FEATURE RESEARCH The intersection of spinal manipulation and the ECS Part 2 I by dr . chris spooner , nd n Part 1 of this series (MAY-JUNE 2022), I discussed the role of the endocannabinoid system (ECS) in inflammatory and neuropathic pain models and the potential of target-ing the ECS to generate an analgesic effect. Recall that cannabinoid re-ceptor agonists, endocannabinoid-regu-lating enzyme inhibitors, and other pharmacological strategies to manipulate the endogenous cannabinoid system can decrease abnormally heightened sensitiv-ity to pain (hyperalgesia) and allodynia found in a diverse range of inflammatory and neuropathic pain states. Clinical studies consistently demonstrate efficacy of cannabis and cannabinoid receptor agonists in reducing neuropathic pain states in humans, but adverse effects associated with use of medical cannabis (specifically THC) as well as challenges in ensuring standardized formulations have resulted in limited uptake by health care professionals and patients. There is, however, a growing body research that has identified numerous non-cannabis compounds and other constituents of cannabis aside from THC, that have therapeutic efficacy and are in common use. Plants have been the predominant source of medicines throughout most of the human history and remain so today outside of industrialized societies. Inves-tigations of Cannabis, with its diverse phytochemistry, has resulted in the www.Cndoctor.ca discovery of the unique and widespread homeostatic physiological regulator, the endocannabinoid system. While it had been the conventional wisdom, that only cannabis harbored active agents affect-ing the endocannabinoid system, more recent research has identified numerous additional plants whose components stimulate, antagonize, or modulate dif-ferent aspects of the endocannabinoid system. These include common food-stuffs, herbs, spices, and more exotic ingredients: kava, chocolate, black pep-per, and many others. 1 As a naturopathic doctor, I am familiar with many of these compounds and have used them frequently without fully real-izing that I was modulating the EC. The same is true for chiropractic practice. To review, the endocannabinoid sys-tem (ECS) is a lipid signalling network in which arachidonic acid (AA) derived lipids act in concert with specific recep-tors and enzymes resulting in the com-plex modulation of numerous physio-logical and pathophysiological processes. The ECS consists of receptors, specifi-cally the cannabinoid receptors, CB1,CB2 and suspected third receptor, GPR55. These receptors are differen-tially activated by the endocannabinoids, 2-arachidonoyl glycerol (2-AG) and N-arachidonoylethanolamine (AEA also referred to as anandamide). AEA and 2-AG, modulate different ion channels and nuclear receptors, including transient receptor potential vanilloid 1 (TRPV1), GABAa receptors and PPAR-Y . The final component of the ECS included the enzymes responsible for degrading the EA and 2-AG, namely, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). These enzymes have been shown to regulate local and paracrine EC concen-trations and are important targets for therapy. 2 THE ENDOCANNABINOID SYSTEM AND PAIN Endocannabinoids are act as a brake on neuronal hyperactivity, being produced in response to high levels of stimulation and feeding back negatively on the cir-cuit through interaction with pre-synap-tic cannabinoid receptors. In pain pathways, these actions produce analge-sia by inhibiting the transmission of pain signals. There are two main types of physical pain, nociceptive pain, and neuropathic pain. Nociceptive pain is the most com-mon type, caused by potentially harmful stimuli being detected by nociceptors around the body. Nociception refers to the central nervous system (CNS) and peripheral nervous system (PNS) pro-cessing of noxious stimuli, such as tissue injury and temperature extremes, which activate nociceptors and their pathways. Pain is the subjective experience one feels because of the activation of these July/August 2022 Chiropractic and Naturopathic Doctor 11
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