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Friday, January 27, 2017

CBD and Chiropractic

Emerging from the shadow of its controversial - and sexier - sibling tetrahydrocannabinol (THC), cannabidiol (CBD) is close to being a panacea. Judging from the amount of research conducted in the last 10 years on this phytochemical, and by a wide range of claims concerning its therapeutic benefit, CBD may be a health-care game-changer.

A non-psychoactive supporter of the human endocannabinoid system, CBD appears to be useful in relieving seizures, pain, anxiety, insomnia, depression, and more, and theoretically replacing painkillers, anxiolytics, sleeping pills, antidepressants and other dangerous prescription drugs. CBD has no unwanted side-effects.

In contrast to medical and recreational cannabis products containing THC, CBD oil, an extract of the low-to-no THC industrial hemp plant, is legal for sale and consumption in all states of the U.S. in spite of the December 2016 Drug Enforcement Administration's (DEA) creation of a new "Code Number" for "Marihuana Extract". CBD oil is legal for consumption in all states.

Background

The hemp plant from which CBD is extracted has been used for thousands of years and across a variety of cultures in dozens of applications including paper, clothing, rope, fuel, plastics, and building materials. In 17th century America, farmers were ordered by law to grow hemp. According to an 1850 census there were 8400 hemp plantations in the U.S. In the early 20th century, the Ford Motor Company produced hemp fuel.

But in 1937 Congress put an end to hemp farming by passing the Marijuana Tax Act, spearheaded by Federal Bureau of Narcotics chief Harry Anslinger. The Marihuana Tax Act made it illegal to grow cannabis of any kind including hemp - and for anyone to possess cannabis - without a tax stamp. The catch-22 here is that the government never issued the tax stamps.

A strict alcohol prohibitionist, Anslinger - as the story goes - looked for another prohibition about which to evangelize when alcohol prohibition ended in 1933. Some say that Anslinger chose this new prohibition to justify the continuation of his job at the Federal Bureau of Narcotics. In any case, growing cannabis of any kind, including industrial hemp, in the U.S. became illegal as it still is today. (The 2015 Industrial Hemp Farming Act, a federal bill that would legalize hemp cultivation in the U.S., would change that.)

Ironically, the U.S. is the largest importer and consumer of hemp and hemp products, and it's the only industrialized nation that can't grow it. (The U.S. imports most of its hemp from China.) On top of that irony is another: CBD oil extracted from industrial hemp is legal to sell and consume in all fifty states.

Biochemistry

CBD was discovered in the cannabis plant in 1940 but its structure wasn't described until 1963. When THC was isolated from hashish in 1964 by Yehiel Gaoni and Raphael Mechoulam at Hebrew University, and subsequently identified as the major active component in cannabis, CBD was considered inactive and it faded from view.

Cell receptors in the human body for the cannabinoids were discovered in the 1980's by Raphael Mechoulam. In the 1990's Mechoulam identified cannabinoids made in the human body (called endocannabinoids) one of which he and his associates called "anandamide", from the Sanskrit "ananda" meaning joy or bliss. With the discovery of anandamide, the cannabinoid receptors, and related enzymes, the "endocannabinoid system" (ECS) emerged.

The human body makes the fatty acid endocannabinoids from arachidonic acid and cell-membrane phospholipids. These fat-related molecules, such as anandamide, have cell receptors identified as CB1 and CB2. Anandamide and THC are "ligands" with respect to the endogenous cannabinoid receptors, especially CB1, which is present mostly in the brain and nervous system. ("Ligands" are molecules, inside or outside of the body, that are alike in their ability to bind to the same receptor.) Another important endocannabinoid derived from arachidonic acid is identified simply as 2-AG.

CBD is an exogenous cannabinoid that has a weak affinity for endogenous receptors CB1 and CB2. However, CBD inhibits the enzyme that breaks down the endogenous anandamide, thus increasing the presence of anandamide. Some researchers speculate that its inhibition of this enzyme accounts for some of CBD's effects on the nervous, immune, and other systems.

Some physiological functions of the endocannabinoid system include homeostasis, neuroprotection, memory processing, heart rate and blood pressure regulation, and lung function.

