I was recently involved in a discussion about how we ignore signs of poor mental health in high-functioning individuals. The overall impression I got was that we as a society consider the functional output of a person's life/career/etc as a good readout of their overall well-being. I think we all know that's a load of shit, yet it also seems to be generally accepted.

Science seems to be a pretty solid example of this phenomenon, if I may comment based on my own experience. Despite a seemingly neverending and contentious debate over what factors (brand names on the CV, CNS journal pubs, lab pedigrees, etc) make for your favorite brand of career success, I think it's pretty clear that it's high-functioning folks of all types who wind up in the senior scientist positions. Speculate (or argue) all you like about how much they contributed to their career status and how much was luck and etc, fact is they somehow got shit done/got papers out with their names in the list positions that mattered.

Yet we seem to have this (anecdotal, but certainly matching my own experience) preponderance of maladjusted personalities and behavioral issues in these positions, if the disgruntlespheres of grad students and postdocs are any account. And it makes me wonder if it doesn't, on some level, boil down to the fact that we are not paying attention to warning signs that we might notice in a more normally-functioning or impaired-functioning individual.

Consider the high-functioning amphetamine abuser vs the turfed out meth abuser. Who requires the intervention? Obviously both, but do we pay attention to the former? Do we notice?

Consider the person with a personality disorder who has a successful career on the surface but clearly creates a toxic work environment that harms everyone involved, vs the person with a personality disorder who is unable to work. Who do we pay attention to?

The difference is level of functioning.

Consider a mental health diagnosis. Many require the presence of clinically significant impairment of functioning in some important aspect of one's life. Work is only one aspect, first of all. Secondly, what about the population of high-functioning folks who manage somehow to continue lives of quiet desperation, under the cloak of being a high-functioning little worker bee?

Perhaps we need to open our eyes a little more.

Compensating for youngness and femaleness in the workplace. As it stands, I do feel a headwind simply because I'm not a member of the Senior Grayhair Dude club that constitutes 90% of the local investigators.

Allow me to relate a general observation.

Dressed up like an office-dweller, it's a lot more perilous for me to get the hands-on science done, but I get less trampled-over by the administrative people whose purpose (seems to me) is to make my life hell. I look like an administrative person, women can be administrative people, that's OK.

Dressed totally badass for some hands-on science (less sitting-in-an-office-dressy, generally wearing a shirt I can afford to replace easily, carrying my set of science tools, hair tossed back out of the way, etc), stopping by the admin group to inquire about some progress? Now I'm the little girl who has a cute little science project she wants to get done, and how adorable that she's all annoyed at the 5 day lag when everyone else has a 2-day turnaround or less. Patience, little girl. Patience.

Events like today make me feel like I can only be taken seriously on days when I don't have hardcore science to do. Guess how often that happens. I have to multitask the admin and the hands-on science duties all. the. time.

I should mention I am extremely fortunate to have scientific career mentors who take me seriously all the time, who value me for my ideas and my work. And I know they have my back. But some of this overarching culture of science shit I need to navigate on my own. And a lot of it is just bullshit.

I am up to my eyeballs in Super Demanding Long Term Experiment. I made a tentative plan for finishing the remainder of what I'm currently working on. The first type of data collection ends about 2 months into my second year of funding.

Holy shit. The time. It is a-flyin' here.

I was just trying to bear the weight of my own experimental ambition until this hit me. My time on this fellowship is quite finite. While I'm getting great use out of the support and resources and other goodness at my avail in my current place, I have to wonder where this will all lead in the end. I have to keep the end in mind, too. Just more stuff to think about.

A baffling trend came to my attention recently. Surely this can't be right, I thought- people taking high-dose niacin to pass a drug test? Really? I lack the proper words... so I'll just cut to the chase.

The Claim:

Taking high doses of niacin aids in detox and/or passing a drug screen.

Let's deconstruct.

First- what is "detox" anyway?

Generally? Beats the hell out of me. Being a real pharmacologist, I don't buy into this whole "toxins" and "detox" nonsense. But in the context of the claim, the intent is to beat a drug test by somehow reducing the concentration of drug (or drug metabolite) in the bloodstream or urine below the detection limits of the test. I say "bloodstream or urine" because what comes out in the urine is a direct result of stuff getting metabolized from your bloodstream.

Ok, so what is niacin, and what does it do?

