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Brainstrom[edit]

I have chosen to evaluate the Wikipedia page for cannabidiol (CBD), not to be confused with cannabinoid. This article lacks large chunks of desirable information. The all-around history of CBD and it's identity independent of cannabis and THC could use a boost. The topic of research is sparse which is possibly a result of CBD's youthful emergence into awareness. (BELIEVE IT OR NOT, THEY HAVE KNOWN ABOUT CANNABIDIOL FOR QUITE A WHILE. LAST I RESEARCHED IN THE FIELD A FEW YEARS AGO, THERE WAS STILL NO FULL UNDERSTANDING OF HOW IT WORKS. SOME HYPOTHESES ABOUT IT BEING AN ANTAGONIST FOR THE KNOWN RECEPTORS [OR POSSIBLY UNKNOWN]. WHAT THEY DO KNOW IS THAT THE COMBINATION OF CBD COUNTERACTS THE PSYCHOTROPIC EFFECTS OF THC. THUS SATIVEX HAS BEEN SHOWN TO BE MORE EFFICACIOUS THAN MARINOL). However, no mention of the medicinal research conducted at UAB has been mentioned (too new? YES, BUT LOTS OF OTHER RESEARCH HAS BEEN DONE ON CBD IN ANIMAL MODELS not enough collaboration to suit wiki? An interesting avenue to explore maybe potential contribution on effects of CBD metabolysis within the gut flora. (LOTS OF INTEREST IN HOW CANNABINOIDS IMPACT THE GUT)

I am quickly understanding that the large gaps are not filled for lack of trying! The main topic on the talk page is the differentiation of THC from CBD. The medication of Sativex being mentioned has been questioned since it is a solution of equal portions of both substances. A point well-made was that this is an article on the cannabidiods only, not to be confused with cannabiniod-based medicine. However, I did find interesting literature supporting that treatments of THC are tolerated with more ease when CBD compounds are present as well. https://ac-els-cdn-com.ezproxy3.lhl.uab.edu/B9780128002131000614/3-s2.0-B9780128002131000614-main.pdf?_tid=51c11536-e439-4187-a6fb-a9dd26d111da&acdnat=1548650368_4502c84d92c8f553eabd4b7ffbbd30c3 (I WASN'T ABLE TO CHECK THIS RESOURCE VIA THIS LINK AS I AM NOT ONLINE AT UAB, SUGGEST LINKING OUT TO PUBMED INSTEAD OF UAB LIBRARIES) SUGGEST YOU REVIEW THE FOLLOWING: https://www.ncbi.nlm.nih.gov/pubmed/30534073

Side note: I found that I was publishing to the rcocker/page rather than my sandbox. Now that I have that figured out...GOTCHA

I was saving my place on the fly with the link. It ishttps://doi.org/10.1016/j.yebeh.2016.11.021 It regards the legal status of cannabis and CBD under US Law as of August 2016. I was thinking that it contains useful information but need to further dissect what is applicable to CBD. However, legalities happens to need the least help currently.

Great article on PK with overviews that I can work with but need some enlightenment within the subject of biochemistry to glean all that may be mention-worthy. GPR55 was published in 2012 so I didn't pursue it any further.

Draft CBD[edit]

2-3-19: Consuming 300-600 mg of CBD orally has shown to elicit beneficial responses in multiple anxiety-based disorders.[1] Other clinical trials suggest a wider range of dosage, 150 mg-600 mg.[2] (Actual citation 38)

2-7-19:

Pharmacodynamics[edit]

Cannabidiol has very low affinity for the cannabinoid CB1 and CB2 receptors but is said to act as an indirect antagonist of these receptors.[3][4] At the same time, it may potentiate the effects of THC by increasing CB1 receptor density or through another CB1 receptor-related mechanism.[5]

