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Cannabis is all the rage these days. From the growing legalization movement to the exponential increase in the research into its potential health benefits. It has over 4000 years of human consumption. Moreover, the body even contains an endogenous cannabinoid receptor system, known as the endocannabinoid system for short. Yet, it still has major social and political stigmas attached to it.

But the big question is can Cannabis help YOU?

There are over 500 known compounds isolated from the cannabis plant [1], of which, at least 113 are cannabinoids [2]. The most commonly known are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD).

While THC is known for its psychoactive effects, CBD does not possess those same properties, but rather has anti-inflammatory, immunomodulatory, neuroprotective, cardiovascular, anticonvulsant, anxiolytic, antipsychotic, antiemetic, and even anticarcinogenic benefits [3]. As such, particularly since cannabidiol is completely legal at this point, it will be the one we focus on today.

Interest in cannabidiol recently hit a fevered pitch when during the post-fight press conference at UFC 202, the ever controversial Nate Diaz was openly vaping. When asked by reporters what he was using, Diaz replied “It’s CBD, it helps with the healing process and inflammation and things like that, so you want to get these for before or after the fights, in training. It’ll make your life a better place.”

While this created quite the uproar in the media and the United States Anti-Doping Agency (USADA) is conducting an investigation, the simple fact of the matter is that provided Nate was speaking truthfully, he violated no regulations.

The USADA specifically prohibits natural and synthetic versions of THC and cannabimimetics, due to the potential for “unfair advantage, safety hazards, adverse health impacts or violation of the spirit of sports” [4]. However, as you can note in the image below, no mention is made of cannabidiol. In fact, the test that is conducted is an urinary analysis looking for THC metabolite 11-nor-9-carboxy-THC (THCCOOH) at concentrations equal to or greater than 15 ng/mL [5]. As such, Nate is in the clear.

Now that we have established why Nate Diaz did not break any rules, let’s discuss why a fighter would want to use CBD. As a lifelong martial artist and mixed martial arts fighter myself, I can tell you from personal experience that the daily grind of training, both in and out of the 8-12 weeks of fight camp is taxing on the body, both physically and psychologically.

Anything that can reduce the inflammation associated with the training, as well as combat mental fatigue, will be beneficial. Things like turmeric, fish oil and systemic enzymes are staples of any successful recovery protocol. This is also, however, where CBD can play an incredible role.

In terms of mechanisms, CBD has been shown to increase the anti-inflammatory cytokine interleukin-10 (IL-10), while inhibiting the pro-inflammatory cytokines such as interleukin-1 beta (IL1β), interleukin-6 (IL-6), interferon gamma (INFγ) and tumor necrosis factorα (TNFα) [6, 7, 8]. These pro-inflammatory cytokines are also associated with the activation of the nociceptive sensory neurons, initiating the experience of pain [9, 10]

Additionally, the endocannabinoid receptor system (specifically the CB1 and CB2 receptors) plays a role in regulating the inflammatory response and the sensory perception of pain. While CBD does not have a strong binding affinity for either CB1 or CB2, it does modulate both of them by acting as an inverse agonist [11, 12]. It acts by increasing the amount of available CB receptors, while competitively inhibiting the breakdown of the endocannabinoid signaling molecules. What this means, essentially, is that while it doesn’t score the touchdown, it blocks the other team while helping to keep open the other wide receivers.

Now, while this all important for fighters and other high level athletes in the recovery process from training, the ability to systemically reduce inflammation has the potential to benefit pretty much everyone. Chronic and excessive inflammation is at the heart of practically every disease [13]. Rather than trying to search for “one symptom, one pill,” address the root cause, in this case inflammation, and you can have a host of positive downstream health effects.

This has been exhibited in vitro and in animal models for acute lung injuries, asthma and even in the inhibition of lung cancer metastasis [14, 15, 16, 17]. If we are talking about athletes, this results in better cardiovascular endurance and higher level performance throughout the entire competition.

