1. AN EVOLVING NATURAL EARTH SCIENCE
(a) Biochemistry and Physiology: Common Ancestral Links Between Flora and Fauna
(b) Contemporary Cannabis Botany Presents a Challenge for Taxonomy.
(c) Genetics Brings Improved Accuracy to Botanical Science
2. CHEMICAL RECEPTORS’ IMPORTANCE TO HEALTHCARE
(a) Botanical Alkaloid Discoveries Receive the Nobel Prize
(b) Trichomes – Where Cannabis Plant’s Chemicals Derive From
(c) Studying Botanical Science is a Moving Target
3. AN APPLIED THERAPEUTIC SCIENCE
(a) Why Would a Plant’s Chemicals Effect an Animal’s Receptors and Behavior?
(b) How Do the Balanced Chemicals in Cannabis Restore “Homeostatic Physiology”?
(c) Cannabis Botany Basic Science Will Advance the Understanding of Our Complex Physiology
Evolutionary natural selection provides indirect evidence of mankind’s effective use of botanical substances. Whether for nutrition or remedies, plant source chemicals are essential to sustain life, and have been exploited by animals since the beginning of time.
Human life’s evolution along with plant life has revealed common ancestral chemicals recognized to be essential to our health and survival. One has only to look at the essential “life blood” molecules of hemoglobin next to chlorophyll to appreciate that these remarkably similar chemistries connect an ancient botanical past to the complexities of our evolved modern human physiology.
In ancient times, healers were depended on as horticultural botanists. If they did not understand how to keep plants alive, healers would have lost their formulary and most certainly have failed at their craft. From the earliest of primitive nomadic tribes, to the advancing agricultural civilizations that followed, botany remains central to mankind’s successful evolution.
Early civilization’s “physician” healers included Imhotep (2667-2648 BC) in Egypt and Hippocrates (460-370 BC) in Greece who understood and responsibly shared the importance of plants to sustain health. These two historical figures are widely regarded as The Fathers of Modern Medicine in that they recorded their botanical findings to herald the beginning of the evidence-based healthcare science.
Unlike most plants that use several methods of distribution such as wind, insect cross-pollination, or seed dispersal by animals; human agriculture is credited for Cannabis’ worldwide transport from Asia began subsequent to the last ice age. There is accumulating genomic evidence that native and natural traditional landrace cannabis strains evolved its ancestral balance of synergistic phytocannabinoids and essential oils that successfully co-evolved with humans to find its way around the world.
Teleological discussions reason that if used by human beings for over 10,000 years, these traditional Cannabis cultivars likely interplayed favorably with human genes to meet the survival needs of an adaptive physiology. Considering mankind’s successful survival along with cannabis since the last ice age, when intuitively regarded as an ethnobotanical “experiment”, the evidence of human survival to indicate a therapeutic tolerance supports evolution as the ultimate “knock-out” design model. (*)
As humans better understood living organisms, several systems to group plants and animals were devised according to the available knowledge of that time. Mankind’s current attempt to categorize plants into an acceptable taxonomy includes both nomenclature and classification. The mid-18th century Linnaean hierarchal order in use for naming organisms is based on eight taxa and includes: domain, kingdom, phylum, class, order, family, genus, and species. Classification is the ordering of items into groups based on similarities and/or differences; in biological classification, species are one of the kinds of item to be classified.(1)
For cannabis botany, “proper” names starting point began in 1753; the year Carl Linnaeus first published Species Plantarum using binomial nomenclature (genus; species). Renderings of herbarium specimens and classical botanical drawings remain as the accepted standard for plant identification because by convention they depict all parts of the plant’s life cycle in a single image; including seeds, roots to stems, and leaves to 5 flowers. The morphology and shape of a plant’s flowering parts was traditionally used to determine many groupings.
Cannabis is also botanically categorized as being dioecious because separate plants contain either male or female reproductive organs, requiring cross-pollination to set seed. One contributing reason why field grown male and female Cannabis plants often have been referred to as “weeds” is because the male plant’s pollen is easily windswept to nearby readily receptive female flowers to create seeds. Because the greatest content of phytocannabinoid and terpene chemicals are found in un-pollinated female flower bracts, the female plants are usually kept separate from males to ensure that more energy contributes to plant chemical production rather than seed production. Hence derives the Spanish word Sinsemilla meaning “without seeds” to describe the female plant flower’s rich chemical content.
