Racetams are... argh, drugs that contain this:
Ok, that’s not saying much… you can create an infinite amount of compounds that contain pyrrolidone… some of which look really weird, and many of which would not be called an Xracetam.
Ok, let’s try again… racetams are: drugs that contain pyrrolidone, are tiny, and have some mild and ambiguous psychoactive effect, where the person that first made them thought “Huh, this feels kinda like that racetam I took once”.
Most of them are pretty poorly studied, especially in light of the fact that most of them have the wonderful characteristics of being stimulants without many of the drawbacks most stimulants suffer from: addiction potential, ease of overdosing, and neurotoxicity.
To the extent that they affect anything specific to the nervous system, they do so by modulating a bunch of receptors that you have no context for (glutamate receptors and the sigma-1 receptor)… but also some of them bind to various neurotransmitters (which ones? most of them, depending on which xRacetam you chose), usually Ach and glutamate.
Depending on your racetam of choice they also do completely unrelated things, like modulating the effects of HIF-1, a protein that changes DNA transcription during hypoxic conditions (and also during other conditions that are no hypoxia, dozens of which are known and thousands of which probably remain unknown)
Thus, two questions ought to be asked first:
Is there even a point in analyzing all (or most) racetams as part of the same class of drugs?
Is there any way to conclusively determine the “primary” mechanism for one or more of the racetams?
Let’s start at the beginning, with one of the most boring and well-understood racetams.
Piracetam
Vaguely psychoactive in only some people, not outright banned anywhere, and old enough that a few pharma companies have figured out how to skim some money off it here and there.
At a neuronal level, piracetam modulates neurotransmission in a range of transmitter systems (including cholinergic and glutamatergic), has neuroprotective and anticonvulsant properties, and improves neuroplasticity. At a vascular level, it appears to reduce erythrocyte adhesion to vascular endothelium, hinder vasospasm, and facilitate microcirculation. This diverse range of physiological effects is consistent with its use in a range of clinical indications. Its efficacy is documented in cognitive disorders and dementia, vertigo, cortical myoclonus, dyslexia, and sickle cell anemia.
Piracetam seems to have negligable affinity for any nuerorecpetor.
It does increase chilingergic and NMDA receptor density in some animal models, and the speculative mechanism of action here is increasing membrane fluidity (which would allow more receptors to embed into it). The evidence for both of these is shacky, thus I’d assing a low probability to this hypothesis — Also I’d expect to see some interesting (very bad) side effects if broad membrane fluidization was at play.
Piracetam significantly reduces adhesion of erythroctes to the endothelium. It also acts as a vasodilator and platele aggregation inhibitor, but it’s unclear to me that these tow mechanisms are related (this latter being caused by increasing prostacyclin production).
I’m primarily avoiding talking about the mechanisms of action here, because there are many, and some seem contradictory. Overall it’s quite hard to say what piracetam actually does, and it seems to be prescribed for a dozen of unrelated conditions.
If one is to take the role of vasocomputation seriously, we could try and reduce piracetam’s role to it’s effects on very few clotting related proteins. But this doesn’t comput with a ton of evidence that it affects other things at a molecular level.
However, given how strong it’s effects are, I’d expect that if the mechanisms of action were indeed so varried, there would be more cases of severe side effects related to these very-generic mechanism.
So ? There’s nothing conclusive, either “it’s complicated” or “nobody has come up with a unifying theory”
Other Racetams
This is all quite confusing. Usually, when a class of closely related compounds causes similar effects it can be easily traced down to “a thing”. E.g. tryptamines almost always bind to this or that subunit of a few serotonin receptors, which their shape would predict, and then based on the binding profile, specific 5HT receptor, and pharmacokinetics their effects vary.
But with racetams, their mechanisms are varied and not always correlated. The typical racetams (piracetam, aniracetam) would usually be described as AMPA receptor modulators first and foremost… though this is very debatable.
Nefiracetam and Fasoracetam have no AMPA effects, and instead seem to have GABAergic effects, which one would expect given the shape of most racetams, but is not a function of most of them. Levetiracetam seems to bind to SV2A, and noopept, as previously mentioned, can be viewed purely from the lens of triggering hypoxia mechanisms.
So are racetams even “a thing”? Well, arguably, yes.
Psychedelics were “a thing” long before we knew about 5HT2Ar binding as being the unifying mechanism, and the reason we grouped them together was a mix of similar~ish structures and similar~ish experiential effects. Even if it turns out the that 5HT2A hypothesis is bunk, psychedelics will remain a thing.
In that vein, if a compound is derived from GABA (or looks like it could easily be derived from GABA), contains pyrrolidone, feels somewhat like piracetam, and is somewhat “stimulating” but in a more “plugged in and evened out” as opposed to “manic” sort of way — I think it’s fair that we call it a whatever-racetam.
But which, if any, should I take?
So, why should you take racetams? Well, as said before, a lot of people seem to think that racetams make them more cognitively apt in some ways, which is quite surprising given how unlike any other simulant they feel.
