Medical education today rarely intersects with botany, and schools and most medical textbooks don’t teach about the neurology of the endocannabinoidome (eCB). Instead, doctors are offered a prescription medication for virtually every symptom or ailment.
As physicians, we can offer a holistic, systems biology approach using sanitation, hygiene, lifestyle medicine, nutrigenomics, spine care and the role of the eCB in healing.
If we were to go back less than a hundred years, botanical medicine was a major part of everyday care. Prior to 1900, chronic illnesses such as heart disease, stroke, cancer and diabetes were rare.
For more than 200 years, doctors studied the pharmacopeia to find the most effective treatment. The most commonly used preparations for illness were derived mainly from plant matter, including cannabis. Today, for many disorders there is a choice to offer a natural medicine or a synthetic copy of one.
Clinical Applications of Cannabidiol
Aside from helping with pain and inflammation, CBD has an allosteric effect on metabolic disorders like type 2 diabetes and obesity. Other endocannabinoid-like receptors have been found, offering potential therapeutic targets around the body; and in the GI tract, CBD has been found useful in the management of inflammatory bowel disorders.1
Our endocannabinoidome (eCB) is a complex endogenous signaling system made up of specialized receptors, mediators and enzymes, and it plays a crucial role in maintaining our health.
Both our brain and our bodies are loaded with endocannabinoid-like receptors. The biochemical pathway shows us that the endogenous endocannabinoids are derived from dietary omega -fats that go on to form the intermediary non-endocannabinoid molecules, N-acylethanolamines (NAEs) and mono-acylglycerols (2-MAGs).
Our bodies have a biosynthetic pathway to convert NAEs to anandamide, and to convert 2-MAGs to 2-arachidonoylglycerol (2-AG). These molecules bind on specific receptors in the brain and spinal cord, and play a role in memory, mood, appetite, metabolism, bone marrow density, fracture healing, sleep, pain response, thermoregulation, mast cell regulation and immunity.
Anandamide and 2-AG bind on a vast number of cannabinoid receptors in the CNS, helping modulate the levels and activity of most of our other neurotransmitters. The phytocannabinoids, like CBD, have a structural similarity to the anandamide and AG2 molecules. When ingested or applied to the skin, they act via a process called molecular mimicry, whereby these exogenous phytocannabinoid molecules bind on these same receptors to regulate homeostasis in the eCB through a process called allosteric modulation.
CBD is a potent therapeutic agent and has a role in reducing inflammation and managing neuropathic pain. More recently, CBD has been studied and has shown to have an effect on bone mineral density, attenuating and reversing bone loss, and promoting faster fracture healing.2
Understanding the Therapeutic Mechanisms of Cannabinoids
CBD seems like magic to many; it is really CBD molecularly mimicking 2-AG. The eCB exists in all creatures with a notochord and over some 600 million years of evolution. It has recently been discovered to be a major regulatory force in the human body.
The eCB is present in nearly all of our systems and has physiological influence over most cell types. In clinical practice, think of CBD as an adaptogen. If we focus on CBD for health benefits, rather than THC, we don’t have to deal with the psychotropic effects or legal issues associated with medical marijuana.
The physiological effects of CBD are mediated by G protein-coupled receptors (GPCRs). The GPCRs participate in many pathophysiological processes, as well as almost all aspects of normal physiology. They are present at the surface of all cell types, making them amenable and attractive targets for therapeutics.
GPCRs possess the ability to be turned on or off and have their constitutive activity suppressed, switching between signaling pathways to which they are coupled.3 The two most common receptors are CB1 and CB2.
The CB1 receptors are highly concentrated in the spinal cord and brain. These receptors, in lower numbers are widely dispersed peripherally. The CB2 receptors are our target for CBD therapy.
One important action CBD has exhibited is allosteric modulation at mu- and delta-opioid receptors; this is a property shared with THC.4 When opioids are not indicated and patients still need relief, CBD’s ability to modulate the mu- and delta-opioid receptors may provide clinicians an alternative.
CBD is also a positive allosteric modulator in micromolar concentration ranges for anionic ligand-gated chloride ion channels, acting much like gamma amino butyric acid (GABA) in quelling neuropathic pain.
