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What To Avoid (and Why)

By Nootopics July 3, 2026

Research and education, not medical advice.

This page collects the warnings I’ve posted over the years into one reference. For each substance I’ve kept my actual reasoning, condensed, with a one-line verdict at the bottom. Where the fuller story lives elsewhere, I link it.

Amphetamine / Low-Dose Stimulants

Amphetamine receives praise across much of reddit, but perhaps it isn’t warranted. There exists studies conducted in non-human primates using amphetamine that show long-lasting axonal damage, withdrawal and schizotypal behavior from low dose amphetamine. The result was a regional depletion of dopamine (30-47%) and neurotoxicity at dopaminergic axon terminals. While the significance of these effects compound with chronic use, it occurs even after a single dose and can last up to 2 years. These studies are the result of chronic use, but it disproves the notion that it is only occurs at high doses. Additionally, amphetamine impairs episodic memory and slows the rate of learning in healthy people.

This, among other things, completely invalidates use of amphetamine as a nootropic substance.

Methylphenidate (Ritalin) is less harmful than amphetamine, but since its relationship with dopamine is linear, it may still be toxic at higher doses. Bromantane and ALCAR deserve more investigation for their ability to produce dopaminergic effects even after discontinuation. More on the whole picture in Dopamine.

Verdict: Not a nootropic. Long-lasting neurotoxicity and withdrawal even at prescription doses.

Uridine

Uridine is sold as Uridine Monophosphate or Triacetyluridine. Many people use it to “upregulate dopamine” (like with Mr. Happy Stack) as it was shown to treat disorders frequently associated with malfunctioning dopamine networks. But we can all agree those are two vastly different contexts.

The carcinogenic action of Uridine is more potent in higher doses, sure, but it is a myth that Uridine isn’t a carcinogen at all doses. Instead of worsening cancer by inducing proliferation, it directly causes DNA damage. These data suggest that uridine homeostatic disorder leads to uracil DNA damage and that pharmacological uridine may be carcinogenic. The facts are that it is a direct carcinogen, albeit low grade, and this doesn’t require a dose threshold due to the mechanisms.

Uridine’s proposed dopamine upregulation can actually be attributed to it inhibiting dopamine release, making it a hormetic response. This effect was pronounced after chronic use and actually potentiated antipsychotics. GABA is most likely responsible for the inhibition of dopamine release. Uridine is a GABA modulator and definitely far from the “dopamine upregulator” it’s portrayed as. So besides Uridine being GABAergic, that has to be part of Nootropic Depot’s motivation to include it in the sleep support stack. In order for a substance to be labeled a “dopamine upregulator”, its effects must persist after discontinuation. Uridine is solidified as an antidopaminergic substance.

The thing that sucks about uridine is that it is gabaergic, even if later on it is disproven to be carcinogenic. I just wouldn’t supplement uridine at all. See Dopamine for the dopamine side.

Verdict: A low-grade direct carcinogen and a GABAergic that inhibits dopamine release. I wouldn’t supplement it at all.

9-Me-BC (9-Methyl-β-carboline)

Years after the introduction of this compound to the nootropics community, there is still no evidence it’s safe. Not even in rodent models. The debate about its proposed conversion to a neurotoxin is controversial, but the idea that it “upregulates dopamine” or “upregulates dopamine receptors” is not, nor is it founded on science. Its ability to inhibit MAO-A and MAO-B is most likely soley responsible for its dopaminergic effects. It’s a neurogenic with MAOI properties, and that would basically explain the anecdotes. But receptor upregulation and sensitization is up for debate. Additionally, I ran it through predictive analysis software, and it was flagged as a potential carcinogen on both ADMETlab and ProTox.

Verdict: No safety data, even in rodents. Flagged as a potential carcinogen. The “dopamine upregulation” claim is unfounded.