The closest stimulants I’ve had to racetams are shou pu erh teas, but that is a very long story for another time. Here I’m referring primarily to the “felt experience”, but the measurable effects are also quite different from most other stimulants.
Racetams don’t necessarily have negative cardiovascular effects, they seem protective against a range of conditions stimulants would induce or exaggerate, and they are not obviously neurotoxic in the way most simulants are.
Thus, racetams are a primary target, in my opinion, for self-experimentation. So the correct question to ask is not “What racetam should I take” but “What should I be looking for in taking racetams”.
Here’s how I’d design a racetam self-experiment:
First, decide on the goal function, which can be something as simple as “be more focused” or “have more moments of open awareness”. But make sure the goal function aligns with what racetams can do, it’s unlikely that any racetam will align with the goal of “improving sleep” or “increasing exercise performance”. Make sure the goal is something you can monitor, even if the endpoint is as simple as writing down a number to represent how well you did at the end of the day.
Second, buy a bunch of racetams. What I’d look for is stuff that’s human tested, can be taken in reasonably low dosages, and is available from not-extremely-shady suppliers in your country, a reasonable list might be: Piracetam, Omberacetam, Aniracetam Coulracetam, Oxiracetam. I suggest you start with 1 to 3 of these at most.
Third, figure out the starting dose, and take that amount. I suggest taking these sublingually, insufflation will be too harsh on your nose and damage your airways, and injecting these compounds can be quite risky if the certificate of analysis is fake, and the absorption profile with oral administration is too varied. Keeping the powder under your tongue for a few minutes is ideal, to the extent that some of it doesn’t absorb sublingually, it’ll go the oral route.
Fourth, monitor the primary expected side effects:
Blood pressure (cuff)
Heart rate (watch, ring, pulseox, or cuff)
Sleeping HRV (watch, ring)
Time to sleep and time asleep (watch, ring)
Headaches (self-assessed)
Undesirable moods (self-assessed)
Gastrointestinal issues (self-assessed)
Ideally, you’d notice no side effects and observe improvements in your HRV and blood pressure while on the racetam of your choice, I’d suggest starting at a low dose and working your way up, don’t go too high since you don’t want to build tolerance.
As with most drugs, it’s probably preferable to cycle through them, so even if you find one that “works” for you it might be good to come off it and try others during the break, you can always do better.
In Conclusion
Racetams make no sense, but a lot of people find them to be quite awesome.
Right now there is no unifying mechanism to explain their effects, but given how similar most of them “look” and “feel” there is a high likelihood, in this author’s humble opinion, that such a mechanism will be found in a more enlightened time.
Given their mild risk profile and purported benefits, these are prime targets for self-experiments.
Building a model that tells you which racetam to take is impossible. So try a bunch of them and making sure they do no harm, then opting for the compound and dosage that feels best.
Footnotes
On diet and supplements
The other thing to keep in mind is synergies with supplements, where the increased level of e.g. cholinergic or ampa activity, or even the hypoxia protein activation, could benefit from certain supplements.
Right now I intuitively would supplement with small doses of d3, nac, glycine, alpha-GPC, and CDP choline when taking racetams. A more “natural” approach could be to add a bit of non-dutched chocolate and beef liver (or some nutritional yeast products for vegans) to your diet — But take these with a gigantic spoon of salt. What I’m saying here is “it seems like you could use common sense to slightly adjust supplements and/or diet to be synergistic with your racetam usage”. I myself don’t do this, I’m skeptical such synergies exist, I think we’re naturally pretty good at balancing our neurotransmitter levels, and in rare cases where a nutrient is absent, I think our food carvings “get it right” after a bit of trial and error. But a lot of people like doing this so I’m mentioning it as an option.
On safety and human studies
Piracetam is by far the most well-studied of racetams, so in terms of safety profile, you should go with that.
Omberacetam (Noopept) is the second best studied, given that it is approved and prescribed as a psychiatric drug in Russia. It’s also the one about which people on internet forms seem to have the most anecdotes. It makes up for the lack of studies by being active at much lower dosages and having more aggressive effects. It’s also surprisingly easy to source.
All other racetams are orders of magnitude less studied in humans than these two, whatever you buy is more likely to be a fake, and the risks you are taking ingesting them are higher. These are all pretty chill compounds, so I wouldn’t be worried about dying or very serious side effects… but I’d still check if there are at least one tiny human pharmacodynamics and safety study on any compounds I’m about to take.
On getting valid compounds
Whatever nootropic vendor you buy from you should:
a. Ask for a certificate of analysis.
b. Validate that the certificate is valid with whoever ran the analysis.
c. Validate the whoever ran the analysis is a testing center trusted by other non-nootropic non-supplement orgs to run tests for them.
d. Pass what you get by a drug-testing facility if any are available in your area.
None of this will ensure purity but it will hedge against the worse type of poisoning and increase the chance that what you’re getting is what it says on the tin.