Can cannabis improve cancer outcomes? Does it cause problems with memory? Is hemp-derived CBD as a good as marijuana? We will answer these questions and more in a very insightful conversation with integrative oncologist, Dr. Donald Abrams.
Dr. Michael Ruscio, DC: Hey everyone, welcome to Dr. Ruscio Radio, this is Dr. Ruscio. Today I’m here with Dr. Donald Abrams, and we’ll be talking about cancer care. I will be following up on our previous episode and looking forward to diving deeper into this pool and hopefully offering people some more pearls and insights. So, Donald, welcome to the show and thanks for being here.
Dr. Donald Abrams: Thanks, it’s a pleasure to be on.
[Continue reading below]
Dr. R’s Fast Facts Summary
- Helps with nausea, pain and stimulates appetite
- Synergy with surviving chemo
- Nabiximols 1:1 ratio of THC to CBD – Has been observed with those being treated for glioblastoma
Hemp versus Marijuana
- Both are Cannabis plants
- THC is low in Hemp and high in Marijuana
- THC may be more important than some realize
- Psychoactive properties are found in Marijuana but not in Hemp
- Still much we do not know about CBD
Cannabis and immunosuppression
- Does NOT appear to cause immunosuppression, may even improve immune system strength
Cannabis’s impact on memory
- Debatable as to whether there is an impact
Other therapies for cancer – Diet & Nutrition
- Diet – fruits, vegetables, whole grains, legumes, fish (polyunsaturated Omega 3 fatty acids)
- Vitamin D, Omega 3
- Mushrooms – but not while on immunotherapy
Where to learn more
- Get help using this information to become healthier.
- Get your personalized plan for optimizing your gut health with my new book.
- Healthcare providers looking to sharpen their clinical skills, check out the Future of Functional Medicine Review Clinical Newsletter.
Download Episode (Right click on link and ‘Save As’)
DrMR: Can you tell us a little bit about your background?
DrDA: So me. So during my training to be an oncologist here at the University of California, San Francisco, suddenly AIDS came out of the blue and I didn’t know what it was or what to do about it or nobody did, so I was working with Harold Varmus, the guy who won the Nobel Prize for discovering retroviruses in his lab when this disease appeared in the early 1980s. The beginning of my career as an oncologist was basically spent being an AIDS oncologist, taking care of people who had malignancies related to HIV.
And then in 1992 somebody challenged me to study cannabis as a treatment for the AIDS wasting syndrome, which was a big problem in those days. Patients wasted away with weight-loss diarrhea and fevers, and I said, “Okay I can do that. I went to college in the 70s.” So I fought the government, and ultimately won, and got marijuana and money to do research, which gave me a strong appreciation of the power of plants as medicine, which ultimately took me to the Telluride Mushroom Festival, where I met Andrew Weil and heard about the fellowship in integrative medicine that’s available at the University of Arizona as a two-year online distance learning fellowship.
So I completed that in ’04 and basically changed my life and said, I’ve done HIV/AIDS for 25 years, what I want to do now is integrative oncology, working with people living with and beyond cancer, and helping them to integrate these other modalities: Nutrition, supplements, Chinese medicine, stress reduction, spirituality, into their conventional cancer care. So that’s what I do now.
DrMR: Awesome. A lot there obviously to wade into, let’s start with what you mentioned previously, which was cannabis and I know that cannabis has been studied for a number of things. We’re starting to see clinical trials roll in for, one of which is inflammatory conditions and how that pertains to cancer I’m kinda curious to get your thoughts. But I asked that to juxtapose that with how I think many people have heard of cannabis or medicinal marijuana for cancer, which is to help partially with pain and with nausea and to help stimulate appetite. So I’m sure people have heard about that, but yeah, tell us more about cannabis, medicinal marijuana, and how this interfaces into integrative cancer care.
DrDA: Yeah, so I was actually fortunate to be one of the 16 members of the National Academies of Sciences, Engineering & Medicine Committee that reviewed 10,000 articles on the health effects of cannabis and cannabinoids in the last half of 2016 in preparation for the elections in November of ’16 where many states were going to approve medical and/or recreational cannabis. So in addition to being someone who’s been studying cannabis itself for 21 years now in clinical trials, I really got a deep delve into the data, if you will, pardon the alliteration.
