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We now understand the mechanism by which cannabis affects the body, modulating pain and analgesia, inflammation, appetite, gastro-intestinal motility, sleep cycles, glucose metabolism, and the ebb and flow of immune cells, hormones, and other mood-altering neurotransmitters such as serotonin, dopamine, and glutamate.41
When a CB1 receptor is "keyed" by THC or one of the body's endogenous doppelgängers, cannabinoid receptors activate a series of cellular level biochemical changes that dampen physiological hyperactivity. Most neurotransmitters incite body responses, creating a reaction to the stimulus applied.
Endocannabinoids are unique amongst neurotransmitters in that their effect is in the opposite direction; their interactions calm cellular and system activities, downshifting other neurotransmitters when they are "firing too fast," a "retrograde signaling" that reduces immune response, inflammation, and blood pressure; relaxes muscles; dilates bronchial passages; and stabilizes overstimulated nerves.32
Biologist Robert Melamede describes the endocannabinoid system, in his lectures and articles, as the "master modulator," triggering the human immune system to fight off viruses or bacteria with fever, and then signaling the immune system to reduce the fever when the threat is past. "Cannabinoids—endo, herbal, and synthetic—are anti-inflammatory; they literally cool the body," a response that may be beneficial: If the immune system is out of control—hyperactive—it may overreact and attack itself, opening the door for the development of an autoimmune disease or condition of chronic inflammation.46
Endocannabinoids play a significant role in embryonic development, particularly in promoting neural cell proliferation and differentiation in the embryonic brain. Surprisingly, CB receptor signaling also regulates adult neurogenesis (brain cell growth) and stem cell migration.46 High brain endocannabinoid levels follow strokes, head trauma, and other neurological "accidents" and appear to be the endocannabinoid system's attempt to protect the brain. Mechoulam believes the endocannabinoid system is "part of the body's 'general protective network, working in conjunction with the immune system and various other physiological systems.'" 46 His Nobel-worthy discoveries challenged the long-held beliefs that brain cells never grew and dead brain cells could never be replaced once a person reached adulthood. We now know that, as Mechoulam so insightfully noted, "The brain has a natural repair kit, an in-built mechanism of protection and regeneration, which can mend damaged nerves and brain cells."46
The Endocannabinoid System
The discovery of the endocannabinoid system not only changes our understanding of human body physiology, it is a game-changer in altering our approach to treating diseases and conditions we previously considered difficult or even impossible to control. Dr. Mauro Maccarrone, University of Teramo, Italy, describes the endocannabinoid system as the "guardian angel" of mammalian reproduction, with the endocannabinoid signaling system controlling the reproduction process—governing spermatogenesis, fertilization, transport of the zygote through the oviduct, implantation, and fetal development. Prolific placental CB receptors "pass messages" between the embryo and the mother. In maternal milk, endocannabinoids activate the newborn suckling response. A dysfunctional endocannabinoid system can be the underlying cause of colic. Israeli neuroscientist Ester Fride noted that No-CB-receptor mice suffered the same fate as human babies with "failure to thrive" syndrome—they weakened and died prematurely.46
PubMed, the US National Library of Medicine, National Institute of Health, lists over 1,200 research papers related to delta-9-tetrahydrocannabinol, 7,800 related to tetrahydrocannabinol, almost 15,600 referencing cannabis, over 21,000 which talk about cannabinoid, and over 1,500 with the term cannabidiol.
One example of a study that had both the terms cannabis and cannabidiol (CBD), "Cannabidiol rather than Cannabis sativa extracts inhibit cell growth and induce apoptosis in cervical cancer cells," reached the conclusion that both concentrated cannabidiol (CBD) and crude (unrefined) Cannabis sativa extracts (the latter of which would have the full range of cannabinoids) "were able to halt cell proliferation in all cell lines (types of cervical cancers) at varying concentrations," meaning that the cancer cells stopped growing and multiplying. They further revealed that apoptosis (cell death) was induced by cannabidiol.47 Stop the cancer cells from making new cells and kill the ones already there? Sounds like a great idea.
Researchers at St. George's Hospital, University of London, evaluated the in vitro effect of six cannabinoids (two forms of cannabidiol [CBD], two forms of cannabigerol [CBG] and two forms of cannabigevarin [CBGV]), separately and in combination, on cancer (leukemia) cells. Conclusions:
- Cannabinoids reduce cell number by being cytostatic. (stopping cell processes)
- Cytotoxicity can be achieved through a break in treatment (recovery phase).
- Cannabinoids alter cell signaling proteins.
- CBD acts non-antagonistically with other cannabinoids to reduce cell number.
