Presence of cannabinoid-related oxidoreductases in non-cannabinoid producing organisms

Could smoking chickpeas get you high? No, but perhaps it could be made possible. While performing searches on NCBI, I noticed a remarkably high prevalence of enzymes that are very similar to cannabinoid oxidoreductases – enzymes responsible for the psychoactivity of Cannabis plants – in plants and fungi that do not produce cannabinoids. The genes coding for these enzymes are automatically annotated in entire genomes stored in GenBank, and are indeed very similar to cannabinoid-producing enzymes.

The best-known of the 85 psychoactive compounds in Cannabis sativa are Tetrahydrocannabinol (THC) and Cannabidiol (CBD). As a result, the chemotype-determining enzymes that regulate the psychoactivity in Cannabis sativa plants are Tetrahydrocannabinolic acid synthase and Cannabidiolic acid synthase. These enzymes are both oxidoreductases that use oxygen as an acceptor, and produce tetrahydrocannabidiolic acid (THCA) and cannabidiolic acid (CBDA), respectively. These acids are proposed precursors in the biological pathways of their respective cannabinoids. THCA is very unstable on its own, and readily decarboxylates to form THC at room temperature in the presence of acid, light or oxygen.

The genes coding for Tetrahydrocannabidiolic acid synthase are present in the genome of Rhizoctonia solania basidiomycete fungus pathogenic to plants. This fungi commonly causes collar rot, root rot, damping off and wire stem in plants. Very similar genes are also found and automatically annotated on the genomes of several other plants, including Field Mustard, Chickpeas, Oranges, Asian Rice, Castor Beans and Wine Grapes. Why are those genes there? Do they indeed code for THCA synthase? Is it possible that these plants can produce THC under the right conditions?

Cannabidiolic acid synthase isn’t exclusive to Cannabis plants either. The genes coding for the enzyme are also present in Rhizoctonia solani (see above), Scedosporium apiospermum (an asexual form of the Pseudallescheria boydii) and Tolypocladium ophioglossoides CBS 100239 (a parasitic fungus that grows on truffle-like fruits). Similar genes can be found in Field Mustard and Chickpeas, which both also contain the genes for THCA Synthase. The genes seem to be entirely absent in the other taxons that do contain the THCA Synthase gene.

All in all this matter has left me with a plethora of questions. This matter seems to be unreported on PubMed. I’ve thought of a few experiments I could conduct:

  • Perform SDS-PAGE on each of the plants to determine the presence of CBDA synthase (74 kDa) and THCA Synthase (unknown weight, determine first).
  • Introduce the substrates of the enzymes (Cannabigerolate) and see whether THCA or CBDA is produced.
  • Isolate the enzymes from the plants and determine their size, weight, sequence and shape by means of PCR, Sanger sequencing and X-Ray Crystallography.

My hypothesis is that THC is formed as a result as the same defense mechanism as the mustard plant, horseradishes and wasabi plants. In these plants this defense mechanism became allyl isothiocyanate, a chemical responsible for the pungent taste in all three. In cannabis plants, this defense mechanism may also have been present, but instead evolved into the production of cannabinoids, disorienting natural consumers of the plants, making them more prone to be eaten by predators and discouraging further consumption of the plant.