While cannabis is often talked about in terms of cultural, medical, political and scientific debates, recent developments may be the most significant yet. Scientists have not only researched modern cannabis, but also traveled backward in time to recreate ancient enzymes found within ancient cannabis relatives. By utilizing modern plant DNA to replicate ancient plant enzymes, researchers opened a biochemical time capsule to examine a basic question with immense significance: how was cannabis able to develop the ability to synthesize cannabinoids like THC, CBD and CBC?

ScienceDaily reported that researchers had "resurrected" ancient cannabis enzymes when reporting that scientists utilized modern plant DNA to create enzymes that existed millions of years ago. These enzymes are not living plants. This is not a Jurassic Park type scenario with cannabis. Rather, this represents a more subtle and potentially more intriguing approach: a glimpse into the internal machinery of cannabis that contributed to the development of its most well-known compounds.

This research has resulted in findings that could significantly alter our understanding of cannabis evolution, rare cannabinoids and the future of cannabinoid production.

What exactly did scientists revive?

The term "revived" creates an air of drama around all of this, but the science involved is relatively straightforward.

Researchers did not dig up an ancient cannabis plant. Researchers did not discover prehistoric seeds. Researchers did not recover a lost super-strain from the era of mammoths.

Rather than doing any of those things, researchers used a method known as ancestral sequence reconstruction.

This process works by studying DNA from modern cannabis strains and using that data to make educated predictions regarding what the ancestor's enzymes likely resembled. After making their educated guesses as to what the old enzyme sequences would resemble, researchers created those sequences in laboratory settings and studied their properties.

Wageningen University & Research reported that the group successfully constructed extinct enzymes from millions of years ago in the ancestors of the cannabis plant. Those enzymes were subsequently tested in experiments to determine how cannabis evolved the ability to create cannabinoids such as THCA, CBDA and CBCA.

These results matter because enzymes serve as much more than biological background in cannabis. Enzymes represent the workers in the conversion of precursor molecules to specific cannabinoids. Absent enzymes, cannabis would not contain the chemical profile that gives it its distinctiveness.

Why do cannabis enzymes matter?

When we discuss cannabis, we typically speak of the final product.

THC. CBD. CBG. CBC. Terpenes. Other minor cannabinoids.

However, inside of each plant, these products are part of a biosynthesis pathway. Plants do not merely "contain CBD" independent of other substances. Instead, cannabinoid acids are synthesized in a series of biochemical reactions that involve various enzymes controlling what is produced.

Enzymes work similar to specialized equipment in manufacturing processes. When you provide a plant with the correct raw materials and utilize different types of enzymes, you can influence the direction of material toward a variety of cannabinoid end-products.

One of the primary examples of this is CBGA — short for Cannabigerolic Acid.

CBGA is commonly referred to as a "precursor cannabinoid" due to its position in the cannabinoid synthesis pathway prior to several of the major cannabinoids. By utilizing different types of enzymes, CBGA can be converted into cannabinoid acids:

1. THCA — The acidic form of THC

2. CBDA — The acidic form of CBD

3. CBCA — The acidic form of CBC

These acidic forms will eventually transform under conditions of temperature, time and processing into the non-acidic forms: THC, CBD and CBC.

At this point, the new research is particularly compelling. The study demonstrates that while today's cannabis utilizes modern day enzymes, this is not how the original synthesis pathways started.

There was an enormous difference in the way that ancient multi-tasking enzymes and modern specialized enzymes work together. Modern-day cannabis plants utilize distinct enzymes to produce separate cannabinoids. Some of these enzymes have specificity towards producing THCA, others are responsible for creating CBDA, while other enzymes produce CBCA.

The results indicate that the re-constructed ancestral enzymes functioned differently. Instead of being biochemically-specific, early cannabinoid enzymes appeared to be "biochemical multi-taskers". In other words, early cannabinoid-producing enzymes produced several cannabinoids simultaneously.

As time passed, gene duplication likely permitted cannabis to transform its general abilities into more defined and specialized biochemical pathways. This is significant since it indicates that cannabis' chemistry developed more precisely over time. Cannabis may not have originally utilized distinct enzymes for each compound; instead, it may have originated using more flexible enzymes that could create numerous cannabinoid acids.