To review, in the human body a very important physiological system of lipid molecules, cell receptors, and enzymes operates to help maintain homeostasis. This system, the endocannabinoid system, responds to lipid chemicals called phytocannabinoids and endogenously-produced cannabinoids such as anandamide and 2-AG. The phytocannabinoids, especially CBD and THC, are produced most abundantly in the cannabis plant. Though legal in some states, at the federal level THC is illegal and still considered a dangerous drug by DEA. However, CBD is legal and the oil can be extracted, sold, and consumed everywhere in the U.S. and is viewed increasingly as a nutritional and therapeutic agent with a wide spectrum of beneficial effects.

Therapeutic effects

A partial list of CBD's pharmacologic characteristics includes anti-inflammatory, anti-convulsant, anti-biotic, anti-fungal, anti-spasmodic, anti-oxidant, anti-psychotic, analgesic, and anxiolytic. CBD has been useful in the treatment of multiple sclerosis, Parkinson's disease, Alzheimer's, Crohn's disease, post-traumatic stress disorder, diabetes, arthritis, and psychiatric disorders ("... cannabidiol may ameliorate psychotic symptoms with a superior side-effect profile compared with established antipsychotics." Leweke, F. Therapeutic Potential of Cannabinoids in Psychosis. doi: dx.doi.org/ 10.1016/j.biopsych.2015.11.018). CBD even can be used in treating acute psychosis induced by THC.

Of the little research that was performed on CBD prior to the 1990's, two studies, one in 1947 and another in 1949, demonstrated CBD's anti-convulsant properties in children, properties comparable to phenobarbitol but without the latter's toxicity. Considering the harmful side-effects of phenobarbitol, which include behavioral and cognitive function issues, it is unfortunate for many families that leads from this research were not followed. Interestingly, a 1924 book by a Dutch neurologist listed Cannabis indica as a drug-adjunct in the treatment of epilepsy. It seems that doctors' fascination with synthetic chemical medicine in the early-to-mid 20th century in the U.S. resulted in the obviation of valuable plant-based medicine and in unnecessary suffering.

As mentioned, endo- and phyto- cannabinoid research has exploded in the last few years. Much of the purpose of this research, however, has been to identify "targets" and "magic bullets" for drug research. There is a compulsion among ECS researchers to isolate the active components of the cannabis plant so that pharmaceutical analogs can be synthesized and marketed for clinical use by doctor prescription. The phrase "ripe for therapeutic exploitation" found in cannabis research articles betrays the modus operandi. ("...the ECS has become one of the main targets for the design of drugs that could act as therapeutic agents in pathological processes." Aizpurua-Olaizola, O et.al. Targeting the endocannabinoid system, dx.doi.org/10.1016/j.drudis.2016.08.005). However, the many and varied regulatory actions of the ECS and the wide effects of the exogenous cannabinoid CBD may frustrate these efforts. There are about 120 molecules identified as cannabinoids, one of which is CBD. And there are cannabinoid receptors everywhere in the body, especially in the nervous and immune system cells, where CBD has effects. CBD also has non-receptor effects. In a sense, these discoveries about the endocannabinoid system and CBD are guiding us to a new, more accurate perception of health and holism.

A recent paper by Ethan B. Russo, M.D., his third in support of his theory of a Clinical Endocannabinoid Deficiency Syndrome (CED), illustrates overlapping relationships between three chronic pain syndromes suffered by many people and whose successful treatment has eluded conventional medical science. These three syndromes - migraine, fibromyalgia, and irritable bowel - have comorbidity and a "commonality of symptomatology", Russo says, that point to a deficiency of endocannabinoids, especially anadamide. Cannabidiol is known to raise anadamide levels ("Cannabidiol inhibits the degradation of anadamide" doi: 10.1038/tp.2012.15).

The identification of a CED was made possible by research into the endocannabinoid system and its cannabinoid ligands. In the conventional manner, we have named three apparently different diseases and have attempted to develop specific drugs to treat these diseases. In the case of CED, however, we see that the three diseases are the same deficiency disease process with symptoms that manifest differently. And we find that, possibly, one plant, that is cannabis, with many synergistic components, is the appropriate treatment. This latter approach is holistic.

Some success has been realized in the "magic bullet/biological target" approach, however. For example, Nabilone, developed by Eli Lilly and Company, is a synthetic THC prescribed for nausea, pain management, fibromyalgia, and multiple sclerosis. Nabilone does have unwanted side effects though. Pharmaceutical extract Sativex, containing about equal amounts of isolated THC and CBD, is prescribed for multiple sclerosis and neuropathic pain and has fewer unwanted side-effects. A CBD pharmaceutical extract called Epidolex currently is the subject of 13 clinical trials in the U.S. alone. These trials are designed to test CBD isolated extract for its effectiveness against epilepsy, seizures, refractory childhood epilepsy, and schizophrenia.

