Church of Psilomethoxin

Psilomethoxin: The History, Testing, Pharmacodynamics, and Pharmacokinetics 

History of Psilomethoxin

In 1965 Marc Julia’s group at the Pasteur Institute synthesized psilomethoxin (4-ho-5-meo-dmt) in a 10-step process from ortho-vanillin extracted from the Mexican vanilla orchid.  The molecule was never bioassayed nor preserved as a reference sample. 

In the early 1990s, German mycologist Jochen Gartz fed DET, DIPT, and DPT to psilocybe cubensis mushroom substrate and created the completely novel compounds 4-ho-DET, 4-ho-DIPT and 4-ho-DPT.  He filed patents on this process, which have since expired.

In 2005, Sasha Shulgin was asked about psilomethoxin.  

4-Hydroxy-5-methoxy-N, N-dimethyltryptamine would be a fascinating compound to explore. The reason it’s not in TIKHAL is that it is virtually unknown. The only report of it in the chemical literature was a paper published by Marc Julia’s group at the Pasteur Institute in 1965. 

They reported the synthesis and physical properties of the compound but to my knowledge, it has never been explored in any way. The synthesis is quite a frightening thing. It starts with ortho-vanillin and takes approximately 10 steps to get to the 4,5-HO-MeO-DMT. I’m not surprised that no one has pursued the compound. However, there is a very interesting study that took place in Leipzig about 15 years ago. Jochen Gartz, a mushroom explorer whom I know quite well, has done some fascinating studies with Psilocybe species by raising them on solid media containing strange tryptamines that are alien to the mushroom.

 Apparently, the enzymes that are responsible for the 4-hydroxy group of psilocin are indifferent to what it is they choose to 4-hydroxylate. He has taken things like DPT or DIPT and put them in the growth media and the fruiting bodies that came out contain 4-hydroxy-DPT or 4-hydroxy-DIPT instead of psilocin. In fact, he has a patent on the process. These active compounds are made by the mushroom so they really are natural and yet they never have been observed in nature. 

I’ll give you even odds that if you put spores of a psilocybe species on cow droppings loaded with 5-MeO-DMT you would come out with mushrooms containing 4,5-HO-MeO-DMT. This way you avoid a 10-step synthesis by growing a psychoactive mushroom that contains no illegal drug.

Testing Psilomethoxin

In November of 2021, the Church of the Sacred Synthesis (aka Church of Psilomethoxin) fed 5-meo-dmt to mushrooms in Mexico and tested the resulting sacrament.  Since then, the members of the church have shared the sacrament with thousands of people with tens of thousands of doses shared.  To date, we have not received any adverse event reports.  

An Anesthesiologist MD in the US who is a member of our church purified the molecule and injected it into numerous persons subcutaneously and reported no adverse responses.  

We have performed GC-MS multiple times on our sacrament and to date, no one has been able to detect the molecule using this destructive testing process.  

GC-MS methods are not capable of directly analyzing drugs that are nonvolatile (does not vaporize easily), polar (water soluble), or thermally labile (destroyed by heat).

We believe that Psilomethoxin is non-volatile, polar, and thermally labile and therefore a poor candidate for testing through this process.  

Our church personally bioassays each batch of our sacrament for efficacy and safety. 

Pharmacokinetics of Psilomethoxin

Pharmacokinetics is what the body does to the drug.  the study of the time course of drug absorption, distribution, metabolism, and excretion. 

How does psilomethoxin compare to dmt, 5-meo-dmt and psilocybin/psilocin for tolerance, half-life, onset, bioavailability, etc.? 


The onset of psilomethoxin is potentially immediate as the molecule is instantly available for absorption in the mouth or in the stomach.  Psilocybin by contrast, is a biologically inactive pro-drug of psilocin.  Psilocybin must be broken down into psilocin in the gut with gastric juices or before consumption with similar chemistry, e.g. lemon tek to be able to be absorbed.  


DMT and 5-meo-dmt are rapidly oxidized in the body by monoamine oxidase (MAO).  Their short half-lives (10-14 min) and (12-18 min) combined with their being metabolized quickly mean that they don’t create a tolerance effect like psilocin (4-ho-DMT).  

This is the reason that psilocin or other so-called classic psychedelics cannot be taken at perceptual amounts daily for microdosing because tolerance develops quickly requiring ever-increasing dosing to achieve the same effects.  This is the genesis of the reason to take days off for microdosing with psilocin.  

The concern with the metabolism of 5-meo-dmt is that it is broken down into the active metabolite 5-ho-DMT (bufotenine).  This is also a concern since this is the only pathway in the body for 5-meo-dmt to be broken down (unlike DMT which has multiple metabolic pathways for breaking down) which can mean potential serotonin syndrome when too much 5-meo-dmt is taken at one time from a backup of excess unmetabolized 5-meo-dmt and 5-ho-DMT in the body. 

Psilomethoxin does not metabolize into 5-meo-dmt or bufotenine thereby eliminating the serotonin syndrome concern.  

The half-life of psilomethoxin seems to parallel that of psilocin of approximately 1-3 hours with direct effects correlating to psilocin for 4-6 hours.  

Pharmacodynamics of Psilomethoxin

Pharmacodynamics is what the drug does to the body and focuses on receptor binding, post-receptor effects and chemical interactions. 

Receptor Binding

5-meo-dmt has a 1000-fold greater affinity for the 5-HT1A receptor site over the 5-HT2A receptor site.  5-HT2A is the primary receptor site for classic psychedelics like dmt and psilocin.  The 5-HT2A receptors are where the so-called hallucinogenic effects are generated: visual, auditory, kinesthetic, olfactory, and gustatory.  5-meo-dmt does not generate these effects since it works at the 5-HT1A receptor site which down-regulates the default mode network but does not generate sensory effects.  Psilomethoxin shares a similar receptor affinity through bioassay testing. 

5-meo-dmt is considered to be a pyschoplastagen which means it promotes rapid and sustained neural plasticity.  We believe Psilomethoxin has similar effects.  

5-meo-dmt promotes neurogenesis which means it grows new brain cells and makes new connections.  We believe that Psilomethoxin has similar effects. 

5-meo-dmt promotes the reduction of inflammation which means it reduces body and brain temperatures to desirable levels.  We believe that Psilomethoxin has similar effects. 

5-meo-dmt induces a natural SSRI effect that lasts beyond the direct effects of the molecule.  We believe that Psilomethoxin has similar effects. 

Common Responses

None.  With Psilomethoxin there is no pupil dilation, heart rate changes, changes in blood pressure, tremor or nausea, whereas all of these are common responses with psilocybin.  

Contraindications of Psilomethoxin

MAOI’s and any other medicines contraindicated for 5-meo-dmt.  We recommend the Pharmacology and Drug Interactions of 5-MeO-DMT Guide provided by Ben Malcom, PharmD aka the Spirit Pharmacist.  

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