on the skin, the gut and the liver, especially in that acute phase. But in the chronic phase we can really see effects on any tissue in the body. We know that Graft-Versus-Host can really be a major cause of hospitalizations in patients post-transplant. It can cause morbidity and so the inability for people to conduct normal lives as well as it can be a result of death in our transplant patients. Something that's very important.

There's been some luck because I mentioned earlier that cannabinoids, especially the CB2 receptor, can have some immunosuppressant effects, and when we see graft-versus-host it's really an immune stimulant kind of effect, so this is looking at trying to use an immunosuppressant effect to help in the management of graft-versus-host disease.

There have been some animal studies that have looked at the use of cannabinoids for graft-versus-host. These animal studies have shown that there has been a decrease in the production of immune cells evolved with the inflammation we see with graft-versus-host disease. These studies have shown mixed results in blood recovery and we'll talk about that. But, some potential there that it may be effective in helping with graft-versus-host disease.

There has been a small phase 2 study that was done. This is done in about 48 patients where they looked at the use of CBD, so they gave 150 mg orally twice daily starting seven days before the transplant through 30 days after a transplant. It was given along with standard with graft-versus-host prophylaxis or treatment. It was not used alone. It was used in conjunction with what we normally do now. The results of the study showed that ... Well, first I'll say it was compared to historical control, so it was not a randomized study. Basically, they took a group of 48 patients, treated them, and then went back and looked in their data base and compared it to 48 patients that were very similar to the 48 patients within this study.

When they looked at the results of the CBD arm or the cannabinoid arm, they showed that these patients did have a longer time to development of acute graft-versus-host symptoms. In their historical controls it was about 20 days on average for those patients to develop graft-versus-host symptoms, where in the CBD arm it appeared that it was about 60 days. All right, so it was a longer time to development of this acute graft-versus-host Disease.

Also, when they looked at the rates of graft-versus-host disease within that first 100 days of looking at acute graft-versus-host, they found that about a third of patients in the CBD arm developed graft-versus-host versus the historical control. There was a decrease incidence in the development of that acute graft-versus-host disease.

When they went on to look at chronic graft-versus-host and then also went on to look at any impact on survival, because we know that graft-versus-host disease can impact mortality, we saw that there was really no change in survival across the two groups.

29:09  Small studies have shown mixed results on the impact of medical marijuana on recovery of blood cell counts after transplant: I mentioned there's some mixed results on its impact for blood cell recovery. Again, what we have are animal studies. We don't have a lot of human studies with these agents because of the federal laws and the legalization issues that we have. What we've seen in blood cancer cells lines in animal studies is that there's been some positives and some negative impacts on blood cell recovery.
In transplant patients that's very, very important, right? We want you, our patients, to engraft. We want them to engraft quickly. We want them to graft very heartily so that their bone marrow is robust, and we can minimize the amount of medications we have to use post- transplant. There's been some studies that have showed that it increases the formation of early, very, very early stem cells or blood cells and that in some cases we've seen faster blood cell recovery. Then on the other hand we've seen that it may impact our neutrophils or white blood cells, those infection fighting cells that we need. Again, the data here is really mixed.

Interestingly, in the patients in the phase 2 study that I just presented, all of the patients, except for one engrafted. The one who didn't engraft, they did not suspect it was the cannabinoid that was the reason for engraftment, it was most likely the disease. Again, we have some mixed data here about, is it safe from an engraftment standpoint. Do your blood cells recover? What's the impact of marijuana here?

30:48  There are concerns about infection in transplant patients who use marijuana: From an infection standpoint, we do have concerns. Especially with smoking marijuana in our patient population. We have concerns with fungal infections. There are some case reports out there looking at patients who are smoking marijuana or who have smoked marijuana or who are immunosuppressed post-transplant who have developed severe fungal infections and have died from those fungal infections. That could be a result of mold spores that may be contained in the buds that are smoked, as well it could be a result of increase in inflammation and causing infection risk in the lungs. Again, when we have patients who are immunosuppressed, who have too few white blood cells, we really do advise them not to use smoked products. We really advise them to use edibles or tinctures of some other nature.

31:45  Synthetic marijuana has been used in conjunction with other medicines to control nausea and vomiting: General supportive care just in cancer in general. There is some data looking at chemotherapy induced nausea and vomiting. Probably the best data that we have are with our synthetic products, or our dronabinol, as well as our nabilone. Again, we use it as adjunctive treatment so along with our standard agents that we use for nausea and vomiting.

There are some small clinical trials looking at smoked or oral THC for the use of treatment of chemotherapy-induced nausea and vomiting. There are mixed results. Again, most of these trials have no more than 15 patients. They're not randomized, so some show benefits. Some don't show benefits, so it's hard to say.

What we've seen anecdotally in my patient population is, again, it's that mixed result. Patients come in, they try it, we deem it safe, they try it, some people get benefits some people don't. I think there's probably more data that we need about how people metabolize these drugs to determine if they really are going to benefit.

Not clear whether natural or synthetic marijuana helps stimulate appetite in cancer patients: Appetite stimulation. There is some data with appetite stimulation. We always hear about people who use marijuana get the munchies. Hopefully this would help. Most of the data there is in HIV patients with some of our synthetics. Again, Marinol or Dronabinol has been shown beneficial in HIV patients. In cancer patients, there's really no studies with natural products and there's been mixed results in our cancer patient population with our synthetic products. Again, the jury is out there.

33:24  Studies seem to indicate a sleep benefit with the use of medical marijuana, but this needs to be studied further: With insomnia, there's been no dedicated studies looking specifically at insomnia with the use of marijuana in cancer patients. Most of the information that we have comes from other studies that have been done where they've done surveys of patients asking about sleep, but not specifically looking at sleep. There was, what we call, a big meta-analysis where they looked at all the information from all these studies. Put it together to try to derive analysis. What they showed is from these studies, looking at both natural and synthetic products, there does seem to be some sleep benefits, but again, we have no big studies or really validated studies to show us that.