It has also shown efficacy in reducing inflammation and subsequent oxidative damage from high-glucose levels in diabetes and in diabetes-related complications [18, 19, 20]. In fact, regarding oxidative stress, cannabidiol has shown stronger in vitro antioxidant activity than either vitamins C or E [7].

These effects also extend to the cardiovascular system, where it reduces the response to stress, vasodilation (improves blood pressure), protects against acute heart damage, cardiovascular cell death and ventricular arrhythmias [21, 22, 23, 24, 25]. Again, regarding athletes, this results in higher cardiovascular endurance and overall performance.

Cannabidiol, both orally and transdermally, has exhibited anti-arthritic activity and the ability to improve joint function [26, 27, 28]. While obviously important in our ever aging population, this is of incredible importance to high-level athletes who regularly take their joints to and unfortunately often past the limits of human ability. Brazilian Jiu Jitsu, submission grappling and mixed martial arts fighters like Nate Diaz try to hyperextend and damage each other’s joints, ligaments and tendons on a daily basis. As such, CBD can have demonstrable benefit in these sports.
If that weren’t enough, where things really start to get interesting is its potential neural and cognitive effects. Sport psychology is a whole field unto itself and improving an athlete’s mindset is a major determinant in said athlete’s success. While never an issue myself, I know many other fighters regularly get the anxious jitters before stepping into the cage.

Beyond the athletic arena, this has the potential to be a game-changer in a wide variety in psychiatric and mood disturbances, including depression, generalized and social anxiety disorder, panic disorder, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD)

That is yet another place where CBD shines insomuch as it has exhibited anxiolytic activity by direct interaction with the 5-HT1A receptors of the serotonergic system [29, 30, 31, 32]. Beyond the athletic arena, this has the potential to be a game-changer in a wide variety in psychiatric and mood disturbances, including depression, generalized and social anxiety disorder, panic disorder, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD). [29, 30, 32, 33].

The benefits of the serotonergic system activation, particularly when combined with the anti-inflammatory effects, also extends to neuroprotection from acute injury and cognitive decline; CBD has shown efficacy in combatting Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Huntington’s disease, Parkinson’s disease, epilepsy and strokes [34, 35, 36, 37, 38, 39]. For athletes engaged in contact sports, such as fighters or football players, cannabidiol is also beneficial for recovery from traumatic brain injuries, such as concussions [40, 41].

But wait, there’s more.

The endocannabinoid system is a major regulator of the status of the gut. Cannabidiol exhibits benefit in the reducing gastrointestinal inflammation and subsequent improvement of intestinal wall integrity, with therapeutic efficacy in gastrointestinal reflux disorder (GERD), irritable bowel disease (IBD), and ulcerative colitis (UC) [42, 43, 44, 45, 46]. Interesting side note, dysregulation of the endocannabinoid system, also plays a role in the development of diverticular disease [42, 43], which famously shortened the career of UFC fighter/WWE wrestler Brock Lesnar.

That intestinal permeability and subsequent translocation of bacteria is associated with a host of other issues, particularly with respect to the immune system. All four layers of immune dysregulation, i.e. under/overreaction to internal/external stimuli, e.g. infection, cancer, allergy/sensitivies and autoimmune disorders, can benefit from the administration of CBD. That is because it is neither inherently immunostimulatory or immunosuppressive, but rather it modulates or regulates the immune system, particularly by way of controlling nuclear factor of activated T cells (NFAT) transcription activity [47].

Accordingly, CBD has shown therapeutic efficacy in combatting allergies, autoimmune conditions, cancer and infections [17, 48, 49, 50, 51]. However, the potential role of CBD in the fight against cancer is incredible in and of itself and warrants its own in depth discussion. Cannabidiol has been shown to induce apoptosis, inhibit angiogenesis, invasion and metastasis, as well as regulate antitumor immunity [52, 53, 54, 55].

Any way you slice it, if you are looking to improve your health, if you are trying to look, feel and perform better, cannabidiol may just be one of the strongest tools in the arsenal that you aren’t using yet.


And In case your friend is still skeptical… we have references. 55 of them.

