The Ultimate Guide to Microdosing

4-AcO-DMT

Microdosing is the act of consuming sub-perceptual (unnoticeable) amounts of a psychedelic substance. Many individuals who have integrated microdosing 4-Acetoxy-N,N-dimethyltryptamine (psilacetin or 4-AcO-DMT) into their weekly routine report higher levels of creativity, more energy, increased focus, and improved relational skills, as well as reduced symptoms of depression. Some enthusiasts also report that microdosing 4-AcO-DMT has helped them heighten their spiritual awareness and enhance their senses.

4-AcO-DMT is a synthetic psychedelic tryptamine with close structural similarities to the “magic mushroom” molecules psilocybin and psilocin.

It was developed by the inventor of LSD, Albert Hofmann—along with Franz Troxler—for Sandoz Ltd., the company that patented the drug in 1963 (incidentally the same year their LSD patents expired). ^[1]

Of the many “grey market” research chemicals out there, 4-AcO-DMT is probably among the safest. At macrodoses, its effects are comparable – although in some ways rather different – to those of psilocybin or psilocin. Most users report a full range of psychedelic visual effects, from color enhancement to vivid hallucinations, along with euphoria, ego loss, and mystical or religious experiences.

How to 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 can lead to profoundly different effects.^[2] Going off of anecdotal reports, effective microdoses range between 0.5 mg and 5 mg, though 5 mg may be too much for most people—that much could produce a noticeable come-up, difficulty focusing, and scattered thoughts in general. ^[3][4][5] 1 mg is a good place to start, knowing that it may be adjusted up or down as required on subsequent occasions. ^[6][7] 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. ^[8]

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) ^[9]

It is possible to use distilled water as a solvent instead, but it will degrade the 4-AcO-DMT faster. 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. ^[10]

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. ^[11]

Topical Microdosing

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. ^[12]

Keep in mind, however, that allergic reactions to propylene glycol are not uncommon and symptoms include dryness, itchiness, swelling, rashes, and burning sensations. ^[13] To minimize the risk, sample a small amount first and wait two or three days for symptoms to appear, discontinuing use if they do. You can also try a vegetable glycerin instead.

What schedule should I follow?

As with dosage, timing should be a matter of preference and one’s individual response. Experts in this area suggest different microdosing regimens, but our microdosing course follows James Fadiman’s system. Fadiman recommends taking a microdose once every three days: Take a microdose on Day 1. Then, do not take a microdose on Day 2 or Day 3. On Day 4, take another microdose.

Continue this process for several weeks.

For most people, morning is the best time because the beneficial effects will last throughout the day without interfering with sleep. It’s also helpful to take daily notes in a journal to observe the effects throughout this process and adjust accordingly—or just notice the positive changes.

It’s also important to follow your usual routine while microdosing. The purpose is to enhance your day-to-day existence by integrating microdoses into your routine, so don’t change what you normally do. However, when you try microdosing for the first time, take a day off from work and social commitments. This will give you a chance to notice any unusual effects before microdosing in a more public situation.

While it may seem like you would only feel the effects of the microdose on the days you actually take it, try to observe the effect on the two days between doses, too. Many people perceive increased feelings of flow, creativity, and energy the day after they microdose in addition to the day of microdosing.

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. Microdosing everyday also brings up safety concerns. 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.

Pharmacology

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. ^[14]

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. ^[15]

There are subjective differences too. While some consider the effects of 4-AcO-DMT to be identical to those of psilocybin mushrooms, others find it mellower, more forgiving, or less ego-disruptive than mushrooms. ^[16][17]

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. Mushrooms also tend to be accompanied by other alkaloids, such as baeocystin and norbaeocystin, which have presumed effects of their own. ^[18][19][20] 4-AcO-DMT doesn’t have the same 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.

The science of microdosing

While there has been some recent research on microdosing, we know a lot more about what large doses of psychedelics do to the brain.

