What is hemp?
Hemp is not marijuana and you will not be high and you will not to test positive for illegal drugs!!!
Cannabis sativa is a flowering plant which is known as marijuana or hemp. Cannabis contains more than 120 chemical constituents - cannabinoids. Two major, scientifically studied cannabinoids are tetrahydrocannabinol (THC) and cannabidiol (CBD), which exert their effects through the endocannabinoid system (1). THC is the main psychoactive compound of marijuana and can alter human senses and induce a “high feeling”. CBD is the main non-psychoactive compound of hemp and does not have mind-altering side effects.
Why are people using CBD?
CBD is well tolerated and safe for human consumption (2). A recent cross-sectional study found that CBD is mainly used to treat chronic pain, arthritis/joint pain, anxiety, depression, insomnia, and headaches. However, only 36% of CBD users confirmed positive effects of CBD on their medical status (3). The major reason for such a low efficacy is the real amount of CBD. Analysis of 84 CBD products from 31 different companies showed that 43% of tested CBD products contained less CBD than declared on their labels (4). Since CBD containing products are not regulated, and are not tested for their efficacy, other compounds in the CBD preparation may decrease the effectiveness of CBD.
Why are people taking CBD?
How does CBD work?
Although CBD is a well-known cannabinoid, Major biological effects of CBD are not mediated through cannabinoid receptors CB1 and CB2, which are the main functional receptors for THC. Pharmacologically, CBD is a non-competitive, negative allosteric modulator of CB1 and CB2, which reduces the potency and efficacy of THC (5, 6). Therefore, CBD exerts its major biological/therapeutic effects through receptors other than CB1 and CB2.
Anti-inflammatory/analgesic effect of CBD. CBD inhibition of inflammation results in pain relief in osteoarthritis, a multifactorial joint disease, which includes joint degeneration, intermittent inflammation, and peripheral neuropathy (7). Anti-inflammatory and analgesic effects are mediated through peroxisome proliferator-activated receptor γ (PPARγ) and vanilloid receptor TRPV1 (8, 9). TRPV1 is involved in acute inflammatory knee joint pain, characteristic of inflammatory arthritis in humans (10). Anti-inflammatory actions of CBD were shown to decrease the pro-inflammatory cytokines (e.g. tumor necrosis factor – alpha (TNF-a) and interleukin-6 (IL-6)) and increase the anti-inflammatory cytokines (IL-4 and IL-10) (11, 12).
CBD effectiveness depends on its absorption. CBD is insoluble in water, therefore its absorption in the human body is low. Several studies demonstrated that only 8% of CBD is absorbed after oral administration (15). Oral co-administration of CBD with lipids enhanced absorption of CBD by 3-fold, compared to lipid-free formulations (15). However, specific delivery method using nanoparticles - “ethosomes” can increase CBD delivery by 15-fold when compared to an aqueous solution (16).
What is an effective CBD dose?
Recent scientific studies and clinical trials have shown that CBD has potential therapeutic benefits for several conditions:
Anti-inflammatory/anti-pain effects of CBD. Oral CBD at 5-40 mg/kg suppressed inflammation and inflammation induced-pain in pre-clinical model of edema (17). This dose corresponds to 400-3200 mg CBD for an 80 kg/176 lbs person. CBD at 50 mg/kg also decreased inflammatory and neuropathic pain in another pre-clinical study (18). 50 mg/kg corresponds to 4000 mg CBD for an 80 kg/176 lbs person. Topical application of CBD 6.2 mg/day and 62 mg/day markedly decreased inflammation and pain in a pre-clinical model of arthritis (19).
Anxiolytic/brain-related effects of CBD. Pre-clinical studies demonstrated anti-stress effects of CBD in anxiety-related clinical disorders such as panic, post-traumatic stress, and obsessive-compulsive disorder (13). CBD demonstrated an anxiolytic effect in the Simulated Public Speaking Test (SPST) at 300 mg CBD but not in the low (150 mg) or high (600 mg) dose of CBD, respectively (20). In addition to the anxiolytic effects, 800 mg/day of CBD for 4 weeks significantly reduced psychotic symptoms in schizophrenia, whereas 300 mg CBD/day significantly improved quality of life and well-beings in patients with Parkinson disease (13). A recent clinical trial showed that highly purified CBD (2.5 - 20 mg/kg/d over a 2-week period) significantly reduced seizures in patients with Dravet syndrome (21).
