Wood Lover Paralysis – Chemist’s Hypothesis – Aeruginascin

Chemist’s Hypothesis for Wood Lover Paralysis

Many people consuming “magic mushrooms” experience a condition called Wood Lover Paralysis (WLP), which consists of late-onset, prolonged muscle impairment. To date, the cause of WLP remains unknown.  Experts in the field have explained that WLP is due solely to the dose of psilocybin consumed.  However, this “dose alone” explanation does not account for two critical facts:

  • First, high doses of pure psilocybin do not cause WLP.
  • Second, WLP only occurs with certain species psilocybin-containing mushrooms.

Clearly, WLP cannot be explained by the dose of psilocybin. However, all the available evidence does support the conclusion that certain kinds of mushrooms contain chemical compounds (aside from psilocybin) which cause WLP.  From a chemist’s perspective, the molecule aeruginascin is one likely candidate for causing WLP.

Summary of Relevant Chemical Facts about Wood Lover Paralysis

  1. Magic mushrooms contain multiple active chemical compounds, including multiple psilocybin derivatives.  When a person consumes mushroom material, they ingest a cocktail of multiple active components, including but not limited to psilocybin.
  2. Different species of mushrooms contain substantially different concentrations of active components, including but not limited to psilocybin.  A person consuming 1 gram of “magic mushrooms” on one occasion probably consumes a different amount of active ingredients than upon consuming 1 gram of different “magic mushrooms” on another occasion.
  3. The chemical composition of “magic mushrooms” varies substantially between different species of magic mushrooms. One species of “magic mushrooms” may contain a substantially different chemical profile than another batch.
  4. Only certain species of “magic mushrooms” cause WLP. Those species all seem to grow on wood substrates, hence the name of the condition. Psilocybe azurescens and Psilocybe cyanescens are two notorious examples of magic mushrooms causing WLP.

Simple Chemical Explanation for Wood Lover Paralysis

Chemist’s Hypothesis: WLP is caused by a chemical compound that is present in some (but not all) species of magic mushrooms.

At a high level, the Chemist’s Hypothesis could be confirmed by studying and comparing the chemical compositions of (A) mushrooms known to cause paralysis, such as Psilocybe azurescens and Psilocybe cyanescens; and (B) and mushrooms not correlated with paralysis, such as Psilocybe cubensis.  (The chemical analysis should account for aeruginascin, which is often ignored because characterizing aeruginascin requires a different separation procedure than other psilocybin derivatives.)

The above study will almost certainly reveal a chemical difference between Group A and Group B. In particular, the analysis will identify chemical compounds present in Group A but not Group B.  Those compounds can then be further studied as potential candidates for motor impairment or paralysis.

One likely candidate for causing WLP is aeruginascin.

Aeruginascin is a naturally occurring molecule present in some (but not all) psychoactive mushrooms.  Aeruginascin is structurally similar to psilocybin.  The “only” difference is that aeruginascin has three methyl groups on the ethanolamine moiety whereas psilocybin has two (Figure 1). This difference means that aeruginascin has a positively charged quaternary trimethylammonium group at this position whereas psilocybin has a dimethylamine.

Figure 1: The structural similarity between aeruginascin and psilocybin. Aeruginascin has 3 methyl groups on the amine whereas psilocybin has two.

Aeruginascin is known to occur in multiple species of magic mushrooms.  See Zhuk, O. et al. Toxins, 2015 Apr; 7(4): 1018–1029.

Although aeruginascin differs from psilocybin by a single methyl group, this same structural difference has substantial consequences in the nearest structural analogs: Bufotenin and BufotenidineSee Figure 2 below.

From a chemical structure standpoint, bufotenin is identical to psilocin except for the position of the phenol (OH) group.  Bufotenin and bufotenidine differ by a single methyl group — two versus three methyl groups — just as aeruginascin differs from psilocybin.  In both cases, the third methyl group creates a quaternary ammonium salt instead of a tertiary amine.  Bufotenin is psilocin with the hydroxy group at the 5-position instead of the 4-position; bufotenidine is bufotenin with a trimethylammonium group instead of a dimethylamine group.  Accordingly, bufotenidine is dephosphorylated aeruginascin w/ the HO- group at the 5-position instead of the 4-position.

Same Change in Nearest Chemical Analogs Converts Psychedelic into paralytic

Bufotenin (akin to psilocin/psilocybin) is a known psychoactive compound.  By contrast, bufotenidine (akin to aeruginascin) causes ataxia, or temporary paralysis.  See the book Anadenanthera: Visionary Plant of Ancient South America by Torres, C., and Repke, D., beginning on page 146, which summarizes bufotenine and bufotenidine research.

Figure 2: Bufotenin and Bufotenidine are close structural analogs of psilocin/psilocybin and aeruginascin.

 

Summary

  • Wood Lover Paralysis is probably due to a chemical difference between different species of magic mushrooms.
  • Known information about the nearest structural analogs, bufotenin and bufotenidine, suggest aeruginascin could play a role in Wood Lover Paralysis.
  • Future studies should compare the chemical composition of (A) mushrooms known to cause paralysis, such as Psilocybe azurescens and Psilocybe cyanescens; and (B) and mushrooms not correlated with paralysis, such as Psilocybe cubensis.

**PLEASE HELP SOLVE THE WOOD LOVER PARALYSIS PROBLEM by filling out this survey on Wood Lover Paralysis.

Note to the reader about structural comparisons above: In the structures above, the phosphorylated versions of aeruginascin and psilocybin are depicted whereas bufotenin and bufotenidine are dephosphorylated compounds.  For all of these molecules, the phosphorylated versions are considered prodrugs of their dephosphorylated counterparts. See psilocinPhosphorylated versions of bufotenin and bufotenidine are not known.