But you know what I think most people don’t appreciate is that the only legal source of cannabis for research in the United States is from NIDA, the National Institute on Drug Abuse, and NIDA has a congressional mandate that they can only study substances of abuse as substances of abuse. So if you wanna do a clinical trial showing the potential health benefits of cannabis, you have to use NIDA cannabis, but they can’t fund that study.
So that’s why in the book that we put out in January of ’17, there’s 1 out of 15 chapters on therapeutics, and about 12 on potential harms, because NIDA funds millions if not hundreds of millions of dollars a year in research looking into the potential harms of cannabis, but they cannot fund any research into the potential benefit, and that’s why there’s really a dearth of data in all of the areas that you actually pointed out.
Although the committee felt that the evidence in the medical literature was certainly strongest for prevention of chemotherapy-induced nausea/vomiting, for pain, and for spasticity in multiple sclerosis, but for example in nausea and vomiting the weight of the evidence comes from studying dronabinol, which is delta-9-tetrahydrocannabinol, the main psychoactive ingredient in cannabis. There were many studies in the 70s and 80s that looked at dronabinol as an anti-nausea medicine for patients receiving chemotherapy, and that’s what was approved. In the medical literature there are only three studies of cannabis itself in patients with chemotherapy-induced nausea and vomiting, and in two of them cannabis was only made available after dronabinol, it’s main component, had failed.
So this is one of the problems. Especially oncologists, we tend to be very much demanding of evidence because we treat a very serious disease and we use pretty serious drugs, so we wanna see evidence and we just don’t find it in the medical literature. Now, again, being an oncologist in San Francisco for 35 years, I’ve appreciated the benefits of inhaled cannabis in my cancer patients for many things, including decreasing nausea and vomiting, increasing appetite, decreasing pain, helping with sleep, anxiety, and depression. So a very, very beneficial medicine and instead of prescribing five or six different pharmaceuticals all of which may interact with each other or the patient’s anticancer therapy I can recommend that they use one botanical.
DrMR: Now, what do you feel the merits are, because I’m sure you’ve heard of these hemp-derived cannabinoids, or I’m not sure if I can technically, can you say that a cannabinoid is derived from hemp or is that improper use of the terminology?
DrDA: Cannabinoids are 21-carbon terpenophenolic compounds that are present in the plant. Cannabis sativa or cannabis indica, and hemp does have cannabinoids. It has a very low level of the main psychoactive cannabinoid delta-9-tetrahydrocannabinol, but it has adequate levels of cannabidiol or CBD.
CBD has been catapulted to the top of the most favored cannabinoid list by Sanjay Gupta in his four-part series ‘Weed’, ‘Weed 2’, ‘Weed 3’ and ‘Weed 4’ where he showed on television young children with refractory seizure disorder stop seizing immediately when they got a drop of CBD, cannabidiol oil under their tongue and that has led to the recent FDA recommendation that a pharmaceutical preparation of CBD that is derived from the plant, Epidiolex, be approved for treatment of seizures in children with these refractory epilepsy conditions, but I’m sure, and also that’s led to the recommendation that CBD be now scheduled as Schedule 5 as opposed to cannabis and THC, well cannabis the plant is Schedule 1 which means it has a high potential for abuse and no accepted medical use.
Delta-9 THC which has been licensed and approved since 1986 dropped from Schedule 2, which required a special prescription pad to Schedule 3 which doesn’t, and now CBD is Schedule 5 is what’s being recommended which means it’s just a regular prescription. So it’s funny that the parent plant of these Schedule 3 and Schedule 5 compounds remains Schedule 1, sort of ironic.
DrMR: And one of the things that’s been a bit difficult for me to parse is it seems like CBD is, as you said, becoming so much more popular in part because of the non-psychoactive effects, I also think in part because you now have different companies popping up that are offering hemp-derived CBD that can be sold over the counter, and so with greater ease of accessibility, it’s easier to recommend it, and then you have the free market getting behind it, but because of that influence it’s been challenging to discern, can one derive some of the medicinal benefits from using, let’s say smoking cannabis? Or using some kind of edible that has a variety of cannabinoids including THC and CBD? Can someone get that same benefit from just a hemp-derived CBD compound? Do you have any thoughts on that?
