Cannabis, from the latin Cannabis sativa L., is a member of the Cannabaceae, a small family of flowering plants containing hemp, hops, and hackberries. Cannabis means “cane-like,” while the genus name sativa refers to that which is “planted or sown,” meaning that the plant is propagated from seed as opposed to perennial roots. The 170 species in the Cannabaceae family are grouped into 10 genera — trees (Celtis), erect herbs (Cannabis), and twining herbs (Humulus) are all represented. Cannabaceae tend to be dioecious, meaning that the plants are distinctly male and female. The flowers are actinomorphic (characterized by radial symmetry) and wind-pollinated.
Cannabis sativa is an annual dioecious flowering plant which is believed to originate in central Asia circa 5000 BC. It’s been used for thousands of years in the production of fibers and oils, and for medicinal purposes. Medicinally active constituents include cannabinoids, terpenoids, flavonoids, and alkaloids. Cannabinoids are a class of terpenophenolic compounds found exclusively in Cannabis plants which accumulate in the cavity of the trichomes. Upwards of 80 cannabinoids have been identified in C. sativa; the dominant psychoactive compound is Δ9-tetrahydrocannabinol (THC) (Farag and Kayser, 2017).
As a consequence of social and legal stigma, Cannabis and its ‘sticky’ lipophilic phytocannabinoids have only recently been legitimized. The respectable institution of scientific research has managed to validate medicinal actions of the plant that have been recognized and documented for millennia. The earliest known records of Cannabis’ medicinal use are found in the 16th century BC Egyptian Ebers papyrus. Later the plant makes an appearance as a medicament in Assyrian texts.
Evidence of Cannabis used as an obstetric aid in the 4th century AD was unearthed in the ashes of a tomb near Jerusalem. The Israel Police Forensic Lab analyzed a grey, carbonized material found near the abdomen of a skeleton and confirmed the presence of Δ6-tetrahydrocannabinol, a minor but highly stable constituent of Cannabis sativa. The remains were thought to be that of a young girl who died in childbirth. As the story goes, Cannabis was administered by a midwife to a 14 year old girl as an inhalant to support a difficult labor. Modern research corroborates traditional usage — medical publications confirm that the plant effectively increases the force of uterine contractions and significantly reduces labor pain (Zlas, et al., 1993).
Cannabis entered the United States Pharmacopoeia in 1850 and was widely employed as a patent medicine until it was stymied by the federal restrictions of the 1937 Marihuana Tax Act. Cannabis was subsequently dropped from the Pharmacopoeia in 1942, with legal penalties for possession escalating in 1951 in response to the Boggs Act, and in 1956 with the Narcotic Control Act. Federal prohibition struck with the 1970 Controlled Substances Act, legislation that simultaneously criminalized Cannabis possession and suffocated research by restricting acquisition for academic purposes.
With the passage of the 1996 Compassionate Use Act, California was the first US state to legalize cannabis for medical use under the supervision of a physician. Over half the states have since followed suit. As of January 1st, 2017, 28 states, as well as the District of Columbia, Puerto Rico, and Guam, have enacted legislation regarding the sale and distribution of medicinal cannabis.
The transition to legalization has been fraught. Controversy stems from concerns over the psychoactive and impairing effects of the plant, stigma of Cannabis as a “gateway drug,” a dearth of randomized, controlled clinical trials to establish efficacy and potential for harm, lack of standardization of potency and quantity of pharmacologically recognized constituents in products, and the potential for dependence, addiction, and abuse. Despite anxieties over “reefer madness,” however, we’ve seen that cannabinoids present an impressive potential for therapeutic use (Bridgeman and Abazia, 2017).
The recent transition towards mainstream medicalization of Cannabis has sparked major shifts in the industry — standardization practices and sophisticated extraction technologies are the new default. It’s an interesting balance to strike for businesses, capitalizing on authoritative Science cred while preserving the vibe of countercultural cool that has historically defined Cannabis use. Consider the copy on the webpage of US company HempMeds, “This Is How CBD Oil Is Made:”
We test like crazy for accurate cannabinoid content and purity. We don’t mess around. And it all starts with quality hemp sources and a superior CO2 extraction process. Why CO2 extraction you ask? Well, because it’s awesome, that’s why. Carbon dioxide is a non-toxic, non-flammable gas used extensively in a variety of industries, including the food industry… CO2 extraction processes don’t contribute to carbon emission increases in the atmosphere, and this process doesn’t bring any flammable petroleum based solvents (like butane) into contact with your product. Extraction using supercritical CO2 is the state-of-the-art way to utilize this inexpensive and safe industrial solvent for creating high quality hemp oil (HempMeds, 2017).
