4-AcO-DMT is not an explicitly controlled substance anywhere in the world as of 2023.[2][1] However, it may technically be a controlled substance under laws throughout the world like the United States'sFederal Analogue Act due to its close structural similarity to psilocybin and psilocin.[1][4] Hence, sale and use of 4-AcO-DMT as arecreational drug exists in a legal grey area.[4][1]
Claims of subjective differences in effects between the acetylated and non-acetylated forms of psilocin vary: some users report that 4-AcO-DMT lasts slightly longer, whilst others report that it lasts for a considerably shorter time.[14][better source needed] Many users report lessbody load and nausea compared with psilocin.[5] Some users find that the visual effects produced by 4-AcO-DMT more closely resemble those produced byDMT than those produced by psilocin or psilocybin. Despite the preceding reports however, there have been no controlled clinical studies to distinguish the subjective effects of psilacetin, psilocin, and psilocybin.
There are noclinical studies of thepharmacokinetics of 4-AcO-DMT as of 2024.[2] However, thepharmacokinetics of 4-AcO-DMT have been studied in rodents.[2] The drug was confirmed to act as aprodrug ofpsilocin similarly topsilocybin (4-PO-DMT).[2] However, given byintraperitoneal injection atequimolar doses, 4-AcO-DMT showed only 70% of therelative bioavailability ortotal exposure of psilocybin.[2] Hence, 4-AcO-DMT results in modestly lower psilocin levels than psilocybin even when the drugs are given at equivalent doses with adjustment for differences inmolecular weight.[2] Along similar lines, the psilocin concentrations with 4-AcO-DMT 15minutes after administration were 75 to 90% of those of an equimolar dose of psilocybin.[2] Theelimination half-life of psilocin was approximately 30minutes and did not differ between 4-AcO-DMT and psilocybin.[2] Psilocinester prodrugs like 4-AcO-DMT arecleaved into psilocin byesteraseenzymes.[17]
A 2025in-vitro study examined the stability and metabolism of several psilocin ester prodrugs, including 4-AcO-DMT.[18] The results showed that 4-AcO-DMT was rapidly broken down into psilocin by esterase enzymes, with over 99.9% of the prodrug converted within 5minutes under conditions mimicking the human body (i.e., in human plasma).[18] These findings support the idea that 4-AcO-DMT is quickly and efficiently converted into psilocin before it enters the bloodstream, and that the prodrug itself likely contributes little to the overall pharmacological effect.[18]
4-AcO-DMT can be obtained byacetylation of psilocin underalkaline or stronglyacidic conditions. It is, therefore, asynthetic compound. 4-AcO-DMT is more resistant than psilocin to oxidation under basic conditions due to its acetoxy group. It is not as difficult as psilocybin to synthesize.
Given enough time in unfavorable conditions, 4-AcO-DMT can sometimes turn into a degraded form which is brown in color and can even progress into a brown/black tar-like substance. Researchers hypothesize this is a polymerization reaction and is said to have no effect on thepotency of the substance. PreliminaryGCMS analysis of the closely relatedhomologue4-AcO-DET suggests that this degraded form of 4-AcO-DMT consists mainly of the hydroxy form of the parent molecule.[19]
4-AcO-DMT and several other esters of psilocin werepatented on January 16, 1963, bySandoz Ltd viaAlbert Hofmann and Franz Troxler.[20][21] Despite this, psilacetin remains a psychedelic compound with a limited history of use. It is theorized to be aprodrug of psilocin, as is psilocybin, which occurs naturally in many species of psychedelic mushrooms. This is because the aromatic acetyl moiety on the 4th position of the indole ring system is subject to deacetylation in acidic conditions such as those found in the stomach.[22] Psilacetin isO-acetylated psilocin, whereas psilocybin isO-phosphorylated.
4-AcO-DMT can be considered an analog ofpsilocin making it a Schedule 9 prohibited substance in Australia under thePoisons Standard (October 2015).[23] A Schedule 9 substance is a substance which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities.[23]
4-AcO-DMT is ambiguously legal for use as a lab reagent or research chemical; however, it is an acetate ester of psilocin, meaning it would be considered akin to a Schedule I Controlled Substance under theFederal Analogue Act if sold for human consumption.