References:

1) Aizpurua-Olaizola, O., Omar, J., Navarro, P., Olivares, M., Etxebarria, N. & Usobiaga, A. (2014). Identification & quantification of cannabinoids in Cannabis sativa L. plants by high performance liquid chromatography-mass spectrometry. Anal Bioanal Chem. Vol. 406(29):7549-7560.

2) Aizpurua-Olaizola, O., Soydaner, U., Öztürk, E., Schibano, D., Simsir, Y., Navarro P., Etxebarria, N. & Usobiaga, A. (2016). Evolution of the cannibinoid & terpene content during the growth of Cannabis sativa plants from different chemotypes. J Nat Prod. Vol. 79(2):324-331.

3) Atakan, Z. (2012). Cannabis, a complex plant: Different compounds & different effects on individuals. Ther Adv Psychopharmacol. Vol. 2(6):241-254.

4) Hilderbrand, R.L. (2011). High-performance sport, marijuana & cannabimimetics. J Anal Toxicol. Vol. 35(9):624-637.

5) Huestis, M.A., Mazzoni, I. & Rabin, O. (2011). Cannabis in sport: Anti-doping perspective. Sports Med. Vol. 41(11):949-966.

6) Burstein, S.H. & Zurier, R.B. (2009). Cannabinoids, endocannabinoids & related analogs in inflammation. AAPS J. Vol. 11(1):109-119.

7) Booz, G.W. (2011). Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress. Free Rad Biol Med. Vol. 51(5):1054-1061.

8) Kozela, E., Juknat, A., Gao, F., Kaushansky, N., Coppola, G. & Vogel, Z. (2016). Pathways & gene networks mediating the regulatory effects of cannabidiol, a nonpsychoactive cannabinoid, in autoimmune T cells. J Neuroinflammation. Vol. 13:136.

9) Zhang, J.M. & An, J. (2007). Cytokines, inflammation & pain. Int Anesthesiol Clin. Vol. 45(2):27-37.

10) Xu, Q. & Yaksh, T.L. (2011). A brief comparison of the pathophysiology of inflammatory versus neuropathic pain. Curr Opin Anaesthesiol. Vol. 24(4):400-407.

11) Thomas, A., Baillie, G.L., Phillips, A.M., Razdan, R.K., Ross, R.A. & Pertwee, R.G. (2007). Cannabidiol displays unexpectedly high potency as an antagonist of CB1 & CB2 receptor agonists in vitro. Br J Pharmacol. Vol. 150(5):613-623.

12) Fine, P.G. & Rosenfeld, M.J. (2013). The endocannabinoid system, cannabinoids & pain. Rambam Maimonides Med J. Vol. 4(4):e0022.

13) Hunter, P. (2012). The inflammation theory of disease: The growing realization that chronic inflammation is crucial in many diseases opens new avenues for treatment. EMBO Rep. Vol. 13(11):968-970.

14) Liu, L., Xiong, H., Ping, J., Ju, Y. & Zhang, X. (2010). Taraxacum officinale protects against lipopolysaccharide-induced acute lung injury in mice. J Ethnopharmacol. Vol. 130(2):392-397.

15) Ramer, R., Bublitz, K., Freimuth, N., Merkord, J., Rohde, H., Haustein, M., Borchert, P., Schmuhl, E., Linnebacher, M. & Hinz, B. (2012). Cannabidiol inhibits lung cancer cell invasion & metastasis via intercellular adhesion molecule-1. FASEB J. Vol. 26(4):1535-1548.

16) Ribeiro, A., Ferraz-de-Paula, V., Pinheiro, M.L., Vitoretti, L.B., Mariano-Souza, D.P., Quinteiro-Filho, W.M., Akamine, A.T., Almeida, V.I,, Quevedo, J., Dal-Pizzol, F., Hallak, J.E., Zuardi, A.W., Crippa, J.A. & Palermo-Neto, J. (2012). Cannabidiol, a non-psychotropic plant-derived cannabinoid, decreases inflammation in a murine model of acute lung injury: Role for the adenosine A(2A) receptor. Eur J Pharmacol. Vol. 678(1-3):78-85.

