Comparing the Effects of 4-AcO-DMT and Psilocybin Mushrooms

According to experience reports, magic mushrooms elicit more emotions and visual effects than 4-AcO-DMT (psilacetin).

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Many experienced psychonauts and newcomers alike believe that the subjective effects of 4-AcO-DMT (psilacetin) and psilocybin “magic” mushrooms are effectively the same. Granted, this may be true for some because of the metabolic differences between individuals. But, the current knowledge base in chemistry and biology confirms that different chemicals cause different effects on the human body, whether perceived by the user or not. By examining experience reports and through an understanding of molecules versus mushrooms, it is easier to understand why they are different.

Psilocybin-assisted therapy is showing promise for treating conditions such as treatment-resistant depression,1 anxiety in terminal cancer patients,2,3 alcohol addiction,4 and tobacco dependence.5 Historically, psilocybin is difficult and expensive to make in the lab and on a larger scale. The original synthesis method designed by Albert Hofmann has a yield of less than 20%.6

Dr. David Nichols, Professor Emeritus of Pharmacology at Purdue University has suggested that 4-AcO-DMT (also known as psilacetin, O-acetylpsilocin, psilocetin, 4-acetoxy-DMT, and 4-acetoxy-N,N-dimethyltryptamine) is a prodrug of psilocin in the body just like psilocybin.6

Figure 1: The chemical structure of psilocybin.

When a person ingests psilocybin (Figure 1) the body readily converts it to psilocin (Figure 2) through the process of dephosphorylation.

Figure 2: The chemical structure of psilocin.

The body also converts 4-AcO-DMT (Figure 3) to psilocin via removal of the acetyl group by deacetylase and acetyltransferase enzymes. Interestingly, scientists don’t know if 4-AcO-DMT is biologically active on its own.

Figure 3: The chemical structure of O-acetylpsilocin, also known as 4-AcO-DMT.

In 1999, Dr. Nichols published an improved synthesis method for psilocybin.6 In the same paper, he also explains a simple method for preparing 4-AcO-DMT which readily crystallizes as the fumarate salt and is more stable than psilocin. Dr. Nichols puts forth the idea that 4-AcO-DMT is an easy and cost-effective alternative for studying the psychopharmacology of psilocin. 4-AcO-DMT is called a semi-synthetic drug meaning it is made synthetically from a naturally-occurring compound.

Those wishing to use 4-AcO-DMT on their own but don’t have a lab can find it available for purchase from websites such as The Indole Shop. 4-AcO-DMT is receiving increased attention in the psychonaut world recently because of the similarity of its effects to those of psilocin without nausea that often accompanies eating magic mushrooms. But how similar are the effects of these compounds?

Comparing the Effects of Psilocin and 4-AcO-DMT

It’s important to understand that ingesting pure psilocybin by itself is very different from the cocktail of chemicals a person receives after eating magic mushrooms. All the psychoactive compounds in magic mushrooms (like baeocystin, norbaeocystin, norpsilocin, and aeruginascin) work together to produce the overall psychedelic experience for the user. For example, researchers have noted that aeruginascin has a synergistic effect on the pharmacological action of psilocybin in magic mushrooms.7 Specifically, Jochen Gartz says, “Aeruginascin seems to modify the pharmacological action of psilocybin to give an always euphoric mood during ingestion of the mushrooms.” In the world of medical cannabis, this synergy is known as the entourage effect.

Notably, psilocybin experience reports come from people who have ingested magic mushrooms, not pure psilocybin (and the dose is not always the same). The types and amount of psychoactive chemicals in magic mushrooms vary from species to species, batch to batch, and even in different parts of the mushroom. Experience reports for 4-AcO-DMT reflect the effects of the pure compound (again, the dosage may not be the same for all users). Also, set and setting (context) are known to be critical components affecting the psychedelic experience.8 This environment varies from user to user and is another reason it can be difficult to draw objective conclusions from experience reports.

The Urban Dictionary describes the effects of magic mushrooms versus 4-AcO-DMT this way:

  • “The effects are VERY similar to a mushroom trip, except it lasts a little longer than mushrooms (around 7 hours). Its effects, however, differ somewhat from mushrooms. It seems to have a much more relaxing quality to it, which makes it harder to have a bad trip. Several available reports of 4-ACO-DMT compare it favorably to psilocybin, describing it as more euphoric, gentle, warm, and colorful. It has also been described as less jarring/scary, and less likely to produce nausea.”

