Chemistry – The future of Psilocybin technology

Chemistry (and increased focus on psilocybin chemistry) will provide the next big breakthrough in psilocybin technology.  With the psilocybin space, the state of the art has been shaped by mycologists.  As a result, our understanding of psilocybin and derivatives remains stuck at the macroscopic scale.  In other words, the community has studied psilocybin mushrooms up to the limits of their microscopes.  But, for the most part, the art has not looked deeper — down to the level of atoms and molecules.

Advances in mycology have led to identifying and classifying Psilocybe azurescens, an extremely potent psilocybin containing mushroom.

Mycologists have done excellent job studying fungi.  They have identified and rigorously categorized over 200 species of “magic mushrooms.”  And, they have developed extremely effective methods of cultivating  these mushrooms.  However, despite considerable progress understanding these fungal organisms, almost no progress has been made studying the underlying chemical components of these organisms.

The path to better psilocybin products requires looking at magic mushrooms from a chemical perspective.  We need to go beyond identifying and categorizing “magic mushrooms” by further elucidating the magic molecules within those mushrooms.  Here’s a high level process for deepening our understanding down to the molecular level:

  1. First, extract all of the potentially “magic” molecules (see Psilocybin Derivatives below) from the mushroom.  In other words, extract all of the relevant pharmacologically active molecules from the mushrooms, leaving behind the structural components (e.g., proteins) of the mushrooms.
  2. Second, separate the individual molecules within the extract.
  3. Third, study the effects of each individual psilocybin derivative.  Presently, administering psilocybin and its derivatives follows all-or-nothing approach.  Users eat mushrooms (or mushroom preparations), thereby consuming whatever molecules happen to be present within the mushroom.  This method overlooks the possibility that certain combinations of those molecules may behave differently when administered together.  For example, one molecule may modulate the effects of another molecule.
  4. Forth, study particular combinations of psilocybin derivatives.   Using the properties of individual psilocybin derivatives as a baseline, study combinations of multiple psilocybin derivatives.  For example, does one of the lesser studied psilocybin derivatives effect the way psilocybin interacts with particular receptors in the brain?
  5. Fifth, for particular combinations of psilocybin derivatives, how does varying the ratio of the psilocybin derivatives change the observed pharmacological effects — either clinically (e.g., changes in mood or bran scan data) and/or at the cellular level.
  6. Sixth, study combinations of (a) psilocybin derivatives with (b) other molecules that are known to interact with the cellular receptors targeted by psilocybin.  For example, how to other serotonergic compounds modulate the effects of psilocybin (or serotonin) at particular serotonin receptors?  At other cellular receptors?

Psilocybin Derivatives – A Library of Active Chemicals

The term “Psilocybin derivatives” refers to a collection molecules sharing the hydroxy-tryptamine core.  These molecule may vary from psilocybin at one or more positions.  Examples of psilocybin derivatives include the following:

  • Psilocybin;
  • Psilocin (sometimes spelled psilocyn);
  • [3-(2-trimethylaminoethyl)-1H-indol-4-yl] dihydrogen phosphate
  • 4-hydroxy-N,N,N-trimethyltryptamine;
  • Baeocystin (aka [3-(2-methylaminoethyl)-1H-indol-4-yl] dihydrogen phosphate);
  • 4-hydroxy-N-methyltryptamine;
  • Norbaeocystin (aka [3-(aminoethyl)-1H-indol-4-yl] dihydrogen phosphate); and
  • 4-hydroxytryptamine

Although “psilocybin” receives almost all attention, the state of the art considers psilocybin to be a pharmacologically inactive molecule.  According to our present understanding, psilocybin is rapidly converted into psilocin. Psilocin is the active chemical that is responsible for the observed psychoactive properties.

A Chemical Perspective: Psilocybin and psilocin are two (of many) different molecules found in magic mushrooms.

Aside from psilocybin and psilocin, none of the other psilocybin derivatives listed above has received much attention.  For example, although baeocystin is found within many species of psychoactive mushrooms, no work has been done to understand its pharmacological properties.  The closest attempt at baeocystin science was reported by Jochen Gartz in the book Magic Mushrooms Around the WorldIn that text, Gartz refers to a report that “10 mg of baeocystin were found to be about as psychoactive as a similar amount of psilocybin.”  Gartz also reported that taking 4 mg of pure baeocystin caused “a gentle hallucinogenic experience”.

Psilocybin technology can be improved by isolating each psilocybin derivative and studying how it affects cellular receptors (e.g., serotonin) alone and in combination with other molecules.  This approach requires bringing a chemical perspective to a field that is currently defined by mycologists.