The molecule Psilacetin (aka 4-AcO-DMT or O-Acetylpsilocin) is a synthetic psilocybin derivative. Like psilocybin, psilacetin serves as a prodrug of psilocin, which is the primary active molecule responsible for the psychedelic effects of magic mushrooms.

As illustrated in the figure below, each of (A) Psilacetin and (B) Psilocybin is readily converted into psilocin under biological conditions. (Note: the figure refers to Psilacetin as O-Acetylpsilocin; the nomenclature is explained below). Equivalent molar amounts of Psilacetin probably produce psychoactive effects that are equivalent to psilocybin. In other words, each of psilacetin and psilocybin serves as a means for administering psilocin. They are both prodrugs of psilocin. Given the molecular weight difference between the compounds, Psilacetin is probably more potent on a gram-for-gram basis.

Psilacetin has a formula weight of 246.3 grams per mole

Psilocybin has a formula weight of 284.2 grams per mole

Assuming equal amounts and equivalent biological conversion of the two substances, psilacetin provides 1.15x of the active drug (psilocin) compared to psilocybin.

Pure psilocybin is currently the only molecule used for scientific research on magic mushroom pharmacology. COMPASS pathways made headlines by developing a (patented) method for making pure psilocybin. But, despite recent efforts to optimize its production, psilocybin is still very expensive. See Cost of Psilocybin. Even after receiving permission to study this schedule-1 molecule, scientists wishing to do so must pay about $7,000-$10,000 per gram.

Psilocybin is heralded as “the” single active ingredient in magic mushrooms. (Not true). As a result, it receives virtually all of the mainstream media attention while the other (known) psilocybin derivatives remain virtually ignored. Psilocybin is also the focus of most regulatory efforts, making psilocybin unquestionably illegal and also extremely difficult to acquire.

Chemical Nomenclature – Psilacetin, 4-AcO-DMT, and Psilacetin all Refer to the Same Molecule.

Psilacetin is also called 4-AcO-DMT or O-Acetylpsilocin.

4-AcO-DMT refers to the molecule DMT (dimethyltryptamine) with an acetoxy group in the 4-position of the tryptamine core. Note, that psilocybin has a phosphate group at this 4-position.

O-Acetylpsilocin refers to the molecule psilocin (see image above) with an acetyl group on the phenol moiety of psilocin.

All of these names simply represent different ways of naming the same molecule.

Opportunities for Research using Psilacetin

The above facts about psilocybin and Psilacetin raise some interesting questions and opportunities for future research.

Psilacetin can be easily converted into psilocin under laboratory conditions. Can we use Psilacetin as a convenient means for generating an otherwise unstable, difficult to attain, and hard to work with molecule from an easy to acquire and handle starting material? Clinically, Psilacetin provides a much less expensive means for administering psilocin to a subject. As a drug, Psilacetin can be considered more or less equivalent to psilocybin. Can we study the clinical effects of Psilacetin, using the lessons learned from psilocybin as a starting point? Psilacetin can be used to provide a simple an inexpensive means for generating pure psilocybin. Were there a particular benefit to psilocybin (over Psilacetin) the former could be easily made from the later by (1) converting Psilacetin into psilocin and then (2) making the phosphate ester of the resulting phenolic group. Here, it seems improbable that pure psilocybin would provided any benefit over Psilacetin — but this could easily depend on the context, e.g., formulating conditions. Because of its widespread availability of Psilacetin on the grey market, the community has much more information about the clinical effects of pure Psilacetin versus pure psilocybin. Could we crowdsource studies on Psilacetin in a manner similar to what we’ve seen in the cannabis industry? Combining pints 2 and 5 above, the community probably has the ability to compare the effects of a pure psilocin prodrug (Psilacetin, psilocybin, or others) versus magic mushrooms. Many anecdotal reports suggest that different species of magic mushrooms produce different kinds of psychoactivity. That observation suggests that the psychoactivity of magic mushrooms is not solely a function of psilocin (which is generated from psilocybin upon consuming magic mushrooms). Accordingly, the scientific community’s focus on pure psilocybin may fail to appreciate the synergistic effects created by the multiple active ingredients in magic mushrooms. (Early attempts to westernizer cannabis also made this mistake before discovering that pure THC was far inferior to the cocktail of activity molecules contained in the cannabis plant. Like cannabis pharmacology, the multiple active ingredients in magic mushrooms work together synergistically to produce the user’s experience. See Analogy between Cannabis and Mushrooms; See also Entourage Effect.) Presently, both psilacetin and psilocybin are considered equivalent means for administering psilocin. Both are believed to be inert prodrugs of psilocin, i.e., they provide psilocin as an active metabolite. As much as psilacetin and psilocybin have in common, they are still different molecules. Accordingly, they will have at least some different properties. Future development could focus on the differences between pure psilacetin versus psilocybin with an eye towards identifying potentially advantageous differences.

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