17) Vuolo, F., Petronilho, F., Sonai, B., Ritter, C., Hallak, J.E.C. Zuardi, A.W., Crippa, J.A. & Dal-Pizzol, F. (2015). Evaluation of serum cytokines levels & the role of cannabidiol treatment in animal model of asthma. Mediators Inflamm. Vol. 2015:538670.

18) Rajesh, M., Mukhopadhyay, P., Bátkai, S., Haskó, G., Liaudet, L., Drel, V.R., Obrosova, I.G. & Pacher, P. (2007). Cannabidiol attenuates high glucose-induced endothelial cell inflammatory response & barrier disruption. Am J Physiol Heart Circ Physiol. Vol. 293(1):H610-19.

19) Liou, G.I. (2010). Diabetic retinopathy: Role of inflammation & potential therapies for anti-inflammation. World J Diabetes. Vol. 1(1):12-18.

20) Horváth, B., Mukhopadhyay, P., Haskó, G. & Pacher, P. (2012). The endocannabinoid system & plant-derived cannabinoids in diabetes & diabetic complications. Am J Pathol. Vol. 180(2):432-442.

21) Stanley, C.P., Hind, W.H. & O’Sullivan, S.E. (2013). Is the cardiovascular system a therapeutic target for cannabidiol? Br J Clin Pharmacol. Vol. 75(2):313-322.

22) Gonca, E. & Darıcı, F. (2015). The effect of cannabidiol on ischemia/reperfusion-induced ventricular arrhythmias: The role of adenosine A1 receptors. J Cardiovasc Pharmacol Ther. Vol. 20(1):76-83.

23) Hao, E., Mukhopadhyay, P., Cao, Z., Erdélyi, K., Holovac, E., Liaudet, L., Lee, W.N., Haskó, G., Mechoulam, R. & Pacher, P. (2015). Cannabidiol protects against doxorubicin-induced cardiomyopathy by modulating mitochondrial function & biogenesis. Mol Med. Vol 21(1):38-45.

24) Stanley, C.P., Hind, W.H., Tufarelli, C. & O’Sullivan, S.E. (2015). Cannabidiol causes endothelium-dependent vasorelaxation of human mesenteric arteries via CB1 activation. Cardiovasc Res. Vol. 107(4):568-578.

25) Walsh, S.K., Hepburn, C.Y., Keown, O., Åstrand, A., Lindblom, A., Ryberg, E., Hjorth, S., Leslie, S.J., Greasley, P.J. & Wainwright, C.L. (2015). Pharmacological profiling of the hemodynamic effects of cannabinoid ligands: A combined in vitro & in vivo approach. Pharm Res Perspect. Vol. 3(3):e00143.

26) Kinsey, S.G., Naidu, P.S., Cravatt, B.F., Dudley, D.T. & Lichtman, A.H. (2011). Fatty acid amide hydrolase blockade attenuates the development of collagen-induced arthritis & related thermal hyperalgesia in mice. Pharmacol Biochem Behav. Vol. 99(4):718–725.

27) Choudhary, M., Kumar, V., Malhotra, H. & Singh, S. (2015). Medicinal plants with potential anti-arthritic activity. J Intercult Ethnopharmacol. Vol. 4(2):147-179.

28) Hammell, D.C., Zhang, L.P., Ma, F., Abshire, S.M., McIlwrath, S.L., Stinchcomb, A.L. & Westlund, K.N. (2016). Transdermal cannabidiol reduces inflammation & pain-related behaviours in a rat model of arthritis. Eur J Pain. Vol. 20(6):936-948.

29) Bergamaschi, M.M., Queiroz, R.H., Chagas, M.H., de Oliveira, D.C., De Martinis, B.S., Kapczinski, F., Quevedo, J., Roesler, R., Schröder, N., Nardi , A.E., Martín-Santos, R., Hallak, J.E.,, Zuardi, A.W. & Crippa, J.A. (2011). Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients. Neuropsychopharmacol. Vol. 36(6):1219-1226.