The language is telling — a slurry of casual banter and technical terms. Companies marketing Cannabis tiptoe a fine line between the Hip and the Institutionally Legitimate. Indeed, the aim of achieving mainstream credibility has led to perhaps an overcompensation for the rougeish reputation of Cannabis. The modern industry’s objective has evolved to encompass strict regulation of plant propagation and constituent extraction, scientific validation of the efficacy of standardized extracts for specific pathologies, and ultimately technical domination and pharmaceuticalization of the plant. Let’s take a look at the strategies of a handful of major Cannabis-producing companies across the globe.
Modern Methods of Cannabis Manufacture
The complexity of the whole Cannabis plant presents a challenge to modern medicinal methodologies. The current game is to prescribe standardized, targeted drugs containing the barebones “active” constituents. Cannabis, on the other hand, contains a surfeit of constituents mingled in highly variable and unpredictable concentrations depending on such factors as plant strain, climate, nutrient availability, photoperiod, and other growing conditions.
With the medicalization of Cannabis and the entanglements of legalization, the industry has shifted from using the whole plant to producing extracts that contain only the “medicinal” cannabinoids without the cognitive effects of THC. International companies, though geographically and culturally disparate, share many of the prevailing ideologies currently imbuing Cannabis product manufacture: aspirations of standardization, quality control, industrial efficiency, ecological stewardship, and harnessing the medicinal virtues of Cannabis while eliminating psychoactive properties to accommodate legal mandates are common.
So how does a major company extract CBDs from Cannabis on a commercial scale with any degree of consistency? Several strategies are at play. We’ll begin with the aforementioned California-based company HempMeds, established in 2012 by parent company MYM Nutraceuticals. HempMeds employs supercritical CO2 (sCO2) extraction, perhaps the most well-known extraction technology to date. Large-scale commercial plants utilizing sCO2 are most common in the food industries, and are particularly popular for the decaffeination of coffee and tea and the extraction of hops.
Macro detail of container with CBD oil (Credit: Istock by Getty Images)
To understand how sCO2 works as a solvent we need to dive into a little chemistry. Supercritical CO2 is essentially carbon dioxide in a fluid state. In daily life we find CO2 behaving as a gas (at standard temperature and pressure (STP), and when frozen it solidifies to form the ever-famous dry ice. If, however, temperature and pressure are brought to CO2’s critical point or above, the substance assumes properties somewhere between a gas and a liquid. Once a compound surpasses its critical values, the boundary of the liquid-vapor phase ceases to exist. A compound in its supercritical state thus possesses a fluid-like density, while adopting the diffusivity, surface tension, and viscosity of a gas. Due to this liquid-esque density, the solvent strength of a supercritical fluid is comparable to that of a liquid, which renders it distinctly favorable for industrial applications (Chemical Engineering, 2010).
This technique took on an important role as a commercial and industrial solvent for its chemical extraction capabilities, with the added bonus of low toxicity and minimal environmental impact. Due to the relatively low temperature and the stability of sCO2, compounds can be extracted with little damage or denaturing. Interestingly, the solubility of extracted compounds varies contingent upon pressure, which allows for a degree of selectivity in extraction. For this reason, sCO2 is known as a “tunable” solvent. In the case of Cannabis, varying pressure settings of the equipment allows for the collections of distinct extracts containing waxes, heavy oils and resins, and light oils.
There are distinct advantages to using supercritical CO2 as a solvent. Traditionally, organic solvents — integral to the chemical process industries — have posed several challenges: Many are carcinogenic and neurotoxic, highly flammable, and hazardous to the environment. Consequently, conventional solvents are regulated as volatile organic compounds (VOC), and some have been banned due to their potential for ozone depletion. CO2 is not considered a VOC, and results in no net increase of atmospheric CO2 as it is initially drawn from the environment into which is it subsequently released. Furthermore, in contrast to many organic solvents, sCO2 is non-flammable. It is inert and non-toxic, inexpensive, and requires relatively lower temperatures and pressure to achieve supercritical status. sCO2 is considered a “green” alternative to hydrocarbon solvents, which are notoriously toxic and persistent in nature. Hydrocarbon solvents demand significant effort to purge from products, whereas sCO2 requires minimal post-processing, and any residual solvent is non-toxic (Eden Labs, 2018).
