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    Features

    Five Cutting-Edge Cannabinoid Production Methods to Watch

    Science continues to transform the cannabis industry.

    Five Cutting-Edge Cannabinoid Production Methods to Watch
    By Andrea Holmes, PhD, Co-Founder & Chief Growth Officer, Precision Plant Molecules04.09.20
    Nature inspires virtually all of the all-time best-selling medicines: aspirin from willow trees, caffeine from the coffee bean—even some with beneficial-but-dangerous qualities, like the poppy flower’s natural opiates which have led to lab-produced opioids.

    Science continues to look to the natural world for solutions to human problems, then takes those solutions and advances them further. Best of all? Costs come down, there is far less environmental impact, and more people can benefit, sooner, from such nature-inspired innovation with the boost that high-tech science and ingenuity
    can provide.

    Now, scientific understanding about the ways the cannabis plant makes its rich and complex mix of phytocompounds that have bioactivity in mammals is shifting the cannabis industry in a whole new direction.

    A New Chapter for Cannabinoids
    Recent technological advances mean scientists can generate cannabinoid molecules identical to those produced by a cannabis plant.

    The vast majority of the cannabis product market has centered around THC and CBD, the two most plentiful compounds in the plant. But alternate methods for sourcing cannabinoids offer researchers the opportunity to produce and explore the potential health benefits of more than 100 of the so-called “minor” cannabinoids, which until now have only been available in trace amounts in existing cannabis cultivars.

    These minor compounds are then available to consumer health-and-wellness product companies to make more effective remedies that are often a compelling alternative to traditional pharmaceuticals.

    At the other end of the spectrum from plant-based wellness products, pharmaceutical companies are gaining access to single cannabinoid molecules at the purity levels they require, and in a consistent supply chain untethered to the environmental conditions of a cannabis plant’s growth cycle.

    Truly personalized cannabinoid profiles for each individual and each need—whether in the form of a clinically proven FDA-approved drug or a safe consumer product—are now possible. All of these advancements are poised to disrupt the marketplace for growers, processors, product formulators, and makers of consumer packaged goods on both the hemp and licensed-THC sides of the regulatory divide, in the U.S. and globally.

    Here are five approaches, ranging from the plant to the beaker, for producing cannabinoid molecules that are reshaping the cannabis business landscape:

    1. Extraction and purification from cannabis biomass. Cross-breeding a female plant and male plant with desirable characteristics and then extracting the plant’s oil is an ancient practice, but technology is taking it to a whole new level. With CRISPR, a powerful new genetic engineering tool, researchers can actually design plants with specific chemovars that could offer plentiful sources of formerly rare cannabinoids such as cannabigerol (CBG). Scientists can now breed a cannabis plant that produces only CBD and no THC—or edit its genes to produce any number of different cannabinoids in large quantities, and in the future, approximate ratios.

    2. Biomimetics. This field is defined as the study of nature and natural phenomena to obtain new ideas, then applying those concepts to science, engineering, or medicine. Famously, the breakthrough antibiotic penicillin was discovered by accident after a scientist observed green mold in a petri dish that was curiously killing bacteria the scientist was trying to grow. When applied with cannabinoids, biomimetics—or as my colleagues and I like to call it, cannamimetics—mimics bioprocesses like oxidation (think UV, temperature, chemical reactions) and enzymatic pathways that occur during a plant’s life cycle. Utilizing nature’s blueprint enables researchers to obtain rare cannabinoids from the more common ones produced by a naturally grown hemp or cannabis plant. This method of derivation starts with cannabis or hemp, and can produce minor cannabinoids in pure oil, distillate, and isolate form.

    3. Botanically derived synthesis. Scientists can now make CBD from botanical sources beyond cannabis plants, such as orange peels and the bark of certain species of pine trees. Natural compounds are extracted from a source and combined with other molecules in order to produce cannabinoids. This method appeals to manufacturers that are reluctant to deal with the constantly shifting legalities of the cannabis plant.

    4. Bioengineered fermentation. Biologists have engineered brewer’s yeast, algae and even E. coli to produce cannabinoids that are molecularly identical to ones produced by the plant. Human insulin is already produced in this manner. Genetically programming a host organism like yeast to manufacture another molecule is the concept. Scaling the exacting conditions required to economically use such a molecule “factory” in a petri dish is the challenge these biochemists and bioengineers are working to overcome. And they will do so in due course, just as with human insulin and other drugs now in the marketplace.

    5. Chemical synthesis. Chemical synthesis is the pharmaceutical industry’s go-to method for producing pure, uniform single molecules for incorporation into drugs. Pharmaceutical companies can harness big data and cutting-edge chemistry to produce the exact same molecules found in nature, as well as various isomers and derivatives of the naturally occurring cannabinoids for use in clinical trials and active pharmaceutical ingredients (APIs).

    Daily Life is Saturated in Nature-Inspired Science
    It’s helpful to remember how many bioengineered products and medicines we use in our daily lives. Prior to 1978, all of the insulin that kept diabetics alive was derived from pig and cattle pancreases, until bioengineering made it possible to create insulin in a lab. Aspirin was originally derived from willow tree leaves, but today there’s no need to cultivate and chop down a forest of these farmed trees to extract this beneficial compound because scientists have chemically produced it. Same with vitamins; virtually all vitamin C consumed is made in factories in Asia.

    And just think—truly personalized cannabinoid treatments may result from figuring out novel ways to “turn on” the human body’s endocannabinoid system. A steppingstone to that reality may be prodrugs, which are biologically inactive compounds scientifically designed to transform themselves into naturally-occurring bioactive cannabinoids using the enzymes in the liver during metabolism. It is inevitable these pathways to address deficiencies in body chemistry and homeostasis will be commercialized in the coming short years.

    Indeed, the ability to generate cannabinoids at scale using cutting-edge science and chemical synthesis is game-changing. And while traditionalists and makers of organic and craft products may continue sourcing cannabinoids derived from plants, regardless of scientific advances, alternatively sourced cannabinoids are opening up a whole new avenue of possibilities for the booming cannabis, hemp, and CPG industries. 

    Andrea Holmes, PhD, is a professor of chemistry at Doane University in Nebraska and co-founder and chief growth officer of Precision Plant Molecules (PPM), based in Welby, CO. PPM is a science-driven, specialty non-psychotropic cannabinoid-based bulk ingredients company that extracts and processes hemp, botanicals, and constituents to create oils, distillates, isolates, extracts, and concentrates. 
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