30) Crippa, J.A., Derenusson, G.N., Ferrari, T.B., Wichert-Ana, L., Duran, F.L., Martin-Santos, R., Simões, M.V., Bhattacharyya, S., Fusar-Poli, P., Atakan, Z., Santos Filho, A., Freitas-Ferrari, M.C., McGuire, P.K., Zuardi, A.W., Busatto, G.F. & Hallak, J.E. (2011). Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. J Psychopharmacol. Vol. 25(1):121-130.

31) Schier, A.R., Ribeiro, N.P., Silva, A.C., Hallak, J,E., Crippa, J.A., Nardi, A.E. & Zuardi, A.W. (2012). Cannabidiol, a Cannabis sativa constituent, as an anxiolytic drug. Rev Bras Psiquiatr. Vol. 34 (Suppl 1):S104-110.

32) Blessing, E.M., Steenkamp, M.M., Manzanares, J. & Marmar, C.R. (2015). Cannabidiol as a potential treatment for anxiety disorders. Neurotherapeutics. Vol. 12(4):825-836.

33) de Mello Schier, A.R., de Oliveira Ribeiro, N.P., Coutinho, D.S., Machado, S., Arias-Carrión, O., Crippa, J.A., Zuardi, A.W., Nardi, A.E. & Silva, A.C. (2014). Antidepressant-like & anxiolytic-like effects of cannabidiol: A chemical compound of Cannabis sativa. CNS Neurol Disord Drug Targets. Vol. 13(6):953-960.

34) Sagredo, O., Pazos, M.R., Satta, V., Ramos, J.A., Pertwee, R.G. & Fernandez-Ruiz, J. (2011). Neuroprotective effects of phytocannabinoid-based medicines in experimental models of Huntington’s disease. J Neurosci Res. Vol. 29(9):1509-1518.

35) Harvey, B.S., Ohlsson, K.S., Mååg, J.L., Musgrave, I.F. &Smid, S.D. (2012). Contrasting protective effects of cannabinoids against oxidative stress & amyloid-β evoked neurotoxicity in vitro. Neurotoxicology. Vol. 33(1):138-146.

36) Devinsky, O., Cilio, M.R., Cross, H., Fernandez-Ruiz, J., French, J., Hill, C., Katz, R., Di Marzo, V., Jutras-Aswad, D., Notcutt, W.G., Martinez-Orgado, J., Robson, P.J., Rohrback, B.G., Thiele, E., Whalley, B. & Friedman, D. (2014). Cannabidiol: Pharmacology & potential therapeutic role in epilepsy & other neuropsychiatric disorders. Epilepsia. Vol. 55(6):791-802.

37) Fernández-Ruiz, J., Moro, M.A. &, Martínez-Orgado, J. (2015). Cannabinoids in neurodegenerative disorders & stroke/brain trauma: From preclinical models to clinical applications. Neurotherapeutics. Vol. 12(4):793-806.

38) Rosenberg, E.C., Tsien, R.W., Whalley, B.J. & Devinsky, O. (2015). Cannabinoids & epilepsy. Neurotherapeutics. Vol. 12(4):747-768.

39) Tzadok, M., Uliel-Siboni, S., Linder, I., Kramer, U., Epstein, O., Menascu, S., Nissenkorn, A., Yosef, O.B., Hyman, E., Granot, D., Dor, M., Lerman-Sagie, T. & Ben-Zeev, B. (2016). CBD-enriched medical cannabis for intractable pediatric epilepsy: The current Israeli experience. Seizure. Vol. 35:41-44.

40) Castillo, A., Tolon, M.R., Fernandez-Ruiz, J., Romero, J. & Martinez-Orgado, J. (2010, February). The neuroprotective effect of cannabidiol in an in vitro model of newborn hypoxic-ischemic brain damage in mice is mediated by CB(2) & adenosine receptors. Neurobiol Dis. Vol. 37(2):434-440.

41) Shohami, E., Cohen-Yeshurun, A., Magid, L., Algali, M. & Mechoulam, R. (2011). Endocannabinoids & traumatic brain injury. Br J Pharmacol. Vol. 163(7):1402-1410.

