# 2,5-Dimethoxy-4-methylamphetamine

2,5-Dimethoxy-4-methylamphetamine (DOM), also known as STP (standing for "Serenity, Tranquility, and Peace" and/or other phrases), is a psychedelic drug of the phenethylamine, amphetamine, and DOx families. It is generally taken orally.
DOM was first synthesized by Alexander Shulgin, and later described in his book PiHKAL: A Chemical Love Story (1991). It is classified as a Schedule I controlled substance in the United States, and is similarly controlled in other parts of the world. Internationally, it is a Schedule I drug under the Convention on Psychotropic Substances.

## Effects

Effects of this drug include substantial perceptual changes such as blurred vision, multiple images, vibration of objects, visual alterations, distorted shapes, enhancement of details, slowed passage of time, increased sexual drive and pleasure, and increased contrasts. It may cause mystical experiences and changes in consciousness. It may also cause pupillary dilation and a rise in systolic blood pressure.
The effects of DOM were assessed in clinical studies in the late 1960s and early 1970s and by other researchers. At low doses, such as 1 to 4 mg, DOM produces effects including stimulation, euphoria, enhanced self-awareness, and mild dose-dependent perceptual disturbances. At higher doses, of above 5 to 7 mg, DOM produces psychedelic effects.

## Side effects

Very little is known about the toxicity of DOM.

## Pharmacology
### Pharmacodynamics
#### Actions

DOM activities :
| Target | Affinity (K$_i$, nM) |
| 5-HT$_{1A}$ | 3,656–14,200 (K$_i$) 12,800–13,900 (EC$_{50}$Tooltip half-maximal effective concentration) 54–74% (E$_{max}$Tooltip maximal efficacy) |
| 5-HT$_{1B}$ | >10,000 |
| 5-HT$_{1D}$ | 209 |
| 5-HT$_{1E}$ | 3,542 |
| 5-HT$_{1F}$ | ND |
| 5-HT$_{2A}$ | 2.1–507 (K$_i$) 1.1–40 (EC$_{50}$) 44–132% (E$_{max}$) |
| 5-HT$_{2B}$ | 12–41 (K$_i$) 128–145 (EC$_{50}$) 85% (E$_{max}$) |
| 5-HT$_{2C}$ | 19–3,980 (K$_i$) 0.23–423 (EC$_{50}$) 81–119% (E$_{max}$) |
| 5-HT$_3$ | >10,000 |
| 5-HT$_4$ | ND |
| 5-HT$_{5A}$ | >10,000 |
| 5-HT$_6$ | 8,155 |
| 5-HT$_7$ | 1,591 |
| α$_{1A}$ | 3,219 |
| α$_{1B}$ | >10,000 |
| α$_{1D}$ | ND |
| α$_{2A}$ | 580 |
| α$_{2B}$ | 874 |
| α$_{2C}$ | 921 |
| β$_1$ | >10,000 |
| β$_2$ | 49 |
| D$_1$–D$_5$ | >10,000 |
| H$_1$–H$_4$ | >10,000 |
| M$_1$, M$_2$, M$_5$ | >10,000 |
| M$_3$, M$_4$ | ND |
| TAAR$_1$ | >10,000 (EC$_{50}$) |
| I$_1$ | >10,000 |
| σ$_1$, σ$_2$ | >10,000 |
| SERTTooltip Serotonin transporter | >100,000 (K$_i$) >100,000 (IC$_{50}$Tooltip half-maximal inhibitory concentration) >100,000 (EC$_{50}$) |
| NETTooltip Norepinephrine transporter | >100,000 (K$_i$) >70,000 (IC$_{50}$) >100,000 (EC$_{50}$) |
| DATTooltip Dopamine transporter | >100,000 (K$_i$) 64,000 (IC$_{50}$) >42,000 (EC$_{50}$) |
| MAO-ATooltip Monoamine oxidase A | 24,000 (IC$_{50}$) (rat) |
| MAO-BTooltip Monoamine oxidase B | >100,000 (IC$_{50}$) (rat) |
| Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: ||
DOM acts as a selective serotonin 5-HT$_{2A}$, 5-HT$_{2B}$, and 5-HT$_{2C}$ receptor full agonist. Its psychedelic effects are mediated by its agonistic properties at the 5-HT$_{2A}$ receptor. Due to its selectivity, DOM is often used in scientific research in studies of the 5-HT$_2$ receptor subfamily. DOM is a chiral molecule, and R-(−)-DOM is the more active enantiomer, functioning as a potent agonist of these receptors.
The drug is inactive as a human trace amine-associated receptor 1 (TAAR1) agonist but is an agonist of the rhesus monkey TAAR1. DOM is inactive as a monoamine reuptake inhibitor and releasing agent. It is a very weak monoamine oxidase inhibitor (MAOI), specifically of monoamine oxidase A (MAO-A), whereas it was inactive at monoamine oxidase B (MAO-B).