In some research, subjects reported preferring the whole plant to the isolated extract or synthetic form of cannabinoid ("... the antiinflammatory and antinociceptive activities of standardized CBD-enriched plant extracts increased with dose, making whole-plant extracts superior to pure CBD for the treatment of inflammatory conditions." Aizpurua-Olaizola, O et.al. Targeting the endocannabinoid system, dx.doi.org/10.1016/j.drudis.2016.08.005). Because there are 483 compounds unique to the cannabis plant there may exist what Raphael Mechoulam calls the "entourage effect" as a way of explaining the supporting or interacting role played by the plant's less well-known molecules. Viewing the variety of beneficial effects of the cannabinoids from the reductionistic "magic bullet/biological target" perpective, conventional medical scientists describe the action of the whole plant as a "synergistic shotgun". The habitual use by the conventional medical system of the ballistic projectile metaphor is revealing.

Descriptors such as "entourage effect" and "synergistic shotgun" also suggest the inherent holism of application of the cannabis plant in addition to a melding of food, dietary supplement, and medicine concepts. Is a full-spectrum CBD oil extract a medicine, food, or dietary supplement? All of the above?

Still the conventional medical system is behind the curve in developing the phytocannabinoid CBD (see Sanjay Gupta's documentary Weed). As a general use extract, a traditional medicine, or a dietary supplement, companies in Colorado, California, and elsewhere, specializing in botanical extracts, are developing and marketing CBD oil, and a doctor's prescription is not needed to obtain these products. This grass-roots, small private-company approach is likely to appeal to independent chiropractors.

Chiropractic

Research published in 2005 in the Journal of the American Osteopathic Association (JAOA) purports to show that osteopathic manipulation increases the body's production of anandamide. From the abstract of the article (J Am Osteopath Assoc. 2005 Jun, 105(6):283-91), "The authors propose that healing modalities popularly associated with changes in the endorphin system, such as OMT [osteopathic manipulative technique], may actually be mediated by the endocannabinoid system." They found posttreatment anandamide levels had increased by 168% over pretreatment levels. (Subsequent research on this subject was inconclusive.)

A 2008 article published in the JAOA (JAOA Vol. 108. ,No. 10, October 2008) provides a comprehensive review of the ECS, and suggests that it "...may reflect OPP [osteopathic principles and practice] on a molecular level." Citing four tenets observed by the profession that represent principles of patient care, the author shows how the ECS relates to and supports these principles. The ECS's wide ranging homeostatic effects as described resonate with osteopathy's more holistic philosophy, according to the article.

Although the beneficial effects of the chiropractic adjustment in the clinic are well-known, the biochemical mechanisms that underlie it are not. It may be that the effect of the adjustment is mediated by the endocannabinoid system, especially anandamide: both spinal adjustments and the ECS produce a downward modulation by "retrograde neurotransmission" at neural synapses of long-term potentiation in spinal neurons caused by persistent glutamate release. Since stretching, torsion, or compression of a nerve or nerve root, as in subluxation, causes damming of CB1 receptors proximal to the damming effect resulting in persistent glutamate release downstream, the adjustment may precipitate the "retrograde neurotransmission" phenomenon and satisfy the feedback loop for pain relief. Thus in this way we can understand at least the biochemical effects of the adjustment. And we might recommend the use of a CBD herbal extract, orally or topically, for increased pain relief. In addition, researchers have discovered that cerebrospinal fluid contains abundant anandamides and may play a role in the production of the cranial rhythmic impulse, which is known to Sacro-Occipital Technique practitioners.


Another irony, this one comic/tragic, is that the best medicine for the inflammation-based diseases that lately affect so many Americans has been discovered in a plant that has been officially villified, outlawed, and sanctioned as having no value. There are similarities to chiropractic in this irony. Possibly, we are emerging from the harmful effects of a deluding, deceptive perception. In any case, for chiropractors who want to provide patients with whole plant-based nutritional support to potentiate the effects of the adjustment or as support against fibromyalgia and other conditions of imbalance, CBD extract is ideal.