Selegiline

Selegiline is often misconceived as solely inhibiting the conversion of dopamine to DOPAL, which in an ideal scenario would simultaneously reduce neurotoxicity and raise dopamine. But more recent data shows Selegiline acting primarily a catecholamine release enhancer, and that BPAP (another CAE) extends lifespan even more. This points to dopamine promoting longevity, not reduced DOPAL. Additionally, MAO-A was found to be responsible for the degradation of dopamine, not MAO-B. Tolerance forms to this effect, which is why patients ultimately resort to L-Dopa treatment. Selegiline has been linked to withdrawal but not addiction.

This reflects negatively on Selegiline being used as a neuroprotective agent. Given this, it would appear that the catecholaldehyde hypothesis lacks proof of concept. More in Dopamine.

Verdict: A failed approach to neuroprotection. Tolerance forms; the neuroprotective rationale doesn’t hold up.

L-Tyrosine / L-Phenylalanine / DLPA

L-Tyrosine and L-Phenylalanine experience a rate-limited conversion to L-Dopa by tyrosine hydroxylase. L-Dopa freely converts to dopamine but L-Tyrosine does not freely convert to L-Dopa. Increased tyrosine concentrations beyond a healthy dietary intake does not result in much more dopamine under normal circumstances. TH is highly regulatory and is only activated as needed. Statistically, the American diet is sufficient in tyrosine. Supplementation with L-Tyrosine or L-Phenylalanine is only effective in a deficiency, and the likelihood of having one is slim. Excess of these amino acids can not only decrease dopamine, but produce oxidative stress. This makes their classification as nootropics unlikely.

I still believe L-Tyrosine, L-Phenylalanine and DLPA are useless for dopamine biosynthesis. Enkephalin inhibits Tyrosine Hydroxylase, and adding more of the building block means nothing if you don’t upregulate this enzyme. Their benefits to stimulant comedown may be explained by stimulants suppressing appetite. See Dopamine.

Verdict: Useless for dopamine biosynthesis in healthy people. Adding building blocks does nothing when the enzyme is rate-limited.

Sulbutiamine

Your idea of dopamine receptor upregulation may be wrong. So many things are said to “upregulate dopamine receptors”, but what does that truly mean? Usually receptor upregulation just hints at temporarily lowered neurotransmitter causing increased sensitivity to maintain homeostasis. So keep that in mind when discussing Uridine. Or Sulbutiamine. L-Tyrosine, Sulbutiamine and Uridine are unnecessary.

Verdict: Unnecessary. The “receptor upregulation” it’s sold on usually just means the neurotransmitter was temporarily lowered.

Tianeptine

In humans, a single dose of tianeptine (12.5 mg) results in ~1 μM maximal concentration of the drug in the plasma. The in vivo concentration range appears sufficient for the activation of MOR, whereas activation of DOR may only become relevant with higher dosing. This dispels the rumors about Tianeptine being somehow unique in its mechanism. It’s just an opioid.

It clearly has withdrawal and I’m starting to believe the low doses would have addiction as well. How does it have a unique mechanism when everything presented just suggests MOR agonism? And if it’s a MOR agonist how would this not lead to significant withdrawal and addiction? It doesn’t make sense that it would be devoid of the same issues as other opioids. I’m not sure if evading respiratory depression is enough incentive to rationalize using an opioid drug. I’d go for agmatine sulfate, bromantane, D serine and ALCAR before bothering with an opioid. For the non-opioid path, see Mood Beyond SSRIs.

Verdict: It’s just an opioid. Withdrawal and likely addiction even at low doses.

Kratom

Kratom is still highly addictive, it’s just unlikely to cause fatality, which is perhaps its only aspect of rationalization. As someone who has been through it with Kratom, I strongly advise anyone considering it to stay far away. I would avoid completely. I’ve had far better results with nootropics. Even 8g/day was a nightmare. Also it’s funny they say it’s like coffee when coffee contains opioid receptor antagonists whereas kratom does the opposite. It shows how manipulative they are to get people hooked.