Over time, natural selection would have refined those flexible capabilities into distinct enzymes for producing specific compounds. The study, which is available as a peer-reviewed journal article in Plant Biotechnology Journal, provides insight into both the origins and functional evolution of cannabinoid synthase genes, the enzyme family responsible for many of the chemical differences in cannabis varieties.

This detail is one of the most critical aspects of cannabis science. While we know that cannabis creates cannabinoids, this research helps explain how cannabis began developing the ability to create different types of cannabinoids.

Why this may matter for the future of cannabinoids

Although the discovery is evolutionary background information, it also potentially has immediate implications. One of the key discoveries is that some of the ancestral enzymes that have been re-constructed seem to be simpler to produce in microorganisms such as yeast compared to their respective modern day cannabis counterparts.

This is particularly significant since biotechnological companies are beginning to explore the possibility of utilizing microorganisms, including yeast, to produce cannabinoids. Utilizing microbes to generate cannabinoids represents an alternative pathway to traditional methods and is particularly useful when it comes to generating rare cannabinoids.

Many cannabinoids exist in nature in low concentration levels within a cannabis plant. Therefore, they are often difficult and costly to extract and purify. With more efficient enzymes capable of generating specific cannabinoid acids, biotechnologists will be able to produce rare cannabinoids more cleanly and consistently.

This does not imply that every rare cannabinoid will be available in stores immediately due to this research, nor does it suggest that this study has generated a new product that will hit store shelves today. However, it does represent potential future possibilities for producing cannabinoids more directly, efficiently and independently of the amount of a specific compound that a plant produces naturally.

This could potentially affect:

• Rare cannabinoid research

• cannabis breeding

• pharmaceutical development

• biotech production

• minor cannabinoid extraction

• future cultivars containing high amounts of cannabinoids

In short, this study presents researchers with potentially improved tools for studying and possibly ultimately producing cannabinoids.

The CBC aspect is particularly exciting

THC and CBD receive much attention in the public eye; however, CBC is another "classic" cannabinoid that could turn out to be one of the most interesting components of this story.

Due to the fact that CBC typically exists in lower concentrations than either CBD or THC, it has received significantly less exposure. As a result of this research regarding enzymes and CBC production, CBC may begin receiving more exposure.

If certain ancestral or genetically-engineered enzymes can enable scientists to produce CBC with greater precision, then CBC may become easier to study, more readily producible and included in studies related to cannabinoids in the future.

That said, CBC should not be viewed as a "miracle compound"; however, it does illustrate why the potential future of cannabis science may not be limited to CBD and THC.

Why is CBG showing up everywhere in cannabinoid science

CBG is already considered one of the next big "waves" in cannabinoids; this study provides some background on why.

More specifically, this study discusses CBGA primarily and therefore indirectly involves CBG, which is generally referred to in the public eye as a parent or precursor cannabinoid.

Therefore, the interest in CBG flower among individuals seeking to investigate cannabinoids outside of CBD is largely an educational introduction to a more complex scientific story: the fact that cannabis produces many cannabinoids.

Although CBD may be the most well-known compound associated with wellness and non-psychoactive cannabis, it represents only a small fraction of the entire cannabinoid family. Other minor cannabinoids including CBG, CBC, CBDV, THCV and others represent a larger discussion regarding how cannabis functions chemically.

The study of the resurrected enzyme provides additional depth to that larger discussion. This study demonstrates that the diversity of cannabinoids is not random, but rather a result of plant evolution, enzymatic function and biochemistry pathways that continue to be understood by scientists today.

How will this affect CBD users?

For everyday CBD users, this research indicates there is no reason to modify your current purchases or use methods when using CBD. As stated previously, this research does not support that CBD can treat any specific conditions; therefore, it should not be utilized to create medical claims. What this research does provide is contextualization.

When individuals purchase CBD flower, they see the end product: the flower, its aroma, cannabinoids and terpenes resulting from the cultivation and processing of the plant. However, behind the end product lies a far greater biological system.

