From the Eurekalert version:

> 44 healthy volunteers aged 18-36 participated in the trial. 23 were given prucalopride, and 21 were given a placebo.

> “Participants who had taken prucalopride for 6 days performed much better than those receiving placebo on the memory test; the prucalopride group identified 81% of previously viewed images versus 76% in the placebo group. Statistical tests indicate that this was a fairly large effect – such an obvious cognitive improvement with the drug was a surprise to us”.

What is the p value of this? There are missing data in the press article, does someone have more information?

My guess is that the variation in the number of images you can recall is like 20% (or more), and ~25 subjects reduce it like sqrt(25), so a 5% of difference between the trial and control group is not very significant (p<.04999).

Not to criticize this finding, but the way to think of these things is in terms of p values corrected for multiple testing over the sample of studies conducted every year. That is, if there's M studies every year, some fraction of those will be significant at whatever significance level just by chance, even in the absence of any questionable research practices. Such is the reason for replication.

I might not be surprised this particular drug has this particular effect, but you have to replicate it rigorously, and then show the mechanism isn't due to something prosaic (like people feeling better because their GI tracts are in better states).

There are two problems:

1) Someone defined "statistically significant" as 5%, and sometimes it's too high and it's too easy to get an interesting result caused by a fluke, specially if there are too many groups trying different things. (As an extreme case, in particle physics they use 5 sigmas to avoid fase discoveries.)I think we agree about this.

2) In this case, reading the paper linked by criticas below in https://news.ycombinator.com/item?id=28745673 , the error bars in Figure 1 are unbelievable small. For example the second points looks like 12.0±.2 vs 13.0±.2 (I can't find he exact data, so I'm just looking at the graphic and guessing.) And they claim p<0.01 T get this level of concentration with only 20 persons, the raw data mus be very concentrated around 12 and 13, but I expect that the number of remembered word to be very noisy and have a wide distribution.

I get excited about these kind of discoveries but improving my memory or even iq wouldn’t matter for me. It’s like upgrading the engine of a car that sits in the garage.

Upgrading my motivation is what I need most or even just finding the right things to work on.

People usually go to a doctor and say they don't have motivation and get Vyvanse for this sort of thing

> People usually go to a doctor and say they don't have motivation and get Vyvanse for this sort of thing

Vyvanse only provides motivation for the first week or so.

After that, nope. Vyvanse gives you the opportunity to focus, but the motivation still has to come from within.

Or to put it another way, a wall street trader using cocaine[1] to work 100 hours a week is already motivated to work 100 hours a week, the drugs just enable the body and mind to do what the will already desires.

[1] Different drug family than Vyvanse

Don’t get me wrong. I have the standard motivation to function in life.

It’s just the things you’d associate with great intelligence I don’t have motivation for. Like building a robot or doing research every day.

It’s not a problem at all, I’m just saying I have no use for more intelligence because I wouldn’t use it for anything.

Nothing wrong with a few more IQ points to do the dishes. An examined life is an examined life, even if it's boring.

Well there are always ADHD drugs (if you have it). Otherwise, check therapy to find out and/or get help with it.

If you really have ADHD and take the drugs, also use them + therapy to form good habits.

Study Source: https://www.cambridge.org/core/journals/psychological-medici...

Results Summary: "Prucalopride increased recall of words in a verbal learning task, increased the accuracy of recall and recognition of words in an incidental emotional memory task and increased the probability of choosing a symbol associated with a high likelihood of reward or absence of loss in a probabilistic instrumental learning task. Thus acute prucalopride produced pro-cognitive effects in healthy volunteers across three separate tasks."

When drugs targeting the gut have effects in the brain, serotonin receptors are usually involved and it's 5-HT4 this time. Taking carbidopa (or benserazide, another peripheral decarboxylase inhibitor) along with prucalopride can potentially enhance the memory effects by preventing gut metabolism.

Blocking 5-HT6 also improves memory (in mice) but it seems to come with circadian disruption.

> Blocking 5-HT6 also improves memory (in mice) but it seems to come with circadian disruption.

So the memory improvement is temporary then I reckon? Because my guess would be that circadian disruption -> poor sleep -> poor memory.

Edit: also, any books you can recommend on this topic? I know nothing about it but find it very interesting.

While this is encouraging for further study, there are only 44 participants, the effects are mild (for the sample size), and it's very early research. Considering publication bias and that early results are often more significant than larger, later trials, I'd be surprised if there was actually any substance to this. More research will tell, but, like, this article is not compelling.

The gut has its own "brain" (enteric nervous system), so if the constipation drug acts on that it could also have effects on the brain.

Or, people who are constipated for six days because they gave them a placebo maybe are not in the best mood for memory tests.

Edit: they were healthy subjects, disregard my comment.

The drug (https://en.wikipedia.org/wiki/Prucalopride) targets serotonin receptors which appear in the intestines and bladder, but also the central nervous system and thalamus. No surprise it has wider effects then?

No surprise here, starvation also enhances your senses, but you wouldn't want to do it all the time...

Why not, intermittent fasting works great! You definitely notice the increased alertness during your fasting period.

I don't notice anything. I am amazed at how little I notice, other than how much time I save by not cooking, eating, cleaning, and shopping for food. Maybe, just maybe, my energy level evens out, but is by no means enhanced. I barely lose any fat, half a pound over 3 days if lucky. The only way to make it noticeable is to walk for 8 hours straight on day 3, just because at that point the body HAS to burn fat.