The two common Cannabis species used for medical purposes are referred to as indica, and sativa. The existing nomenclature for the genus Cannabis is used to legally distinguish its contrasting commercial uses.
Whereas few if any true pure landrace varietals actually still exist, today’s “medical marijuana” as developed under Federal Prohibition more accurately refers to a collective term representing man-made hybrids between traditional sativa and recreationally popular indica species of the genus Cannabis.
Despite its cultivation as a source of food, fiber and medicine, and its global status as the most frequently used illicit drug, the genus Cannabis currently has an inconclusive taxonomic organization and evolutionary history. Drug types of Cannabis (marijuana), which contain high amounts of the psychoactive cannabinoid THC, are used for medical purposes and as a recreational drug. Hemp types are grown for the production of seed and fiber, and contain low amounts of THC.
Hemp is a variety of Cannabis sativa plant species that is grown specifically for the industrial uses of its derived products.(2) that can be refined into a variety of commercial items including paper, textiles, clothing, biodegradable plastics, paint, insulation, biofuel, food, and animal feed. (3)
Hemp plants are primarily male, without representing flowering buds at any stage in their life cycle. Instead, centuries of selective Cannabis botany breeding have resulted in relatively low concentrations of THC, and tall, fast growing plants optimized for higher stalk harvests.(5) Hemp is usually grown outdoors to maximize its size and yield and less attention is paid to individual plants, while in contrast achieving maximum THC levels in Cannabis sativa as a drug requires close attention to horticultural conditions.
Certain Cannabis strains known to contain more CBD than THC are found within industrial hemp that have recently been of therapeutic interest for treating neuro-movement disorders.
As the science of genetics vastly improves our understanding evolutionary nature, the widely accepted genus and species binomial nomenclature designation has increasingly been challenged, requiring frequent reconfigurations.
DNA-based research can offer botanists a better understanding of the relationships between plant species. This knowledge will help them select plants that share similar biochemical assays, thus guiding their screening and selection of plants for potential medicinal use.
Marijuana strain names usually do not reflect a meaningful genetic identity. When marijuana and hemp were differentiated at a genome-wide level, only a moderate correlation between the genetic structure of marijuana strains and their reported C. sativa and C. indica ancestry could be correlated. (5) Accurate data acquisition from patient’s receiving a known cultivar’s chemical constituents will be essential to responsibly advance therapeutic whole plant use, so reliable methods for identifying whole plant genotypes are needed to safely advance translational endocannabinoid research.
It had been known for thousands of years that plants had healing and curative properties to restore physiological balances needed to sustain life. What was still unknown were the chemical compounds responsible. That all changed in 1947 when post-World War Two science finally recognized one of the plant world’s most powerful weapons against human disease: Alkaloids.
That year’s Nobel Prize in Chemistry went to Sir Robert Robinson, whose citation speech including the following passage: “They usually have striking, sometimes sensational physiological effects. Among them are quinine, cocaine and atropine, all of which have important medicinal qualities. Plants containing alkaloids have generally drawn the attention of primitive peoples, and in the cases where they are met within countries with ancient culture, the knowledge of their properties often goes back to prehistoric age.” (6)
Botanical alkaloid sources derive ephedrine, curare, and aspirin, as well as addicting substances such as cocaine, nicotine. Additional plant alkaloids also include caffeine and chocolate that also bring habit-forming potential, but yet are common to every-day life.
Similar to how opium from the poppy flower eventually identified the endorphin receptor system, so has the plant’s essential Cannabis Botany revealed the endocannabinoid receptor system it effects. These “hard-wired” receptors are found not only in recently evolved human beings, but also in phylogenetically primitive animals including invertebrates.
Although not an alkaloid, the chemical structure of Cannabis’ principal psychotropic chemical, Δ9-tetrahydrocannabinol (THC) was elucidated in 1963, and its biosynthetic pathways were determined soon after. However, the more significant discovery occurred three decades later when the receptor system’s discovery quickly led to finding its endogenous ligands discoveries that influence an extraordinarily wide range of physiological activity.
Cannabis is a genus of flowering plants that includes multiple subspecies. Scientists have identified over 400 chemical compounds produced by the cannabis plant. More than 65 of these compounds are unique to the cannabis plant, and are referred to as cannabinoids, or phytocannabinoids. Some examples of phytocannabinoids include Δ9-tetrahydrocannabinol (THC), tetra- hydrocannabivarin (THCV), cannabidiol (CBD), cannabichromene (CBC), and cannabigerol (CBG).
