THE SCIENCE OF 4-ACO-DMT MICRODOSING
4-AcO-DMT is also known as O-Acetylpsilocin; that is, the O-acetylated form or ester of psilocin (4-HO-DMT) – psilocybin (4-PO-DMT) being the O-phosphorylated form. In other words, 4-AcO-DMT has the same basic structure as both psilocin and psilocybin, but with an acetoxy group bonded to its indole ring.
Like psilocybin, 4-AcO-DMT is considered a prodrug of psilocin, converting into the latter through metabolism by the body. Pharmacologist David Nichols even went so far as to advocate its replacement of psilocybin in psilocin research, since 4-AcO-DMT is by far the easier ester to synthesize.
The prodrug theory is not without its critics, however. According to some, the immediate psychoactivity of 4-AcO-DMT when injected or smoked (i.e. when bypassing the metabolism), as well as its higher average dose than psilocin, suggests the compound is uniquely psychoactive in its own right and not just, or even necessarily, as a metabolic precursor to psilocin.
There are subjective differences too. While some consider the effects of 4-AcO-DMT to be identical to those of psilocybin mushrooms, others point out differences. They may find it mellower, more forgiving, or less ego-disruptive than mushrooms, while some even liken it to DMT, especially at high doses.
Still, it’s important to note that naturally occurring levels of psilocybin and psilocin vary significantly even between mushrooms of the same species, so no two experiences are likely to be the same. They also tend to be accompanied by other alkaloids, such as baeocystin and norbaeocystin, which have presumed effects of their own. 4-AcO-DMT, meanwhile, has no such variability, so it ensures greater consistency for microdosing at least, even if its subjective effects are different from psilocybin mushrooms.
Given its chemical similarities to psilocin, though, we can safely assume that 4-AcO-DMT has roughly the same mechanism of action – primarily activating the 5-HT2A serotonin receptors.
Much of what we understand about how psychedelics work involves serotonin, a chemical that keeps our brains ticking. It is one of the most important neurotransmitters, affecting nearly everything we do – from how we feel to how we process information.
Indeed, much like other classical psychedelics (including LSD), psilocybin, psilocin, and 4-AcO-DMT actually share a similar molecular structure to serotonin. So while SSRI (selective serotonin reuptake inhibitor) antidepressants work to alleviate low mood by increasing serotonin levels in the brain, 4-AcO-DMT would be expected to work more directly by actually mimicking serotonin itself, and stimulating serotonin receptors.
The stimulation of the 5-HT2A receptor in particular has two very important results:
- The production of “Brain Derived Neurotrophic Factor” (BDNF). BDNF is “like Miracle-Gro for your brain. It stimulates growth, connections, and activity.”
- The increased transmission of “Glutamate.” Glutamate is the neurotransmitter most responsible for brain functions like cognition, learning, and memory.
Glutamate and BDNF work together in ways we’re still investigating, but it has become clear that having more of each leads to many of the benefits we seek from microdosing.
Another thing the classical psychedelics are capable of doing is causing parts of the brain that wouldn’t usually communicate with one another… to communicate with one another!
Psychedelics facilitate these unique connections by dampening the activity of an often-overused part of our brain called the “Default Mode Network” (DMN). The DMN features in a range of mental activities, including daydreaming, self-reflection, and thinking about the past or future. And some studies suggest depression may be linked to an overactive DMN, possibly causing us to ruminate, over-analyze or criticize ourselves, and continually step out of the present moment to fret about the past or the future.
This helps to explain the remarkable efficacy of psilocin and related substances in the treatment of depression and anxiety, with some patients even reporting lasting (six months+) relief from a single high dose of psilocybin. It could also help to explain how the use of these substances can lead to creative insights and perspectives that otherwise remain inaccessible.
HOW DO YOU MICRODOSE WITH 4-ACO-DMT?
Usually sold in powder form, 4-AcO-DMT can be taken orally or intranasally, among other methods. But for microdosing, oral administration seems to be the most obvious choice – if only for ease and simplicity. Be warned, though: it tastes pretty foul.
When measuring out doses, keep in mind that just a few milligrams more or less can lead to profoundly different effects. Going by anecdotal reports, effective microdoses range between 0.5 mg and 5 mg (although 5 mg may be too much for most people, producing a noticeable come-up, difficulties focusing, and scattered thoughts in general). 1 mg seems a reasonable microdose to start with, to be adjusted up or down as required on subsequent occasions. But since most affordable scales (such as the Gemini-20) are incapable of accurately weighing such tiny amounts, volumetric microdosing is probably your best bet.