DrDA: Well there are a few things that you brought up here. First of all, there’s what we call the entourage effect, that the sum of the parts is greater than any of the individuals. I certainly believe that the plant is the best medicine, and we’ve seen that in dronabinol when dronabinol’s indication was expanded in 1992 to include patients with the AIDS wasting syndrome, that we started giving it to AIDS patients and they said, “You know what? You can keep this, I prefer to smoke cannabis because it takes too long to kick in and I get too zonked.” And what the patients were really describing is the difference between inhaled THC versus orally ingested THC.
When inhaled the peak plasma concentration is reached in 2-1/2 minutes and it dissipates quite rapidly over the next 30 minutes. When taken by mouth the absorption is much more variable and the peak plasma concentration, which is much lower than when it’s inhaled, occurs in 2-1/2 hours instead of 2-1/2 minutes. And also when taken by mouth delta-9 THC, the main psychoactive component, when it goes through the liver, gets broken down into an even more psychoactive metabolite, an 11-hydroxy THC, which is why people sometimes overdose more easily on edible products.
DrMR: So a quick question there, ’cause I’ve heard people remark that when you take the edible you feel it more in your body because it absorbs through your gut and that never really made a lot of sense to me. It always seemed that THC, irrespective of how you dose it, hits you more in the head rather than maybe CBD. So it sounds like, well you’re kind of corroborating that it’s not really dependent upon how you ingest it but rather the compounds that are in the cannabis who dictate whether it hits you more so in the head or “the body.”
DrDA: Well, I don’t know, I mean there’s this old lore that cannabis sativa is up and mental and cannabis indica is more down and physical, but other people who were plant botanists say that’s not really correct. But again, it brings up a response to the second part of your question, you know, there are more than just the cannabinoids in the plant as well. There are terpenoids which given the different chemovars. We like to call them chemovars, chemical variety, as opposed to strains which many people think is more appropriate for bacteria or viruses. But the turpines give the chemovars their unique smells. This one is like skunk, this one is more lemon-y, this one is piney. But they also probably have some medicinal benefit. And then there are other compounds called flavonoids which are present in many of the foods that we eat that have health benefits. So if you just take CBD itself out of the background of all those other chemicals or even THC itself, it becomes a very different medicine than what nature gave us.
DrMR: Hey, everyone, I’d like to tell you about BIOHM, who helped to make this podcast possible. Now, BIOHM offers a line of gut-healing products, including a probiotic, a prebiotic, and a green powder. Now, their probiotic is interesting in the sense that it combines strains from both category 1 and category 2.
So from category 1, you have lactobacillus, acidophilus, lactobacillus rhamnosus, and Bifidobacterium breve. And from category 2, you have S. boulardii, so a nice combination of category 1 and category 2.
And if you go over to BIOHMHealth.com/Ruscio and use the code RUSCIO at checkout, you’ll get 15% off your first order. So BIOHM, they’ve got a good line of probiotic and prebiotic and the greens powder, all to help you improve your gut health, which we know has such massive and far-reaching impacts. So check them out over at BIOHMHealth.com/Ruscio.
DrMR: And so do you see any indications in the research literature, you know, going toward more isolated compounds? I know drug companies like to lean in that direction. You see the same thing happening with Helminth research search for GI conditions and for fecal microbio transplant, trying to kind of take out the one particle or compound that may vector the benefit where it actually may be a derivative of the totality of the compound. But do you see the same kind of pull with the cannabis research?
DrDA: Well, I think, you know, yeah, I think that the plant can’t be patented and it’s schedule one in this country still. And you know, that also makes it very difficult to do research with it. So companies are going to look at the various cannabinoids, CBD being the second cannabis derived chemical that’s been pharmaceuticalized, but there are others. For example, tetrahydrocannabivarin, or THCV, seems to be very potent at decreasing appetite for food, for tobacco, and for opiates. So that’s something that I’m sure will be developed.
And then there are these cannabinolic acids, tetrahydrocannabinolic acid, and cannabidialic acid or whatever, which are present in the plant and they get converted when the plant is combusted to the active ingredients, THC and CBD. But people believe that these acid forms also have some potential medicinal benefit.
So all of these things, as you say, are going to be individually probably developed but, you know, during my fellowship in integrative medicine, I really became very much fond of traditional Chinese medicine where, you know, most of their herbal products are whole plants or mixtures of different plants and they use the whole plant because if you remove the single most active component from the plant and put it in the sesame oil, it’s just a very different medicine than the whole plant. Because you remove it from the Yin and the Yang, if you will, of the things that balance the good and the bad effects of that single most active component in the plant.