42) Guagnini, F., Valenti, M., Mukenge, S., Matias, I., Bianchetti, A., Palo, S.D., Ferla, G., Di Marzo, V. & Croci, T. (2006). Neural contractions in colonic strips from patients with diverticular disease: Role of endocannabinoids & substance P. Gut. Vol. 55(7):946-953.

43) Wright, K.L., Duncan, M. & Sharkey, K.A. (2008). Cannabinoid CB2 receptors in the gastrointestinal tract: A regulatory system in states of inflammation. Br J Pharmacol. Vol. 153(2):263-270.

44) Cluny, N.L., Naylor, R.J., Whittle, B.A. & Javid, F.A. (2011). The effects of cannabidiolic acid & cannabidiol on contractility of the gastrointestinal tract of Suncus murinus. Arch Pharm Res. Vol. 34(9):1509-1517.

45) De Filippis, D., Esposito, G., Cirillo, C., Cipriano, M., De Winter, B.Y., Scuderi, C., Sarnelli, G., Cuomo, R., Steardo, L., De Man, J.G. & Iuvone, T. (2011). Cannabidiol reduces intestinal inflammation through the control of neuroimmune axis. PLoS ONE. Vol. 6(12):e28159.

46) Alhamoruni, A., Wright, K., Larvin, M. & O’Sullivan, S. (2012). Cannabinoids mediate opposing effects on inflammation-induced intestinal permeability. Br J Pharmacol. Vol. 165(8):2598-2610.

47) Kaplan, B.L., Springs, A.E. & Kaminski, N.E. (2008). The profile of immune modulation by cannabidiol (CBD) involves deregulation of nuclear factor of activated T cells (NFAT). Biochem Pharmacol. Vol. 76(6):726-737.

48) Kogan, N.M. & Mechoulam, R. (2007). Cannabinoids in health & disease. Dialogues Clin Neurosci. Vol. 9(4):413-430.

49) Kozela, E., Lev, N., Kaushansky, N., Eilam, R., Rimmerman, N., Levy, R., Ben-Nun, A., Juknat, A. & Vogel, Z. (2011). Cannabidiol inhibits pathogenic T cells, decreases spinal microglial activation & ameliorates multiple sclerosis-like disease in C57BL/6 mice. Br J Pharmacol. Vol. 163(7):1507-1519.

50) Oláh, A., Tóth, B. I., Borbíró, I., Sugawara, K., Szöllõsi, A. G., Czifra, G., Pál, B., Ambrus, L., Kloepper, J., Camera, E., Ludovici, M., Picardo, M., Voets, T., Zouboulis, C.C., Paus, R. & Bíró, T. (2014). Cannabidiol exerts sebostatic & antiinflammatory effects on human sebocytes. J Clin Invest. Vol. 124(9):3713-3724.

51) Mao, K., You, C., Lei, D. & Zhang, H. (2015). High dosage of cannabidiol (CBD) alleviates pentylenetetrazole-induced epilepsy in rats by exerting an anticonvulsive effect. Int J Clin Exp Med. Vol. 8(6):8820-8827.

52) Rieder, S.A., Chauhan, A., Singh, U., Nagarkatti, M. & Nagarkatti, P. (2010). Cannabinoid-induced apoptosis in immune cells as a pathway to immunosuppression. Immunobiology. Vol. 215(8):598-605.

53) McAllister, S.D., Soroceanu, L. & Desprez, P.Y. (2015). The antitumor activity of plant-derived non-psychoactive cannabinoids. J Neuroimmune Pharmacol. Vol. 10(2):255-267.

54) Pyszniak, M., Tabarkiewicz, J. & Łuszczki, J.J. (2016). Endocannabinoid system as a regulator of tumor cell malignancy: Biological pathways & clinical significance. Onco Targets Ther. Vol. 9:4323-4336.

55) Velasco, G., Sánchez, C. & Guzmán, M. (2016). Anticancer mechanisms of cannabinoids. Curr Oncol. Vol. 23(Suppl 2):S23-S32.

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