Harry’s World: The Science Of CBDs

The term CBD has been all over the media lately. Both Dr. Sanjay Gupta and the New York Times are talking about the helpful benefits. As a result of strains like Charlotte’s Web and other pioneering CBD-based medicine, demand has skyrocketed. But what exactly is a CBD? The name is an acronym for a cannabinoid called cannabidiol. I had the chance to interview Dr. Joshua Hartsel, P.H.D, a senior research scientist at The CannaVest Corp.

I had the pleasure of meeting Joshua at the 2013 Cannabis Cup in Amsterdam and was fascinated by his knowledge of one of the most interesting and medically valuable cannabinoids, CBD. He had entered that Cup with a CBD oil that was over 80 percent pure CBD, and went on to win the CBD category that year. It was his third time entering a Cup that year. I thought it would be interesting to ask him a few questions about the cannabinoid.

High Times: CBD is one type of cannabinoid — what makes it so amazing?

Dr. Joshua Hartsel: Until recently, CBD was not a topic of discussion in the cannabis community. People really started to talk about the benefits of CBD around 2011, and now there is a category in the High Times Cannabis Cup dedicated to high-CBD strains and concentrates, as well as extensive media exposure. This increased visibility has garnered significant interest from clinical studies for various medical indications, but also because it is a non-psychoactive substance that does not induce a “high.” Many people are familiar with Charlotte’s Web due to the documentary “Weed: Dr. Sanjay Gupta Reports,” released after Dr. Gupta’s public recanting of his position, saying the DEA “didn’t have the science to support (their) claim.” Now researchers from all over the world, including CannaVest, are focused on this interesting molecule.

Most people familiar with cannabis know what the THC gland looks like with its traditional ball and stock structure, where do the CBDs fit into that? Are they in the head with the THC or in the stock.

I was personally surprised when I tested my first batch of trichome-rich kief at Delta-9 Technologies. The crystalline trichome material, produced with the pollinator, all tested within the range of 25 – 35 percent THC, which seemed odd from a material that looked so pure. We expected much higher numbers and retested to confirm. This result indicated to me that there was an abundance of non-cannabinoids present in the trichome. After a literature review on the topic I learned that there are actually three different types of trichomes present on cannabis; 1. Bulbous, 2. Capitate sessile (stems, leaves, and bracts), and 3. Capitate stalked (develops during flower formation) that most people are familiar with based upon images captured using microscopy.

Interestingly, only the capitate sessile and capitate stalk secrete the cannabinoids. Therefore, it is highly likely that the CBD isolated from industrial hemp occurs in the capitate sessile-type trichomes, because flowering is generally not induced before harvest. The biosynthetic process occurs in the secretory cavity located in the head of the trichome, where vacuoles and plastids containing terpenoid and olivetolic acid building blocks are found. The cannabinoid precursors are transported through the stalk and combined in the head where they are highly concentrated. The mother cannabinoid, CBGA, is the precursor to all other cannabinoids, and is generated through a olivetolate geranyltransferase catalyzed reaction between olivetolic acid and geranyl diphosphate. It is interesting to note the common lineage shared between cannabinoids and terpenes within the plant kingdom. Geranyl diphosphate is a precursor for a variety of terpenes found in plants, but is also the precursor to CBGA. This vital key ingredient is a building block for all the best cannabis ingredients.

THC is secreted into the head of the gland via a small sack that sits at its base. Is there also a place where the CBDs are manufactured by the plant?

Our understanding is that geranyl diphosphate and olivetolic acid building blocks are secreted to the head of the gland and then converted to the phytocannabinoid, CBGA. This enzymatic transformation is catalyzed within the trichome head by olivetolate geranyltransferase. Relative cannabinoid content is regulated by the concentration of a unique group of cannabinoid synthase proteins called THCA synthase, CBDA synthase, CBCA synthase, etc. Generally, medical cannabis is high in THCA content relative to CBDA due to high levels of THCA synthase expression, whereas hemp varieties tend to be higher in CBDA content relative to THCA for the opposite reason. Only a limited quantity of CBGA is produced in the plant and is consumed at a rate controlled by the relative cannabinoid synthase levels. Therefore, if hemp varieties contain high levels of CBDA synthase, then it is likely that the CBGA will be transformed into high levels of CBDA with lower levels of co-cannabinoid production.

There are lots of discussions about CBDs being extracted from hemp; is there a big difference between extracting them from commercial hemp vs CBD-rich medical marijuana strains?

I am hesitant to use the acronym CBDs for cannabinoid nomenclature. For example, there is only one cannabidiol (CBD). CBDs is an acronym for cannabinoids and can be confusing when talking about CBD. The main difference between extracting CBD from hemp versus CBD-rich medical cannabis is the low cannabinoid content compared to medical strains. I have seen medical cannabis strains test as high as 17 percent CBD (ACDC), which would give a very pure product directly off of the initial extraction. However, hemp strains tend to be much lower, in the one to four percent CBD range. This presents its own set of challenges when refining the oil to an acceptable quality. We have spent the past few years improving on specialized techniques to purify CBD-rich hemp oil and we are currently working on some of the first patents in this area. We have been able to purify CBD to pharmaceutical-grade levels using these techniques.

What is the best way to extract the oils? There have been lots of stories lately regarding people blowing themselves up because of butane extractions would it not be better to extract using something like Olive Oil or Co2?