THC and its analogues are derived from the cannabis plant, and can interact with endogenous (endocannabinoid) receptors to affect the endocannabinoid system. Phytocannabinoids have biological activity due to their receptor-based effects on the endocannabinoid system. Additional pharmacological effects, such as anti- inflammatory mechanisms may be non-receptor mediated. (7)
Trichomes are structures found on many plants that typically are involved as a defense against desiccation. In the cannabis plant, capitate glandular trichomes serve as chemical factories that process and store concentrations of biologically active chemicals that include phytocannabinoids and essential oils. Under a microscope they resemble crystalline mushrooms.
When collected from the plant flower’s leaf buds, the concentrate gathered is commonly referred to as hashish.
The optimal harvest time for cannabis is regarded to be when a full complement of trichomes are evidenced. This can be measured as a greater dry weight of the sought after secondary metabolite chemicals, particularly the sole psychoactive component, THC. Under optimal conditions, from sowing seed through germination and on to harvest generally requires between two and four months. The past quarter century’s hybridized cultivars that have been systematically selected under Cannabis Prohibition to feature the principal psychotropic chemical constituent in cannabis. Selective hybridizing has concentrated the plant’s psychotropic Δ9-tetrahydrocannabinol (THC) from what typically averaged 5% dry weight in the 1970’s, to yields upward of 25%; a most remarkable horticultural feat in search of a single secondary metabolite.
Alongside ethno-medical pointers from traditional medical plant lore, there are modern hi-tech complements currently under development. Varied methods of cultivation cause plants to differentially express their quantities of balanced chemicals. This results from stressors that developing plants encounter reflecting the conditions where and how they are grown. Quality improvement metrics attempt to define cultivation and processing “best practice” parameters as needed standards for plant production and chemical extraction techniques. Cannabis botany and the associated agricultural and biochemical science industries consistently strive for improvements in product safety and efficacy.
Botany is both a natural earth and evolutionary science attempting to study components of plant traits by investigating chemotypes or genotypes, however these are relatively incomplete pictures of the plant as a successfully adapting life form.
Phenotype describes the overall composite expression of any organism’s observable characteristics, including the biochemical and physiological properties within that organism. (8)
In both plants and animals, phenotypic variation is due to underlying heritable genetic variation, and is a fundamental prerequisite determining evolution by natural selection.
The success or failure of a plant or animal as a whole contributes to the next generation, so natural selection affects the genetic structure of a population indirectly via the contribution of phenotypes. Without phenotypic variation, there would be no evolution by natural selection. (9)
Modern advances in biochemistry and pharmacology have revealed many plant- based molecule’s bioactive mechanisms of action to be channeled through receptors serving as protein-molecules to receive chemical signals from outside cells.
Most biochemically active plant molecules used for medical purposes are bitter tasting alkaloids that the plant has evolved as a defense against herbivores. Although not an alkaloid, phytocannabinoids also appear to be anti-herbivorous.
Their bioactivity mimics aspects of endocannabinoid ligand functions, and are effected through the largest single family of receptors known as Type 2, or G protein-coupled receptors that include receptors for several hormones and slow transmitters including dopamine (10)
How Do the Balanced Chemicals in Cannabis Restore “Homeostatic Physiology”?
In a clinical sense, the complex endocannabinoid receptor system’s principal health function is simply to sustain an organism by constantly adjusting its physiology in response to life’s stresses.
From birth, CB1 receptor’s effect the ability to relax, eat, sleep, and forget; while CB2 receptors appear to help protect from the consequence(s) of a disease essentially allowing them to become “chronic”. (11) End of life issues often overwhelm the CB2 receptor’s far-reaching compensatory effects to sustain life. Without the contribution of CB2 receptor function and an effective immune system, life’s balanced physiology ceases, and death will ensue.
In addition to the best known phytocannabinoids including -9- tetrahydrocannabidiol (THC), cannabidiol (CBD), and cannabinol (CBN), several essential oil terpenes and flavonoids appear to be responsible for Cannabis strain’s distinctive scents and character of effects but are far less well represented in today’s limited formularies compared with a generation ago. Combinations of plant derived chemicals are thought to interact with synergy referred to as an “entourage effect”. (12)
The same Afghani #1 widely used within most hybrids contains a not only sedating, but particularly hypnotic terpene known as myrcene; however, myrcene’s properties can be counter-balanced by combining or substituting it with one of several other essential oils. For example, the terpene linalool is also found in the fragrance associated with lavender.