PsychonautWiki says:

  • “Users frequently describe 4-AcO-DMT as being extremely similar to psilocybin mushrooms. It is generally described as euphoric, gentle, warm, and colorful. Visuals are reported by some users to be brighter and more neon in a manner reminiscent of DMT. It is also reported to be less nauseating than psilocybin mushrooms, which may be due to the fact that it does not require digesting mushroom matter.”

And, from Tripsit Wiki:

  • “Its effects and duration are similar to those of Psilocybin/Psilocin although it is sometimes described as ‘warmer’ or ‘more euphoric’ than psilocybin-containing mushrooms. Ingesting mushrooms often creates feelings of nausea for the user due to the flesh of the fungi containing chitin, and for this reason it seems that 4-AcO-DMT has far fewer reports of feelings of nausea or vomiting.”

Below are excerpts that are taken from individual experience reports on the websites Reddit, Erowid, and BlueLight comparing the effects of 4-AcO-DMT and psilocybin mushrooms. There are people who report no difference in effects between the compounds. This may be due to the dosage, context, individual metabolic differences or a combination thereof as mentioned earlier. For those that did notice a difference, this compilation represents some of the most frequently mentioned similarities and differences between the compounds.

  • “I find 4-Aco-Dmt to be more introspective/introverted without any magic feeling to it. While on shrooms I feel like happy child again. Also realizations on shrooms are better, more positive.”
  • “I find 4aco to be a lot less emotional and ‘spiritual’ than psilocybin mushrooms- it’s a more clear headed ‘space age mushroom’ great for introspection but a bit more cerebral than the mushrooms.”
  • “Amazing visions and teachings as much or more then [sic] mushrooms. It was very sad in parts but also very euphoric. I even had more visions with this medicine then [sic] mushrooms.”
  • “I found that the lower doses (8-15 mg) of this compound [4-AcO-DMT] we’re [sic] almost identical to a low dose of psilocybe cubensis (1-1.5 grams). I find it interesting that this chemical doesn’t produce as many visuals as psilocybe mushrooms. Maybe because of the lack of baeocystin, norbaeocystin and other compounds that produce an entourage effect of sorts.”
  • “It’s [4-AcO-DMT] almost identical to shrooms but more DMTish.”
  • “Space age shrooms without the nausea. I was also really euphoric in a silly kinda way. Mushrooms make me euphoric in a wow this is so beautiful kinda way.”
  • “I’ve always found the two to be very similar. Mushrooms of course produce nausea and discomfort on the come up that I never feel from 4-AcO-DMT. Mushrooms are also a bit more unpredictable emotionally in my experience, whereas 4-AcO-DMT has almost always felt peaceful and serene at doses under 30 mg.”
  • “Very similar, but I find 4-aco-dmt to not be as lucid as mushrooms.”
  • “In my experience I find shrooms more emotional and psychologically intense. perhaps just more intense in general.”
  • “I find 4-AcO-DMT is able to produce a more DMT like experience in higher doses. Especially when snorted after the initial oral dose.”
  • “The differences for me were just the duration and bodyload. Shrooms have a heavier bodyload and make me salivate much more and is a bit more stoning. 4-aco also comes on a lil [sic] quicker.”
  • “Visuals are definitely different from my experience, 4 aco dmt visuals seemed as a cross between psilocybin and n-n dmt. Shrooms showed me a new world, 4 aco dmt put me in a new world.”
  • “Within 30 minutes I was feeling a significant body high, similar to the come up of mushrooms. Within 60 minutes, I was experiencing a very comfortable mental headspace with mild visuals. The visuals were certainly similar to some of the mushroom trips I’ve had, with somewhat less distortion. 4-aco-DMT definitely has a lot going for it. I virtually no nausea or stomach upset. Duration lasted for a good 6 hours, but with a much more gradual come-down than mushrooms had (at least another 2 hours).”
  • “4-ACO-DMT feels much more ‘digital’ and has an easier head-space. While mushrooms feel more natural, much more earthy, and have a much heavier headspace. 4-aco feels ‘cleaner’ but mushrooms feel more ‘natural'”
  • “In my experience, AcO tends to be less mystical/magical, and more “electric” somehow…They feel like different animals to me.”
  •  “I find that the 4-AcO trip provides a ‘cleaner’ headspace, gives me better visuals, and keeps nausea to a minimum. Shrooms, on the other hand, gives me more of a body load that can be uncomfortable, and almost always gives me bad nausea.”
  • “In my experience 4-AcO-DMT feels like a mix of shrooms and DMT. The comeup feels exactly like mushrooms but once I reach the peak it’s more clearheaded, more digital, and more stimulating than mushrooms.”
  • “In my experience (I have experienced both dozens of times) 4-AcO-DMT is no replacement for psilocybin mushrooms. 4-AcO feels more synthetic to me, and doesn’t make me analyze important things in my life like mushrooms. It also doesn’t give me the giggles or euphoria like mushrooms do. I’ve learned a multitude of lessons, spiritual and emotional, with psilocybe mushrooms. However 4-AcO usually just makes me throw up on the come up, trip really hard for 4 hours (I like 60+mg) and then come down with a headache. No lessons or revelations. It sucks because I figured, as a literal prodrug to psilocin, it should be mushrooms in a pill. But it’s just not the same.”
  • “I find 4-AcO-DMT to be more sedentary than magic mushrooms. Mushrooms are pretty chill too, but 4-AcO-DMT especially makes me especially inclined to recline and vegetate.”
  • “On mushrooms I tend to feel more crazed, but the emotional rollercoaster often left me refreshed afterwards… on 4-AcO-DMT it was more sneaky and I could be deep without fully realizing it, less obvious and less of a guided journey but a similar / generic effect on wellbeing.”