Niacin, also known as nicotinic acid, is typically used as an aid in treatment of hypercholesterolemia (high cholesterol). It does this by inhibiting mobilization of free fatty acids to the bloodstream (thereby preventing the liver from turning those free fatty acids into triglycerides, which affect synthesis of the "bad" LDL cholesterol), but it also has some other effects. The most notable side effect of niacin treatment for hypercholesterolemia is flushing, which can be severe enough to prevent people from using niacin regularly enough to keep their cholesterol under control.

Flushing in this context refers to a skin reaction. Niacin use can trigger skin redness, heat, itching, and tingling. The flush may be limited to the face and upper body with a lower dose, though a higher dose might cause more widespread flushing. The mechanism largely considered to be behind this is a vasodilation, or dilation of the small blood vessels near the surface of the skin.

So I guess this is where the "flush" the drug out of your system idea comes from? It sounds like a stretch, in my mind, but that's all I can gather.

How do drugs wind up at detectable concentrations in the bloodstream to begin with?

Pharmacokinetics! I thought it was just one class I had to take some years ago- but no, it just keeps on showing up in real world situations. I wrote a couple posts that might serve as useful background here (Part 1) and here (Part 2).

When you take any drug, it distributes to your body via the bloodstream. Your liver breaks it down, and then you have metabolites circulating until you eliminate them in the urine or feces or sweat or other excretion. The body takes a bit of time to do all this breaking down and elimination, so for a certain time period after drug use, your drug exposure can be determined using a test of urine or blood. This is directly related to the elimination half-life of the drug, and of its metabolites. (And these vary by drug.) You come up with a sensitive enough test, and you can detect vanishingly small quantities of drug or metabolite. This means you end up with a longer period of drug exposure detection.

For drugs that store in the fat, like THC, elimination requires the drug coming out of storage in fat tissue before the liver metabolism step. The slowest step by far is coaxing that fat-soluble drug out of the fat tissue, where it's perfectly happy to just hang out. This is achieved by gradient equilibration. That means that if there is more THC in the fat tissue than the bloodstream, it will follow the concentration gradient to the lower-concentration side, the bloodstream.

Then how does one go about "flushing" the drug molecules from the body?

Simply put? (Using THC as a common example...)

You can't convince all the THC that may be stored up in fat cells to come hang out in the bloodstream for your convenience. There are next to no feasible ways to actively modify the concentration of a drug or its metabolites in your bloodstream, at least in the downward direction. Vasodilation and the increased blood flow that comes with it does not change the concentration of a drug in your bloodstream, does not change the concentration gradient, and does not coax anything out of your tissues. (And we're talking about molecules here. Most especially in the case of fat-soluble molecules, they don't need vasodilation- they get into the tiny blood vessels just fine on their own.)

Bottom line. What will niacin do to decrease or mask the concentrations of drug in the bloodstream?

While niacin is known for causing "flushing" of the skin (and by that I mean redness), I want it to be absolutely clear that it does not "flush" anything else. That means it does not flush the drug molecules from your body. Not only does this regimen fail to have the desired effect, at the doses that I've heard or in attempting this detox myth, this can also fall into the "more harm than good" category. Folks, the only sure way to pass a drug test is to abstain from the drug for a long enough time to eliminate all of it. Period.

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delayed h/t goes out to WhizBang! for the inspiration.

Genomic Repairman is spearheading a Scientopian effort to study the science of Charlie Sheen. I come to find out, several days late, that I'm in charge of the pharmacology core.

Like I don't have enough paperwork to do.

And hey. I was on some work-related thing last weekend. Don't give me that look.

So I looked into this. Turns out Charlie Sheen claims that he's on a drug. And that drug is Charlie Sheen. Effects appear to be winning, being able to cure diseases with your brain, and several other currently uncharacterized phenomena. Sounds like a pharmacology project to me.

This got me thinking- what kind of drug is Charlie? Any good pharmacology study has a dose-response curve, has a little agonist and a little antagonist action going on to parse out the role of the drug/physiological event/signaling/whatever dependent variable you choose, so surely we need to identify our pharmacological tools before running the experiment. Then it hit me that Charlie Sheen seems to be acting as an agonist *and* an antagonist. We're identifying whole new avenues of pharmacology here, people.

Scientopia: Winning.

Oh, science. I feel like I'm pedaling harder and harder, but I also seem to be dropping gears quickly. It takes so much more just to keep pace. One disruption today and I felt like I was going to hit the ground face first.

I keep meaning to get a few more things organized so I can plan a little time away to refresh and reset. Something always comes up and keeps me from even thinking about time away.