Cannabinoids do not occur randomly in the plant. Rather, they are formed via enzymatically driven pathways that developed over millions of years.

This is why two cultivars can possess vastly differing cannabinoid content. Additionally, this is why a single plant can be rich in either CBD, THC or CBG while another plant may present a potentially unique profile due to higher levels of CBC. These differences are created by genetics, enzymes, growing practices, plant chemical makeup and post-harvest treatment.

The recent research offers insights into the engine producing these differences.

This is not "ancient weed"

I think it's time to clearly define what this discovery isn't.

This research is NOT ancient cannabis being grown again. This research is NOT a relic from prehistory. There is NO proof that ancient cannabis was stronger medicinally than modern cannabis.

As mentioned before, the term "ancient" relates to enzymes thought to exist during cannabis' evolutionary past based on inference from historical data and recreation within the laboratory. These enzymes allow researchers to envision early cannabinoid-producing apparatus.

The difference is significant since cannabis science is often sensationalized. Headlines can quickly turn into hyperbole. But the true story here is quite interesting without needing to exaggerate.

Researchers have successfully constructed ancestral enzymes. Researchers have demonstrated that early cannabinoid enzymes were more general and versatile than modern specialized enzymes. Researchers have shed light upon how cannabis evolved to produce THC, CBD and CBC. Researchers may have also identified tools for future biotechnology.

That is the story. No exaggerations necessary.

The Significance of This Study

In the cannabis industry there seems to be a disconnect between the speed of development and the amount of scientific evidence behind those developments. The development of new cannabinoids is driven by marketing, social media, and consumer trends; however, when it comes to developing these new cannabinoids, the public does not always know the basic information surrounding the cannabinoid.

There is no standard method for evaluating these products, and therefore there is little way for the public to truly understand their use. These same marketing terms spread quickly through out the market prior to being supported by science.

This study is different. This study is an example of going back to the basics. The purpose of this study was to determine how cannabis developed the enzymatic pathway responsible for producing cannabinoids.

The significance of this lies in the fact that the future of cannabis will be more than just creating stronger products or identifying new and trendy cannabinoids. The future of cannabis will depend on our ability to fully understand the plant: its enzymes, genetics, evolution, and chemistry.

A major goal of this study was to provide researchers with a new tool for studying the enzymatic pathways that are involved in the synthesis of cannabinoids. Using this knowledge can help us answer many important questions such as:

• Why are some cannabis strains capable of producing higher levels of Cannabidiol (CBD) compared to Tetrahydrocannabinol (THC)?

• How did the synthesizing enzymes in Cannabis evolve to become specialized?

• Could we develop methods for increasing the efficiency of producing rare cannabinoids?

• Can we utilize ancient enzyme structures to improve modern biotechnological approaches?

• Will future cannabis breeding allow for the selection of specific cannabinoid profiles?

These are not trivial questions. These questions represent the core of potential areas of research for cannabis science.

Conclusion

To date, using modern genetic tools to "resurrect" or "recreate" ancient forms of enzymes from ancestor plants would seem to be nothing short of science fiction. However, this is exactly what scientists have done.

Scientists have utilized modern genetics to recreate ancestral forms of the enzymes that were likely present in early ancestor plants of cannabis. After recreating these enzymes, scientists have successfully tested them and have been able to learn how early forms of cannabis evolved their cannabinoid-synthesizing machinery.

According to the results presented in this study, it appears that cannabis originally had more flexible enzymes which ultimately lead to the development of the highly specialized systems that produce THC, CBD, and CBC.

For consumers, this study highlights that while cannabinoids are a very interesting aspect of cannabis, they also tell a larger story about the plant itself. For scientists, this study represents an opportunity to advance our current level of knowledge in biotechnology and potentially enable more efficient ways of producing rare cannabinoids. For companies within the cannabis industry, this represents an indication of where we might be headed in the future: beyond simply talking about CBD vs. THC, and closer to understanding how the plant actually functions.

The future of cannabinoids may not only be based upon discovering what is currently available in cannabis. The future of cannabinoids may also rely on understanding what cannabis once was.