Abstract
In the last few years research into Cannabis and its constituent phytocannabinoids has burgeoned, particularly in the potential application of novel cannabis phytochemicals for the treatment of diverse illnesses related to neurodegeneration and dementia, including Alzheimer’s (AD), Parkinson’s (PD) and Huntington’s disease (HD). To date, these neurological diseases have mostly relied on symptomatological management. However, with an aging population globally, the search for more efficient and disease-modifying treatments that could delay or mitigate disease progression is imperative. In this context, this review aims to present state of the art in the research with cannabinoids and novel cannabinoid-based drug candidates that have been emerged as novel promising alternatives for drug development and innovation in the therapeutics of a number of diseases, especially those related to CNS-disturbance and impairment.
Keywords: Phytocannabinoids, endocannabinoid system, neurodegenerative diseases, cannabis sp. cannabinoid receptors, neurological disorders.
Graphical Abstract
[http://dx.doi.org/10.1152/physrev.00002.2016] [PMID: 27630175]
[http://dx.doi.org/10.3390/medicines5040107]
[http://dx.doi.org/10.1039/C5FO01281C] [PMID: 26815043]
[http://dx.doi.org/10.3389/fnint.2018.00051] [PMID: 30405366]
[http://dx.doi.org/10.1016/S0924-977X(10)70232-7]
[http://dx.doi.org/10.1038/s41598-018-31120-2] [PMID: 30166613]
[http://dx.doi.org/10.1021/acsomega.7b00996] [PMID: 30023762]
[http://dx.doi.org/10.1039/C6NP00074F] [PMID: 27722705]
[http://dx.doi.org/10.21577/1984-6835.20170103]
[http://dx.doi.org/10.1016/j.ejim.2018.01.019] [PMID: 29398248]
[http://dx.doi.org/10.1007/s13311-015-0375-5] [PMID: 26282273]
[http://dx.doi.org/10.5740/jaoacint.18-0208] [PMID: 30139415]
[http://dx.doi.org/10.1016/j.pharmthera.2017.02.041] [PMID: 28232276]
[http://dx.doi.org/10.1016/j.jep.2018.09.004] [PMID: 30205181]
[http://dx.doi.org/10.2174/0929867325666180226095132] [PMID: 29484980]
[http://dx.doi.org/10.1155/2018/1691428]] [PMID: 30627539]
[PMID: 31822395]
[http://dx.doi.org/10.1590/S1516-44462006000200015] [PMID: 16810401]
[http://dx.doi.org/10.1038/s41570-017-0101]
[http://dx.doi.org/10.1016/j.cbi.2018.07.018] [PMID: 30040916]
[http://dx.doi.org/10.1016/j.pharmthera.2018.10.006] [PMID: 30347211]
[http://dx.doi.org/10.21577/1984-6835.20170049]
[http://dx.doi.org/10.1016/j.tips.2016.04.005] [PMID: 27179600]
[http://dx.doi.org/10.1007/978-3-319-45541-9_4] [PMID: 28120232]
[http://dx.doi.org/10.1016/j.tips.2016.12.004] [PMID: 28089139]
[http://dx.doi.org/10.1177/1934578X1801300922]
[http://dx.doi.org/10.1126/science.169.3945.611] [PMID: 4987683]
[http://dx.doi.org/10.1002/cbdv.200790149] [PMID: 17712816]
[http://dx.doi.org/10.1007/s13311-015-0374-6] [PMID: 26271952]
[http://dx.doi.org/10.2174/1568026616666160204122033] [PMID: 26845552]
[http://dx.doi.org/10.3389/fphar.2018.00632] [PMID: 29977202]
[http://dx.doi.org/10.1007/s13311-014-0304-z] [PMID: 25252936]
[http://dx.doi.org/10.1186/s40035-019-0148-x] [PMID: 30899454]
[PMID: 31752240]
[http://dx.doi.org/10.3390/molecules24142567] [PMID: 31311157]
[http://dx.doi.org/10.1038/srep29789] [PMID: 27430371]
[http://dx.doi.org/10.3390/ijms19071992] [PMID: 29986533]
[http://dx.doi.org/10.1111/bph.14815] [PMID: 31368508]
