Artsy Shot: A psychedelic mushroom formation.
This text is for educational and harm reduction purposes only. It is not a recommendation, solicitation, or instruction – especially not for consumption. For new research chemicals, it is especially true that: The data is scarce, the risks are real, and the legal situation is dynamic.
Executive Summary
4-PrO-MET is an innovative research chemical that is chemically and experientially described as rather mild, friendly, and approachable compared to other psychedelics. It has become a more frequent topic of discussion among psychonauts and is available in various assortments from research chemical suppliers. This is a good reason to take a closer look at 4-PrO-MET.
☝🏻 Disclaimer: Please be sure to observe our risk warnings.
What are Tryptamine Compounds?
4-PrO-MET belongs to the tryptamine family. Well-known tryptamines include serotonin, the so-called "happiness hormone," or melatonin, an endogenous hormone that regulates the sleep cycle in humans. Tryptamines like 4-PrO-MET are very similar to the basic form of serotonin. By mimicking this neurotransmitter and binding to 5HT2A receptors (as well as 5HT1A receptors), i.e., serotonin receptors, tryptamines modulate the brain's signaling pathways. This leads to profound changes in consciousness and sensory perception, which are by no means sufficiently researched yet (but certainly known to some readers here).
Incidentally, the first designer tryptamine was αMT (α-Methyltryptamine), which probably existed since the 1920s. The pharmaceutical company Upjohn synthesized αMT in the 1960s as an antidepressant. However, after clinical trials, Upjohn discontinued its distribution.
4-PrO-MET is similar to the molecule 4-HO-MET (Metocin). Chemist Alexander Shulgin first discovered and synthesized Metocin in the 1970s. 4-HO-MET, in turn, is closely related to the classic Psilocin, the main active ingredient in magic mushrooms.
Like all synthetic (but also naturally occurring) tryptamines, 4-PrO-MET is threatened by illegalization. Whether we are talking about magic mushrooms, ayahuasca, iboga, or 5-MeO-DMT: prohibition tries to get its foot (or at least a toe) in the door.
If you are interested, we would like to delve into the sociology and criminology of "moral panic" (Stanley Cohen) and the construction of "outsiders" (Howard S. Becker) from time to time in the future. For at least the last 100 years, the persecution of certain minorities and subcultures has been accompanied by the stigmatization of substances and their use. Please leave us a comment here!
Natural Tryptamines
Most designer tryptamines were inspired by naturally occurring plants, fungi, and animals. Ayahuasca, for example, the classic psychedelic substance of indigenous South Americans, is a mixture of the two plants Banisteriopsis Caapi (which contains MAO inhibitors that make DMT orally active) and Psychotria Viridis (which contains DMT). Fungi such as Psilocybe Cubensis or Psilocybe Semilanceata produce, as we have already mentioned, the tryptamines psilocybin and baeocystin. The Bufo Alvarius toad, often licked in various comics and series, in turn produces tryptamines such as 5-MeO-DMT (and in small amounts bufotenin) in poison glands on its back.
4-PrO-MET and the Psilocybin Connection: The Chemical Background
Structurally, 4-PrO-MET is closely related to psilocin (4-HO-DMT). Psilocin is the product of world-famous psilocybin. It is formed after the dephosphorylation of psilocybin. This means that psilocybin and psilocin are also DMT derivatives. They dock directly to serotonin receptors in the brain. This is primarily (but not solely!) responsible for the typical psychedelic effect.
It has been proven that psilocybin poorly crosses the blood-brain barrier. It is therefore dephosphorylated in the body by phosphatases: 4-phosphoryloxy-N,N-dimethyltryptamine, psilocybin, becomes 4-HO-DMT, psilocin. Psilocybin is therefore a so-called prodrug: a substance that must first be converted before it takes effect in the body. [1]
It is assumed that the process is analogous for 4-PrO-MET: The propionyl group of 4-PrO-MET is cleaved by enzymes in the body. What would remain then would be 4-HO-MET, the metocin first discovered by Alexander Shulgin. 4-PrO-MET is thus (in all probability) the precursor of 4-HO-MET. 4-PrO-MET then consequently (to put it somewhat simply) relates to 4-HO-MET (metocin) as 4-PO-DMT (psilocybin) relates to 4-HO-DMT (psilocin). However, the effect remains similar for now: both bind to the same receptors due to their close chemical relationship.
By the way: The acronym DMT stands for dimethyltryptamine. The amine is substituted with two methyl groups (CH₃). Chemists can now experiment with this amine to develop completely new molecules. This has long been done, for example, with 4-MeO-DMT, 5-MeO-MiPT, 5-Bromo-DMT, 4-AcO-MET, 5-Fluoro-DMT, 5-MEO-NMT, and many others.
What does research report?
Currently, there are no studies on the mechanism of action of 4-PrO-MET that have undergone peer review and/or been published in specialist journals. So we will have to wait a little longer for truly robust results. We must work with what research has found out about structurally similar substances so far:
A study published in Pharmacology & Translational Science by Grant C. Glatfelter et al. from 2023 (DOI: 10.1021/acsptsci.2c00222), for example, confirms, among other things, the finding that 4-PO-DMT, i.e., psilocybin, docks to serotonin receptors. In addition, an effect on α-adrenergic receptors, i.e., receptors of the noradrenaline system (e.g., responsible for blood pressure), dopamine (responsible for motivation, i.e., psychomotor drive), and histamine receptors (which, for example, regulate wakefulness) was also found. The effect of psilocybin, to summarize somewhat crudely, is neurologically complex.
Although it is reasonable to assume similar or perhaps even identical modes of action between psilocybin/psilocin and 4-PrO-MET/metocin due to their close chemical relationship, empirical confirmation has not yet been obtained, as far as we know.
Can statements still be made about the effect?
Strong psychedelics such as 5-MeO-DMT and N,N-DMT generally lead to subjectively profound experiences. Many describe them as almost out-of-body. More intense psychedelic experiences can induce a subjective state that appears as a temporary dissolution of the self; as a so-called ego death. Milder psychedelics such as the many psilocin prodrugs or the aforementioned αMT can also have profound introspective effects, but they less often or less quickly lead to such ego dissolution.
Based on the experience reports published so far and the existing research on the mechanism of action of psilocybin and psilocin, it can be reasonably assumed that 4-PrO-MET is a relatively mild psychedelic substance. Of course, further research and a keen eye are needed to more precisely determine its mechanisms of action and possible uses. As with all substances, the paradox holds true that an open-minded but 'sober' (and not 'morally panicking') approach to 4-PrO-MET is the best prerequisite for being able to broaden one's horizons beyond the sobering everyday.
Footnotes:
[1] 4-PrO-MET differs from psilocybin in two structural details. The first difference concerns the substitution at the amine nitrogen: while psilocybin carries two methyl groups (N,N-dimethyl) there, 4-PrO-MET has one methyl and one ethyl group (N-methyl-N-ethyl). This is a difference of only a single carbon atom. For precisely this reason, the substance is called MET (methylethyltryptamine) and not DMT (dimethyltryptamine).
The second difference concerns the functional group at position 4 of the indole ring. In 4-PrO-MET, a propionyl group is bound there. This is an ester (a compound in which an acid is 'docked' to a molecule) of three carbon atoms. In psilocybin, on the other hand, a phosphoryloxy group (O-PO₃H₂), i.e., a phosphate ester of phosphorus, oxygen, and hydrogen, is located at the same position. These two groups are fundamentally different structurally and explain, among other things, why the two substances differ in their bioavailability.
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