This scent is used in aromatherapy, in certain soaps, and is known to be calming, but is not particularly hypnotic as myrcene appears to be. An awake, but calming effect is often cited by users of strains of Cannabis that have synergistic levels of linalool, a common terpene.
Considering the wide array of cannabinoid and essential oil combinations available to create any given patient’s safe and effective formulary, a determination of optimally safe and balanced dose plant chemicals currently presents significant therapeutic challenges for healthcare providers.
Despite cannabis’ widespread and frequent use, of additional concern is that little data has been accumulated to understand its chemical’s effects on long-term down-regulating the endocannabinoid system.
The contemporary cannabis plant’s chemical constituents contrast markedly with a traditional landrace form’s native and evolution balanced formulary. Associated with the creation of this “modern plant”, includes the loss of several other additional phytocannabinoids and essential oils; each known to have their own unique bioactivity and potential clinical effects.
While under the influence of human agricultural horticulture in a Darwinian sense, Cannabis species have been both naturally and un-naturally selected for complements of its most desirable chemicals.
Contemporary western medicine regularly confronts the consequences of single chemical “magic bullets” in treating disease. Failed therapeutic results from using ala carte single plant molecules confound many physicians who underappreciate why and how using a multi-combinatorial balanced therapeutic formulary can provide improved, risk-assessed outcomes.
This offers an important advance for “modern medicine” in that combinations of medicines, directly or derived from plant-based chemical have frequently held therapeutic solutions for many of healthcare’s most notorious diseases.
A basic dictum of traditional Chinese medicine is to use combinations of several herb-based chemicals to help control a disease, and is referred to as “surrounding the dragon”; in Victorian times, a combination of up to four quinine alkaloids from cinchona bark was determined to be more effective in treating the scourge of malaria, likely by controlling more resistant parasites; and when HIV and AIDS treatments began in the mid-1980’s, a combined “cocktail” of different drugs were similarly used to help control the disease.
Because nearly all Cannabis cultivars available today are man-made hybrids, agricultural science and genomics have started to reveal common ancestral genes in a search for the heirloom plant’s ancestral strains that existed in the past. 21st-century botanical genomics can select for plants having beneficial traits such as disease resistance, higher yields, and unique balances of therapeutic chemicals.
A March, 2016 acknowledgement concerning the clinical importance to investigate representative mixtures of balanced phytocannabinoid and essential oil chemicals was recently shared by the Commissioner of the United States Food and Drug Administration (FDA) at an open access collaborative summit sponsored by the National Institutes of Health. (13)
The FDA has been evaluating Sativex that represents a combination of phytocannabinoid chemicals for adult patients suffering from debilitating muscle spasms associated with multiple sclerosis.
The value of multiple pathway approaches to understanding disease is part of a new goal to find cures for cancer that complement immune system function.
A multi- factorial interaction approach to healthcare has been increasingly appreciated by the United States government, and endocannabinoid science’s contributions to understand homeostatic physiology’s effect on the immune system’s optimal function appear central to this task.
“Stemming” from ten thousand years of a most common plant’s cultural usage, The National Institute of Health now envisions that “modulating the endocannabinoid system may have therapeutic potential in almost all diseases affecting humans.” (14)
This most remarkable statement reconnects Cannabis botany to the future for healthcare.
Dr. Block is a nationally respected authority in both the healthcare and natural earth sciences concerning botanical medicine education and its research & development. He is the founding principal partner of Nurturing Nature® Group Consultants; an independent professional consultancy providing client organizations with advanced scientific guidance. This industry-wide consultancy expertise provides insight by translating an evolving new science’s objective evidence-based data into clinical applications. These essential analyses benefit his client’s ultimate success by providing knowledge of critical competitive advantages needed to reach their performance goals.
He achieved his bachelor’s degree from Emory University (1978) majoring in analytical chemistry with a minor in psychology and received his Medical Doctorate from the University of Miami (1982). Dr. Block is an American Board-Certified Anesthesiologist who is additionally Fellowship trained in Pain Management & Addiction Medicine. Professor Block’s pragmatic advice is widely sought by legislators, judicial officials & attorneys, and public health experts alike. As a highly qualified and trusted national educator, he has educated thousands of physicians according to the American Medical Association’s highest continuing medical education (CME) standards.