4-AcO-DMT is listed (often under 4-Aco-DMT) as a controlled substance at the state level in multiple states in the USA, includingAlabama which has made it a schedule I at the state level on March 18, 2014, along with several other tryptamine analogs.[24]
The Riksdag added 4-AcO-DMT toNarcotic Drugs Punishments Act underswedish schedule I ("substances, plant materials and fungi which normally do not have medical use" ) as of January 25, 2017, published byMedical Products Agency (MPA) in regulationHSLF-FS 2017:1 listed as "4-acetoxi-N,N-dimetyltryptamin".[27]
^abcdefghijklmGeiger HA, Wurst MG, Daniels RN (October 2018)."DARK Classics in Chemical Neuroscience: Psilocybin"(PDF).ACS Chem Neurosci.9 (10):2438–2447.doi:10.1021/acschemneuro.8b00186.PMID29956917.A chemically modified psilocin precursor, known as psilacetin (20), O-acetylpsilocin, or 4-acetoxy-N,N-dimethyltryptamine, which replaces the phosphoryloxy group found on psilocybin with an acetoxy group, is also readily available. The substituted acetoxy group is believed to be metabolized in an equivalent manner to the phosphoryloxy group, both producing psilocin during first-pass metabolism.37 This simple modification skirts written laws in the United States when the product is clearly designated "not for human consumption," allowing pseudolegal import and possession for research purposes only; however, if it were to be used in vivo, the user would be in violation of the Federal Analogue Act.38 Although psilacetin has been hypothesized to act as an identical pharmacological substitute for psilocybin, many users report a small, yet significant, difference in the effects of each drug.39 Psilacetin is often described as having a faster onset of action without the anxiety and nausea associated with psilocybin-containing mushroom ingestion (which could be due to avoiding the ingestion of the significant amounts of chitin usually found in these mushrooms) and to have a shorter duration of action with a more peaceful experience throughout, leaving most users with a positive afterglow.37,39
^abcdefPalamar JJ, Acosta P (January 2020)."A qualitative descriptive analysis of effects of psychedelic phenethylamines and tryptamines".Human Psychopharmacology.35 (1): e2719.doi:10.1002/hup.2719.PMC6995261.PMID31909513.4-AcO-DMT (4-acetoxyN,N-dimethyltryptamine, O-acetylpsilocin, or psilacetin) was the most prevalent tryptamine reported with 30.8% of the sample reporting use and two thirds (66.7%) of tryptamine users reporting use. 4-AcO-DMT—often pronounced as "4-akko-DMT"—was reported by most users as producing similar effects as psilocybin mushrooms with less nausea. One participant referred to this compound as "silly pills," which is a play on the name psilocybin. This particular compound was often preferred over natural mushrooms due to the lack of adverse side effects such as nausea, which the natural mushroom tends to produce. Thus, participants often suggested that 4-AcODMT allows one to achieve the same high as psilocybin without adverse physical effects such as nausea and heavy body load. One participant did complain of dry mouth and mentioned that although 4-AcO-DMT feels similar to psilocybin, he said it lacks the "organic" feel produced by psilocybin. [...] Of the most common tryptamines used by this sample, the majority of these compounds were first discovered or first synthesized as early as the 1930s (e.g., 5-MeO-DMT), 1950s (e.g., 4-AcO-DMT), or in the 1970s (e.g., 4-HO-MET and 5-MeO-DIPT). [...] 4-AcO-DMT was the most commonly used tryptamine by participants, and this compound also appears to be among the most prevalent novel tryptamines in recent years (Palamar & Le, 2019; PalmaConesa et al., 2017). [...] 4-AcO-DMT is often described as having a faster onset of action than psilocybin with a high of shorter duration, and as many of our participants noted, use allows them to avoid the nausea commonly associated mushroom ingestion (Geiger et al., 2018). Despite 4-AcO-DMT being among the most prevalent tryptamines, and having been discovered in the 1950s, little academic research has focused on recreational use of this compound.
^ab"Poisons Standard October 2015".Federal Register of Legislation. Australian Government. 30 September 2015.Archived from the original on 2016-01-19. Retrieved2016-01-06.
Notes: (1) TAAR1 activity of ligands varies significantly between species. Some agents that are TAAR1 ligands in some species are not in other species. This navbox includes all TAAR1 ligands regardless of species. (2) See the individual pages for references, as well as theList of trace amines,TAAR, andTAAR1 pages.See also:Receptor/signaling modulators