Supercritical CO2 has been around since the ‘80s, but as the Cannabis industry evolves, so does the technology. Precision Extraction Solutions, headquartered in Troy, Michigan, manufactures closed loop light hydrocarbon extraction equipment which utilizes hydrocarbon solvents to commercially extract constituents from Cannabis. In a closed loop system botanical material is contained in a column and flooded with a solvent, in this case butane and propane, which draws out the desired oils. The mixture is collected and the solvent evaporated off, leaving a botanical extract. In an open system propane and butane, gases at standard temperature and pressure, would evaporate off and be lost. The closed loop retains the solvent which is more efficient, not to mention safe.
Precision claims closed loop hydrocarbon extraction is the most efficient method: “Seven times the throughput of comparable CO2 supercritical extraction equipment at a fraction of the cost.” Their industrial-scale equipment is graced with edgy names like “the Judge,” “the Predator,” and “the Executioner.” As their vision statement declares, “We work with many large scale producers and are experts in both local and state level code compliance. Our expertise covers a wide range of competencies including ASME Section VIII code, UL, International Fire Code, and 3A food processing compliance. We help our clients succeed through safety, innovation, service, and meticulous quality control.” Again, the copy recapitulates the industry ethos: cutting edge cool (Precision, 2018).
Canadian company Abattis Bioceuticals, founded in 1997, recently developed a Cannabis extraction technology using column chromatography. According to president and CEO Rob Abenante in their December 12, 2017 press release:
The extraction method using proprietary polymers has very distinct competitive advantages over traditional methods. The technology is capable of extraction on an industrial scale, which delivers significant cost advantages. It is also capable of separating cannabinoids on a molecular level which allows for the extraction of pure isolates such as CBD and THCA and even the separation pesticides from the biomass.
Column chromatography isolates individual chemical compounds from a mixture based on the differential adsorption of compounds to the adsorbent. Compounds move through the column at divergent rates, which allows them to be separated into distinct fractions. The developer of the technology performed a quantitative recovery measurement which demonstrated 99% recovery of all cannabinoids from the biomass material. These yields are compared to “conventional methods,” which yield less than 80%. The press release enthusiastically heralds the advantages of the innovation, claiming, “The technology successfully removes all traces of any pesticides or harmful residues from the cultivation and transportation process,” and concludes that “The cost of capital equipment and overall cost of operation is less than half of conventional CO2.” With the advent of ‘proprietary polymers,’ novel technology rises to meet consumer demand (Abattis, 2017).
Perhaps the most fastidious of all, Netherlands-based company Bedrocan proclaims “Consistency through standardisation” as their procedural motto. On their webpage “Our Method” they delve into the relevance of standardization. “Why should you care?” they inquire, then answer:
For one, it’s not just about stable THC and CBD content from one batch to another. It is also about balancing over one hundred potential active components, from cannabinoids to terpenes. Standardisation is the only method of ensuring that prescribers and patients can achieve a consistent therapeutic effect over time. Standardisation helps assure dosage composition, the repeatability of dose, and greater ability for patients and prescribers to adjust dose by titration. This allows for proper monitoring of the product’s efficacy, safety and potential side effects. Standardisation enables the comparison of findings from different clinical trials and studies across time. It is a critical factor for building the evidence-base of for the efficacy medicinal cannabis.
Interestingly, the standardization aims of the industry seem to be predominantly driven by the the manner in which contemporary scientific research is conducted. In vitro assays, animal studies, and clinical trials are currently the only valid means of assessing medical efficacy in mainstream culture. Thus, plants must be converted to products that interpretable within this reductionist paradigm. Certainly scientific research is a useful tool, but with this model much is lost. The healing power of a plant often emerges through the synergy of its constituents; the whole is abundantly greater than the sum of its parts.
Bedrocan’s strict commitment to their discipline is remarkable. They’ve quashed every imaginable quirk of capricious nature; “control” is the mantra. Behold:
Our indoor growing rooms use state-of-the-art environmental control technologies to control all variables, including light, temperature, nutrients, and water. Each of these rooms is sealed with special doors to prevent contact with airborne contaminants. Our production process has been specifically refined to grow standardised cannabis flos without the use of any pesticides. In addition, our international quality assurance measures are proudly achieved with very high hygiene standards, relevant testing requirements, and strict pesticide and fungicide restrictions. Every week a fresh batch can be harvested, 52 weeks per year, to a schedule we can predict years in advance.
Each cultivar originates from one single seed. Our plants are grown by multiplying the original plant material. Bedrocan uses proprietary vegetative propagation techniques to give our products remarkable genetic stability. This method prevents ‘genetic drift’, a problem resulting from repeated vegetative propagation of the mother plants, which can cause major changes and weakness in the plant over time (Bedrocan, 2017).