Cannabidiol has been found to act as an antagonist of GPR55, a G protein-coupled receptor and putative cannabinoid receptor that is expressed in the caudate nucleus and putamen in the brain.[6] It has also been found to act as an inverse agonist of GPR3, GPR6, and GPR12.[7] Although currently classified as orphan receptors, these receptors are most closely related phylogenetically to the cannabinoid receptors.[7] In addition to orphan receptors, CBD has been shown to act as a serotonin 5-HT1A receptor partial agonist,[8] and this action may be involved in its antidepressant,[9][10] anxiolytic,[10][11] and neuroprotective effects.[12][13] It is an allosteric modulator of the μ- and δ-opioid receptors as well.[14] The pharmacological effects of CBD have additionally been attributed to PPARγ agonism and intracellular calcium release.[15]

Research suggests that CBD may exert some of its pharmacological action through its inhibition of fatty acid amide hydrolase (FAAH), which may in turn increase the levels of endocannabinoids, such as anandamide, produced by the body.[15] It has also been speculated that some of the metabolites of CBD have pharmacological effects that contribute to the biological activity of CBD.[16]

Pharmacokinetics[edit]

The oral bioavailability of CBD is 13 to 19%, while its bioavailability via inhalation is 11 to 45% (mean 31%).[17] (29 should be the addition of #97 to citation list) The elimination half-life of CBD is 18–32 hours.[18] Oral routes of administration may be most beneficial for long-term treatments. Consumption via vaporization decreases the negative impacts to the respiratory system when compared to smoking inhalation of the the full cannabis plant to acquire any form of cannabinoids. Trans-dermal administrations are found to have a higher permeability of epidermal tissues then is similarly studies cannabinoid constituents. Trans-dermal CBD is not a clinically available option as of 2018.[17] (29 should be the addition of #97 to citation list)

Cannabidiol is metabolized in the liver as well as in the intestines by CYP2C19 and CYP3A4 enzymes, and UGT1A7, UGT1A9, and UGT2B7 isoforms.

[19]

Research[edit]

A 2016 literature review indicated that cannabidiol was under basic research to identify its possible neurological effects,[20]



https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412699/ add citation for additional support of low affinity to pharmacodynamics section A couple of interesting reviews that might (emphasis on might) help with the pharmacodynamic search [it still seems to me that little is known, particularly in humans] https://www.ncbi.nlm.nih.gov/pubmed/29766540 https://www.ncbi.nlm.nih.gov/pubmed/30001569

History of CBD[edit]

The history of CBD is intertwined with that of the entire Cannabis sativa plant's medicinal usage dating back to approximately 5000 years ago. [21] [2]CBD, as a lone constituent of the cannabis plant, has a short history. Roger Adams et al., were the first to discover and isolate CBD from the full plant.[22] Dr. Walter S. Loewe was the first to conduct research on CBD in 1946. In 1963, Dr. Raphael Mechoulam was the first to describe the chemical structure of CBD as an isolated compound and conducted research with CBD on into the 1980's.[23][22] (The two sources have conflicting dates 40 says 1964 and 39 says 1963 as the publication date implies in the sources section of article. How to resolve this?)

Update 3/10/19: Continuing to filter thru the sources that are already cited within the wikipage to find possible additions. Currently learning more about the eCB system and the pharmacological aspects of CBD.

3/27/19-3/30/19 Update:[edit]

Animal and human trials confirm positive results in treating neuropsychiatric disorders, like PTSD thru an extinction process of averse memories in combination of exposure therapy. (DOI: 10.3389/fnins.2018.00502)

Cannabinoids have potential effects on neuro-degenerative and psychiatric disorders. In CBD showed neuroprotective properties with an increase of anti-oxidation properties, depending on their structures, relieving oxidation stress by remove oxidant species. (Lucas, and Aline) CBD regulates STAT1 and STAT3 homeostasis with TH17, decreasing IL-6, IL-17. and upregulate inhibition of regulatory effects on CD4+ and CD25- T-cells. (Cannabidiol, neuroprotection and neuropsychiatric disorders

Alline C. Camposa,b,∗, Manoela V. Fogac¸ aa,b, Andreza B. Sonegoa,b,

Francisco S. Guimarãesa,b eCB retrograde signaling. (1)

CBD reports a bell-shaped response curve with a wide margin in dosing suggesting that higher doses are less effective while lower doses produce an anxiolytic effect. (1).