- Cannabinoid activity is influenced by drug combination and treatment schedule.48
Cannabinoids, an amazing complex of biochemicals, support the homeostatic system of the human body. Homeostasis is defined as "A state of equilibrium, as in an organism or cell, maintained by self-regulating processes."49 We can think of a human's homeostatic system as a "regulator" that keeps the body's physiological, chemical, and electrical systems in balance. Thus, we can see how a nutritional deficiency that affects the body's homeostatic system can impact the entire body, causing problems ranging from aberrations at the cellular metabolic level (e.g., cancer and autoimmune diseases) to gross changes in physiological, mental, and emotional functioning. Cannabinoids provide vital nutrients necessary for the normal functioning of the human body and the prevention of disease.
Whether the result of poor diet, lack of exercise, drug abuse, environmental toxins or genetic factors, endocannabinoid deficits are associated with a reduced ability or inability to adapt to chronic stress. Prolonged exposure to stress depletes endocannabinoid tone, and this, in turn, has an adverse impact on a plethora of physiological processes. Ironically, the US government's unending search for marijuana's harmful properties yielded not only information about one of the human body's most critical systems but also astonishing scientific insights that validate the herb's therapeutic utility.
Sources of External Cannabinoids
Traditionally, hemp was grown for fiber and oil, but what is often overlooked is that hemp was used as livestock fodder for farm animals, including chickens, cows, goats, and pigs. Cannabinoids are lipids—fat soluble—and, once consumed, would be retained in the animals' meat, dairy products, and eggs. People who ate animal products would get these residual cannabinoids.
A second source prior to 1937 were the many over-the-counter and prescription medicines that included hemp/cannabis products. A third source for those who grew hemp would have been through physical contact. Farmers who worked in the hemp fields would invariably brush against the plants, and, in all likelihood, absorb some of the terpenes, flavonoids, and cannabinoids through the oils that clung to their clothes and skin.
Interestingly, a centuries-old method of harvesting these oils, used in the Chu Valley between Kyrgyzstan and Kazkhstan, involves sending a clean and naked rider on a well-washed horse through the fields of an extremely potent variety of cannabis for a few hours, then scraping off the oily, sticky residue from both horse and rider. One might expect that, by the end of the ride, after breathing and wearing the oils for four hours or more, both horse and rider would be feeling no pain.50
The primary natural sources of cannabinoids are the two phytocannabinoid-rich botanicals, Cannabis sativa and Cannabis indica. A third variety of cannabis, Cannabis ruderalis, appears to be unimportant as a source of cannabinoids.51 Aside from cannabis, some other plants have small amounts of cannabinoids, which may or may not have affinity for human cannabinoid receptors. Four members of the Asteraceae flower family—Echinacea purpurea, Echinacea angustifolia, Helichrysum umbraculigerum, and Acmella oleracea (common name—toothache plant)—and a liverwort, Radula marginata,bear minor amounts of phytocannabinoids, predominantly, but not exclusively, in the roots and flowers. Yangonin, a chemical in the Kava plant, has a significant affinity for the CB1 receptor. Both human cannabinoid receptors respond to tea (Camellia sinensis) catechins, and black truffles contain anandamide. Whether the body has any way to use the cannabinoids in these herbs/mushrooms is not known, and it is unlikely that these alternative cannabinoid sources will be researched until all of the cannabinoids in cannabis have been thoroughly profiled.52
Nov. 2017: Part 3 is online.
Dec 2017: Part 4 is online.
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Sir Jonn Desnoes, OMD, MD, PhD, is a physician, who is board certified in homeopathy and Chinese medicine. He is a former nationally syndicated radio talk show host, writer, researcher, athlete, and visionary. He was knighted for his humanitarian work as a medical missionary.
Jonn became interested in the study of cannabis and its health-restoring properties when a friend gave him a bottle of CBD hemp oil. He had suffered with intractable back pain for years as a result of multiple sports injuries incurred over 30 years as an athlete. Within 20 minutes of taking the CBD oil, his excruciating pain stopped. He has found that, as long as he continues to take the oil, he is virtually pain-free.
Sandra Kischuk, BSBA, MSMIS, MCPM, is a writer, editor, life coach, Toastmaster, and master gardener. Author of Fighting the Dragon: How I Beat Multiple Sclerosis, Sandra's writing interests include fiction, non-fiction, poetry, scripts, and other people's résumés. She has written web content for physicians, informational/marketing literature for attorneys, and continuing education courses for dental professionals, and edited professional communications and doctoral theses on subjects as diverse as religion, education, engineering, and psychology.