4-AcO-DMT
4-Acetoxy-N,''N-dimethyltryptamine, also known as O''-acetylpsilocin or psilacetin, is a psychedelic drug of the tryptamine family related to psilocybin and psilocin. It is a synthetic derivative of psilocin in which the hydroxyl group has been acetylated, and is the analogue of psilocybin in which the phosphate ester has been replaced with an acetate ester. The drug is a prodrug of psilocin and is used orally similarly to psilocybin.
As a prodrug of psilocin, 4-AcO-DMT acts as a non-selective serotonin receptor agonist, including of the serotonin 5-HT2A receptor. The hallucinogenic effects of psilocin are thought to be mediated by activation of this receptor, although other receptors also contribute to its effects. 4-AcO-DMT's effects are reported to be similar to those of psilocybin and psilocybin mushrooms. However, it has been said to have reduced side effects such as nausea and body load that can be caused by ingestion of whole psilocybin mushrooms. It is also said to have a faster onset and shorter duration than psilocybin. The drug is not expected to differ from psilocybin or psilocin in terms of safety. 4-AcO-DMT is modestly less potent by weight than psilocybin in animals when they are given at equimolar doses.
4-AcO-DMT was first described in a patent by Albert Hofmann in 1963 and its chemical synthesis was improved by David E. Nichols and colleagues in 1999. It was suggested by Nichols as a more economical and accessible alternative to psilocybin for use in scientific research, as the synthesis of psilocybin is more challenging and as psilocybin is a controlled substance. 4-AcO-DMT was first detected as a designer drug in Europe in 2009. It became increasingly prevalent as a recreational drug in the 2010s and has been the most commonly used novel tryptamine. In the 2020s, 4-AcO-DMT became widely encountered in the form of mushroom edibles in the United States as an alternative to psilocybin. Relatedly, it has sometimes been referred to as "synthetic shrooms". Mushrooms edibles may contain 4-AcO-DMT, Amanita muscaria mushroom constituents, or non-mushroom drugs such as bath salts, and have been linked to poisonings and deaths.
4-AcO-DMT is not scheduled under United States law or any international drug schedules, including the United Nations 1971 Convention on Psychotropic Substances, making it a potentially more accessible alternative to psilocybin for research. It can be imported and possessed for research in the United States if labeled “not for human consumption,” but using it in vivo is illegal and violates the Federal Analogue Act.
Use and effects
In his book TiHKAL, Alexander Shulgin lists the same dose range of 10 to 20 mgorally and duration of 3 to 6hours for psilocin, psilocybin, and 4-AcO-DMT. Another publication gave a 4-AcO-DMT dose range of 10 to 15mg orally, with a typical dose of 12.5mg orally, and a duration of about 5 to 8hours. A further source gave a dose range for the drug of 5 to 30mg orally, an onset of 15 to 40minutes, and a duration of 4 to 7hours. 4-AcO-DMT is a prodrug of psilocin similarly to psilocybin and its effects are reported to be similar or identical to those of psilocybin and psilocybin-containing mushrooms. However, it is said to produce less nausea and body load than psilocybin-containing mushrooms. The drug is also often described as having a faster onset and shorter duration than psilocybin. 4-AcO-DMT is modestly less potent by weight than psilocybin in animals when they are given at equimolar doses.Specific effects of 4-AcO-DMT have been reported to include psychedelic visuals, closed-eye imagery, synesthesia, insights, disembodiment, euphoria, feelings of bliss and unity, oceanic boundlessness, ego dissolution, sedation, cognitive impairment, and spiritual experiences, among others. Adverse effects have been reported to include psychological side effects such as anxiety, paranoia, and low mood as well as gastrointestinal side effects such as nausea and vomiting.
Contraindications
Side effects
4-AcO-DMT, as a prodrug of psilocin, is not expected to differ from psilocybin or psilocin in terms of safety.Interactions
Pharmacology
Pharmacodynamics
4-AcO-DMT is a prodrug of psilocin. As a prodrug of psilocin, 4-AcO-DMT acts as a non-selective agonist of serotonin receptors, including of the serotonin 5-HT2A receptor. The psychedelic effects of 4-AcO-DMT are mediated specifically by activation of the serotonin 5-HT2A receptor.Similarly to psilocybin, psilocin, and other serotonergic psychedelics, 4-AcO-DMT produces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents. In addition, like psilocybin and other psychedelics, 4-AcO-DMT fully substitutes for the psychedelic DOM in rodent drug discrimination tests. 4-AcO-DMT produces effects such as hypolocomotion and hypothermia in rodents as with psilocin as well.
Pharmacokinetics
There are no clinical studies of the pharmacokinetics of 4-AcO-DMT as of 2024. However, the pharmacokinetics of 4-AcO-DMT have been studied in rodents. The drug was confirmed to act as a prodrug of psilocin similarly to psilocybin. However, given by intraperitoneal injection at equimolar doses, 4-AcO-DMT showed only 70% of the relative bioavailability or total exposure of psilocybin. 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 in molecular weight. 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. The elimination half-life of psilocin was approximately 30minutes and did not differ between 4-AcO-DMT and psilocybin. Psilocin ester prodrugs like 4-AcO-DMT are cleaved into psilocin by esterase enzymes.A 2025 in-vitro study examined the stability and metabolism of several psilocin ester prodrugs, including 4-AcO-DMT. 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. 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.