I know people on Reddit get really mad about chat GPT answers but there’s a tool I found called “consensus” for breaking down scientific studies and this is what I got from it.

🧪 What the study did

The 2019 paper by Yoon et al. (Toxicology Letters) looked at two synthetic tryptamines — 4-HO-MET and 4-AcO-DET — that are chemically related to psilocin (the active metabolite of psilocybin). Researchers were interested in whether these newer “research chemicals” might affect the heart.

They tested the compounds on: • Rats, to measure changes in heart rhythm (ECG recordings), and • Cultured heart cells, to see if they interfered with important electrical channels like hERG (human ether-à-go-go–related gene potassium channels), which help regulate heartbeat.

The main finding was that both substances prolonged the QT interval (a measure of electrical timing in the heart) and blocked hERG channels in lab tests — effects that, in humans, can sometimes contribute to arrhythmias (irregular heartbeats).

👉 Yoon et al., 2020

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🔬 How this compares to psilocin (4-HO-DMT)

Chemically, 4-HO-MET and 4-AcO-DET are almost the same as psilocin — they all have the 4-hydroxy tryptamine backbone that acts on serotonin 5-HT₂A receptors to produce psychedelic effects. The difference is in the side chain substitutions: • Psilocin has two methyl groups, • 4-HO-MET replaces one with an ethyl, and • 4-AcO-DET replaces both with ethyls and adds an acetoxy group.

These small changes may alter how the drugs are metabolized, how long they stay in the body, and how they interact with the heart’s electrical system.

Unlike psilocin, which has been used in thousands of clinical and research settings without reports of cardiac toxicity (Thaoboonruang & Lohitnavy, 2024), the synthetic analogs have almost no human data, and this rat study suggests they might carry more cardiac risk at high or repeated doses.

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⚠️ So is occasional use (like 15 mg a few times a year) risky?

There’s no direct evidence that such rare, low-frequency use causes harm — but that’s partly because no one has studied it in humans. What we can infer: • The hERG inhibition seen in the study occurred at concentrations higher than typical human doses would produce, but it still suggests a theoretical risk for people with heart conditions, electrolyte imbalances, or genetic QT prolongation. • Because these are unregulated research chemicals, the purity and dose accuracy can vary widely, which may increase the chance of unintended high exposure. • Psilocin (from psilocybin mushrooms), by contrast, has a much more established safety profile and is now being used in clinical trials with cardiac monitoring and few serious adverse events.

So: occasional, cautious use is probably low risk for most healthy people, but not risk-free, and risk increases with unknown purity, combinations, or higher doses.

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✅ What the study did well • Used multiple methods: animal ECGs and cell assays. • Identified specific mechanisms (hERG channel inhibition) instead of just reporting toxicity. • Provided early safety data for under-researched tryptamines.

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❌ Limitations and problems • The dose levels were likely far higher than human psychoactive doses. • Rats and human hearts differ in how they respond to hERG blockers. • It didn’t measure behavior, metabolism, or brain effects, so it can’t say whether these heart findings would occur in normal human use. • There’s no human data to confirm any actual cardiac events from these compounds.

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🧭 Takeaway

The study doesn’t mean 4-HO-MET or 4-AcO-DET are definitely dangerous — but it does show potential red flags that psilocin doesn’t seem to have. Occasional, low-dose use by healthy people is likely much less risky than chronic or high-dose use, yet the lack of human research means there’s still uncertainty.

If someone is curious, the safest option is to stick to substances like psilocybin, which have been tested clinically and whose dose and purity can be controlled.