[http://dx.doi.org/10.1016/j.ntt.2014.09.003] [PMID: 25311884]
[http://dx.doi.org/10.1016/0306-3623(81)90090-2] [PMID: 6269951]
[http://dx.doi.org/10.1002/jps.2600691136] [PMID: 7452475]
[http://dx.doi.org/10.1124/jpet.117.244368] [PMID: 29632236]
[http://dx.doi.org/10.1007/s12035-019-1637-8] [PMID: 31104297]
[http://dx.doi.org/10.1021/ja01858a058]
[http://dx.doi.org/10.1016/0040-4020(63)85022-X] [PMID: 5879214]
[http://dx.doi.org/10.1097/FBP.0000000000000247] [PMID: 27471947]
[http://dx.doi.org/10.1111/bph.13250] [PMID: 26218440]
[http://dx.doi.org/10.2174/1874467212666190215112036] [PMID: 30767756]
[http://dx.doi.org/10.1038/nrd.2018.115] [PMID: 30116049]
[http://dx.doi.org/10.1111/bph.13497] [PMID: 27077495]
[http://dx.doi.org/10.1111/j.1476-5381.2008.00046.x] [PMID: 19133999]
[http://dx.doi.org/10.1159/000362689] [PMID: 25171128]
[http://dx.doi.org/10.1111/j.1471-4159.2003.02327.x] [PMID: 15030397]
[http://dx.doi.org/10.3389/fphar.2017.00020] [PMID: 28217094]
[http://dx.doi.org/10.1007/s10571-013-9984-x] [PMID: 24030360]
[http://dx.doi.org/10.3390/ijms18010026] [PMID: 28025562]
[http://dx.doi.org/10.1097/QAD.0000000000002345] [PMID: 31764093]
[http://dx.doi.org/10.1002/ptr.5095] [PMID: 24288245]
[http://dx.doi.org/10.1371/journal.pone.0028668]
[http://dx.doi.org/10.1093/abbs/gmx073] [PMID: 28981597]
[http://dx.doi.org/10.1124/mol.111.071290] [PMID: 21350020]
[http://dx.doi.org/10.1007/s00406-019-00982-6] [PMID: 30706171]
[http://dx.doi.org/10.1016/j.lfs.2019.03.053] [PMID: 30910646]
[http://dx.doi.org/10.1016/j.neuropharm.2019.107808]] [PMID: 31706993]
[http://dx.doi.org/10.3389/fphar.2016.00343] [PMID: 27733830]
[http://dx.doi.org/10.1039/C9AN00890J] [PMID: 31318364]
[http://dx.doi.org/10.2174/1570159X17666190603171901] [PMID: 31161980]
[http://dx.doi.org/10.1111/bcp.13710] [PMID: 30001569]
[http://dx.doi.org/10.3390/molecules25030631] [PMID: 32024009]
[http://dx.doi.org/10.1021/acsmedchemlett.6b00009] [PMID: 27096053]
[http://dx.doi.org/10.1016/j.pnpbp.2015.05.010] [PMID: 26071989]
[http://dx.doi.org/10.1016/j.archoralbio.2019.05.028] [PMID: 31158702]
[http://dx.doi.org/10.1002/ejp.1085] [PMID: 28722246]
[http://dx.doi.org/10.1111/j.1365-2990.2011.01248.x] [PMID: 22236282]
[http://dx.doi.org/10.1002/ptr.5712] [PMID: 27654887]
[http://dx.doi.org/10.1016/j.cell.2013.10.042] [PMID: 24267894]
[http://dx.doi.org/10.3233/JAD-141014] [PMID: 25125475]
[http://dx.doi.org/10.1038/nm.4311] [PMID: 28481360]
[http://dx.doi.org/10.1111/bph.12944] [PMID: 25257544]
[http://dx.doi.org/10.1111/j.1476-5381.2011.01278.x] [PMID: 21323909]
[http://dx.doi.org/10.1016/j.phrs.2018.08.021] [PMID: 30170189]
[http://dx.doi.org/10.1007/s00213-011-2415-0] [PMID: 21796370]
[http://dx.doi.org/10.1016/S0021-9673(01)94980-5] [PMID: 4635939]
[http://dx.doi.org/10.1016/S0040-4039(01)97472-6]
[http://dx.doi.org/10.1016/S0040-4020(01)97114-5]
[http://dx.doi.org/10.1271/bbb1961.30.619]
[http://dx.doi.org/10.1146/annurev-pharmtox-010818-021441] [PMID: 31580774]
[http://dx.doi.org/10.3389/fphar.2020.00124] [PMID: 32210795]
[http://dx.doi.org/10.3233/JAD-130137] [PMID: 23515018]
[http://dx.doi.org/10.1590/S1516-44462008000300015] [PMID: 18833429]
[http://dx.doi.org/10.2174/187152711794480483] [PMID: 20874702]
[http://dx.doi.org/10.1038/nature20153] [PMID: 27853201]
[http://dx.doi.org/10.1002/dta.1425] [PMID: 23109356]
