Improved colour blindness symptoms associated with recreational psychedelic use: Results from the Global Drug Survey 2017

This analysis of data from the Global Drug Survey 2017 shows that 23 respondents indicated improved color blindness. Possible theories for these improvements included enhanced experience/labelling of colors or new neural connections.

Abstract

“It is well documented that psychedelic drugs can have a profound effect on colour perception. After previous research involving psychedelic drug ingestion, several participants had written to the authors describing how symptoms of their colour blindness had improved. The Global Drugs Survey runs the world’s largest annual online drug survey. In the Global Drugs Survey 2017, participants reporting the use of lysergic acid diethylamide or psilocybin in the last 12 months were asked:

We have received reports from some people with colour-blindness that this improves after they use psychedelics. If you have experienced such an effect can you please describe it in the box below, say what drug you took and how long the effect lasted.

We received 47 responses that could be usefully categorised of which 23 described improved colour blindness. Commonly cited drugs were LSD and psilocybin; however, several other psychedelic compounds were also listed. Some respondents cited that the changes in colour blindness persisted, from a period of several days to years. Improved colour blindness may be a result of new photisms experienced in the psychedelic state aligning with pre-existing concepts of colour to be ascribed a label. Connections between visual and linguistic cortical areas may be enhanced due to disorder in the brain’s neural connections induced by psychedelics allowing these new photisms and concepts to become linked. This paper provides preliminary data regarding improved colour blindness accompanying recreational psychedelic use which may be further investigated in future iterations of the Global Drugs Survey or in a stand-alone Global Drugs Survey-managed psychedelics survey.“

Authors: J. E. C. Anthony, A. Winstock, J. A. Ferris, David J. Nutt

Summary

Numerous mushrooms of the genus Psilocybe produce psychotropically active natural products that profoundly change perception when ingested. The main chemical constituent is psilocybin, which is rapidly dephosphorylated upon oral ingestion to yield the actual psychotropic agent psilocin.

Hofmann and co-workers elucidated the structures of 1 and 2 in 1959, and in 1968 the order of biosynthetic events leading to 1 was proposed. Here, we report on the enzymes for the biosynthesis of 1 in P. cubensis.

In the genomes of P. cubensis and P. cyanescens, genes encoding aparticular biosynthesis were found to be clustered around genes encoding polyketide synthases,peptide synthetases,orterpene cyclases. However, the biosynthesis of compound 1 does not require such genes.

We used an in vitro approach to produce N-terminal hexahistidine fusion proteins in Escherichia coli KRX to provide evidence that these loci govern the biosynthesis of compound 1.

PsiD is a 49.6 kDa enzyme that belongs to the PLP-independent phosphatidylserine decarboxylase family and is most similar to hypothetical proteins of other basidiomycetes. It can be used for the biosynthesis of 1 that belongs to a class of decarboxylases for which 6 has previously not been described as asubstrate.

We next investigated the putative SAM-dependent methyltransferase PsiM, which is similar to other hypothetical basidiomycete methyltransferases. However, assays containing SAM and 6, 7, 8, or 9 did not result in methylated products, suggesting that the phosphoryloxy group is a structural prerequisite for PsiM substrates.

The hypothetical kinase PsiK converts 2 into 1, asevident by LC-MS analysis, and requires adecarboxylated substrate. A coupled PsiD/PsiK assay results in the formation of 4, asevident by LC-MS analysis.

PsiK is one of very few biochemically characterized natural product kinases,and it is responsible for paeninodine and calyculin biosynthesis. It is also involved in the methyltransferase activity,which may be a protective mechanism to re-phosphorylate the instable compound 2 to the stable 1 in the case of intracellular ester cleavage.

Iterative methyl transfer to small molecules by enzymes has been investigated previously,and RemG and EgtD are not closely related. Similarly, PsiM is unrelated to mammalian indolethylamine-N-methyltransferase.

Psilocybe cubensis produces 1 by a virtually linear process, initiated by PsiD-catalyzed decarboxylation as a gateway step, and ending with PsiH-catalyzed 4-hydroxylation as an intermediate. Nonenzymatic conversion of 1 into 2 during isolation may additionally increase the apparent concentration of 2.

Acknowledgements

We thank J. Greßler, J. Wick, and A. Perner for their help with cDNAsynthesis, psilocybin, and high-resolution mass spectra, respectively.