Much of what we understand about how psychedelics work involves serotonin, a chemical that is among the brain’s most important neurotransmitters. Serotonin affects nearly everything we do, from how we feel to how we process information. It keeps our brains ticking.

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.” ^[21]
• The increased transmission of “Glutamate.” Glutamate is the neurotransmitter most responsible for brain functions like cognition, learning, and memory. ^[22]

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. ^[23]

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). ^[24]

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, ^[25] 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, ^[26][27] with some patients even reporting lasting (six months+) relief from a single high dose of psilocybin. ^[28] It could also help to explain how the use of these substances can lead to creative insights and perspectives that otherwise remain inaccessible.

Potential Benefits

The immediate effects of microdosing 4-AcO-DMT should last no more than six hours, but some experience secondary benefits for a couple of days after. ^[29][30] It’s to experience increased sociability as well as a gentle stimulant effect— although some find it more sedating, suggesting that it may not be ideal for productivity. ^[20][30][31] One user preferred to take 1.5-2.5 mg before sleep (with 1 mg melatonin) with the intention of feeling after-effects the next day. ^[32]

One the other hand, some might find this sedative effect beneficial, especially if they are prone to stress. As one user put it: “I was not in the zone [while microdosing 4-AcO-DMT at work] by any stretch of the imagination. But I also was not absent minded or forgetful.” There was “a feeling of peace and joy and willingness to get my work done at a reasonable pace while still feeling as if I got enough done.” ^[33]

Nevertheless, many people report enhanced mental clarity, focus, and better-structured thoughts when microdosing 4-AcO-DMT, and find it easier to grasp complex concepts. ^[30][34] Visual clarity may also be enhanced, along with the perception of colors, and some find themselves unusually engrossed in creative tasks. ^[30][35] Others have remarked on positive lifestyle changes while microdosing, such as eating healthier food. ^[30]

Depressed or anxious users tend to notice a significant mood lift and anxiolytic effect that lasts for days after the initial euphoria. ^[31][34][36] Microdosing 4-AcO-DMT is also thought to help to wean people off prescribed medications (under the supervision of a medical professional), many of which are potentially dangerous and highly addictive. ^[30]

Risks

There are some potential downsides to microdosing 4-AcO-DMT, though. Higher doses may be linked to blackouts, vomiting, and even seizures, while even microdoses can lead to nausea.^[37][38]

The safety of 4-AcO-DMT has never been studied in detail, but its chemical similarities to psilocybin and psilocin suggest the risks are likely comparable. For the same reason, it is physically non-addictive and unlikely to be habit-forming. Even so, there is the potential for heart problems or cardiotoxicity. ^[39][40] One user who took a very high dose of 150 mg, for example, suffered from elevated blood pressure and weakness that lasted into the following day. ^[41] This dovetails with concerns about the long-term use of any serotonergic psychedelic—although we don’t know if these concerns are justified when it comes to microdosing.

As always, it is up to the individual to weigh the potential risks and benefits of microdosing 4-AcO-DMT. And while many prescribed medications are riskier, it should be approached with caution. This is especially true if you suffer from psychosis, seizures, schizophrenia, severe anxiety, and so on, since microdosing can lead to manic states that exacerbate underlying conditions.

Also avoid taking 4-AcO-DMT alongside other substances, especially tramadol, amphetamines, and cocaine. ^[30][42] It’s a good idea to avoid alcohol too; while some users feel more in control of their drunken behavior while microdosing 4-AcO-DMT, it reportedly increases alcohol intake. ^[43]

Depending on the reason you’re microdosing, you’ll need to prepare and integrate appropriately. Our extensive Microdosing Course will guide you through the various protocols for getting the most out of microdosing, specific to your needs.

Given that researchers are only just beginning to scratch the surface of the science of microdosing in general—even with the much-more-common LSD and psilocybin mushrooms—we’ll likely have to wait a while for 4-AcO-DMT-specific microdosing studies. Anecdotally, however, depressed and anxious individuals have reported a mood lift and emotional stability that lasts for days. Some have also used it to wean off dangerous and addictive pharmaceuticals.