Little is known about potential drug interactions but CBD-mediates decrease in clobazam metabolism. (DOI:10.1111/bcp.13710) Add as cited source on CBR affinity

  1. ^ Blessing, Esther M.; Steenkamp, Maria M.; Manzanares, Jorge; Marmar, Charles R. (2015-10). "Cannabidiol as a Potential Treatment for Anxiety Disorders". Neurotherapeutics. 12 (4): 825–836. doi:10.1007/s13311-015-0387-1. ISSN 1933-7213. PMC 4604171. PMID 26341731. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  2. ^ a b Bridgeman, Mary Barna; Abazia, Daniel T. (2017-3). "Medicinal Cannabis: History, Pharmacology, And Implications for the Acute Care Setting". Pharmacy and Therapeutics. 42 (3): 180–188. ISSN 1052-1372. PMC 5312634. PMID 28250701. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  3. ^ Mechoulam R, Peters M, Murillo-Rodriguez E, Hanus LO (August 2007). "Cannabidiol--recent advances". Chemistry & Biodiversity (Review). 4 (8): 1678–92. doi:10.1002/cbdv.200790147. PMID 17712814.
  4. ^ Pertwee RG (January 2008). "The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin". British Journal of Pharmacology. 153 (2): 199–215. doi:10.1038/sj.bjp.0707442. PMC 2219532. PMID 17828291.
  5. ^ Hayakawa K, Mishima K, Hazekawa M, Sano K, Irie K, Orito K, Egawa T, Kitamura Y, Uchida N, Nishimura R, Egashira N, Iwasaki K, Fujiwara M (January 2008). "Cannabidiol potentiates pharmacological effects of Delta(9)-tetrahydrocannabinol via CB(1) receptor-dependent mechanism". Brain Research. 1188: 157–64. doi:10.1016/j.brainres.2007.09.090. PMID 18021759.
  6. ^ Ryberg E, Larsson N, Sjögren S, Hjorth S, Hermansson NO, Leonova J, Elebring T, Nilsson K, Drmota T, Greasley PJ (December 2007). "The orphan receptor GPR55 is a novel cannabinoid receptor". British Journal of Pharmacology. 152 (7): 1092–101. doi:10.1038/sj.bjp.0707460. PMC 2095107. PMID 17876302.
  7. ^ a b Laun AS, Shrader SH, Brown KJ, Song ZH (June 2018). "GPR3, GPR6, and GPR12 as novel molecular targets: their biological functions and interaction with cannabidiol". Acta Pharmacol. Sin. doi:10.1038/s41401-018-0031-9. PMID 29941868.
  8. ^ Russo EB, Burnett A, Hall B, Parker KK (August 2005). "Agonistic properties of cannabidiol at 5-HT1a receptors". Neurochemical Research. 30 (8): 1037–43. doi:10.1007/s11064-005-6978-1. PMID 16258853.
  9. ^ Zanelati TV, Biojone C, Moreira FA, Guimarães FS, Joca SR (January 2010). "Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT1A receptors". British Journal of Pharmacology. 159 (1): 122–8. doi:10.1111/j.1476-5381.2009.00521.x. PMC 2823358. PMID 20002102.
  10. ^ a b Resstel LB, Tavares RF, Lisboa SF, Joca SR, Corrêa FM, Guimarães FS (January 2009). "5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats". British Journal of Pharmacology. 156 (1): 181–8. doi:10.1111/j.1476-5381.2008.00046.x. PMC 2697769. PMID 19133999.
  11. ^ Campos AC, Guimarães FS (August 2008). "Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats". Psychopharmacology. 199 (2): 223–30. doi:10.1007/s00213-008-1168-x. PMID 18446323.
  12. ^ Mishima K, Hayakawa K, Abe K, Ikeda T, Egashira N, Iwasaki K, Fujiwara M (May 2005). "Cannabidiol prevents cerebral infarction via a serotonergic 5-hydroxytryptamine1A receptor-dependent mechanism". Stroke. 36 (5): 1077–82. doi:10.1161/01.STR.0000163083.59201.34. PMID 15845890.