Conclusion

Despite the uncontrolled variables between users like the set, setting, and dose, the anecdotal evidence indicates that the effects of pure 4-AcO-DMT are different from the mixtures provided by naturally-occurring mushrooms. In general, 4-AcO-DMT appears to give a more colorful experience and imparts more feelings of warmth, relaxation, and euphoria than psilocybin mushrooms. Also, there is little or no nausea reported like magic mushroom users often experience. In contrast, magic mushrooms elicit more emotions and more visuals than 4-AcO-DMT. These differences make sense because they are 100% consistent with current scientific understanding—including how G-protein coupled receptors work, different chemicals causing different effects, and using multiple drugs to treat diseases and conditions (polypharmacy).

The different effects of these two compounds could also be due to the entourage effect caused by the other psychoactive chemicals present in magic mushrooms. The increased emotions and visuals experienced with psilocybin mushrooms could be evidence of allosteric modulation of receptors, enzymes, molecular transporters or a combination of these factors in the brain. This is a wide-open research area for studying and starting to unravel the mysteries of how psilocybin and its derivatives interact with each other and the brain to produce the overall psychedelic experience.

    References
  1. Carhart-Harris RL, Bolstridge M, Rucker J, et al. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry. 2016;3(7):619-627. doi:10.1016/S2215-0366(16)30065-7
  2. Ross S, Bossis A, Guss J, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. Journal of Psychopharmacology. 2016;30(12):1165-1180. doi:10.1177/0269881116675512
  3. Griffiths RR, Johnson MW, Carducci MA, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol. 2016;30(12):1181-1197. doi:10.1177/0269881116675513
  4. Bogenschutz MP, Podrebarac SK, Duane JH, et al. Clinical Interpretations of Patient Experience in a Trial of Psilocybin-Assisted Psychotherapy for Alcohol Use Disorder. Front Pharmacol. 2018;9. doi:10.3389/fphar.2018.00100
  5. Johnson MW, Garcia-Romeu A, Cosimano MP, Griffiths RR. Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. J Psychopharmacol. 2014;28(11):983-992. doi:10.1177/0269881114548296
  6. Nichols DE. Improvements to the Synthesis of Psilocybin and a Facile Method for Preparing the O-Acetyl Prodrug of Psilocin. Synthesis. 1999;1999(06):935-938. doi:10.1055/s-1999-3490
  7. Gartz J. Analysis of aeruginascin in fruit bodies of the mushroom Inocybe aeruginascens. International Journal of Crude Drug Research. 1989;27(3):141-144. doi:10.3109/13880208909053954
  8. Carhart-Harris RL, Roseman L, Haijen E, et al. Psychedelics and the essential importance of context. J Psychopharmacol (Oxford). 2018;32(7):725-731. doi:10.1177/0269881118754710