Cannabis A Natural History – Rob DeSalle (1)

An important intermediate in this pathway is olivetolic acid, which after a simple reaction produces cannabigerolic acid (CBGA). CBGA is somewhat versatile as it can be converted to cannabidiol (CBDA), cannabichromene (CBCA), and delta-9-tetrahydrocannabinoid (THCA). The ultimate production of CBDA and THCA is accomplished by CBD synthase and THC synthase, respectively. The real beauty of these pathways is that they can sequester their products into different parts of the plant cell, and they seem to be able to feed each other raw materials.

What this means for cannabis growers and breeders is that getting a particular strain to produce more THCA or CBDA is not a simple task of overexpressing the synthase genes for these compounds, but instead involves complex interactions that are not so simple. It is remarkable that four major pathways can account for most of the phytochemicals of cannabis.

All the major kinds of phytochemicals—lignans, flavonoids, terpenes, and cannabinoids— spring from these four pathways. Figure 9.7. The major phytochrome or secondary compound pathways in cannabis. In addition, it is not too wild to think that the lignins and especially flavonoids are involved in synergistic relationships with cannabinoids that increase the potency of different cannabis strains.

Getting a plant to produce a lot of THCA may not be as simple as controlling the expression of the synthase that converts CBGA into THCA. It could happen that way if a robust synthase arose by mutation that was more efficient than existing ones. But that would require a change in the actual synthase. Evolution of function has been studied by many researchers. One of the earliest and most informative studies in this realm was undertaken by geneticists Mary Claire King and Allan Wilson in the 1970s.

They discovered that the amino acid sequence divergence was minimal in many of the proteins of very different organisms such as humans and frogs. In other words, both organisms had the same protein structures, even though they are morphologically, behaviorally, and physiologically quite different.

Published on the foundation established in memory of William Chauncey Williams of the Class of 1822, Yale Medical School, and of William Cook Williams of the Class of 1850, Yale Medical School. Copyright © 2025 by Rob DeSalle. Illustrations by Patricia J. Wynne copyright © 2025 by Yale University. Chapter opening and frontispiece ornaments by KyivnataliS/Adobe Stock. All rights reserved. This book may not be reproduced, in whole or in part, including illustrations, in any form (beyond that copying permitted by Sections 107 and 108 of the U.S.

Copyright Law and except by reviewers for the public press), without written permission from the publishers. The information in this book is provided for informational and historical purposes only, it is not meant as a substitute for medical advice or treatment or as an endorsement of the efficacy of cannabis for the uses described. Your use of the information provided in this book is at your discretion and risk. In addition, some uses of cannabis and manners of ingestion may be harmful to human health.

If you are seeking to use cannabis, whether for recreational or for medicinal purposes, you should be aware of such risks. And as with any medicine or medicinal use, always consult your physician or health care provider before commencing any new medicine, especially if you are pregnant or have a medical condition or concern.

The author has attempted to make the book as accurate and complete with respect to the information provided, but it may nevertheless contain errors, omissions, or material that is out of date by the time you read it. Neither the author nor the publisher has any legal responsibility or liability for errors, omissions, out-of-date material or the reader’s use or application of the information contained in the book.

Yale University Press books may be purchased in quantity for educational, business, or promotional use. For information, please e-mail [email protected] (U.S. office) or [email protected] (U.K. office). Set in Adobe Text Pro type by Integrated Publishing Solutions. Printed in the United States of America.

This is a short excerpt from the opening of “” by Unknown, quoted for review and introduction purposes. All rights belong to the copyright holders.

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