It’s also worth noting that the precise concentration of your 4-AcO-DMT powder will depend on whether it’s in the form of a fumarate or hydrochloride (HCl) salt. Every 1.24 mg fumarate, for example, is expected to contain 1 mg 4-AcO-DMT, while the equivalent amount in HCl would be 1.15 mg for 1 mg 4-AcO-DMT.
Microdosing 4-AcO-DMT Volumetrically
A good way to keep your microdoses consistent is to dissolve a known amount of 4-AcO-DMT in a liquid solution and take proportionate amounts of that. If you dissolve 50 mg 4-AcO-DMT in 50 ml alcohol, for instance, then 1 ml of the solution will contain a reliable 1 mg of the substance – and this dose can be adjusted up or down in accordance with concentration, as well as squirted into the mouth, with a blunt 1-2 ml syringe.
To prepare a 4-AcO-DMT solution for microdosing:
- Weigh out 50 mg 4-AcO-DMT on an accurate milligram scale
- Add to a sterile amber glass (or opaque, e.g. foil-wrapped) bottle of 50 ml ethanol/ethyl alcohol or vodka
- Seal and shake the bottle, then leave to stand overnight
- Store in the freezer
- 4-AcO-DMT should last for up to two years if stored in ethanol at -20° C (-4°F)
It is possible to use distilled water as a solvent instead, but it will degrade the 4-AcO-DMT more rapidly. This is especially true if you keep thawing and refreezing it between each dose, although a potential workaround could be to freeze individual microdoses separately in syringes.
Regardless of the choice of solvent, though, 4-AcO-DMT will generally last longer when it’s dry. For this reason, it’s best to prepare only small batches of the solution at once – perhaps no more than 10 mg at a time or enough to last a few weeks, depending on your microdose schedule. 
A more novel, and much less talked about, method of microdosing is to rub 4-AcO-DMT directly into the skin. For this, you’ll need to dissolve it in food grade propylene glycol to ensure efficient delivery into the bloodstream. One user discovered this method accidentally while preparing a solution for vaping; they mixed 100 mg 4-AcO-DMT in 3 ml propylene glycol and rubbed two to three drops into their neck after showering.
Keep in mind, however, that allergic reactions to propylene glycol are not uncommon and symptoms include dryness, itchiness, swelling, rashes, and burning sensations. To minimize the risk, sample a small amount first and wait two or three days for symptoms to appear, discontinuing use if they do or maybe trying a vegetable glycerin instead.
What Schedule Should I Follow?
Dr. James Fadiman, author of The Psychedelic Explorer’s Guide, suggests microdosing no more than once every three days. That means taking a microdose on Day 1 and Day 4 from whenever you start your schedule, but not on Day 2 or Day 3.
You should observe the effects throughout this process and, ideally, keep notes in a daily journal. Be sure to include both short-term, in-the-moment effects and long-term changes to your mood, energy, and social behavior. And be especially observant on the two days between microdoses, since this is when many people report increased feelings of flow, creativity, and energy.
In line with Fadiman’s protocol, the process of microdosing twice per week should continue for several weeks. But you should otherwise follow your daily routine. Don’t change what you do. The purpose is to enhance, not replace, your day-to-day existence by integrating microdoses into it.
That said, when you first try microdosing it’s probably a good idea to take the day off work and avoid any social commitments as well as operating motor vehicles. This will give you a chance to observe any unusual effects and gauge their suitability for you before microdosing in a more public situation.
Microdosing 4-AcO-DMT every day is not recommended. Psychedelics generally produce a tolerance effect, even at microdoses, so you’re likely to see diminishing returns after just a few days of doing so. This can be likened to the use of coffee for productivity purposes. If you drink coffee every day, you’ll find you need to continually increase the dose to get the same effect, and one cup of coffee turns into two or three or four cups within a few months. This is exactly why Dr. Fadiman suggests taking a couple of days off between each microdose.
Safety is another reason to avoid microdosing every day. Although research is limited, there is a potential heart risk associated with frequent psychedelic use over a long period of time. And while we don’t know how this translates to microdosing, it’s always best to err on the side of caution and stick to Fadiman’s protocol – and even then for no more than a few months at a time.