Abnormal cannabidiol explained

Abnormal cannabidiol (Abn-CBD) is a synthetic regioisomer of cannabidiol, which unlike most other cannabinoids produces vasodilator effects, lowers blood pressure, and induces cell migration, cell proliferation and mitogen-activated protein kinase activation in microglia, but without producing any psychoactive or sedative effects.[1] [2]

Receptor activity

It has been shown that the actions of abnormal cannabidiol are mediated through a site separate from the CB1 and CB2 receptors,[2] [3] which responds to abnormal cannabidiol, O-1602, and the endogenous ligands: anandamide (AEA), N-arachidonoyl glycine (NAGly) and N-arachidonoyl L-serine.[2] [4] [5] [6] Multiple lines of evidence support the proposed identification of this novel target in microglia as the previously "orphan" receptor GPR18.[2] Another possible target of abnormal cannabidiol is GPR55, which has also received much attention as a putative cannabinoid receptor,[7] [8] although a growing body of evidence points to lysophosphatidylinositol (LPI) as the endogenous ligand for GPR55.[9] [10] Further research suggests there are yet more additional cannabinoid receptors.[11] [12] [13] [14]

Pharmacodynamics

Research of the effects on abnormal cannabidiol in mice has indicated that atypical cannabinoids have therapeutic potential in a variety of inflammatory conditions, including those of the gastrointestinal tract. After inducing colitis by means of trinitrobenzene sulfonic acid, wound healing of both human umbilical vein endothelial and epithelial cells was enhanced by the Abn-CBD.[15]

See also

Notes and References

  1. Adams MD, Earnhardt JT, Martin BR, Harris LS, Dewey WL, Razdan RK . A cannabinoid with cardiovascular activity but no overt behavioral effects . Experientia . 33 . 9 . 1204–1205 . September 1977 . 891878 . 10.1007/BF01922330 . 21488700 .
  2. McHugh D, Hu SS, Rimmerman N, Juknat A, Vogel Z, Walker JM, Bradshaw HB . N-arachidonoyl glycine, an abundant endogenous lipid, potently drives directed cellular migration through GPR18, the putative abnormal cannabidiol receptor . BMC Neuroscience . 11 . 44 . March 2010 . 20346144 . 2865488 . 10.1186/1471-2202-11-44 . free .
  3. Járai Z, Wagner JA, Varga K, Lake KD, Compton DR, Martin BR, Zimmer AM, Bonner TI, Buckley NE, Mezey E, Razdan RK, Zimmer A, Kunos G . 6 . Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors . Proceedings of the National Academy of Sciences of the United States of America . 96 . 24 . 14136–14141 . November 1999 . 10570211 . 24203 . 10.1073/pnas.96.24.14136 . free . 1999PNAS...9614136J .
  4. Walter L, Franklin A, Witting A, Wade C, Xie Y, Kunos G, Mackie K, Stella N . 6 . Nonpsychotropic cannabinoid receptors regulate microglial cell migration . The Journal of Neuroscience . 23 . 4 . 1398–1405 . February 2003 . 12598628 . 6742252 . 10.1523/JNEUROSCI.23-04-01398.2003 .
  5. Offertáler L, Mo FM, Bátkai S, Liu J, Begg M, Razdan RK, Martin BR, Bukoski RD, Kunos G . 6 . Selective ligands and cellular effectors of a G protein-coupled endothelial cannabinoid receptor . Molecular Pharmacology . 63 . 3 . 699–705 . March 2003 . 12606780 . 10.1124/mol.63.3.699 .
  6. Milman G, Maor Y, Abu-Lafi S, Horowitz M, Gallily R, Batkai S, Mo FM, Offertaler L, Pacher P, Kunos G, Mechoulam R . 6 . N-arachidonoyl L-serine, an endocannabinoid-like brain constituent with vasodilatory properties . Proceedings of the National Academy of Sciences of the United States of America . 103 . 7 . 2428–2433 . February 2006 . 16467152 . 1413724 . 10.1073/pnas.0510676103 . free . 2006PNAS..103.2428M .
  7. McCollum L, Howlett AC, Mukhopadhyay S . Anandamide-mediated CB1/CB2 cannabinoid receptor--independent nitric oxide production in rabbit aortic endothelial cells . The Journal of Pharmacology and Experimental Therapeutics . 321 . 3 . 930–937 . June 2007 . 17379772 . 10.1124/jpet.106.117549 . 24492397 .
  8. Ryberg E, Larsson N, Sjögren S, Hjorth S, Hermansson NO, Leonova J, Elebring T, Nilsson K, Drmota T, Greasley PJ . 6 . The orphan receptor GPR55 is a novel cannabinoid receptor . British Journal of Pharmacology . 152 . 7 . 1092–1101 . December 2007 . 17876302 . 2095107 . 10.1038/sj.bjp.0707460 .
  9. Kapur A, Zhao P, Sharir H, Bai Y, Caron MG, Barak LS, Abood ME . Atypical responsiveness of the orphan receptor GPR55 to cannabinoid ligands . The Journal of Biological Chemistry . 284 . 43 . 29817–29827 . October 2009 . 19723626 . 2785612 . 10.1074/jbc.M109.050187 . free .
  10. Henstridge CM, Balenga NA, Ford LA, Ross RA, Waldhoer M, Irving AJ . The GPR55 ligand L-alpha-lysophosphatidylinositol promotes RhoA-dependent Ca2+ signaling and NFAT activation . FASEB Journal . 23 . 1 . 183–193 . January 2009 . 18757503 . 10.1096/fj.08-108670 . free . 27142069 .
  11. Brown AJ . Novel cannabinoid receptors . British Journal of Pharmacology . 152 . 5 . 567–575 . November 2007 . 17906678 . 2190013 . 10.1038/sj.bjp.0707481 .
  12. Johns DG, Behm DJ, Walker DJ, Ao Z, Shapland EM, Daniels DA, Riddick M, Dowell S, Staton PC, Green P, Shabon U, Bao W, Aiyar N, Yue TL, Brown AJ, Morrison AD, Douglas SA . 6 . The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects . British Journal of Pharmacology . 152 . 5 . 825–831 . November 2007 . 17704827 . 2190033 . 10.1038/sj.bjp.0707419 .
  13. McHugh D, Tanner C, Mechoulam R, Pertwee RG, Ross RA . Inhibition of human neutrophil chemotaxis by endogenous cannabinoids and phytocannabinoids: evidence for a site distinct from CB1 and CB2 . Molecular Pharmacology . 73 . 2 . 441–450 . February 2008 . 17965195 . 10.1124/mol.107.041863 . 15182303 .
  14. Kreutz S, Koch M, Böttger C, Ghadban C, Korf HW, Dehghani F . 2-Arachidonoylglycerol elicits neuroprotective effects on excitotoxically lesioned dentate gyrus granule cells via abnormal-cannabidiol-sensitive receptors on microglial cells . Glia . 57 . 3 . 286–294 . February 2009 . 18837048 . 10.1002/glia.20756 . 37531270 .
  15. Krohn RM, Parsons SA, Fichna J, Patel KD, Yates RM, Sharkey KA, Storr MA . Abnormal cannabidiol attenuates experimental colitis in mice, promotes wound healing and inhibits neutrophil recruitment . Journal of Inflammation . 13 . 21 . 21 . 2016 . 27418880 . 4944257 . 10.1186/s12950-016-0129-0 . free .

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