#### Effects

In contrast to amphetamines like (–)-cathinone but similarly to mescaline, DOM has shown no stimulant-like or reinforcing effects in rhesus monkeys. Conversely however, DOC has shown reinforcing effects, including conditioned place preference (CPP) and self-administration, in rodents similarly to methamphetamine. This is analogous to other findings in which various 2C and NBOMe drugs have been found to produce dopaminergic elevations and reinforcing effects in rodents.

### Pharmacokinetics

According to Alexander Shulgin, the effects of DOM typically last 14 to 20 hours, though other clinical trials indicate a duration of 7 to 8 hours.

## Chemistry

DOM, also known as 2,5-dimethoxy-4-methylamphetamine or as 2,5-dimethoxy-4-methyl-α-methylphenethylamine, is a substituted phenethylamine and amphetamine and is a member of the DOx group of drugs. It is structurally related to the naturally occurring phenethylamine psychedelic mescaline (3,4,5-trimethoxyphenethylamine). Analogues of DOM include other DOx drugs such as DOET, DOB, DOI, DOC, and TMA, among others. The α-desmethyl or phenethylamine analogue of DOM is 2C-D. Ariadne is the α-ethyl or phenylisobutylamine analogue of DOM.
The 2,6-dimethoxy positional isomer of DOM, known as Ψ-DOM, is also mentioned in PiHKAL as being active, as is the α-ethyl homologue Ariadne. Analogues where the methoxy groups at the 2,5- positions of the aromatic ring have been altered have also been synthesised and tested as part of an effort to identify the binding mode of DOM at the serotonin 5-HT$_{2A}$ receptor. Both the 2- and 5- O-desmethyl derivatives 2-DM-DOM and 5-DM-DOM, and the 2- and 5- ethyl analogues 2-Et-DOM and 5-Et-DOM, have been tested, but in all cases were significantly less potent than the corresponding methoxy compound, showing the importance of the oxygen lone pairs in 5-HT$_{2A}$ binding.

## History

STP was first synthesized and tested in 1963 by Alexander Shulgin, who was investigating the effect of 4-position substitutions on psychedelic amphetamines.
In mid-1967, tablets containing 20 mg (later 10 mg) of STP were widely distributed in the Haight-Ashbury District of San Francisco under the name of STP, having been manufactured by underground chemists Owsley Stanley and Tim Scully. This short-lived appearance of STP on the black market proved disastrous for several reasons. First, the tablets contained an excessively high dose of the chemical. This, combined with DOM's slow onset of action (which encouraged some users, familiar with drugs that have quicker onsets, such as LSD, to re-dose) and its remarkably long duration, caused many users to panic and sent some to the emergency room. Second, treatment of such overdoses was complicated by the fact that no one at the time knew that the tablets called STP were, in fact, DOM, and there was no effective antidote.

## Society and culture
### Legal status
#### Australia

DOM is schedule 9 under the Australia Poisons standard. A schedule 9 substance is a "Substances 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."

#### Canada

Listed as a Schedule 1, as it is an analogue of amphetamine.

#### United Kingdom

DOM is a Class A drug in the United Kingdom under the Misuse of Drugs Act 1971.

#### United States

DOM is Schedule I in the United States. This means it is illegal to manufacture, buy, possess, or distribute (make, trade, own or give) without a DEA license.