The technical mastery that makes such standardization possible is impressive, certainly, but does this process produce the best medicine?
Diversity, Synergy, and the Old Ways of Knowing
The implicit supposition that “control” is the superior way to relate to Nature is nothing new. English philosopher, statesman, and scientist Francis Bacon wrote in his 1620 publication The Great Instauration, “The nature of things betrays itself more readily under the vexations of art than in its natural freedom.” By “art” Bacon means the manipulations of technology; the constraints applied to phenomena through the establishment of meticulous experimental conditions (Bacon, et al., 1937).
This attitude prefigures the ethos of the Enlightenment — the belief that everything can be rationally known, and once known, controlled. As Greek mathematician Archimedes famously said, “Give me a fulcrum and I shall move the world.” With the right leverage, in this case scientific data, we can manage the material realm and remodel it to our liking. 21st century technology has at last caught up with our metaphysical ambitions, and we are finally in position to execute the age-old Western objective of manipulating nature through intellectual and technological mastery. The belief in the preeminence of control, however, is an authoritarian doctrine; in politics we call it “fascism.”
Identifying “active” constituents and standardizing them in an extract may satisfy the compulsion for order, but it does so at the expense of other ways of knowing and encountering the natural world. So what are the alternatives? The natural variability of plants may be precisely what makes medicines derived from them so powerful. Nature is infinitely complex, synergistic; emergent properties abound. A whole plant tends to be more vibrant and medicinally viable than single-constituent extracts, a phenomenon even observed in the lab with the discovery of the “entourage effect.” Consider the case of palmitoylethanolamide (PEA), a cannabinoid that lacks an affinity for the CB1 and CB2 receptors, and yet has been found to augment anandamide activity (Ho, et al., 2008).
In contrast to the reductionism of modern science, we have the traditional healer’s method of “Simpling,” one which acknowledges the participation of the whole plant in medicine. Appalachian folk herbalist Phyllis Light describes the practice of Simpling, which asserts that one herb can be used in “umpteen thousand ways.” She tells the story of her grandmother and father, saying, “They didn’t need complex formulas because they really, really knew their plants. My father used Ginseng for most ailments and knew exactly how much to decoct for how long or whether it should be taken raw” (Hardin, 2014). I was told a story by word of mouth that when Light had someone to heal, she would go out and talk to the ginseng. She’d ask the ginseng which plant should be harvested for her purposes, which part, and what preparation. The ginseng answered her. The remedies worked.
This might sound absurd, and yet many professional healers communicate with plants in this manner to inform their clinical practice. Perhaps it’s not so unbelievable that plants might communicate with us considering that they communicate with each other using an “internet” of fungus (Fleming, 2014). We might not think about it much, but plants are highly skilled at capturing the attention of potential symbiotic partners. Just think of the vibrant hues and lush aroma of mouthwateringly ripe fruit.
Our senses provide us with sophisticated information about the natural world. There’s a name for this — organoleptics. We engage this system every time we sniff milk to see if it’s gone off, when we choose attractively colored vegetables for the dinner table, or identify the subtle notes in wine.
It’s powerful stuff. Consider the anecdote presented in the 1952 article “Organoleptic Panel Testing as a Research Tool” published in Analytical Chemistry: Consumers complained that their cigarettes were plagued by an “objectionable odor” that experts guessed might be caused by a specific insecticide. An organoleptic panel was convened to verify the hypothesis, and after tasting dilutions of that insecticide and samples from the cigarette packaging, the panel confirmed that the suspected insecticide was the culprit. It was present in the cardboard container at 1/10th of a pound of insecticide per ton of packaging material; 0.005% contaminant by mass. At the time, the authors concluded that this was the sole means of identifying the contaminant. Technological advancements may have since rendered this problem irrelevant, but it is still an illustration of the human sensorium as a potent analytical tool (Cartwright, et al., 1952).
These days, it seems like everyone is hanging on by the skin of their teeth. Chronic diseases, skin pathologies included, are on the rise in the industrialized world. Outbreaks of acne are associated with increased air pollution (Krutmann, et al., 2017), while psychological stress is known to exacerbate psoriasis, urticaria, eczematous dermatitis, and herpes simplex (Kimyai-Asadi et al., 2001). In our hectic modern lives we must use all the tools available to us, whether technological or traditional, to bring ourselves back to health, back to balance.
The skin, hardly superficial, offers a clue.
End of Part III: Cannabis: Plant, Industry, and Ideology. If you missed the first two, here are links:
Part I: Skin Deep: The Role of the Endocannabinoid System in Cutaneous Homeostasis
Part II: CBD Oil: The Skinny According to Science
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