Hypothetical biosynthetic pathways of pharmaceutically potential hallucinogenic metabolites in Myristicaceae, mechanistic convergence and co-evolutionary trends in plants and humans.

The Myristicaceae plant family produces mind-altering compounds including phenylpropanoids (myristicin, elemicin, safrole), tryptamine derivatives (DMT, 5-MeO-DMT), and β-carbolines. This review proposes biosynthetic pathways for these hallucinogenic metabolites. In plants, serotonin biosynthesis is catalyzed by tryptamine 5-hydroxylase (T5H) and tryptophan 5-hydroxylase (TPH), whereas in animals only TPH is involved. The enzyme indolethylamine-N-methyltransferase catalyzes DMT biosynthesis in both plants and mammalian brains. Protein sequence data from NCBI revealed a co-evolutionary relationship between plant and animal enzymes on a phylogenetic tree. The review suggests that DMT, 5-MeO-DMT, and β-carbolines serve as natural protectants against plant stress and neurodegenerative diseases, reflecting co-evolutionary mutualism between plants and humans.

Study at a glance

Abstract

The family Myristicaceae harbour mind-altering phenylpropanoids like myristicin, elemicin, safrole, tryptamine derivatives such as N,N-dimethyltryptamine (DMT) and 5-methoxy N,N-dimethyltryptamine (5-MeO-DMT) and β-carbolines such as 1-methyl-6-methoxy-dihydro-β-carboline and 2-methyl-6-methoxy-1,2,3,4-tetrahydro-β-carboline. This study aimed to systematically review and propose the hypothetical biosynthetic pathways of hallucinogenic metabolites of Myristicaceae which have the potential to be used pharmaceutically. Relevant publications were retrieved from online databases, including Google Scholar, PubMed Central, Science Direct and the distribution of the hallucinogens among the family was compiled. The review revealed that the biosynthesis of serotonin in plants was catalysed by tryptamine 5-hydroxylase (T5H) and tryptophan 5-hydroxylase (TPH), whereas in invertebrates and vertebrates only by tryptophan 5-hydroxylase (TPH). Indolethylamine-N-methyltransferase catalyses the biosynthesis of DMT in plants and the brains of humans and other mammals. Caffeic acid 3-O-methyltransferase catalyses the biosynthesis of both phenylpropanoids and tryptamines in plants. All the hallucinogenic markers exhibited neuropsychiatric effects in humans as mechanistic convergence. The review noted that DMT, 5-MeO-DMT, and β-carbolines were natural protectants against both plant stress and neurodegenerative human ailments. The protein sequence data of tryptophan 5-hydroxylase and tryptamine 5-hydroxylase retrieved from NCBI showed a co-evolutionary relationship in between animals and plants on the phylogenetic framework of a Maximum Parsimony tree. The review also demonstrates that the biosynthesis of serotonin, DMT, 5-MeO-DMT, 5-hydroxy dimethyltryptamine, and β-carbolines in plants, as well as endogenous secretion of these compounds in the brain and blood of humans and rodents, reflects co-evolutionary mutualism in plants and humans.