There are pluses and minuses to both procedures. Although light hydrocarbons (i.e. butane and propane) produce excellent shatter and wax products due to extremely high acidic cannabinoid content, these extraction techniques potentially pose a health risk for the extractor and consumer. Most CO2 extracts in the medical cannabis industry decarboxylate the plant material prior to extraction making it impossible to attain a crystalline shatter and wax product. Individuals who blow themselves up with butane generally have little training in chemistry and are simply following YouTube instructions. It is dangerous to use open columns to blast butane into the atmosphere, especially indoors! However, recent advances in closed-loop systems by trained personnel offer a viable solution to this problem. Butane requires long purge times under high vacuum to remove residual solvent content. In the process you generally remove the desirable aromatic and flavorful terpenes as well. In contrast, CO2 systems pose no threat of residual solvent contamination and residual carbon dioxide can be removed without high vacuum. We feel that CO2 is the best option for industrial hemp since we are producing a nutraceutical product for human consumption. Using CO2 we have avoided the safety and health concerns associated with light hydrocarbons altogether. In addition, the CO2 can be recycled, which is an environmentally friendly process.

A lot of people know the pioneering work that Rick Simpson has done with his hemp oil. Is that indeed the best way to ingest it, as a raw oil?

Raw oil contains higher levels of the CBDA versus CBD, while decarboxylated oil contains much higher levels of CBD with insignificant quantities of CBDA. Due to the pluripotent effect of CBD and CBDA it would be hard to say that there is a “best” way to ingest the oil. Each person responds differently and would need to evaluate both types to see what best suits their needs. It is worth noting that during my recent visit to Italy for the ICRS conference, there were several academic experts discussing CBDA and its therapeutic efficacy for medical indications. The diverse biological activity of CBD is truly impressive.

Can someone out there who is in a medical state make their own oil from self grown CBD rich cannabis?

Although certain individuals with botanical extraction experience could easily prepare small quantities of CBD oil from home, current legislation could define this activity as criminal. With the recent passing of the 2014 Farm Act it is now legal to grow hemp for research and development purposes. It is not legal to grow hemp for commercial purposes. Further, it is still illegal in many states to grow and possess cannabis for medical purposes. CannaVest offers an alternative to many people around the country who do not have the legal ability, time or expertise to prepare their own CBD oil. Our hemp is legally imported from Europe and avoids the legal issues with hemp grown in the USA.

You’ve won several awards with your CBD oil. What sets your product apart as a Cup-winning product?

I was classically trained in the art of organic chemistry and have been lucky to work beside some of the most talented minds in chemistry. I earned my Ph.D. at Virginia Tech designing, synthesizing, and purifying safe mosquitocides for malaria control. I was fortunate as a Ph.D. and postgraduate scholar to work on projects funded from the National Institutes of Health and The Bill and Melinda Gates Foundation, and this gave me the resources to explore many different biochemistry, organic chemistry, analytical chemistry, and separation methodologies. After completing a three-year postdoctoral fellowship at the University of California, Irvine I welcomed a new career in the medical marijuana industry. I served the board member of the Association of California Cannabis Laboratories, founded Delta-9 Technologies, and have most recently led the research and development efforts at CannaVest Corporation. It has been an honor to be covered on major news networks (CNN and ABC 10 San Diego News), win three consecutive HIGH TIMES Cannabis Cups (Seattle, Amsterdam and Los Angeles), and The Michigan “Green Cup” for the highest cannabidiol (CBD) concentrate. Basically, we use state of the art techniques to attain such high purity. The lengthy orthogonal purification techniques are not straight forward, and have required years of experience and development to attain a pharmaceutical-grade CBD from a raw CO2 oil that starts at 18 percent. The 18 percent CBD in the raw oil is equivalent to the average THC concentration in the flowers of medical grade cannabis. I have seen concentrates that are as high as 83 percent THCA directly from the plant material. Turning 83% THCA into pharmaceutical-grade product seems trivial in comparison.

What do you think of companies like GW pharmaceuticals? Is this a good thing for our industry or more of a beware of Monsanto type of situation?

There is something special about cannabis that can’t be put into a spray or pill. Many people prefer to smoke cannabis and that is a personal decision. Our society is moving towards legalization for recreational purposes and as that happens, it will be hard for any one company to control well-known botanical compounds. However, there will always be a need for cannabinoid drugs specifically engineered to treat specific medical indications. GW has been at the forefront of cannabis science and has worked with many companies and academic institutions to further our understanding of cannabis. In my view, GW Pharmaceuticals has been very positive for the cannabis industry. They are currently working with US regulatory agencies to gain approval in recognizing cannabis as a medicine. They have also demonstrated that many of the compounds found in cannabis do have therapeutic value. Perhaps most important, they have been able to do this using clinical studies and hard facts as opposed to anecdotal evidence that is so common in the cannabis industry. We don’t know what the future holds, but hope both the traditional cannabis industry and the pharmaceutical segments of our industry each can have their place and perhaps complement each other.

The public demand for CBD is impressive and growing. We believe that change in market perception will lead to change in public policy as indicated by the bipartisan 2014 Agricultural legislation signed into law earlier this year. It is hard to take a stance against the legalization of hemp and CBD when they have no psychoactive effects and clearly have exciting biological activity that may improve health. Anyone who is against legalizing CBD needs to educate themselves on the history and science of the subject. As we continue to learn more about CBD and its benefits, there will be no stopping this exciting molecule from being embraced as one of the most important nutraceutical discoveries of the century.

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