How to Sequence Through CBD & Cannabis
DrMR: Sure. So I’m wondering what you would offer someone who is considering, for whatever ailment, they’re considering dabbling with maybe hemp-derived CBD or cannabis, and would you say it’d be reasonable for someone to first perform a trial on the easy to obtain hemp-derived CBD, see if that leads to an improvement, let’s say in their joint pain and their insomnia and their anxiety, and give that maybe, I don’t know, two to three weeks, and if that doesn’t yield a notable benefit to then go through what might be a bit more rigor to obtain the marijuana cannabis-derived, you know, total package that may have some THC in addition to CBD. Do you think, you know, is that a decent way for someone who’s saying, okay, you know, I have these different options. How do I kind of sequence through them?
DrDA: I suppose. I mean, I live in California where we’ve had medicinal cannabis and now recreational cannabis. Certainly medicinal since 1996. So nobody’s really had a difficult time here obtaining THC. The thing about CBD is, we have these receptors in our body, the CB1, the cannabinoid one receptor is actually probably one of the most densely populated receptors in the human brain. Nobody learns about that in medical school. The CB2 receptor is present mainly in cells of the immune system. THC fits like a lock into the key of the receptor. CBD does not. So, you know, how CBD works is a bit of a mystery to me still.
I think people in our Puritan-derived, Judaeo-Christian dominated country are sort of phobic about euphoria and feel that being high is not a good thing. So they want to avoid THC. Now, granted, some people can’t do the work that they’re doing during the course of a day if they’re stoned if you will, but you know, I think that THC is really the medicine. CBD, we just don’t know anything about. These studies in children with epilepsy are the largest studies. Prior to the epilepsy studies, the largest study of CBD was in 24 people with social anxiety disorder. Twelve got CBD and 12 got placebo before a simulated public speaking test. And those patients getting the CBD were less anxious than those getting placebo. And that’s pretty much the largest study that we have.
DrMR: I’m really glad to hear you say that because again, and as I noted earlier, I sometimes feel the market pressure of the more, you know, readily accessible CBD. You know, when I perform an inquisition, it seems like much of the narrative is a bit skewed by CBD and I’m always trying to guard against bias so that we don’t get a skewing of the information because of, in this case, market pressures and try to stay true to what might be the more effective. So it’s very interesting to hear you say that, that we may want to be careful to not throw out the THC, that there may be some real medicinal benefit to that amongst, you know, the entire plant. But you know, not to just throw out the psychoactive component.
Cannabis And Chemo
DrDA: Well, I mean, it’s really amazing that CBD has gained such momentum when there, again, I am an oncologist and we do like evidence. You know, right now we’re doing a study in San Francisco, San Diego, and in Chicago at three integrative medicine sites and a few dispensaries in each city, looking for patients who are using CBD enriched rich products to find out what they’re using, how they’re using it, what they’re using it for, and if it works. To determine from this observational one time survey, you know, what might be a fruitful field to evaluate in a formal prospective clinical trial.
DrMR: Great. What about any synergy of cannabis with chemo? I, of course, know that there’s some of the suggestion for, as you mentioned earlier, you know, guarding against decreased appetite, nausea, pain. Do you feel there to be any synergistic benefit with maybe chemo or radiation or with other active forms of cancer treatment?
DrDA: Synergistic against the tumor itself?
DrMR: Yeah. And in an anti-cancer way or maybe in some kind of indirect way that ends up being anti-cancer.
DrDA: Well, so one product that we haven’t mentioned is nabiximols, this whole plant extract that has a one to one ratio of THC to CBD has been studied in patients with recurrent brain tumor. The most aggressive form, the Glioblastoma multiforme. And what they did, this is an under the tongue spray, and they found that patients, there were 12 patients spraying the nabiximols under their tongue while they were getting chemotherapy, and nine sprayed placebo. And the survival, the number of patients surviving one year was significantly increased in the group getting the nabiximols and their overall survival was also increased.
DrDA: This has only been reported, unfortunately, as a press release in February of 2017, and no manuscript describing the results of the study has been made available. Nor is it a very large study with only 12 people in one arm, and nine receiving placeboes. But it is the closest we get to showing that there is any synergy, if you will, between cannabis based medicine and chemotherapy.
