Genetic Mapping of Cannabis: Purpose, History, and the Future of Cannabis Genomics
The First Complete Cannabis Genome Map
In August 2011, Medicinal Genomics, a Massachusetts-based company, announced that its scientists had created the first complete map of the Cannabis sativa genome. This breakthrough opened new opportunities for medicine and the legal cannabis industry, especially in developing and applying cannabis as a therapeutic agent.
The company’s founder, Dr. Kevin McKernan, shared that he had long wanted to work on mapping the plant’s genome. He first became interested in the active components and therapeutic properties of cannabis years ago while working as a clinical oncologist, studying the DNA of people with various types of cancer.
“The complete cannabis genome map is the result of many years of work,” he told journalists. “It all started with conversations with several DNA donors who asked me and other doctors what we thought about using cannabis and its extracts in cancer therapy.”
After that discussion, Dr. McKernan decided to personally review the available public information on the use of cannabis’s active compounds, cannabinoids, in treating different diseases. He read Dr. Manuel Guzmán’s work, which described the practical effectiveness of various cannabinoid compounds in treating different types of cancer cells, based on his own experiments with volunteers and animal models. “Reading that work, I realized it was possible that a cancer cure could be hidden within cannabis,” McKernan said.
At the same time, he read Etienne de Meijer’s work, “Variation of Cannabis,” which categorized unique cannabis chemotypes (the full set of compounds in a particular plant variety) according to their genetic structure. “Back then, science was just beginning to study cannabinoids, so the classification divided plants based on the genetic mechanisms responsible for synthesizing the only widely known cannabinoids at the time: CBD and THC,” McKernan noted.
“It’s funny, but I thought the genome analysis project would take a couple of years and cost no more than $50,000,” he recalled. “But even in the early stages, our team realized just how complex the cannabis genome is, capable of producing a wide variety of cannabinoid compounds and combinations.”
Although several other companies have since released their own cannabis genome maps, Medicinal Genomics remains a leader in the field, with a map identifying 131 billion base pairs in the plant’s chromosomes. The project’s data was first made public on August 18, 2011, when McKernan’s company released the genomic information online. The full cannabis genome map is now available on the company’s website in a special section.
How Cannabis Genome Sequencing Impacts Medical Cannabis
According to Dr. McKernan, before the cannabis genome project, scientists had studied only 12 genes in the plant. Now, after the project’s completion, several tens of thousands of cannabis genes have been fully studied and cataloged. The project also revealed over 2 million nucleotide variations in the cannabis genome, enabling researchers to make many new discoveries about the genetic mechanisms behind cannabinoid synthesis.
One major discovery was that THC synthase is not a single diploid gene producing only one compound, but a complex of genes that, depending on their variation, can produce structurally related THC compounds—other active cannabinoids. “Contrary to previous data, genome sequencing showed that the genes responsible for THC synthesis have undergone about eight replications via DNA transposable elements, resulting in a chemical structure that allows for high variation in the production of unique cannabinoid compounds in different concentrations,” McKernan explained.
Dr. Ethan Russo, a leading U.S. expert in medical cannabis, told journalists that knowing the exact structure and variations of the genes responsible for cannabinoid synthesis will allow geneticists to create unique “synthetic” cannabis hybrids. These plants could naturally produce cannabinoids—including those rarely found in nature—in the required amounts.
“Undoubtedly, publishing the cannabis genome map will greatly stimulate new developments in medical cannabis,” Dr. Russo said. “Currently, the development of unique therapeutic cannabis strains through genetic manipulation is still in its infancy, but the available information opens up a sea of new opportunities to increase the effectiveness of medical cannabis. The first step could be creating cannabis varieties with fixed THC or CBD concentrations, avoiding the fluctuations seen in natural hybrids.”
In the future, Russo believes that applying epigenetics to cannabis genomics could allow scientists to create plants with genomes that produce high concentrations of cannabinoids not found in nature, or plants where the effects of certain therapeutic compounds are enhanced by increased production of synergistic terpenes and flavonoids.
