4-Acetoxy-''N'',''N''-dimethyltryptamine (4-AcO-DMT or 4-acetoxy-DMT), also known as ''O''-acetylpsilocin or psilacetin, is a psychedelic

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

of the

tryptamine Tryptamine is an indolamine metabolite of the essential amino acid tryptophan. The chemical structure is defined by an indole—a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the firs ...

family related to

psilocybin Psilocybin, also known as 4-phosphoryloxy-''N'',''N''-dimethyltryptamine (4-PO-DMT), is a natural product, naturally occurring tryptamine alkaloid and Investigational New Drug, investigational drug found in more than List of psilocybin mushroom ...

and

psilocin Psilocin, also known as 4-hydroxy-''N'',''N''-dimethyltryptamine (4-HO-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic. It is present in most psychedelic mushrooms together with its phosphorylated counterpart psilocy ...

. It is a synthetic

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

of psilocin (4-HO-DMT) in which the

hydroxyl group In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...

has been acetylated, and is the analogue of psilocybin (4-PO-DMT) in which the

phosphate Phosphates are the naturally occurring form of the element phosphorus. In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthop ...

ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

has been replaced with an acetate

. The drug is a

prodrug A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be ...

of psilocin and is orally active similarly to psilocybin. As a prodrug of psilocin, 4-AcO-DMT acts as a non-selective serotonin receptor agonist, including of the

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

5-HT_2A receptor. The

hallucinogen Hallucinogens, also known as psychedelics, entheogens, or historically as psychotomimetics, are a large and diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mo ...

ic effects of psilocin are thought to be mediated by activation of this receptor, although other

receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...

s also contribute to its effects. 4-AcO-DMT's effects are reported to be similar to those of psilocybin and

psilocybin mushroom Psilocybin mushrooms, or psilocybin-containing mushrooms, commonly known as magic mushrooms or as shrooms, are a type of hallucinogenic mushroom and a polyphyletic informal group of fungi that contain the prodrug psilocybin, which turns into t ...

s. However, it has been said to have reduced

side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s such as

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

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 Safety is the state of being protected from harm or other danger. Safety can also refer to the control of recognized hazards in order to achieve an acceptable level of risk. Meanings The word 'safety' entered the English language in the 1 ...

. 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 A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an sufficiency of disclosure, enabling discl ...

by Albert Hofmann in 1963 and its

chemical synthesis Chemical synthesis (chemical combination) is the artificial execution of chemical reactions to obtain one or several products. This occurs by physical and chemical manipulations usually involving one or more reactions. In modern laboratory uses ...

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 The scientific method is an empirical method for acquiring knowledge that has been referred to while doing science since at least the 17th century. Historically, it was developed through the centuries from the ancient and medieval world. The ...

, 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 A designer drug is a structural or functional analog of a controlled substance that has been designed to mimic the pharmacological effects of the original drug, while avoiding classification as illegal and/or detection in standard drug tests. ...

Europe Europe is a continent located entirely in the Northern Hemisphere and mostly in the Eastern Hemisphere. It is bordered by the Arctic Ocean to the north, the Atlantic Ocean to the west, the Mediterranean Sea to the south, and Asia to the east ...

in 2009. It became increasingly prevalent as a

recreational drug Recreational drug use is the use of one or more psychoactive drugs to induce an altered state of consciousness, either for pleasure or for some other casual purpose or pastime. When a psychoactive drug enters the user's body, it induces an Sub ...

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 The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

as an alternative to psilocybin. Relatedly, it has sometimes been referred to as "synthetic shrooms". Mushrooms edibles may contain 4-AcO-DMT, ''

Amanita muscaria ''Amanita muscaria'', commonly known as the fly agaric or fly amanita, is a basidiomycete fungus of the genus ''Amanita''. It is a large white-lamella (mycology), gilled, white-spotted mushroom typically featuring a bright red cap covered with ...