DrMR: Okay, so some early evidence, much to learn still it sounds like.
DrDA: Well, I mean, you know, as an oncologist, the thing that pains me the most are patients waiting to see me in my integrative oncology practice for six months who had a potentially curable malignancy, who have been treating themselves for that six months with either a highly concentrated THC oil or CBD oil thinking that it’s going to cure their cancer and now they have metastatic disease and can’t be cured. In my experience, I have never seen a cannabis product itself cure cancer, and my patients who were out there on the internet claiming that their cancer was cured by cannabis seem to be amnestic for the fact that they also got surgery and chemotherapy as well.
DrMR: Yeah, and bias is detrimental when it creeps in.
DrDA: It’s a problem.
DrMR: So anything else on cannabis that you want to touch on? I mean, I’m sure there’s probably a few other integrative therapies that you want to get to but before we leave this, anything else noteworthy?
DrDA: You know, just that this whole question I mentioned about the receptors that we’re learning by looking at different tumors as we’re looking for genes that are expressed or have gotten mutated, people are now starting to look for increased or decreased expression of these cannabinoid receptors on specific tumors, and how they correlate with prognosis and maybe this will ultimately be an intervention that we can use adjunctively with conventional cancer therapies in the future, but as you said, we still have a lot to learn.
Cannabis And Immunosuppression
DrMR: All right, and one final question I do want to ask you there, just popped back into my mind. Cannabis and immunosuppression, it does seem that, and I know immunosuppression is very broad or there are many different types of immune responses, but it does seem at least from some of the review papers I’ve read, that overuse of cannabis and again, how we find overuse I think is a bit vague, but may lead to immunosuppression, that may lead to increased risk of infection.
DrDA: That’s incorrect. We did not find any evidence of that in the review that we did for the National Academies of Sciences, Engineering, and Medicine, the health effects of cannabis and cannabinoids. That is, if you will, a reefer madness, old wives’ tale. I did a study in patients with HIV, it was the longest study I did. It was only 21 days of smoking a cigarette three times a day, a cannabis cigarette, taking dronabinol three times a day, or taking dronabinol placebo, and it was probably the most intensive battery of immune studies in any clinical trial done to date with cannabis. We saw no immunosuppression at all. If anything, we saw some potential immune enhancement in patients using cannabis with HIV.
“…we did the most intensive battery of immune studies in any clinical trial done to date with cannabis. We saw no immunosuppression at all. If anything, we saw some potential immune enhancement in patients using cannabis with HIV.”
DrMR: Wow, that’s great to know.
DrDA: Now, that being said, Israel, where they have a lot of good observational data because every Israeli patient has to get a license and gets interviewed while they’re using their cannabis. They have reported in a retrospective analysis, in a poster, in a number of patients, 80 or so patients with non-small cell lung cancer receiving our new immunotherapies, that those patients who had a history of using cannabis, while they’re getting the immunotherapy had less robust outcomes, or poorer outcomes than the groups not using cannabis, although their survivals were the same. So that’s a little bit of a cautionary note that needs further investigation in my opinion.
DrMR: Gotcha, okay. So you lean to concluding that there’s no immunosuppressive effect, or they’re maybe?
DrDA: I don’t know that it would be necessarily immunosuppressive. Again, one thing that oncologists are always concerned about is the fungal infection Aspergillosis. And we found a number, about two dozen cases in the medical literature, mostly single case reports, of people with various malignancies or immune suppressed states using cannabis, developing this severe lung, fungus infection.
The largest series in patients with HIV, actually did not demonstrate cannabis use as a predictor of who was going to get Aspergillosis. So, I think the fear that it suppresses the immune system. Although, again, with the cannabinoid two receptor being located predominantly on cells of the immune system, there may be some interaction between cannabinoids and the immune system.
Now, again, we do have our own endogenous cannabinoids just like we have our own endogenous opiates, the endorphins, we make endocannabinoids, which complex with these receptors. They’re not just there because we’re all expected to smoke cannabis.
Cannabis’s Impact On Memory
DrMR: Right. And I guess while we’re on the topic of some of the potential side effects, what about memory? Of course, that’s something that you hear a lot about, and I’m unclear as to whether that is mostly stigmatized, or there’s some evidence actually support that habitual use of cannabis may impair one’s memory?