34:10  There are no studies in cancer patients about the effect of marijuana on anxiety or depression: When we look at anxiety and depression interestingly enough there's no studies in cancer patients. There have been some studies in other disease states like diabetes, heart failure where they have patients who have kind of chronic diseases. In that patient population they really found no difference versus marijuana products in placebo. What has been seen in these other patient populations is that patients who have social anxiety or who have anxiety as a result as chronic pain do appear to get some benefit. Again, these are small studies not well designed. These are again kind of information that we have.

34:54  Quality control is a concern in marijuana products not regulated by the FDA: Just limitations in use. As I keep mentioning, we don't have a lot of information. These drugs don't go through the FDA, especially the natural products don't go through the FDA, and aren't quality-controlled in the way that I'm used to dealing with quality control in our other medications.

We really must think about what is in these products. We worry about varying concentrations of our cannabinoids. There's been two studies that have looked at this. This is a study looking at the quality control of cannabinoid products. It was looking at edible cannabis products from three major metropolitan areas. This looked at San Francisco, LA and it also looked in Seattle. They looked at the THC accuracy in these products.

They sent people out randomly across these cities to different dispensaries. They had them purchase a variety of different products, they brought them back to the lab and they tested them. In testing them they found out looking at the THC accuracy that 60% had a THC level over what was labeled. 23% were under, and then 17% were accurate. Again, if you're trying to figure out what kind of product do you want, do you want CBD, THC, don't want the high, this is what they found with these products that they made, that they tended to be over labeled from a THC standpoint.

Another study was done looking at cannabinoid products. This was looking at products purchased online. They purchased 84 products, they were analyzed. They looked at the accuracy of labeling of the cannabinoid part of these products. What they saw was again, they saw that 43% of the patients were under labeling. 31% were accurate, and 26% were over. Again, just the accuracy of this labeling doesn't appear to be a quite perfect Science quite yet. Probably more information really and more kind of standardization of how we test these products need to be done. It's interesting, these are supposed to be CBD products only, and in these products, there was THC detected in 21 of these samples.

37:20  FDA has required some distributors of marijuana products to label the product accurately about safety and efficacy: This really has led to the FDA to send out some statements about these products making sure that people understand what the products are and how they can be used safely and effectively.

We really do see a lot of people that want to use these products for the treatment of their cancer even though the data in cancer treatment is relatively small. Our data in supportive care treatment is a little bit larger. We do see that there is some preying upon patients, so the FDA really did send out some statements.

Dr. Scott Gottlieb who was the former FDA Commissioner sent out a statement on the importance of conducting proper research to prove the safe and effective medical uses of these marijuana components. The FDA, I think is starting to understand the necessity, understand the safety and efficacy of these products and is putting more resources behind that.

Then they also had to send out some warnings to several companies about their labeling that these products may be treating or can cure cancers. We've seen some of those stores, dispensaries within Colorado received some of these letters about potentially fraudulent advertising of the efficacy of their products. Again, limitations in use because we don't have the same kind of quality control systems in place that we do for our FDA approved drugs.

38:56  Microbe contamination of marijuana products is a concern: There's no standard manufacturing, so we worry about microbe contamination just like we would worry about smoking those natural products with mold spores.

Micro contamination, we worry about pesticide contamination from how the crops were raised. With that, in our immunosuppressed patient population this is a real concern because patients can be more susceptible to these types of toxicities. Then there's just an unmonitored chain supply. Again, with FDA approved drugs as they go through quality control we do monitor where the drugs are and what temperatures they are and when they've been where. In this situation, there really is an unmonitored chain supply so we don't know where there might be potential places for contamination to occur as the product is being prepared for patient use.

39:48  Key points to keep in mind when considering marijuana use: What you need to know. Just realize there's variability in the quality and the concentration of cannabis. If you're out looking for cannabis products just be aware of that.

Try to go to a place that has a pretty good reputation. Different states have different forms of medical marijuana delivery. In Colorado, it's just kind of a free for all. You can just go anywhere. In other states, it's much more highly regulated by the state.

Just realize that dosing and dosage forms may not be accurately labeled, so we always tell our patients start slowly and start low. We always tell them if you're going to use an edible product go buy a brownie, eat a quarter of it, sit and wait and see what happens. Right? You've got to wait for a while because the edibles don't take effect as quickly as our smoked products. I say wait a couple of hours, see how you feel, if you don't get a whole lot you can eat another quarter.

Really, just having them adjust and understand how their body reacts to marijuana, how their body metabolizes marijuana, what side effects they might have.

Realize the potential effects of cannabis, right? What is the short-term and long-term side effects that we talked about? What is the potential for drug-drug interaction? I highly recommend that if you want to use a medical marijuana product or a marijuana product then please just ask your pharmacist or your physician or your nurse is this safe? Can I use it? Then just make sure that you put safe guards in place to prevent diversion. We always worry about that with any kind of what we consider controlled substance.

Lastly, just the use of marijuana to manage treatment related side effects is becoming more and more common in cancer patients. There's a limited amount of data for efficacy and safety in transplant patients. I mean, cancer patients in general, but especially in transplant patients. Again, be smart, ask good questions. Continued research really is essential for the understanding of where marijuana fits in the treatment of patients with cancer and post-transplant. I think we're going to get there. I think over the last couple of years I've seen a real resurgence in looking at these products and understanding them more fully. I think we'll be able to, sometime within the next decade, really be able to understand its place and its role.