'' mushroom constituents, or non-mushroom drugs such as bath salts, and have been linked to

poisoning Poisoning is the harmful effect which occurs when Toxicity, toxic substances are introduced into the body. The term "poisoning" is a derivative of poison, a term describing any chemical substance that may harm or kill a living organism upon ...

s and deaths. 4-AcO-DMT is not scheduled under United States law or any international drug schedules, including the

United Nations The United Nations (UN) is the Earth, global intergovernmental organization established by the signing of the Charter of the United Nations, UN Charter on 26 June 1945 with the stated purpose of maintaining international peace and internationa ...

1971

Convention on Psychotropic Substances The Convention on Psychotropic Substances of 1971 is a United Nations treaty designed to control psychoactive drugs such as amphetamine-type stimulants, barbiturates, benzodiazepines, and psychedelics signed in Vienna, Austria on 21 February ...

, 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.

Effects

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. Many users report less body load and nausea compared with psilocin. Some users find that the visual effects produced by 4-AcO-DMT more closely resemble those produced by DMT 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.

Interactions

Pharmacology

Pharmacodynamics

4-AcO-DMT is a

(4-HO-DMT). As a prodrug of psilocin, 4-AcO-DMT acts as a non-selective

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

serotonin receptor 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in multiple tissues including the central and peripheral nervous systems. They mediate both ex ...

s, including of the

5-HT_2A receptor. The psychedelic effects of 4-AcO-DMT are mediated specifically by activation of the serotonin 5-HT_2A receptor. Similarly to

, psilocin, and other

serotonergic psychedelic Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic halluci ...

s, 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 Hypothermia is defined as a body core temperature below in humans. Symptoms depend on the temperature. In mild hypothermia, there is shivering and mental confusion. In moderate hypothermia, shivering stops and confusion increases. In severe ...

in rodents as with psilocin as well.

Pharmacokinetics

There are no

clinical studies Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

of the

pharmacokinetics Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific su ...

of 4-AcO-DMT as of 2024. However, the

of 4-AcO-DMT have been studied in rodents. The drug was confirmed to act as a

similarly to

(4-PO-DMT). 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 A molecule is a group of two or more atoms that are held together by Force, attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemi ...

. 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 Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. ...

of psilocin was approximately 30minutes and did not differ between 4-AcO-DMT and psilocybin. Psilocin

prodrugs like 4-AcO-DMT are cleaved into psilocin by

esterase In biochemistry, an esterase is a class of enzyme that splits esters into an acid and an alcohol in a chemical reaction with water called hydrolysis (and as such, it is a type of hydrolase). A wide range of different esterases exist that differ ...

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

s. 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 (i.e., in human plasma). 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.

Chemistry

4-AcO-DMT can be obtained by

acetylation : In chemistry, acetylation is an organic esterification reaction with acetic acid. It introduces an acetyl group into a chemical compound. Such compounds are termed ''acetate esters'' or simply ''acetates''. Deacetylation is the opposite react ...

of psilocin under

alkaline In chemistry, an alkali (; from the Arabic word , ) is a basic salt of an alkali metal or an alkaline earth metal. An alkali can also be defined as a base that dissolves in water. A solution of a soluble base has a pH greater than 7.0. The ...

or strongly

acid An acid is a molecule or ion capable of either donating a proton (i.e. Hydron, hydrogen cation, H+), known as a Brønsted–Lowry acid–base theory, Brønsted–Lowry acid, or forming a covalent bond with an electron pair, known as a Lewis ...

ic conditions. It is, therefore, a synthetic 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 the potency of the substance. Preliminary GCMS analysis of the closely related homologue 4-AcO-DET suggests that this degraded form of 4-AcO-DMT consists mainly of the hydroxy form of the parent molecule. 4-AcO-DMT is a lower homologue of 4-AcO-MET, 4-AcO-DET, 4-AcO-MiPT and 4-AcO-DiPT. Other analogues of 4-AcO-DMT include 4-AcO-DPT, 4-MeO-DMT, and

4-PrO-DMT 4-Propionoxy-''N,N''-dimethyltryptamine (4-PrO-DMT, or O-Propionylpsilocin) is a synthetic psychedelic drug from the tryptamine family with psychedelic effects, and is believed to act as a prodrug for psilocin. It produces a head-twitch response ...