DrDA: Well, I think acute use of cannabis, impairs short-term memory, but Igor Grant, who’s the lead of the University of California, Center for Medicinal Cannabis Research, and a psychiatrist published many years ago, a study on the long-term cognitive effects of cannabis in a large series of patients, and found actually, I believe, no significant deficits in that direction.
DrMR: Okay. And you feel that to be probably the most comprehensive study looking at memory?
DrDA: Well, I mean, you know, all of these studies, you have to understand are observational and recreational users because we can’t do a study of randomizing this 50,000 people to use cannabis three times a day, for the next 20 years, and this 50,000 people not to, and comparing the effect on their memory.
So all of these studies are hampered by the fact that there’re observational and when did they use the cannabis, et cetera. So that difficult to do studies in looking at either the benefits or the harms really, of cannabis.
Other Therapies For Cancer Care
DrMR: What other therapies do you think are worth considering for cancer care? I know that’s a broad question, but where would you take it? Immunotherapy has been one that’s come up. I’m not sure if there are any other natural agents that you think are really ones to consider?
DrDA: Well again, it could be a whole other show, I guess, but I’m very big on nutrition and cancer. And 40% of all cancer in the United States today is related to overweight and obesity. And the number one cause of morbidity and mortality in the United States, they are so-called dietary issues according to the state of the U.S. health 1990 to 2016. And these dietary issues are mainly the consumption of the so-called standard American diet, abbreviated S-A-D for good reason.
So people need to be aware that even after a cancer diagnosis, I do think it makes a difference, that we need to eat a more prudent diet, rich in fruits, vegetables, whole grains, legumes, maybe marine seafood, polyunsaturated omega-3 fatty acids, et cetera. And avoid the junk food and the sugary drinks that Americans drink. So that’s something I really stress with my patients.
As far as supplements, other than cannabis, I like vitamin D levels to be normal in my patients. I’m a big fan of omega-3 supplements. I mentioned seafood, but people aren’t going to eat fish every day, so I’d say, take an omega-3. I like turmeric as an anti-inflammatory, and then there are a number of medicinal mushrooms that I often recommend. But again, caution patients getting immunotherapy is that, I don’t want the mushrooms immune enhancing effect to compete with the immunotherapy. So I recommend that those patients avoid medicinal mushrooms.
DrDA: Andrew Weil and I co-edited a textbook called Integrative Oncology, that’s, it’s a medical textbook and it’s pretty heavy. It’s Oxford University Press. My husband, Clint Werner wrote the book, Marijuana Gateway to Health: How Cannabis Protects Us from Cancer and Alzheimer’s. And I think for people that are not familiar with cannabinoid receptors and the endocannabinoids that Marijuana Gateway to Health is a pretty good read, I must say.
Episode Wrap Up
DrMR: Awesome, okay. As we move to a close here, are there any other resources that you want to point people to, a website, or a blog, or anything else?
DrDA: Yeah, so, if you Google Abrams Osher, you’ll see my website at the UCSF Osher Center for Integrative Medicine. And at the bottom of my page, there’s a link to four videos that were produced by Commonweal, which is a cancer resource and retreat center for patients here in Bolinas, California. One on integrative oncology, one on nutrition and cancer, one on supplements, and one on cannabis in cancer care. And that’ll give people and patients better ideas to what it is that I do.
DrMR: Awesome. And Donald, any parting words that you want to leave people with?
DrDA: Just be well.
DrMR: Awesome. Well thank you again for taking the time, I really appreciate it. Some really insightful stuff on cannabis that I was not aware of, so thank you again for that.
DrDA: My pleasure.
What do you think? I would like to hear your thoughts or experience with this.
- Get help using this information to become healthier.
- Get your personalized plan for optimizing your gut health with my new book.
- Healthcare providers looking to sharpen their clinical skills, check out the Future of Functional Medicine Review Clinical Newsletter.
Dr. Ruscio is your leading functional and integrative doctor specializing in gut related disorders such as SIBO, leaky gut, Celiac, IBS and in thyroid disorders such as hypothyroid and hyperthyroid. For more information on how to become a patient, please contact our office. Serving the San Francisco bay area and distance patients via phone and Skype.