Worth naming the vendors too: selling and popularizing kratom, getting people addicted to shit they’d probably otherwise ignore on a shop publicly thought to be for nootropics. Overcharging customers. For the non-opioid path to mood, see Mood Beyond SSRIs.

Verdict: Highly addictive. Stay far away. Its only point of “rationalization” is that it’s unlikely to kill you.

MK-677

In terms of appetite stimulants, MK-677 can cause severe pancreatic insulin insensitivity, edema, tachyphylaxis and other longevity-related harm associated with elevated HGH. In fact, MK-677 has one clinical trial that needed to be terminated after multiple people nearly suffered congestive heart failure. It’s our hope that people eventually stop selling and consuming MK-677. The vast majority of weight-gain related effects in some people are simply due to its role as an appetite stimulant; it’s already shown that the HGH-stimulation builds a rapid tolerance.

HGH-related growth is incredibly non-selective. In one study MK-677 didn’t improve muscular strength or function and somehow reduced the lean:fat mass ratio in limbs. The amount of HGH increase by it is actually pretty minimal, and it rapidly builds tolerance. So I don’t really agree with the purported uses of MK-677 as a bodybuilding drug. More on building tissue properly in Anabolism.

Verdict: A trial was terminated over near congestive heart failure. The anabolic case is weak and tolerance is rapid. Stop consuming it.

Magnesium L-Threonate (Magtein)

For a while I have advocated against using Magnesium L-Threonate due to L-Threonate facilitating supraphysiological brain levels of Magnesium through enhancing its transport across the BBB, which could easily saturate the synapse causing preferential accumulation outside of that domain and antagonism of extrasynaptic NMDA. While this may be good in the context of excitotoxicity and can cause rapid synaptogenesis, extrasynaptic NMDA are required for stress resilience and adaptation, and antagonizing them may increase susceptibility to social defeat. This raises concerns about someone’s mental stability and social performance while using Magtein (and Memantine, which is also an eNMDA-biased NMDA antagonist). By not trying to bypass the BBB’s limitations of Magnesium penetration, Magnesium can be allowed to play a more constructive role in memory guidance and the fine tuning of memories.

Verdict: Saturating the brain with magnesium antagonizes extrasynaptic NMDA, which you need for stress resilience. I advocate against it.

Pitolisant

I tried pitolisant and it gave me awful reactions, felt like crap, definitely not energized and couldn’t sleep through it. I also redact my proposal of pitolisant as a cognitive enhancer because after looking into it more, not only are positive results mixed but H3 antagonists actually impaired cognition in higher performing individuals.

Verdict: I retract my old recommendation. Mixed results, and H3 antagonists impaired cognition in higher performers.

Oral ALCAR (the TMAO caveat)

I still recommend ALCAR, but the oral route has a real pitfall worth stating here. Acetyl-L-Carnitine has a poor oral bioavailability of just 2.1-2.4%. Injecting ALCAR solves its greatest pitfalls, that being poor absorption and its high metabolism into TMAO caused by its disassembly into L-Carnitine in the gut. On the surface the danger of TMAO may seem debatable, but upon deeper inspection, is a legitimate problem.

This is a “know what you’re taking” caution, not a ban. The full story, including the acetyl-donation mechanism and the case for Magnesium Acetate, lives in The Acetyl Story.

Verdict: Not a ban. Oral ALCAR absorbs poorly and converts to TMAO in the gut; read The Acetyl Story before choosing your acetyl source.

Shilajit → Iodine Interaction

This one is a “do this if you use it” caution, not a ban. Fulvic acid, the nootropic and testosterone-boosting component of shilajit, can cause greatly enhanced excretion of iodine. This may result in a deficiency over time, which can greatly reduce IQ in children or impair thyroid in adults which may also be detrimental towards cognition. It’s unclear if iodized salt is truly enough to prevent such a radical change. Therefore I suggest using an iodine supplement alongside it.

Verdict: Fine to use, but it depletes iodine. Pair shilajit with an iodine supplement.

Sources

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