Transcription
All right, thanks for coming to the presentation. It's about academic doping. So everybody's heard of doping in the sports sense. So obviously there's a lot of line in the Olympics, for example.
Uh, so there we have some unofficially, maybe in some cases officially, in the case of Russians, sponsored programs of doping, and that's have a very long history of use. Here is poetin, used extensively in endurance uh sports like cycling, and people are pretty familiar with this concept. But there's also cognitive doping, which has as long of a history as sports doping, and also has some considerable overlap.
Um, you got some compounds there like amphetamine. I'm sure everybody's familiar with that one. Not only does it have effects on the mind, but there's a psycho motor relationship. So it also improves sports capacity and endurance in that sense too. And then these are some other stimulants: Medafyl, some people might have heard about, caffeine, right? And nicotine too. That's another agent that's both has cognitive and physical effects. So there's substantial overlap there.
But unlike sports, uh, sometimes it's actually professionally sanctioned. And and some examples of this are military, specifically in aviation, and also amongst astronauts. Uh, there are certain things called go pills, which are officially sanctioned by the US Air Force. Um, and there are also drugs that are available on the space station for astronauts. This is one medapanyl that I mentioned earlier. It was first introduced about 1989, and it continues to be used in the US Air Force, as well as on the space station, and it's a wakefulness promoting agent that's used for fatigue management, uh, especially on long missions or during sleep deprivation.
And then there's also unofficial use of professions that are under a lot of stress or pressure, uh, who may take it upon themselves to use either prescription or or non-prescription aids, like emergency medical services. Truck drivers have an astonishingly high use of empetamine. Some studies build it around 10 to 20%. Commercial pilots, night shift workers. In fact, that medafanol, we talked about, is officially approved for a night shift as a medical condition. You can get it prescribed to you if you work irregular hours.
And then students, which is uh, the focus here. Uh, but I want to talk more broadly about cognitive enhancers, because uh, the use is pretty indiscriminate across a variety of domains. Uh, and you can, in this sense, consider students, the way that students are using it, a parallel to to how some professionals might use it. Well, let's not forget about the the most common cognitive enhancer that I think most of us use here. Uh, in the United States, about 90% use it on a semi-regular basis, some most of the time daily. Uh, and it's a cognitive enhancer that is comparable in some sense to prescription aids. Uh, of course, weaker than what you might think of, um, amphetamine or ADHD drugs when it comes to motivation and such. But there's going to be some research that we'll discuss later where you can really appreciate that Kathleen actually does have cognition enhancing effects.
I wanted to bring into discussion how did this come to be, uh, at least the professionally sanctioned part of cognition enhancing drugs. And, uh, like like all good things, you know, it came from the military, right? The internet, uh, are are getting to the moon, and such. It was some sort of political or militaristic incentive to to getting the ball rolling there. Um, so there was, in the Cold War, you know, we know the various technological races, uh, that occurred, uh, notably the space race and the arms case. And but within each individual science that was involved, there were plenty of cases in which, uh, there was a financial incentive provided by the military, the governments, to advance them. And psychopharmarmacology benefited greatly from this in that period. On the Soviet side, it was a bit more direct than on on the western side, but there was a push to develop agents that could be used to enhance cognition, um, in in certain cases, especially amongst high stress or or sleep deprived states, to aid in the other technological races that were occurring, and also improve the military readiness of the time.
So the comparison here is mostly amongst what the Soviets called neutropics, which I'm not sure if anyone's heard of that term nowadays. Now it's used a bit by the supplement industry, to to describe a cognition enhancing thing generally, but not using the word drug, because that's a bit aversive to some people. But originally, it actually had a different definition, and this is in contrast to the psycho stimulants, which were primarily psycho stimulants, which were used in the West, starting off with dextroetamine, which was used in World War II amongst US Air Force, and continued to be used amongst pilots during the Cold War.
And I put a little asterisk here, because, you know, I say neutropics versus psycho stimulants. These are not classes on the same level. There are plenty of neutropics that have psycho stimulant like effects, and the Soviets were a little bit elitist in their psychopharmarmacopia and didn't want to to officially call these things, uh, in ways that were were used by the West. We just understand that this does not mean that it's a, it's a different effect profile, but rather that it meets this criteria, uh, which was put forth by a guy called Corno Julia. And he he coined this term, uh, to describe a drug called paracetam, which was the first neutropic. And he provides some criteria stating that neutropics are drugs which enhance learning and memory, they provide resistance to cognitive insults like sleep deprivation, stress, they increase cortical control, which, you know, you have to understand that back then psychopharmarmacology was in its infancy, and there's these handwavy kind of terms that now make people's eyes roll, but that's what he used to describe it. And it lacked traditional sedative and stimulatory effects. So it was not overtly psychotropic, like what you would think of as a pure cognitive enhancer, if you will, and that they had low toxicity. Uh, specifically uses to compare to to drugs like empetamine, which he said worked by an exhaustive action.