“For example, we could produce cannabis varieties containing only high concentrations of CBD, combined with synergistic terpenes, to maximize the controlled therapeutic effect of the plant or its extracts,” Russo suggested. “Similarly, we could create specialized cannabis strains with precise, unchanging dosages of certain compounds, making them easy to use for treating specific diseases or conditions.”
Russo and many colleagues also support developing such “artificial” cannabis types as an effective way to bypass legal barriers that restrict the production and distribution of medical cannabis or its components in the U.S. and other countries. McKernan believes that with bioinformatics, specialists will be able to “program” cannabis genes to breed unique cannabinoid compounds not found in nature.
“This technology won’t completely replace traditional cannabis cultivation, but it will allow scientists to legally produce new therapeutic compounds using available industrial cannabis varieties, which can be programmed to create cannabinoids with highly specialized properties,” he said.
Some medical professionals, like Dr. Donald Abrams, a hematologist and oncologist at San Francisco General Hospital, believe geneticists should focus on already studied, natural cannabinoids rather than synthetics, citing the often poor results of using synthetic analogs as substitutes for phytocompounds. “Even without fully studying the cannabis genome, we know the properties of phytocannabinoids and their effects on the human body,” Abrams said. “Patients need proven and accessible medicines or access to the plant itself and the right to cultivate it. Why take unnecessary risks with unknown substances when science already knows effective and fairly universal therapeutic compounds in cannabis?”
Previous Work in Cannabis Genomics
Although Dr. McKernan’s project received significant media attention, he told the American Society of Botanists that his work is just a new milestone in the long-standing study of cannabis, built on the foundation of earlier research into the plant’s genome and components.
“In mapping the cannabis genome, we relied on the vast body of knowledge generated over a century of studying cannabis and its psychoactive properties,” McKernan said. “Where possible, our team actively collaborated with other specialists, including scientists who made truly radical discoveries in cannabis research. We hope our work will become a foundation for further research in medicine and cannabis cultivation.”
“Of course, the main active components of cannabis—THC and CBD—were discovered and described in detail about half a century before the completion of the cannabis genome project,” Dr. Russo noted. “However, the exact genome map will allow us to study the existing gene variations in cannabis in more detail, especially the mechanisms of physiological interaction between known cannabinoids and CB receptors, as well as the properties of rarer, less-studied exotic cannabinoids.”
Dr. Russo also summarized the main breakthroughs made possible by McKernan and his team, including identifying and characterizing the mechanism of THC synthase, cloning and crystallizing THCA synthase (tetrahydrocannabinolic acid, the direct precursor to THC), isolating and purifying THCA synthase for natural production of high concentrations of this compound in plant tissues, and identifying a unique nucleotide polymorphism in the cannabis genome found in a seed sample from ancient Chinese tombs.
Russo also noted that over the past 10 years, legal cannabis cultivators in the U.S. and Europe have already managed, through artificial selection, to breed plants capable of producing not only high concentrations of THC and CBD, but also other cannabinoids like CBG and CBC, as well as acid precursors such as THCA, CBDA, CBGA, and CBCA.
“These agronomists have done equally monumental work, which will not be devalued by the production of synthetic cannabis plant variations,” McKernan said. “But with new knowledge about the cannabis genome, especially the structure and properties of THC synthesis, we can finally begin synthesizing and studying the properties of the 77 cannabinoid compounds present in cannabis in such tiny concentrations that detailed analysis and testing have not been possible.”
Finally, McKernan is open to the possibility of selectively modifying the cannabis genome to improve traits like yield, resistance to weather and temperature changes, and resistance to pests and parasites. “For example, these qualities could be enhanced by adding segments of the genetic code from Arabidopsis, one of the first plants to have a detailed genetic map,” he told journalists.
Currently, Medical Genomics continues to expand its database, adding new information about gene expression variations in cannabis, while McKernan himself is studying the plant’s genome map to answer why most known cannabinoids are produced in such tiny amounts in cannabis tissues, as well as analyzing their possible effects on human health.