The Endocannabiniod System

Evidence for the scientific efficacy of CBD is mounting over the past two years, with the removal of the substance from the Federal Schedule I Narcotics list. But research on cannabinoids dates back much further and the medical applications of cannabis have ancient roots. Much of what we understand about the mechanisms of CBD come from discoveries made in the early 1990s. Researchers were able to clone Cannabinoid Receptors 1 and 2 in 1990 and 1993 respectively, from animal and human cells <1>. These discoveries laid the foundation of what is now referred to as the Endocannabinoid System in medicine.

As it turns out, the human body produces cannabinoids endogenously, or within itself, in order to execute certain physiological processes. Receptor CB1 is predominantly expressed in the nervous system, though it can be found in a surprising variety of cells <2>. This can largely explain and attribute the effects of marijuana usage on the brain and motor system when CB1 receptors interact with the THC cannabinoid. It is through CB1 receptors that psychoactive effects can be commuted to the brain, though it may play a role in the mobilization of a number of neurotransmitters related to mood and general motor function.

CB2, however, is largely found in immune support cells, notably white blood cells who combat against bodily infections. This leads to early postulation that CB2 must play an important role in immune function, a theory that continues to require further study and investigation. Immune system responses are complex based on the conditions and CB2 receptor stimulation can have suppression effects, like inhibiting immune gene expression, or support effects, by mobilizing various immune cell types. Our understanding is further limited by the common underminer of much of the scientific literature on CBD: most of the studies are done on rats, mice, or with in vitro human cells. Little is understood or documented on the in vivo interaction between CB2 receptors and various cannabinoids. But what’s emerging appears to show some real promise for those with autoimmune disorders.

Arthritis and Autoimmune Disease

Arthritis affects over 50 million Americans, or one in six, which means there are good odds you don’t need a formal education on it’s existence. Pain and stiffness of the joints from chronic inflammation reduces function and decreases quality of life. Particularly punishing forms of autoimmune disease like rheumatoid arthritis or multiple sclerosis stem from attacks by the body’s own immune system. In these cases, the systems meant to protect from infection and disease are the wired to eat away at the body’s structures, and can even ultimately lead to death. The causes of such diseases is still unknown and largely not understood, which has made mitigating or curing these conditions even more difficult. In both cases, managing and reducing the chronic inflammation on the body can offset it’s more debilitating effects.

CB Receptors and Inflammatory Response

Past research has demonstrated the importance of CB receptors in bodily functions. Mice without CB2 exhibited dangerously high levels of inflammation and an inability to recover from it <3>. In non-autoimmune conditions such as the more common osteoarthritis, clinical usage of CBD demonstrated a reduction in general pain symptoms and decreases in localized inflammation <4>.

General immune suppression isn’t a typically desirable response for most physiological processes, but when the immune system itself is responsible for the damage, slowing the system down may be the only hope. Activation of CB2 receptors can reduce the production of pro-inflammatory cytokines, peptides that may commute the painful attacks on joints seen in conditions like rheumatoid arthritis. Further, preventing activation of the CB1 receptors may double down on reduction in pro-inflammatory cellular response, an outcome not possible with a cannabinoid like the psychoactive THC which, as mentioned previously, has a strong reaction on the CB1 receptors. A recent research review in Germany, suggested this strategy of targeting CB2 receptor activation while blunting the CB1 receptor response may provide the most ideal support possible for autoimmune diseases <5>. The review went further to declare that CBD itself appeared to demonstrate anti-inflammatory effects on users that was entirely independent of the endocannabinoid system’s response, an exciting suggestion about the inherent recovery properties of non-psychoactive CBD.

Treatment of inflammation and autoimmune disease is a complicated issue that should be monitored and orchestrated by your physician. Trialing with CBD may be a helpful addition to a carefully constructed exercise regimen and dietary recommendations.

References

  1. Basu, S., & Dittel, B. N. (2011). Unraveling the complexities of cannabinoid receptor 2 (CB2) immune regulation in health and disease. Immunologic Research, 51(1), 26–38. doi: 10.1007/s12026-011-8210-5.

  2. Elphick, M. R., & Egertova, M. (2001). The neurobiology and evolution of cannabinoid signalling. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences, 356(1407), 381–408. doi: 10.1098/rstb.2000.0787

  3. Turcotte, C., Blanchet, M.-R., Laviolette, M., & Flamand, N. (2016). The CB2 receptor and its role as a regulator of inflammation. Cellular and Molecular Life Sciences, 73(23), 4449–4470. doi: 10.1007/s00018-016-2300-4

  4. Philpott, H. T., Oʼbrien, M., & Mcdougall, J. J. (2017). Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis. Pain, 158(12), 2442–2451. doi: 10.1097/j.pain.0000000000001052

  5. Lowin, T., Schneider, M., & Pongratz, G. (2019). Joints for joints. Current Opinion in Rheumatology, 31(3), 271–278. doi: 10.1097/bor.0000000000000590


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