Over time, the definition has deteriorated, and some of the things that he put forward are not really able to be substantiated with modern science. But this did create legitimately interesting drugs. Of course, you know, them being the Soviets and later Russia, it was used for things like the Olympic team. Uh, but also there was one drug that was was used by Soviet cosmod called phenoparacetam. And this is a quote from Alexander Cerebrov describing his experience with the drug. Uh, and that was that was one of the first cases of occupational drugs being used in space. And romantine, as well, uh, which was used for for the Olympic team.
And on the western side, we used, uh, our good old dextroetamine. Here's the Apollo 11 medical kit. There was dextroetamine available. And in fact, the first drug used in space, the first, I mean, drug ever used in space, I'm not only talking about psychotropic drugs, was actually dextroetamine. And then later on, we continued to go with this, leading into to what we now know of as occupational use at the highest level, maybe the level which you can more readily justify, you know, what are you doping against, uh, the void of space, rather than someone else working on an Excel sheet and you work on it faster, right? So, it's a little bit more ethical. And that's how we get got to this, where now we have medafanolon and zulpadm. You might not think of as a cognition enhancing drug, it's ambient, but when you consider how it's used, um, it's used to improve the sleep in space, which is not that great to begin with. And in that sense, it is performance-enhancing because they they performed their duties better the next day, right?
So, which makes it all the more funny when you consider that there's actually been a recent wave of, uh, of people on Tik Tok and such, who who are talking about using these drugs for performance-enhancing purposes, but they're not astronauts, and and and fighter pilots, but rather they're taking a business exam or something like that. Uh, and then they're on drugs that that you didn't even know existed. So, I guess we'll talk about it. What is the reality of cognitive enhancers, right? Um, maybe the people, uh, previously in those Tik Toks would have you to believe it's, it's something like this: >> for a week. It seemed to cut my learning curve. Is that the reality of cognition enhancing drugs? Right? Do they make you into this super genius who makes $2 million on the stock market in less than a week? Unfortunately, it isn't. I, I don't know how else to say it. You know, there's nuance to these things, but this is pretty sure that it's not like this.
So, what, what is the reality? So, you have to consider that, um, cognition has some dimensionality to it. Uh, and some aspects of cognition are are more, uh, responsive to to pharmacological enhancement. Usually, it's what you would think of as the lower forms of cognition, the more simple, uh, forms. So, so motivation, reaction time, tension, whereas the least sensitive ones are higher level cognitive functions like memory, fluid reasoning, and intelligence. When you consider this, it makes it easier to understand that, you know, there are benefits, indisputable benefits in some areas, while there might not be some in others. So, when you consider, when you ask the question, are these drugs cognition enhancing? It's better to split it up in these cognitive domains, because overall, the answer might be very, very slightly, or not at all. Uh, whereas in these specific domains, it might be more so.
And also, you have to define enhancement versus restoration. Um, cognitive enhancers are actually much more effective when they're restoring cognition that is impaired by either a condition or a cognitive insult, like sleep deprivation, pain, stress, and conditions like ADHD. And this ties into the idea of the Jüks do curve. There's low levels of arousal, where obviously you're not at at at maximum cognition, and then there's an optimal arousal, and going beyond that actually impairs performance. You can think of the, the stimulants, maybe, and these these cognition enhancing drugs as pushing you up to that that optimal arousal, but if you're already quite close to that, it's not going to have all that much of an impact. And then if it pushes you even further, you're going to start getting a detriment.
You know, talking about sleep deprivation as as the cognitive insult that I think most people can relate to. Um, here's where the drugs have the biggest effect, and this is comparing caffeine, medylol, and dextrine. I think it's important that, you know, we've noticed that caffeine is here too, because it does have an appreciable effect. I mean, look, it, it's not doing as well, and this is after, here I'll define this better. So, this is after 60 hours of sleep deprivation on the bottom here, and then they administered the drug or placebo, and they tested them on a psycho motor vigilance tasks. Uh, and this mainly has to do with more simple measures of cognition. Right? So, we're not talking about higher forms, like in the things that relate to intelligence. And you can see that it restores it somewhat. It doesn't really bring them all the way back to what you'd expect their normal level to be. That's in another figure on the study, but it doesn't bring them back to that, but it restores them definitely from where they were before. I mean, you can see that they were about to dip, like they were in the previous hour, and probably much more severe. And it mitigated that dip across all the conditions, uh, with medafanyl doing the best, wakefulness drug, dextrin, and then caffeine. Right.
