Direct Phosphorylation of Psilocin Enables Optimized cGMP Kilogram-Scale Manufacture of Psilocybin

This paper (2020) describes and makes available the method for producing psilocybin on a large (1kg) scale.


A second-generation kilogram-scale synthesis of the psychedelic tryptamine psilocybin has been developed. The synthesis was designed to address several challenges first encountered with the scale-up of previously described literature procedures, which were not optimized for providing consistent yield and purity of products, atom economy, or being run in pilot plant-scale reactors. These challenges were addressed and circumvented with the design of the second-generation route, which featured an optimized cGMP large-scale Speeter–Anthony tryptamine synthesis to the intermediate psilocin with improved in-process control and impurity removal over the three steps. Psilocin was subsequently phosphorylated directly with phosphorous oxychloride for the first time, avoiding a tedious and poor atom economy benzyl-protecting group strategy common to all previously described methods for producing psilocybin. In this report, the challenges encountered in a 100 g scale first-generation literature-based synthesis are highlighted, followed by a detailed description of the newly developed second-generation synthesis to provide over one kilogram of high-purity psilocybin under cGMP.

Authors: Robert B. Kargbo, Alexander Sherwood, Andrew Walker, Nicholas V. Cozzi, Raymond E. Dagger, Jessica Sable, Kelsey O’Hern, Kristi Kaylo, Tura Patterson, Gary Tarpley & Poncho Meisenheimer


This paper is included in our ‘Top 10 Articles on Psychedelics in the Year 2020

This open-access paper describes how one could make psilocybin on a large scale. This work is made available by the non-profit Usona Institute, and (partially) prevents for-profit companies from taking out patents on a/this method for making psilocybin at scale.


Institutes associated with this publication

Usona Institute
The Usona Institute was founded by Bill Linton and Malynn Utzinger. Currently, 18 people are associated with it. The institute is a non-profit that sponsors psilocybin research (and is funded by sponsors/philanthropists).

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