Very little research around the therapeutic effects of 4-AcO-DMT in general, too, but the fact that it’s a more stable prodrug of psilocin than psilocybin (and one that’s more easily synthesized) means it could prove useful for clinical research.^[44] In one study, for example, it was used to test the hypothesis that 5-HT2A agonists can alleviate withdrawal symptoms and even prevent addictions from forming: opiate-dependent rodents given 4-AcO-DMT were effectively cured of their addiction, and rodents given a single dose of 4-AcO-DMT before being exposed to nicotine did not become addicted. How 4-AcO-DMT may be used to treat addiction in humans remains to be seen, but these results support neurobiological theories of dependence. ^[45]

The authors of this study also suggest that 4-AcO-DMT could be useful for treating depression and could offer substantially longer-lasting relief than drugs.^[45]

Anecdotal reports support these hypotheses. While prescribed antidepressants can have a “numbing” effect on people, 4-AcO-DMT is said to help resolve underlying emotional damage rather than push it away. Consider one man who was able to overcome his PTSD through just six trips, describing the compound as “life-changing.” His experience, he said, made him feel as though he was “unknotting scar tissue” and led him to rediscover his “inner confident self.” Another self-medicator—a victim of childhood abuse—said that she was not only able to work through her trauma with 4-AcO-DMT, but that the substance helped her move on with her life in a way that prescribed medications seemed to actively prevent.^[46] And yet another, frustrated with conventional antidepressants, credited 4-AcO-DMT with allowing him to “experience happiness and connection,” while also decreasing his reliance on alcohol.^[47]

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Microdosing 4-AcO-DMT is known to spur personal growth, while at the same time enhancing mental clarity, creativity, and flow.^[30][34] One user reported feeling “a sense of mental clarity comparable to a mild cup of coffee, as well as a general mood lift and sense of drive,” concluding that the experience is “focused, sexual, and analytical, and seems to be fairly anxiolytic as compared to other psychedelics.”^[48]

Gratitude, acceptance, trust, and letting go are some other common themes associated with this compound, albeit at higher doses. As one psychonaut put it, “whereas mushrooms operate in a part of the brain that could be considered about language or intellect, 4-AcO-DMT acts on the emotional thought processes.” By taking 4-AcO-DMT once every couple of months, he said, he was better able to manage his “warped” emotions.^[49]

It could also facilitate positive lifestyle changes. One self-experimenter, for example, decided to stop smoking weed every day and fulfill his untapped potential—a resolution made after a lengthy discussion with a surprisingly real-looking lion he took to be God.^[50]

Though a very different experience than microdosing, a full dose of 4-AcO-DMT can also be deeply healing and transformational. Trips with 4-AcO-DMT can unfold in many ways, but two common—and often life-changing—effects are a spiritual or mystical experience and renewed compassion for the people in one’s life.^[51][52] Openness with family is also a recurring theme. One person found 4-AcO-DMT’s ego-softening effect allowed him to have a long-overdue conversation with his brother about their mother’s death, finally telling him things that he “should have said much earlier.” He was also able to reconnect and “productively engage” with his father.^[53] Another self-medicator felt similarly empowered, coming to understand the “problematic tension” between himself and his father, which resulted in him resolving “to mend [their] fractured state.”^[54]

The 4-AcO-DMT experience is often compared to that of psilocybin, but with a more mellow, euphoric sensibility. At high doses, 4-AcO-DMT is known for its vivid visionary effects, but moderate doses produce a visual experience similar to psilocybin, with objects appearing to breathe and wave. Many people who have taken 4-AcO-DMT say that while it can be more intense than mushrooms, it’s also more predictable—which is why it’s also good for microdosing. ^{[55][56][57][51]}

A 4-AcO-DMT experience can last anywhere between two and eight hours. During the peak, people report experiencing feelings of euphoria, laughter, enhanced creativity and “flow,” introspective insights, an interest in usually mundane tasks, feelings of wonder and more.