(''O''-propionylpsilocin).

History

4-AcO-DMT and several other esters of psilocin were

ed on January 16, 1963, by Sandoz Ltd via Albert Hofmann and Franz Troxler. Despite this, psilacetin remains a psychedelic compound with a limited history of use. It is theorized to be a

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. Psilacetin is ''O''-acetylated psilocin, whereas psilocybin is ''O''-phosphorylated.

Society and culture

Legal status

International law

4-AcO-DMT is not scheduled under any international drug schedules, including the

1971

, making it a potentially more accessible alternative to psilocybin for research.

Australia

4-AcO-DMT can be considered an analog of

making it a Schedule 9 prohibited substance in Australia under the Poisons Standard (October 2015). 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.

United States

In the United States, psilacetin can be legally sold and possessed when labeled as “not for human consumption” and intended solely for research purposes. However, its use in humans is prohibited under the Federal Analogue Act, as it is considered a controlled substance analogue of psilocybin. The Controlled Substance Analogue Enforcement Act of 1986 (of which the Federal Analogue Act is part) criminalized the creation of

designer drugs A designer drug is a structural or functional analog of a controlled substance that has been designed to mimic the pharmacological effects of the original drug, while avoiding classification as illegal and/or detection in standard drug tests. ...

. As such, it is illegal in the United States. 4-AcO-DMT is listed (often under 4-Aco-DMT) as a controlled substance at the state level in multiple states in the USA, including

Alabama Alabama ( ) is a U.S. state, state in the Southeastern United States, Southeastern and Deep South, Deep Southern regions of the United States. It borders Tennessee to the north, Georgia (U.S. state), Georgia to the east, Florida and the Gu ...

which has made it a schedule I at the state level on March 18, 2014, along with several other tryptamine analogs.

United Kingdom

4-AcO-DMT, being an ester of psilocin, is a Class A drug in the UK under the Misuse of Drugs Act 1971.

Czech Republic

4-AcO-DMT is prohibited in Czech republic except strictly limited research and therapeutical purposes.

Italy

4-AcO-DMT is illegal in Italy as it is an

of a prohibited substance.

Sweden

The Riksdag added 4-AcO-DMT to Narcotic Drugs Punishments Act under ''swedish schedule I'' (''"substances, plant materials and fungi which normally do not have medical use"'' ) as of January 25, 2017, published by Medical Products Agency (MPA) in regulation ''HSLF-FS 2017:1'' listed as "4-acetoxi-''N'',''N''-dimetyltryptamin".

Israel

4-AcO-DMT is technically illegal in Israel as of being a derivative of DMT.

Germany

4-AcO-DMT is banned according to the BtMG since it's an ester of psilocin.

References

External links

4-AcO-DMT - Isomer Design

4-AcO-DMT - PsychonautWiki

4-Acetoxy-DMT - Erowid

The State of the Art of Psilacetin (4-AcO-DMT) - Psychedelic Science Review

The Complete Guide to 4-AcO-DMT: Synthetic Shrooms or in a Class of Its Own? - Double Blind Magazine

4-AcO-DMT Is the Most Accessible (and Mysterious) Drug on the Market Right Now - Double Blind Magazine

4-AcO-DMT: The Ultimate Guide to Synthetic Shrooms - Tripsitter

What is 4-AcO-DMT? Understanding The Synthetic Psilocybin Analog - ACS Laboratory
{{DEFAULTSORT:Acetylpsilocin, ''O''- 5-HT1A agonists 5-HT1B agonists 5-HT2A agonists 5-HT2B agonists 5-HT2C agonists Acetate esters 4-Acyloxytryptamines Designer drugs N,N-Dialkyltryptamines Dimethylamino compounds Entheogens Experimental hallucinogens Partial monoamine releasing agents Prodrugs Psychedelic tryptamines Serotonin receptor agonists Serotonin releasing agents TAAR1 agonists