By comparison, when we're testing in people who are well-slept, the effect is is smaller, if any. Uh, this was a meta-analysis that looked at a variety of cognitive domains, and it kind of tried to sum them all up and see if there was an appreciable difference with dexetamine, medafanyl, and methylendate. Uh, methylendate is rolin for context. Dexetamine is dexadrine. Here, there was enhancement in some domains, uh, slightly above baseline people who are also healthy. But, you know, these effect sizes were in total quite small. Uh, in fact, you know, you can see here, amphetamine was not even statistically significant for this. I mean, you think of all drugs that would be statistically significant for this, amphetamine would be. And you can see the effect size here, you know, to put this in perspective, in statistics, the G right is the effect size, and and something below .3 is considered quite small. And the these are are are very small effect size. Medafanyl seems to be barely po 2.1, maybe. Right? So that's the movie that that that clip I showed you was based off of. This is the drug that they're basing it off of. Uh, and it doesn't seem to be so, so limitless after all. Right. It seems maybe they embellished a bit in their their portrayal of it.
Zooming into rolin, the methylenate, the one that had the biggest effect size. You can see that in certain domains, it had more of an effect size. And remember, this is the people who are healthy, who are well-slept, don't have ADHD, things like that. And there, there seems to be a moderate effect size in things like sustained attention, which drugs that are used for an attention disorder, you would expect to improve attention. Of course, not everybody is at, even people who do not have ADHD are not always at perfect attention all the time. So there's some room for improvement. But compared to what we see in ADHD, the effect sizes are larger, something like 7.8. To answer the question, you know, here, there does seem to be an enhancement above baseline for people who are otherwise healthy, but it's not like what you would think about it being limitless or or something like that.
Getting back to students, does this actually translate into better grades, right? You know, these abstract measures where I'm telling you when they test these things, you know, it's not at all practical. In a more practical sense, does this actually translate to better grades? And there was there was a study that looked at this, uh, in students who admitted to using, uh, stimulants non-medically. They didn't see an increase in in GPA relative to people who did not use them. But that's not to say that these drugs would not improve a metric like GPA, but rather that there might be, uh, an element to consider of selection bias. People who are most likely to use these drugs may actually have some sort of impairment at baseline. Maybe they might not have clinical ADHD, but they might be struggling more than their peers. And these drugs might bring them up to to baseline, to a level that's comparable to their peers. So, it's hard to tell whether or not this suggests that these drugs actually have no practical benefit, or if they're just masking an impairment and the people who tend to use them, right?
And then there's ethical questions to be made here. Cases of zero sum, right? An exam that is being curved based on the average, what good is there if everyone takes a drug? None. Because then the average just goes up by about an even degree across, maybe a little bit more for people who have a pre-existing impairment, but you're not really gaining against anyone else, right? But there are cases like with astronauts, where it's like, who is being cheated? Or the void is space, right? And and do we, why would we not want an unfair advantage? But whereas in a desk job situation, who are you cheating? Other people who are working on Excel sheets at that point, you know, you can say that's not all that ethical.
There's also safety concerns for the user. A lot of these drugs have been used extensively. The ADHD drugs, we have lots of data for those for ADHD. Now, of course, it's a different risk-to-reward benefit when it's being used for ADHD versus people who do not have an underlying impairment, but it's unlikely that these drugs have extraordinarily more cardiovascular concerns in people who are not ADHD versus ADHD. So, there is something to be gleaned from that evidence. Um, but that's to be weighed with the pretty marginal benefit that people without pre-existing impairment seem to get from these drugs, and and also tying that into when is it a medical treatment versus an unfair advantage.
Um, I think more recently, we've seen that, uh, well, the the criteria for ADHD has not changed, since the DSM5's release. The amount of people who have been diagnosed, and perhaps the the ease of getting diagnosed, has changed. Right. Tellahalth, there was quite a flood. There was actually a lawsuit against a company that was being a bit too overzealous with their prescription and diagnosis of ADHD. So, it comes to the question, you know, when is it human inattentiveness? When is it ADHD? When can we use these drugs, which are fundamentally cognitive enhancers, for one thing over another? Um, that's the question to ask. And that's it.