Some people also experience an “additional layer” to reality, sometimes manifesting as an “energy field” around objects. Changes in perception of gravity or bodily sensations are also commonly reported. In addition to visual patterns, some people also experience “external” hallucinations, such as seemingly autonomous entities or spirits. At high doses, “ego-death” can occur, and many self-experimenters temporarily forget their own names. Like with many psychedelics, mystical-type experiences are also common, which could be beneficial to mental health. ^{[52][58][51][46]}

The legality of 4-AcO-DMT can be ambiguous. Although it’s federally unscheduled in the US, for instance, manufacturing, distributing, or possessing the compound for human consumption technically violates the Federal Analogue Act.^[59] But prosecutions are practically unheard of.

In the UK, however, as an ester of psilocin, it’s a Class A substance by default under the Misuse of Drugs Act 1971.^[60] Scandalously, this places 4-AcO-DMT in the same category as fentanyl, one of the most dangerous drugs known to humanity. It therefore potentially carries the harshest drug crime sentences. As a “psychoactive substance,” it’s also prohibited under the UK’s Psychoactive Substances Act 2016.^[61]

In Australia, the situation is much the same; as an ester of psilocin, 4-AcO-DMT is, by default, a strictly prohibited substance.^[62] The same is true in New Zealand and a number of European countries, including Germany and Italy. ^[63][51] In Sweden, 4-AcO-DMT was specifically singled out for prohibition in January 2017.^[64]

It does, however, remain perfectly legal in a number of other countries—including Canada, where many vendors are based. ^[65]

Brief history

4-AcO-DMT was first synthesized by Albert Hofmann—who famously discovered LSD—and his colleague Franz Troxler at Sandoz laboratories in Switzerland. It was patented by the company, along with a number of other indole esters, in 1963.^[66] But it wasn’t until the 1990s that we first saw 4-AcO-DMT for sale alongside various “research chemicals” and “designer drugs.”^[16]

The history of microdosing

While the modern history of psychedelics reaches back to the 1950s, interest in microdosing saw a major revitalization with the publishing of psychologist and psychedelic advocate Dr. James Fadiman’s book, The Psychedelic Explorer’s Guide: Safe, Therapeutic, and Sacred Journeys in 2011, which explores microdosing as a subculture of psychedelic use. While a number of indigenous cultures—as well as modern professionals—have used microdosing to unlock a host of personal benefits, Fadiman’s book formally introduced the term “microdosing” into the mainstream.

Beyond coining the term, The Psychedelic Explorer’s Guide awakened the curiosity and imaginations of millions of people and provided practical information for anyone interested in giving microdosing a try. Much of this information has been integrated into this guide.

Outside of the book, Fadiman’s ongoing research also serves as one of the few modern studies into the effects of microdosing specifically—most current psychedelic research looks at the effects of larger doses on specific therapeutic outcomes.

Following the publication of The Psychedelic Explorer’s Guide, the next boost in the public’s awareness of microdosing came from a podcast interview Fadiman gave with investor and author Tim Ferriss in March 2015. Ferriss, who rose to fame after authoring the bestseller, The 4-Hour Work Week, has an enormous audience of individuals interested in entrepreneurship, “biohacking,” self-experimentation, psychology, spirituality, and other subjects that predispose them to an interest in the benefits of microdosing. The interview boosted Fadiman’s core microdosing messages and created more mainstream interest in the practice: soon after its air date, Ferris fans began experimenting with microdosing and discussing it in their own personal networks. Journalists also jumped on board and began writing articles about microdosing, creating even greater awareness and interest.

Interest in microdosing got another boost when author Ayelet Waldman’s published her 2016 book, A Really Good Day: How Microdosing Made a Mega Difference in My Mood, My Marriage, and My Life, which tracked her 30-day protocol of microdosing LSD to her unstable moods caused by menopause. Before she started microdosing, Waldman says her mood swings had become severe enough to put her marriage and relationship with her children at risk. After the 30-day protocol, everything changed. “This month changed my life,” she said in an interview with Third Wave, “and I am sad every day that I can’t keep doing it legally.”

