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The case for biosynthesis: 5 problems with cannabinoids derived from plant cultivation

As we look at the current and future market demands for cannabinoid ingredients, large consumer buyers are focused on purity, consistency and stability of supply. For a host of reasons, cannabinoid suppliers will find it extraordinarily difficult to meet this demand with plant-based production systems.

Inspired by these challenges, the founders of LAVVAN created a cellular agriculture platform that utilizes biosynthesis and fermentation to form a better ‘biological’ factory for cannabinoids. Through our partnership with Amyris Inc., this platform, provides a scalable process that consistently produces high-quality, reliably sourced, and cost-competitive cannabinoid ingredients. From this starting point, one can formulate them into a variety of products or recreate the efficacious formulations that are found in cannabis plant varieties.

There are several problems that make working with cannabis plants an inefficient and costly method of producing high-quality cannabinoids. In this blog, I will look at five of these problems and discuss how biosynthesis provides a far superior method for producing cannabinoids.

1. Cannabis is an opportunistic weed

The first problem is that the crop is (to borrow a colloquial expression) a weed that evolved as weeds do: to rapidly grow and reproduce. They certainly didn’t evolve to be a cannabinoid factory. Cannabis is an opportunistic plant, happily encouraging all kinds of other microorganisms to live inside and on it to improve its ability to succeed as a weed. 

However, many of those microorganisms are harmful to humans, even though they don’t negatively affect the plant. In some cases, they can be beneficial to the plant. From that perspective, the plant wants to be ‘dirty,’ and for cultivators, it is a continuous battle to keep it ‘clean’.

This is a common problem for many crop plants. From a production point of view, and given the ways cannabinoids are being used, this poses a significant risk of crop loss and more importantly has a potentially negative impact on human health. We need ‘clean’ cannabinoid products without any of those extra microorganisms or the dangerous compounds (e.g. aflatoxins) that microorganisms can produce that can persist in the products.

2. Cannabis is a living system

It is important to recognize that plant cultivators are working with a living system, essentially producing compounds out of a dynamic organism at the whims of an ever-changing environment. Despite how many controls one places on the cultivation environment, the nature of living organisms is that they are variable and the products they produce are variable. In contrast, large cannabinoid buyers require consistency and stable supply from their suppliers.

To complicate this further, only certain parts of the plant produce the target compounds. It is generally the female flower structures that produce cannabinoids rather than the rest of the plant. Up until now we’ve been bound to this plant as the sole source of cannabinoids but compared to the productivity of other organisms, it is by no means an optimal production system for cannabinoids.

3. Lack of agronomic tools 

In regulated jurisdictions, cannabis cultivators cannot use typical agricultural chemical inputs like pesticides (such as myclobutanil) and fungicides. This leaves crops susceptible to plant pathogens that can impact yield. A more significant concern is that some of these chemicals, when combusted, become toxic to anyone inhaling smoke or vapours.

In contrast, and for example, these chemicals would normally be allowed in tomato production and consumption because people don’t try to burn and inhale tomatoes. The only recourse is to develop disease-resistant varieties: a process that is well underway but years away from having a meaningful impact. In general, cultivators are left with a crop production system fraught with risks.

4. Legal definitions cause problems for plant growers

In the cannabis regulatory world, there exist both botanical and legal descriptions of plant varieties. These legal distinctions are focused around the level of total THC/THCa in cannabis plant varieties. This issue primarily affects hemp, which is a variety of cannabis that is bred for fibre.

In the United States and Canada:

  • If a Cannabis sativa plant tissue, or processed material, contains THC levels equal to, or less than 0.3% w/w1, it is automatically classified to be hemp or associated derivative product as hemp-derived.
  • If a Cannabis sativa plant tissue, or processed material, contains THC levels greater than 0.3% w/w, it is automatically classified to be marijuana or associated derivative product as marijuana-derived.

This designation causes much confusion in the industry due to the wide variability that can exist in cannabis plant production systems. Changing field conditions can alter cannabinoid levels and thus a cannabis plant or crop can fluctuate between the designation of hemp and marijuana yet remain in the same variety.

Similarly, as cannabis tissues are dried and processed, their relative concentrations of cannabinoids can vary resulting in a fluctuation between the designation of hemp and marijuana while remaining in the same variety. Operators or cultivators are typically licensed according to the legal or regulatory designations and because of the variability in the crop system, THC concentrations can fluctuate in and out of legal compliance

Some jurisdictions are looking for this to change, and in some European countries, the threshold THC level is lower. The serious risk this variability poses to growers’ businesses recently came into sharp focus in Arizona, where the State Department for Agriculture published statistics on hemp producers that showed 40 per cent of hemp production in that state failed the THC concentration test.

5. Cannabis growing has an enormous carbon footprint

It is impossible to ignore the environmental impact of cannabis plant production, which is huge. In a recent report from the Lawrence Berkeley National Laboratory, it was found that up to one per cent of energy consumption in the United States is now going to cannabis production.

Setting aside other environmental impacts of cannabis cultivation, including water use and fertilizer, that massive energy use adds up to make a significant impact on the carbon footprint of this industry – despite the fact that it is a plant, a carbon sucking photosynthetic plant.

The case for cellular agriculture 

Cellular agriculture employs both biosynthesis and large-scale fermentation to make products. The process is analogous to plant agriculture but instead of harvesting crops of plants, we harvest crops yeast. It’s an agricultural approach that has been used for over forty years producing a variety of new molecules from biofuels to food ingredients. LAVVAN is now applying this approach to the production of cannabinoids.

The research on the efficacy, safety and utility of cannabinoids like cannabidiol (CBD) and cannabigerol (CBG) is revealing these molecules to have a variety of important benefits. The research into CBD is also showing significant utility as an anti-spasmatic, anti-epileptic, and has been shown to have the ability to dampen the effects of THC.

In general, THC and CBD are widely available as two primary cannabinoids. But there are many other cannabinoids with enormous potential including CBG, CBC, CBN, CBL, as well as the verin and acidic forms of all the cannabinoids. 

The issue is that most of these cannabinoids are found in trace amounts in the plant and are extremely expensive to recover. Regardless of the rarity of cannabinoids in the plant, the cellular agriculture approach allows us to produce any cannabinoids in desired quantities with consistency, high purity and at low-cost.

From a global perspective, our cellular agriculture method for producing cannabinoid molecules, employs vast fermentation vessels in a controlled closed system, mitigating many if not all of the challenges in plant cultivation for cannabinoid Isolate. 

There will always be a market for the cultivated flower but to efficiently and safely meet the vast market demand for cannabinoid raw ingredients, I believe it is a method the cannabinoid industry can and will embrace.

Jeremy Friedberg is CSO at LAVVAN.

Don’t miss out on the International Cannabinoid-Based Drug Discovery & Development Congress next week – there is still time to register here.

Footnotes:

1 Weight for weight, the proportion of a particular substance within a mixture, as measured by weight or mass.

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