These GPCRs seven-fold-transmembrane domain receptors are located in the cell’s plasma membrane. GPCRs can be seen crossing the cell membrane and reacting with light-sensitive compounds like beta carotene, terpenes, pheromones, hormones, and neurotransmitters. The GPCRs are the largest superfamily of receptor (sensory) proteins in multicellular animals.
Allosteric regulation is critical for the functioning of G protein-coupled receptors (GPCRs) and their signaling pathways in numerous disease states. Endogenous allosteric regulators of GPCRs are simple ions, various biomolecules, and protein components of GPCR signaling (G proteins and ß-arrestins).5
CBD also has the ability to activate the different isoforms of PPARs (ɑ, ß and y), as shown through the use of reporter gene assays, binding studies, selective antagonists and knockout studies. Activation of all isoforms, but primarily PPAR ɑ and y, mediates some (but not all) of the analgesic, neuroprotective, neuronal function modulation, anti-inflammatory, metabolic, anti-tumor, gastrointestinal and cardiovascular effects of cannabinoids like CBD.
This PPAR response is often in conjunction with activation of the more traditional target sites of action, such as the cannabinoid CB1 and CB2 receptors and the TRPV1 ion channel. PPARs also mediate some of the effects of inhibitors of endocannabinoid degradation or transport.6
Recently, it has been shown that CBD has the ability to neutralize the SARS-CoV-2 virus and prevent the cytokine storm associated with the spike protein on the ACE 2 receptor. Studies have found that CBD and its metabolite, 7-OH-CBD, can block SARS-CoV-2 replication.
CBD acts after viral entry in the cell by reversing the transcription of host genes and their expression, preventing viral replication by bolstering interferon pathways.7 This ability of CBD to disrupt viral replication is expected to occur with other retroviruses, including hepatitis C and the common cold virus. A cohort study highlights CBD as a potential preventative agent for early-stage SARS-CoV-2 infection and merits future clinical trials.8
Practical Clinical Applications in Chiropractic Medicine
The cannabinoids are a heterogenous group of 100-plus different molecules present in the cannabis plant; some are called terpenes, and they have healing properties, too. The effects of these terpenoids are supported by numerous in vitro, animal and clinical trials showing they exhibit potent anti-inflammatory, antioxidant, analgesic, anti-convulsive, anti-depressant, anxiolytic, anti-cancer, anti-tumor, neuroprotective, anti-mutagenic, anti-allergic, antibiotic, and anti-diabetic attributes at the cellular level.
Because of very low toxicity, these terpenes are widely used as food additives and in cosmetic products. Thus, they have been proven safe and well-tolerated.9
Over the past five years, we have found transdermal CBD to be helpful in regional pain disorders, including small-fiber neuropathy. For generalized musculoskeletal pain syndromes, including spine problems, with or without inflammation, we recommend using sublingual CBD oil (first-pass administration). The oromucosal application of CBD promotes rapid absorption and greater bioavailability than capsules or gummies.
Sublingual administration offers an almost-immediate onset of physiological effects, and is significantly more effective than digested CBD, which has been metabolized by the liver before it enters circulation.10
CBD also now has an established role in the management of epilepsy. Clinical studies are ongoing, we believe the evidence also supports the utilization of CBD in chiropractic practice as an anti-oxidant and anti-inflammatory, for radicular and neuropathic pain, fibromyalgia, IBS, anxiety, PTSD, Parkinson’s disease, and sleep.
References
Continuing to impress the advertising and marketing world, The Foundation for Chiropractic Progress (F4CP) has again been recognized by industry organizations for its excellence in educating consumers on the benefits of chiropractic, this time through social media, newsletters, and demonstrating thought leadership by promoting holistic well-being.
Dr. Louis Sportelli received the Lee-Homewood Chiropractic Heritage Award during the annual conference of the Association for the History of Chiropractic (AHC). During his nearly 60-year career, Dr. Sportelli has embodied the spirit of the award, given to “living individuals who have made outstanding contributions to the chiropractic profession.”
Presently there is no consensus on the best treatment for Achilles tendon rupture; and its management is still controversial. The treatment options are conservative treatment and surgical repair. With either treatment, be it conservative or surgical, Achilles tendon tears necessitate prolonged recovery and rehabilitative management.
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