This is a cool segment where Dr. El-Mallakh tells us a little about his experience using lithium to treat acne, and again discusses another very cool mechanism of action. We also talk about some possible solutions to bad research.
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Ethan/Intro: There are a couple other segments that Dr. El-Mallakh and I recorded that didn't fit particularly well into any of the other segments, but were so interesting that I felt the need to include them in the series. As you'll notice, some of the recordings are a little bit mixed together. There's an AC unit running in the background of one of the recordings, and some of the questions that I asked were added in after the fact, just full disclosure. But hopefully you enjoy the information on mites and how lithium may affect mites and in turn may [01:00] affect acne as well, as well as a commentary on one of the primary sources of lithium in the world today.
Ethan: You said some interesting things about how lithium can cause acne or affect the oils in the face. Can you expound upon that a little bit?
Rif: We know that lithium changes the oils in the face. Lithium may cause acne by doing something to the mites that live in the hair follicles. There are 2 types of mites. There are mites that actually live in the sweat glands, and mites that live in just hair follicles. The mites that cause the acne are probably mites that live in the glands or in a part of the skin that actually excretes oils. So there's Demodex Folliculorum and Demodex Brevis and Brevis is the one that lives in the hair [02:00] follicles, and those can give you like blepharitis. Everybody has Demodex, so it's hard to actually associate them with a specific disease. I've always wanted to do this experiment of taking folks that have acne, and treating them with insecticides, as if they're having lice. But just put it on the face and see if the mites just go away. But lithium does alter the oil, and, if what we're seeing with Varroa mites suggests a particular vulnerability of mites to lithium, then it may be that lithium just kills the Demodex, and it could be 1 of 2 things. You either have dead mites that plug up. In that case, you treat the person with insecticide and nothing happens, or it actually changes the protein or the food value of our [03:00] sweat or oil, so that there's a huge dramatic population explosion because these mites can now lay twice as many eggs, and you're now getting 3 or 4 mites per follicle, rather than 1 or 2 mites per follicle.
One of my students, a long time ago, ultimately became a dermatologist. I contacted her about doing a small study and I told her that I wanted to treat 1 side of the face with, whatever she does, and the other side of the face with insecticide. The same person is their own control and you can just take a picture, and have the people blinded that actually do the rating. You randomize which side, and then you have somebody who's blind as to which side got which rate the severity of the disease, and you do it all by pictures [04:00] and you can do it even in such a way that they don't know the sequence, so you have some kind of scale that you're going to use and you're only getting the part of the face that's affected, so just the cheeks, and you don't know where they are in treatment. You don't know if it's baseline, you don't know if it's week 1. You don't know if it's week 2. You just don't know. You just have a picture. You have nothing to prejudge you. This is actually something that was published in New England Journal of Medicine, I think both the Ingrezza and the Austedo studies, the tardive dyskinesia studies. They did them in that fashion. They would videotape the actual, the entire AIMS (Abnormal Involuntary Movement Scale) Exam. And that videotape would be saved, and wouldn't be evaluated until [05:00] enough patients were done, or until the patient was done, and then they would randomize the videos, and send them to a neurologist who was blind. You don't know whether they're active or placebo. You don't know where they are in the sequence early, late.
Ethan: I've always thought that a potential solution to our research problem would be to set up, and obviously the IRB would have problems with this, but to set up an online platform where anybody can do any type of simple experiment, as long as it's safe, right. And then you have evaluators that build credit over time that then look at the research and then you use that bank of publicly available, Internet available research to drive official studies. But, it would solve the blinding problem, similar to what you're talking about, to have the evaluators so [06:00] far removed from it.
Rif: It makes a difference, in both of these designs, the Demodex, or the TD, the removal of the time, because, as a researcher, I expect you to be sick when you 1st come into the study, and I expect there's a chance of improvement, I don't know what you're taking, but there's a chance of improvement, so, always, you get a dramatic decline between the baseline and the 1st evaluation, and that's actually based on our expectations. I'm a scientist, and I think I’m, you know, careful about all this stuff, but I have all of these prejudices. I try to do my best, but I still have that, so that's why everybody gets better when they go into a study. Everybody has expectations to be better. Maybe the patient reports that they're better. But everybody has expectations to be better, [07:00] whether there's a placebo control, doesn't matter.
Ethan: Yeah, or the opposite, if the patient expects to get worse, the expectation (Rif: Right) drives, it doesn’t just drive outcomes, if I'm speaking correctly, it drives actual neurotransmitter release. The more optimism you have, the more dopamine that, it was some study in Parkinson's and they use the DAT scan to look at how much dopamine transmission there was. They gave everybody the same active drug, but they told ½ of them that it was an inactive drug and told the other ½ that it was a dopamine-promoting drug, and they literally had significantly more dopamine release just because of the expectation. (It is interesting)
Ethan: Where does most of the lithium that we use now come from?
Rif: Most of lithium comes from old oceans. You can take new ocean water and distill it, but it's full of a lot [08:00] of other salts, but some places, particularly in the Andes, most of the Andes was actually underwater, and all of that stuff got raised up when the continental plates collided and the Andes are still being raised up. But, the Andes are full of essentially ocean bottoms, currently are the major source of lithium in the world. It doesn't really rain very much up there, so they get dehydrated, you can just go up and literally just harvest the salt.