“DocBlock” has served as President of UM’s Miller School of Medicine’s Medical Alumni Association and responsibly extends his expertise as adjunct Professor of Anesthesiology.
He additionally brings accomplished backgrounds in the agricultural sciences as an internationally awarded horticulturist and water quality expert directing Block Botanical Gardens in Miami, Florida; a leading Institutional Member of the American Public Gardens Association (APGA). Dr. Block also serves the Florida Department of Agriculture Extension Office’s programming as a highly regarded Certified Master Gardener and course educator for the University of Florida Institute of Food and Agricultural Sciences. He serves on the Advisory Committee of the Florida Hemp Pilot Project researching the industrial use of hemp as a textile and source of cannabinoids.
Subsequent to Florida’s Compassionate Medical Cannabis Act of 2014 mandating physician education, Dr. Block was chosen as the Florida Medical Association’s “Designated Expert on Botanical Medicines” and was appointed to structure the framework and author their physician’s education. Thereafter, he was selected by Florida’s Surgeon General to serve as the only physician appointed to Florida’s Department of Health Negotiated Rule-Making Committee to determine the existing rules for their original botanical medicine legislation concerning Cannabis.
Jeffrey Block’s integrated clinical understandings of both the therapeutic potential and public health concerns surrounding the contemporary cannabis plant is widely sought. He is author of the peer-reviewed chapter Endocannabinoid Receptors and Medical Cannabis featured in 2020’s CRC Press textbook: Advanced Therapeutics in Pain Medicine. Widely regarded as the Father of Cannabinoid Medicine, Professor Raphael Mechoulam praised Dr. Block’s contributions to the science: “Your outstanding review has addressed many important aspects very well indeed. I do hope that it reaches the hands of many readers, clinicians in particular! Congratulations. -R”
(*) Re: Author’s exception: Teleological paragraph’s inclusion within cannabis (ethno)botany education.
“In modern science, explanations that rely on teleology are often, but not always, avoided, either because they are unnecessary or because whether they are true or false is thought to be beyond the ability of human perception and understanding to judge.”
Ransom Johnson, Monte (2008), Aristotle on Teleology, Oxford University Press pages 23-24.
(1) Manktelow, M. (2010) History of Taxonomy – Lecture from Dept. of Systematic Biology, Uppsala University.
(2) Swanson, TE (2015), “Controlled Substances Chaos: The Department of Justice’s New Policy Position on Marijuana and What It Means for Industrial Hemp Farming in North Dakota” (PDF), North Dakota Law Review, 90 (3): 613
(3) “Erowid Cannabis Vault : Culture #2”. erowid.org. Retrieved 2008-06-20.
(5) The Genetic Structure of Marijuana and Hemp
Jason Sawler, Jake M. Stout, Kyle M. Gardner, Darryl Hudson, John Vidmar, Laura Butler, Jonathan E. Page, Sean Myles PLoS One. 2015; 10(8): e0133292. Published online 2015 August 26.
Plants – Roots to Riches (pg. 200) Willis; Fry – (Kew Gardens) Botanical Medicine – August, 2014
(7) Pacher et al. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacological Reviews 2006; 58: 389-462.
(9) Lewontin, R. C. (November 1970). “The Units of Selection” (PDF). Annual Review of Ecology and Systematics. Palo Alto, CA: Annual Reviews. 1: 1–18. doi:10.1146/annurev.es.01.110170.000245. ISSN 1545-2069. JSTOR 2096764.
(11) Vincenzo Di Marzo, et al. Trends Neuroscience (1998) 21, 521-528
(12) Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects Br J Pharmacol. 2011 Aug; 163(7): 1344–1364. doi: 10.1111/j.1476-5381.2011.01238.x
(13)https://www.youtube.com/watch?v=nhl_3sPHIRw&index=12&list=PLE4ZNGaomJBnFoW82EjtVAtRi mC84B3Bm Robert M. Califf, M.D., Commissioner, FDA (Closing Remarks 6:15-6:50 min.)
(14) Modulating the endocannabinoid system in human health and disease – successes and failures
FEBS J. 2013 May; 280(9): 1918–1943. Published online 2013 Apr 22.
doi: 10.1111/febs.12260 Pal Pacher and George Kunos Laboratory of Physiologic Studies, NIAAA, NIH, Bethesda, MD, USA.