[http://dx.doi.org/10.1016/j.neuroscience.2016.10.031] [PMID: 27771531]
[http://dx.doi.org/10.1016/j.pnpbp.2018.06.002] [PMID: 29885468]
[http://dx.doi.org/10.1111/bph.14019] [PMID: 28853159]
[http://dx.doi.org/10.1016/j.brainres.2014.09.008] [PMID: 25218556]
[http://dx.doi.org/10.1134/S0006297918090122] [PMID: 30472949]
[PMID: 29533978]
[http://dx.doi.org/10.1016/j.ijdevneu.2019.03.002] [PMID: 30858029]
[http://dx.doi.org/10.1016/j.phrs.2016.07.021] [PMID: 27450295]
[http://dx.doi.org/10.1016/j.plipres.2016.02.002] [PMID: 26965148]
[http://dx.doi.org/10.1097/CCO.0000000000000523] [PMID: 30789867]
[http://dx.doi.org/10.1124/pr.110.003004] [PMID: 21079038]
[http://dx.doi.org/10.1038/nature20613] [PMID: 27851727]
[http://dx.doi.org/10.1016/j.cell.2016.10.004] [PMID: 27768894]
[http://dx.doi.org/10.1016/j.cell.2018.12.011] [PMID: 30639103]
[http://dx.doi.org/10.1016/j.disamonth.2016.05.014] [PMID: 27364691]
[http://dx.doi.org/10.1038/s41401-019-0210-3] [PMID: 30670816]
[http://dx.doi.org/10.1111/febs.12125] [PMID: 23305292]
[http://dx.doi.org/10.1016/j.plefa.2018.11.016] [PMID: 30553404]
[http://dx.doi.org/10.1089/ars.2017.7144] [PMID: 28497982]
[http://dx.doi.org/10.1038/s41598-019-49177-y] [PMID: 31537814]
[http://dx.doi.org/10.1016/j.smim.2014.04.002] [PMID: 24877594]
[http://dx.doi.org/10.1590/S0047-20852011000200006]
[http://dx.doi.org/10.3389/fnbeh.2012.00009] [PMID: 22457644]
[http://dx.doi.org/10.1016/j.pnpbp.2019.109745]] [PMID: 31442553]
[http://dx.doi.org/10.1038/nrd2553] [PMID: 18446159]
[http://dx.doi.org/10.3389/fpls.2016.00019] [PMID: 26870049]
[http://dx.doi.org/10.1021/acs.jnatprod.6b01126] [PMID: 28165233]
[http://dx.doi.org/10.1523/JNEUROSCI.5183-12.2013] [PMID: 23785163]
[http://dx.doi.org/10.1016/0006-2952(85)90325-9] [PMID: 3859295]
[http://dx.doi.org/10.1016/j.phanu.2014.05.001]
[http://dx.doi.org/10.1016/j.bmc.2017.05.041] [PMID: 28559058]
[http://dx.doi.org/10.1073/pnas.0910723107] [PMID: 20385841]
[http://dx.doi.org/10.1016/j.bcp.2019.08.011]] [PMID: 31437460]
[http://dx.doi.org/10.3389/fonc.2019.00660] [PMID: 31396485]
[http://dx.doi.org/10.1055/s-0043-122240] [PMID: 29161743]
[http://dx.doi.org/10.1111/j.1476-5381.2011.01238.x] [PMID: 21749363]
[http://dx.doi.org/10.1016/bs.apha.2017.03.004] [PMID: 28826544]
[http://dx.doi.org/10.1089/can.2019.0016] [PMID: 31559333]
[http://dx.doi.org/10.1515/znc-2014-4135] [PMID: 27352445]
[http://dx.doi.org/10.1016/j.ejmech.2017.10.017] [PMID: 29150331]
[http://dx.doi.org/10.1271/bbb.120378] [PMID: 23047102]
[http://dx.doi.org/10.1016/j.cbi.2016.11.015] [PMID: 27871898]
[http://dx.doi.org/10.3233/JAD-140921] [PMID: 25024347]
[http://dx.doi.org/10.1016/j.bioorg.2019.102935]] [PMID: 31030060]
[http://dx.doi.org/10.1248/bpb.b19-00495] [PMID: 31875578]
[http://dx.doi.org/10.1089/can.2016.0008] [PMID: 28861488]
[http://dx.doi.org/10.1177/2042098619846993]] [PMID: 31205674]
[http://dx.doi.org/10.9758/cpn.2017.15.4.301] [PMID: 29073741]
[http://dx.doi.org/10.1177/0269881114550355] [PMID: 25237116]
[http://dx.doi.org/10.1016/bs.pmbts.2019.06.005] [PMID: 31601406]
[http://dx.doi.org/10.3233/JAD-150915] [PMID: 26757043]
[http://dx.doi.org/10.1007/s00415-016-8145-9] [PMID: 27159993]
[http://dx.doi.org/10.1523/JNEUROSCI.0708-19.2019] [PMID: 31570536]
[http://dx.doi.org/10.3389/fpsyt.2013.00130] [PMID: 24137134]