I feel insecure in my ability to keep this up, exhausted of energy (I put it all into this and I need a break!), and even the piles upon piles of cool data rolling in are not feeling like enough to sustain me through this particularly intense period. I'm taking down barriers only seconds before my science blows past them.

On one hand, it's really great that I'm making this kind of progress and learning to handle these kinds of challenges. Kind of a make-up for some lost time/missed opportunities in a previous career stage. The other hand is punching me in the back of the head.

I find myself wishing for the simpler days of grad school lately. I love my job, but this stuff is really beating the hell out of me.

When I was an undergrad, the education I was getting seemed like a lot of new stuff and a lot of work. In hindsight, though, that was not so bad. Grad school was tougher, and there were by far many more hurdles and hardships than I saw in undergrad... but mostly there was a lot of persistence and perseveration and really weird hours (and diagnostics. i am a pharmacological assay diagnostic ninja.) until that huge burst of novel thesis-writing effort. I complained plenty, but persistence is pretty much my middle name, so I got it done.

Here I am now (below, see arrow) and the only thing I can say to express how this feels is, "whoaaaaaaaaaaaaaaaaaaaa"

Growing pains are just that, and really it's easy to forget that they're a good thing for the long haul, but they can still totally suck when you're in it.

Figure 1. Leigh subjectively approximates the amount of ass-kicking she received from science over various training phases.

In the mornings, I'm a bench scientist all the way. I have so much going on that I really could use a second pair of hands. Still waiting on those to get here. The important thing is to just keep the experiments on schedule, juggling several subgroups of subjects and making sure everything that needs to be up in the air remains there. (Splat on the floor spells wasted time, wasted research dollars, slower progress, and more paperwork... none of which are desirable.)

I spend my time in my own head, with all the shuttling back and forth from room to room. Pondering the wider web that my awareness now encompasses. From the back and forth in the lab, to the conference room where I present my data and do the politicking with important types, to the chained-to-desk condition in which I crank out the facilitative paperwork to keep the science up and running. It all interacts- some ways are good, and some ways are kind of stupid. Like how doing the politicking is apparently good for me to get my name and face out there to the big important people, but it gets me more administrative stuff to do, which distracts from the central purpose of my presence here: the science. (Sure, I can't stay locked away in a lab or office all day every day. But when you're hit with several big politicking events in a row, you maybe get just a little tired of juggling it all.)

Part of the mornings and most of the afternoons are for data- putting new stuff together, new ways of processing old stuff, running analyses, deciding what to do next. Late lunch if I'm lucky (though I haven't had that good fortune in a while) and then let's not forget the confusing world of administration. Who wants what report from me and when, how do I get the next big thing coordinated with the powers that be, who do I call about the support services we're going to need for the next experiment, holy shit is this form really 30 pages long, oh and thanks for the 3 days notice that I need some long ass training module to stay in compliance with regulations. Ack, and I need to decide on and order and change some paperwork for a new compound... note to self for tomorrow.

Now that I'm handling bench and non-bench work, with non-bench being the clear time-dominator (and my own first point of failure), I can start to see how PIs don't have time to work at the bench anymore if they want to keep on top of everything. I can really see how one begins to rely on others to do things that others can do. This staircase I'm climbing goes farther... how about we see what's up the way a bit?

Scientopia has launched a new guest blogging initiative, which can be found on the shiny new Guest Blogge. We're very excited to feature some awesome non-Scientopia bloggers that we are reading. So what are you waiting for? Go! Read! Find new and great material to add to your RSS reader!

My current position has seen me do some pretty major skillset-expansion in a short period of time. That was a steep curve to climb, but I think I've at least sorta got the hang of it. Since the purpose of acquiring some new administrative skillz was to get the hands-on science up and running, I turned around and spent some time with my nose to the grindstone bench. I was getting a ton of shit done, it was amazing! And then I slipped into grad student mode. Focused heavily on the bench science, let some of the other things in the air just hang. The bench science is exciting, so it became easy to tell myself the dealing with paperwork can wait until this next batch of results comes in- or until I get this next thing up and going in the lab. Or whatever else sounds more fun than filling out more paperwork.

Wrong-o!

Now I have some incredible data-collection efforts ongoing (and frankly I couldn't get any more up and running without expanding facilities) but am in a bit of a crunch to keep the path clear for them to continue going.

Hi there... nice to meet you, double-edged sword.

Back to learning to stand on both sides of facilitating the science and doing the science. And I'm supposed to be learning how to balance work and life in here somewhere too... right? Sigh...