Don't feel magically better. Don't feel hungry after the first 12 hours. Just feels the same. Hopefully, all the magical stories about autophagy, HGH, eth aren't COMPLETELY exaggerated.

I hate reading about fasting, meditation, cold showers, contrast baths, ketosis, etc because it's always made out to be this magical thing, and as far as I can tell, it's just not, and the "science" turns out to be made up eventually.

>I hate reading about fasting, meditation, cold showers, contrast baths, ketosis, etc because it's always made out to be this magical thing, and as far as I can tell, it's just not, and the "science" turns out to be made up eventually.

The discrepancy can be explained very well by one theory.. the set point lipostat theory.

The basic principle is that everyone's body has a 'set weight' point at a given time that the brain targets(just like a thermostat targets a certain temperature). And body functions are highly regulated to meet this target, just like the thermostat turns on the heat furnace or AC to keep temperature constant. So if you eat more, the body burns more calories and makes you less hungry to meet the goal, and if you eat less the body burns less calories and makes you hungry to put you back. Not just those two but a lot more, like converting calories to fat or not.

In your case your body seems to have decided that your weight is lower than your set point, so that's why you're not losing weight even with fasting. You need to sustain that lower weight for a while before your set point is automatically lowered.

I am currently rebuilding my body after few years of eating paints and building materials and whatnot that's in the walls of old construction before renovation. What prompted me was getting food poisoning this winter, four times in the space of three months. I did not recover. Like at all.

Using keto and intermittent fasting techniques I've successfully ping-ponged my weight between 72 and 62kg (that's the _normal_ BMI range for my height) precisely 15 times starting late May.

First three times did not feel great. Felt like getting poisoned again, but mildly, no vomiting all night for three days straight and all that jazz.

I am currently on the way to 53kg, so that I get rid of all that muscle mass acquired in menial jobs and rebuild to something flexible.

In that time my eyesight improved from -2.25 to -1.75

I exist, am real, and did really do all that.

Ask me anything.

A lot of compounds get stored in fat cells, so losing fat can slowly release them back into your bloodstream. Not fun, hope it works out for you.

Yeah, but eating my own poisons was over with in the space of three-four months. Now it's just enjoyable.

On OMAD or fasting days you can feel the added energy in motivation, the added processing in the enjoyment you get from living your life.

On the days where you don't follow a strict diet you feel the food, eh, very much. The joy of it, and the weight of it.

It is definitely worth it to, come winter, evaluate how happy or not you are with your body, and just do what is required. I regret not having the clarity on that subject before my hand was forced.

But you learn, that's why there's reflexion on past experience. You wouldn't need memory if it weren't for that.

> Maybe, just maybe, my energy level evens out, but is by no means enhanced

I said alertness, as in mental alertness, not energy levels. I doubt I would be able to perform physically as well while fasted. Cortisol levels slowly increase the longer you faster to mobilize stored energy and maintain blood glucose levels. Cortisol is also implicated in alertness.

> I barely lose any fat, half a pound over 3 days if lucky.

Not sure if you mean half a pound after fasting for 3 days, or half a pound after fasting intermittently for 3 days. Either way, you don't want to lose weight any faster than 2 lbs per week, tops. Adverse health effects are possible if you go any faster, so it sounds like you're on a good trajectory.

Hehe, this title is brilliant, I really hope this turns out to be true.

Would you really take a constipation drug to boost your memory performance by 5%, despite not being constipated?

Unless there are serious side effects, whats a free 5%?

5% extra time on the john

There's absolutely no data that could lead to this conclusion - the difference in time spent in the toilet could be anything, even negative values.

Lol, maybe the boost comes from the 5% increase in reading time =P

You have to see the numbers behind that 5%.

I too tired to go into what entails a promising good result in medicine, but it's usually just slightly better than placebo on a good day in a small study at the right lab even with approved drugs. (Too tired to use commas.)

> Prucalopride is a 5-HT4 agonist which is taken primarily for constipation. It doesn’t have significant side effects if taken under medical supervision, although doctors caution of the possibility of headache, gastro-intestinal symptoms such as abdominal pain, nausea and diarrhoea, and fatigue or dizziness; there were no significant side-effects shown by any of the volunteers taking prucalopride in this study.

Seems like it only does its usual work if you're actually constipated, otherwise it does nothing (aside from this possible memory stuff).

Further up, the wording is:

> Prucalopride is primarily prescribed for constipation, and has an acceptable level of side effects if taken under medical supervision. (Italics mine.)

That seems rather different, and far less reassuring.

Although:

> there were no significant side-effects shown by any of the volunteers taking prucalopride in this study.

So, you can experience them and if you do they're acceptable (medically speaking, I'm not sure how acceptable I'd find them experentially). The supervision level is light touch, the volunteers weren't rigged up to a drip in an ICU.

I'm not advocating this drug, you may as well purchase some 5HTP from your choice of shop, but it doesn't seem dangerous at all. Exercise and diets have similar warnings and possibly worse side effects.

Yea. I take magnesium. Helps with muscle aches and reducing migraines.

In larger doses it acts as a laxatives

Having a better memory would feel good, on the whole.

first thing I wonder is whether it's a stimulant or not.

Non pay-walled article

https://www.eurekalert.org/news-releases/930043

Dang or other mods, please change URL, the eureka alert article is concise and informative, apart from not being paywalled.

Gives a new, positive meaning to the phrase "shit for brains".

New Marketing slogan: "Take Prucalopride When You Can't Remember Shit!"