Smart drugs are great, if only they worked

Nootropics are substances that are claimed to improve cognitive function, attention, memory, creativity and motivation, they can be natural or synthetic. you might've heard of the movie limitless (2011) directed by Neil Burger in which a man comes in contact with a substance that makes him a genius, well that’s the idea of nootropics, only in a drastically smaller fraction of strength.

Just like coffee (probably the most commonly used nootropic) blocks the adenosine receptor which is responsible for slowing you down when you’re tired, most of the nootropics work by changing some part of our metabolism it could be GABA, BDNF or they can increase blood and oxygen circulation in the brain.

Now, its all great until you start looking at the research, and I will come back to why this could be, but now I want to go over one of the better researched substances out there, Lion’s Mane mushroom it grows in many places so naturally it has many names among them, Yamabushitake, monkey head mushroom, bearded tooth mushroom, satyr’s beard, bearded hedgehog mushroom, pom pom mushroom, or bearded tooth fungus and its scientific name, Hericium erinaceus. There are hundreds of research papers on it but only a mighty small fraction of them are on humans and not on rats or in vitro, and since I suppose, most of you reading this right now are humans, I will only go over those. By limiting our reach only to humans we go from around 280 research papers to a mere 5 and they are as follows, in chronological order:

- Therapy on chronic atrophic gastritis
- Effects on mild cognitive impairment
-Reduction of depression and anxiety
-Improvement of cognitive functions by oral intake
-Effects on the Aging Gut Microbiota

So we have two on cognitive function and only one on the young and healthy, lets go over it shall we?

In this research they evaluate cognitive improvement with supplementation of the mushroom for 12 weeks. There are the following problems with the research methodology (not necessarily the researchers fault).

1. they performed three kinds of tests: Mini Mental State Examination (MMSE), Benton visual retention test, and Standard verbal paired-associate learning test (S-PA).
none of them are great, they involve remembering stuff for a couple of minutes, reproducing shapes and very basic math questions. none of them require the full capacity of the participants, so it most likely wont show subtle differences (for example if I ask regular people and geniuses to do 1+1 we wont be able to observe how much different the two groups are). A test like this has to be designed in a way that most people will barely be able to finish.

2. The selected participants were all over 50.
That is the age in which cognitive degradation tends to begin to happen so the effect of the mushroom in this group would be a lot more noticeable, cause the cognitive decline is ongoing, a participant that is getting smarter would be statically highlighted in two ways (the fact that they are getting better while everyone is getting worse). Its not great methodology because the people are not entirely healthy so the question “will this make you smarter” is answered less assertively (because the mushroom might be stopping the cognitive decline so in healthy people it would do nothing).

3. In order for the results to be noticeable they used analysis of covariance (ANCOVA). which corrects for other reasons a person might be getting better or worse on the test, its sometimes necessary for a subtle statistical significance to be observable but it weakens the result.


the only test that showed a significant difference between the groups was MMSE and these are the results:

Table of results, explain in an organic way in the body of the text

not presented in a graph for some reason, so I made it:

As you can now see the difference is very subtle between to two groups so the researcher performed ANCOVA which gave us some good P-values, that indicate the probability of the result happening by chance, a small value means that the outcome is unlikely to happen by chance (meaning the substance is actually doing something) and shows a significant difference between the two group, meaning the treatment works.

I wouldn't blame you for being skeptical about the efficacy of the mushroom after reading all this (not only the results were subtle, the methodology was flawed) but there are reasons to that and they are:

1. clinical trials are very expensive.
Considering we are talking about a mushroom it’s not possible to hold a patent over, if the researchers find that its a miracle substance, anyone will be able to sell it so pharmaceutical companies are not interested in investing in this kind of research. So this creates a situation in which there are tons of cheap in vitro and rats studies, but there is no interest in performing any further work on them even if they do show potential, and the clinical trials (clinical trial means it has to be done in humans) are done as cheaply as possible in a way that increases the chances of success (in our case using older people).

2. Nature is unpredictable.
It’s an organic material not every dose will have the same amount of psychoactive compound, maybe the ones sourced from during winter will have better effect, so no to doses will be identical, and that adds one more layer of complication to any of the research.

3. Our brains are unpredictable.
It is very difficult to research drugs for depression anxiety and mental illness, because each brain reacts differently to substances. If a drug is very effective on a five of the patients it is not enough for it to be considered successful, even if its life changing for those five people

And that is without the lack of incentives that plants have so indeed it’s unlikely that we will get quality research about natural substances. with that said, this, as a kind of pilot study, does present promising data on the topic, and considering that the only consesus that all the researchers have is that it is a safe so who knows, You could be among the five people for whom the substance is a miracle drug, so maybe worth it?
As usual more research is needed.

Um Biólogo que gosta de escrever