There seems to be an underground community of people who guineapig with a large variety of unregulated and under-studied Eastern-bloc molecules, including various racetams, noopept, selank, semax, and bromantane. The mechanism of action of none of these is known, and neither is safety.
Piracetam, a nootropic drug given to dementia patients, and levetiracetam, an anticonvulsant, are two racetams that have been studied more thoroughly.
Personal experience
I tried pharmaceutical-grade piracetam in low doses a couple of times but I never felt anything (though 800mg is the highest I ever took). However, I only tried it while I was on low doses of moclobemide, so I do not know whether that has affected my experience. A friend tried some of my piracetam and liked it, though every time he took it, he felt tired the day after. We are all different.
To see what all of the fuss and hype is about, I have also experimented briefly with a variety of similar molecules (oxiracetam, aniracetam, phenylpiracetam, and noopept).
I felt some stimulation when I tried oxiracetam and phenylpiracetam, though nothing out of the ordinary, and nothing that I cannot get from modafinil, caffeine, or ephedrine.
After not feeling much, I decided to thrash all of my non-pharmaceutical grade racetams for a variety of reasons.
Most of the racetams supplied to the market come from underground “laboratories” (piracetam is an exception). They are not produced by highly regulated and monitored pharmaceutical companies or even high-quality supplement companies. Racetams could come from subpar manufacturing in someone’s bathtub.
This could mean that either the dosages are off, or I am getting something different, and unless I had access to high-performance liquid chromatography (HLPC) or mass-spectrometry (MS) equipment I would not be able to tell.
Or it could mean that the substance in question is impure and laced with potentially dangerous byproducts. In many cases, “white powders from the internet” (even from “reputed” sellers”) are laced with something else. For example, protein powders are known to be laced with microdoses of anabolic steroids, “herbal” appetite suppressants with sibutramine, and “natural” testosterone boosters with tadalafil.
Even if I got what I think I got (and this is a big “if”), I have little to no reliable data about these molecules. I do not know how they work, nor do I know whether they are safe to consume. All of the little data available comes from a small number of “research groups” from Eastern Europe and Russia, which all seem to be affiliated with each other.
People think that because something is published on Medline (PubMed) it must be true, but nothing could be further from the truth. The whole scientific enterprise is far less “scientific” than most people think it is.
Additionally, there have been anecdotal reports indicating that racetams seemed to have negatively affected some people’s cognitive abilities for a long time after they stopped taking them. Some people report extended brain fog and feeling “weird”. Could be neurotoxicity. Could be counterregulation. Could be choline deficiency. Could be off-target effects. Could be placebo. I do not know. Why would I play Russian roulette if the payout is so meager?
Given that racetams may be useful nootropics (at least as per the online bro-science community), I hope for an independent double-blinded trial that tests the long-term safety of these agents in animal models (given that different animal tissues can be thoroughly examined post-mortem, animal studies are much more useful for toxicology purposes than human studies).
Modafinil, caffeine, methylphenidate, amphetamine, ephedrine, bupropion (links to all of these drugs here) and any other drug available in a Western healthcare system has been rigorously evaluated on a number of dimensions, including extensive pre-approval toxicology. At least in terms of health, safety, purity, quality, consistency, and mechanism of action, there is enough reliable data to make my own educated decision about these compounds.
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Mechanism of action
It is not fully known how racetams work but the most likely mechanism of action seems to be the potentiation of AMPA receptor signaling. AMPA is the primary excitatory receptor in the central nervous system, glutamate being its ligand. Glutamate & AMPA are discussed in more detail here.
If this receptor is modified by a positive allosteric ligand, a so-called AMPAkine (an AMPAkine is to the AMPA receptor what a benzodiazepine is to the GABA-A receptor), the result is an uptick in glutamate signaling, and consequently an increase in global CNS excitation, increased mitochondrial activity, and increased cerebral perfusion.
While this is helpful for brain fog, executive functions, and energy levels, too much of this may be neurotoxic. In fact, this is the main reason why the clinical development of most AMPAkines has been abandoned.
Safety
While little is known about racetam safety, some things can be extrapolated from the known safety of other molecules that potentiate glutamate signaling. The following discussion is based on the premise that racetams do indeed function as AMPAkines, which is not known for certain.
- Cortisol: At high doses, glucocorticoids are excitotoxic to hippocampal and prefrontal neurons, in part because cortisol potently upregulates glutamate signaling, which causes excessive calcium influx, which then causes excitotoxic cell death. Cortisol is discussed here.
- Ketamine: At high doses, ketamine causes widespread grey and white matter death, possibly due to AMPA receptor signaling mediated excitotoxicity. Ketamine is discussed here.
- GHB: Through its action on the GHB receptor, GHB causes a potent increase in glutamate signaling. In animal models, high doses of GHB are measurably neurotoxic, and human data on GHB abuse does paint a similar picture (correlated with clinical endpoints of cognitive function such as short-term memory).
- Alcohol/BZD withdrawal: Both alcohol and benzodiazepines potentiate GABA signaling. Counterregulation happens. If alcohol or benzodiazepines are withdrawn suddenly, glutamate signaling rises to overly high levels, causing widespread excitotoxicity. In fact, benzodiazepines and alcohol produce two of the most lethal withdrawal syndromes.
- AMPAkines: AMPAkines hold significant theoretical promise for treating anhedonia and cognitive impairment. However, the development of various AMPAkines was stopped in part due to indicators of neurotoxicity (based on histological data), especially at high doses. Whether this is also true for low doses is unknown, but many suspect it to be. Furthermore, piracetam, the only AMPAkine available for clinical use, was withdrawn from the market in a couple of Central European countries, in part because more and more doctors recommended against its use (though I could not find the exact reason why this happened and the neurologists I asked did not know it either).
Therefore, it can be tentatively concluded, that while occasional low-dose use is likely (?) safe, high-dose or prolonged use might be neurotoxic – again, based on the premise that racetams do act indeed as AMPAkines.
Furthermore, racetams are generally ingested in relatively large quantities (e.g., 500mg-1g range), and whenever a large number of molecules is ingested, chances for off-target effects increase. This means that simply due to the sheer number of molecules ingested, racetams may bind to, and affect, a variety of different proteins throughout the body.
Other experience reports
For a general discussion of stimulants, and links to accounts of stimulants I have experimented with, click here.
For a full list of experience reports, including non-stimulants, click here.
Sources & further reading
- Scientific review: Positive AMPA receptor modulation in the treatment of neuropsychiatric disorders: A long and winding road
- Opinion article: Self-hacked – Why I Do Not Supplement With Piracetam
- Opinion article: Racetams & Nootropic Drugs: Does the Limitless Pill Exist?
Disclaimer
The content available on this website is based on the author’s individual research, opinions, and personal experiences. It is intended solely for informational and entertainment purposes and does not constitute medical advice. The author does not endorse the use of supplements, pharmaceutical drugs, or hormones without the direct oversight of a qualified physician. People should never disregard professional medical advice or delay in seeking it because of something they have read on the internet.