  13. ^ Hayakawa K, Mishima K, Nozako M, Ogata A, Hazekawa M, Liu AX, Fujioka M, Abe K, Hasebe N, Egashira N, Iwasaki K, Fujiwara M (March 2007). "Repeated treatment with cannabidiol but not Delta9-tetrahydrocannabinol has a neuroprotective effect without the development of tolerance". Neuropharmacology. 52 (4): 1079–87. doi:10.1016/j.neuropharm.2006.11.005. PMID 17320118.
  14. ^ Kathmann M, Flau K, Redmer A, Tränkle C, Schlicker E (February 2006). "Cannabidiol is an allosteric modulator at mu- and delta-opioid receptors". Naunyn-Schmiedeberg's Archives of Pharmacology. 372 (5): 354–61. doi:10.1007/s00210-006-0033-x. PMID 16489449.
  15. ^ a b Campos AC, Moreira FA, Gomes FV, Del Bel EA, Guimarães FS (December 2012). "Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences (Review). 367 (1607): 3364–78. doi:10.1098/rstb.2011.0389. PMC 3481531. PMID 23108553.
  16. ^ Ujváry I, Hanuš L (2014). "Human Metabolites of Cannabidiol: A Review on Their Formation, Biological Activity, and Relevance in Therapy". Cannabis and Cannabinoid Research. 1 (1): 90–101. doi:10.1089/can.2015.0012. PMC 5576600. PMID 28861484.
  17. ^ a b Lucas, Catherine J.; Galettis, Peter; Schneider, Jennifer (2018-11). "The pharmacokinetics and the pharmacodynamics of cannabinoids". British Journal of Clinical Pharmacology. 84 (11): 2477–2482. doi:10.1111/bcp.13710. ISSN 1365-2125. PMC 6177698. PMID 30001569. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  18. ^ Devinsky, Orrin; Cilio, Maria Roberta; Cross, Helen; Fernandez-Ruiz, Javier; French, Jacqueline; Hill, Charlotte; Katz, Russell; Di Marzo, Vincenzo; Jutras-Aswad, Didier; Notcutt, William George; Martinez-Orgado, Jose; Robson, Philip J.; Rohrback, Brian G.; Thiele, Elizabeth; Whalley, Benjamin; Friedman, Daniel (22 May 2014). "Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders". Epilepsia. 55 (6): 791–802. doi:10.1111/epi.12631. PMC 4707667. PMID 24854329.
  19. ^ Russo, E. B. (2008). "Cannabinoids in the management of difficult to treat pain". Therapeutics and Clinical Risk Management. 4 (1): 245–259. PMC 2503660. PMID 18728714.
  20. ^ Jurkus R, Day HL, Guimarães FS, Lee JL, Bertoglio LJ, Stevenson CW (2016). "Cannabidiol Regulation of Learned Fear: Implications for Treating Anxiety-Related Disorders". Frontiers in Pharmacology. 7: 454. doi:10.3389/fphar.2016.00454. PMC 5121237. PMID 27932983.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  21. ^ Pertwee, Roger G (2006-01). "Cannabinoid pharmacology: the first 66 years". British Journal of Pharmacology. 147 (Suppl 1): S163–S171. doi:10.1038/sj.bjp.0706406. ISSN 0007-1188. PMC 1760722. PMID 16402100. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  22. ^ a b Maurya, Nancy; Velmurugan, Bharath Kumar (2018-09-25). "Therapeutic applications of cannabinoids". Chemico-Biological Interactions. 293: 77–88. doi:10.1016/j.cbi.2018.07.018. ISSN 1872-7786. PMID 30040916.
  23. ^ "Cannabis History 101: A Brief Timeline on the History of CBD". MarijuanaBreak. 2018-01-28. Retrieved 2019-02-25.
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