Mycologist and psilocybin-enthusiast Paul Stamets has also had a hand in pushing microdosing into the mainstream. One of the most reputable, decorated, and self-practiced mycologists in the world, Stamets has dedicated his life to the study of medicinal and psychedelic fungi. His most recent patent application is for a nootropic stack (a combination of cognitive enhancers) that contains a microdose of psilocybin, lions mane, and niacin. He would like to see this supplement available as a vitamin, claiming that its efficacy in epigenetic neurogenesis has the potential to initiate “the next quantum leap in human consciousness.”

Now, tens of thousands of people around the globe are experimenting with taking small doses of psychedelics in the name of mental health, creativity, and inspiration.

Can 4-AcO-DMT be detected in a drug test?

Psilocin is rarely screened for, so 4-AcO-DMT is unlikely to show up on a standard drug test. ^[67] Some types of extended drug tests (e.g. for criminal probation) are capable of detecting psilocin, but typically they’re only used when its presence is suspected.

According to Erowid, psilocin can remain in the system for several weeks, and in the urine specifically for up to one week.

Can I test my 4-AcO-DMT to see it it’s safe to take?

Testing your 4-AcO-DMT is always good practice even when you trust your supplier. Reagent test kits from Bunk Police can identify hundreds of adulterants and substitutes—offering peace of mind and potentially saving your life.

The Marquis, Mecke, and Mandelin reagents, for example, can help identify real 4-AcO-DMT. Simply place a tiny amount of 4-AcO-DMT into a sterile test tube or onto a sterile white ceramic surface and add a few drops of the reagent. Then check the color change (or lack thereof) against the supplied spectrum booklet.

Do I have real 4-AcO-DMT?

It’s unlikely you received anything else if you ordered through a reputable vendor, but research chemicals can and do get missold. Whether you trust a supplier or not, it’s always sensible to confirm the identity of a substance before trying it. Testing kits (available online) are far from perfect, since a number of chemicals produce matching results, but they’ll at least rule out the presence of 4-AcO-DMT if you’ve inadvertently bought something else.

Real 4-AcO-DMT should react like this to the Marquis, Mecke, and Mandelin reagents.

Where can I get 4-AcO-DMT?

If it’s legal where you live, 4-AcO-DMT can usually be purchased online. For help finding a legal supplier, click here.

As with many psychedelics, perhaps the greatest risk when it comes to microdosing 4-AcO-DMT is simply getting caught. Although it’s federally unscheduled in the U.S., a case could easily be made that 4-AcO-DMT is an analogue of psilocin and therefore illegal under the Federal Analogue Act. ^[68] In the UK, 4-AcO-DMT is illegal for much the same reason, as it has been since even before the Psychoactive Substances Act was brought in. ^[69] It remains perfectly legal in a number of other countries, however, including Canada, where many research chemical vendors are based.

Is microdosing 4-AcO-DMT illegal?

4-AcO-DMT falls into a bit of a legal gray area. In countries like the U.S., for instance, where it isn’t specifically prohibited, it may still be considered an illegal analogue of the scheduled substance psilocin.

Always research the legality of a substance before microdosing. And be aware that even if 4-AcO-DMT is legal in your area, since it degrades into psilocin over time it could rapidly become illegal in storage.

Is microdosing 4-AcO-DMT safe?

Although 4-AcO-DMT is non-addictive and apparently well tolerated, there are a number of health concerns to be aware of. See our risks section for more details.

How do I get started with microdosing?

There are lots of things to cover before you get started with microdosing – depending on the reasons you’re interested in the first place!

Sign up to our extensive microdosing course to gain access to curated materials that will help you design the ideal microdosing regimen for your needs. You’ll also gain access to an exclusive community of enthusiastic, helpful microdosers!

Various subreddits and forums, including r/Drugs, r/Microdosing, r/ResearchChemicals, and Shroomery.org, might also help you get started.