Psilomethoxin, My Case Report

February 16, 2023

At the end of 2022, a new psychedelic became available. Psilomethoxin (Pm) offers a subjective experience similar to MDMA, but without MDMA’s stimulant-like effects.

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In 1965, Marc Julia’s group at the Pasteur Institute synthesized psilomethoxin (Pm) from ortho-vanillin extracted from the Mexican vanilla orchid. The molecule was never bioassayed nor preserved as a reference sample, and that is how things stood for decades. The synthesis of Pm is an intricate and time-consuming process, with some chemists claiming that it would take a month. In approximately 2005, Alexander Shulgin published an article on his website Cognitive Liberty wherein he theorized that Pm might be produced by feeding 5-MeO-DMT to Psilocybe mushroom substrates. In late 2021, Ian Benouis discovered the Shulgin article, tried it, and found that it worked. Pm is chemically similar to 5-MeO-DMT, with the mere addition of a 4-hydroxyl group. The psychedelic 5-MeO-DMT is not orally active and is typically vaporized for inhalation. When inhaled, the experience lasts for 10-20 minutes. Pm is thought to be an orally active version of 5-MeO-DMT.¹

Pm might be the most important psychotherapeutic drug discovery of our time. Systematic research has not been done yet, but case reports from people who have experienced both MDMA and Pm are tantalizing. Both drugs produce euphoria and emotional clarity. In contrast to 5-MeO-DMT, Pm time course is similar to MDMA with a one-hour onset, two-hour plateau, and one to three-hour come down. MDMA is a social drug; the love and empathy you can feel is mostly directed at other people. In contrast, Pm guides focus to the Self and is less about other people. On MDMA, some report an urge to hug and kiss people. Pm is much less sensual and person-focused.

Another major difference is that MDMA is an amphetamine while Pm is a tryptamine. Amphetamines are typically stimulants; that is part of what makes MDMA a marvelous drug for dancing. In contrast, there is a case report of falling asleep at the peak of a Pm journey. This would be impossible on MDMA. One person reported, “Yes I can fall asleep with no issues at the peak. Highest dose has been 600mg [of dried mushroom powder or 15mg of Pm]. I’ve taken it two hours before bed every night for the last two weeks.”

This case report highlights another difference between the two substances. Pm does not seem to exhibit any tolerance effect. While the length of an MDMA journey can be extended by taking a booster dose (half of the first dose, 80-120 minutes after the first dose), the body builds up a tolerance to MDMA. You cannot take MDMA daily without suffering from side effects. Although the harms from MDMA are not as severe as suggested by the exaggerated claims from the 1980s,² there is no dispute that MDMA has immunosuppressive effects in the peripheral nervous system and pro-inflammatory effects in the central nervous system.³ In addition, MDMA is a moderately teratogenic drug (i.e., it is toxic to a fetus).⁴

Once a simple way to synthesize Pm was discovered, Benouis and colleagues formed the Church of Sacred Synthesis⁵ and started collecting safety data. Reports on the toxicology of Pm are not yet published, but we can hazard some educated guesses. Pm is chemically similar to psilocin, the active metabolite of the psychedelic psilocybin. Psilocin has extremely low toxicity, is anti-inflammatory, and promotes neurogenesis.⁶ Pm is also chemically similar to 5-MeO-DMT. Like psilocin, 5-MeO-DMT is anti-inflammatory and promotes neurogenesis.⁷ The Church of Sacred Synthesis has, since Nov 2021, distributed some tens of thousands of doses. Community members have reported taking 50mg Pm in a single session without obvious ill effect. We hope these data can be peer-reviewed and published soon.

Legal status #

Another motivation to form the Church of Sacred Synthesis was to protect Pm from legal restriction. At the time of writing, Pm is not regulated in the USA, however, possession could be prosecuted under the Federal Analogue Act due to its structural similarity to both psilocin and 5-MeO-DMT. The Religious Freedom Restoration Act of 1993 has been used successfully in the past to protect psychedelic churches from federal encroachment (e.g., Santo Daime in CHLQ v. Mukasey). The Church of Sacred Synthesis accepts members from both the USA and internationally, and distributes sacrament (i.e. Pm) using ordinary mail delivery. According to the Church of Sacred Synthesis, dried Psilocybe powdered fruiting body contains 2-3% Pm by weight and negligible traces of psilocybin or psilocin.

Mental health professionals such as psychiatrists have often held a patronizing attitude about psychoactive drugs; there is an inclination to restrict access and bar use except by prescription. In his 2021 book, “This Is Your Mind on Plants,” Micheal Pollan pointed out that which psychoactive substances are socially acceptable and which are denigrated or restricted is not much a matter of drug characteristics or safety, but largely culturally determined. Our society’s current drug prohibitions are arbitrary and capricious.⁸ I suggest that our goal for Pm should be to avoid either extreme of prohibition or unrestricted access. It is not clear what legal regime is most appropriate for Pm, but prohibition would be a huge missed opportunity. The Psychedelic Bar Association is currently drafting a Uniform Model Plant and Fungi Medicine Act. Lawmakers should monitor the development of this promising regulatory framework.

Open questions #

• How is Pm metabolized? Why doesn’t the body build up a tolerance to Pm?
• What is the LD50 dose for Pm? Are there short or long-term side effects to using Pm?

Addendum #

• Psilomethoxin, My Case Report (Addendum #1).
• Psilomethoxin, My Case Report (Addendum #2).

Notes #