1. Boggs DL, Nguyen JD, Morgenson D, Taffe MA, Ranganathan M. Clinical and Preclinical Evidence for Functional Interactions of Cannabidiol and Δ(9)-Tetrahydrocannabinol. Neuropsychopharmacology. 2018;43:142-154.
2. Iffland K, Grotenhermen F. An update on safety and side effects of cannabidiol: a review of clinical data and relevant animal studies. Cannabis Cannabinoid Res. 2017;2:139–154.
3. Corroon J, Phillips JA. A cross-sectional study of cannabidiol users. Cannabis and Cannabinoid Res. 2018;3:152–161.
4. Bonn-Miller MO, Loflin MJE, Thomas BF, et al. Labeling accuracy of cannabidiol extracts sold online. JAMA. 2017;318:1708–1709.
5. Laprairie RB, Bagher AM, Kelly ME, Denovan-Wright EM. Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. Br J Pharmacol. 2015;172:4790-805.
6. Martínez-Pinilla E., Varani K., Reyes-Resina I., Angelats E., Vincenzi F., Ferreiro-Vera C., et al. Binding and signaling studies disclose a potential allosteric site for cannabidiol in cannabinoid CB2 receptors. Front. Pharmacol. 2017;8:744.
7. Philpott HT, O'Brien N, McDougall JJ. Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis. Pain. 2017;158:2442-51.
8. O'Sullivan SE, Sun Y, Bennett AJ, Randall MD, Kendall DA. Time-dependent vascular actions of cannabidiol in the rat aorta. Eur J Pharmacol. 2009;612:61-8.
9. De Gregorio D, McLaughlin RJ, Posa L, Ochoa-Sanchez R, Enns J, Lopez-Canul M, Aboud M, Maione Comai S, Gobbi G. Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain. Pain. 2018 Aug 27. [Epub ahead of print]
10. Chakrabarti S, Pattison LA, Singhal K, Hockley JRF, Callejo G, Smith ESJ. Acute inflammation sensitizes knee-innervating sensory neurons and decreases mouse digging behavior in a TRPV1-dependent manner. Neuropharmacology. 2018;143:49-62.
11. Watzl B, Scuderi P, Watson RR. Influence of marijuana components (THC and CBD)on human mononuclear cell cytokine secretion in vitro. Adv Exp Med Biol. 1991;288:63-70.
12. Weiss L, Zeira M, Reich S, Har-Noy M, Mechoulam R, Slavin S, Gallily R. Cannabidiol lowers incidence of diabetes in non-obese diabetic mice. Autoimmunity. 2006;39:143-51.
15. Zgair A, Wong JC, Lee JB, Mistry J, Sivak O, Wasan KM, Hennig IM, Barrett DA, Constantinescu CS, Fischer PM, Gershkovich P. Dietary fats and pharmaceutical lipid excipients increase systemic exposure to orally administered cannabis and cannabis-based medicines. Am J Transl Res. 2016;8:3448-59.
16. Abdulbaqi IM, Darwis Y, Khan NA, Assi RA, Khan AA. Ethosomal nanocarriers: the impact of constituents and formulation techniques on ethosomal properties, in vivo studies, and clinical trials. Int J Nanomedicine. 2016; 11:2279-304.
17. Costa B, Colleoni M, Conti S, Parolaro D, Franke C, Trovato AE, Giagnoni G. Oral anti-inflammatory activity of cannabidiol, a non-psychoactive constituent of cannabis, in acute carrageenan-induced inflammation in the rat paw. Naunyn Schmiedebergs Arch Pharmacol. 2004;369:294-9.
18. Xiong W, Cui T, Cheng K, Yang F, Chen SR, Willenbring D, Guan Y, Pan HL, Ren K, Xu Y, Zhang L. Cannabinoids suppress inflammatory and neuropathic pain by targeting α3 glycine receptors. J Exp Med. 2012;209:1121-34.
19. Hammell DC, Zhang LP, Ma F, Abshire SM, McIlwrath SL, Stinchcomb AL, Westlund KN. Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis. Eur J Pain. 2016;20:936-48.
20. Linares I, Zuardi AW, Pereira LC, Hallak JEC, Queiroz RHC, Guimarães FS, et al. Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test. Eur. Neuropsychopharmacol. 2018;26:S617.
21. Devinsky O, Nabbout R, Miller I, Laux L, Zolnowska M, Wright S, Roberts C. Long-term cannabidiol treatment in patients with Dravet syndrome: An open-label extension trial. Epilepsia. 2018 Dec 23. [Epub ahead of print]