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Elevating endocannabinoid levels: pharmacological strategies and potential therapeutic applications

  • Roger G. Pertwee (a1)

Abstract

The endocannabinoid system consists of cannabinoid CB1 and CB2 receptors, of endogenous agonists for these receptors known as ‘endocannabinoids’, and of processes responsible for endocannabinoid biosynthesis, cellular uptake and metabolism. There is strong evidence first, that this system up-regulates in certain disorders as indicated by an increased release of endocannabinoids onto their receptors and/or by increases in the expression levels or coupling efficiency of these receptors, and second, that this up-regulation often appears to reduce or abolish unwanted effects of these disorders or to slow their progression. This discovery has raised the possibility of developing a medicine that enhances up-regulation of the endocannabinoid system associated with these disorders by inhibiting the cellular uptake or intracellular metabolism of an endocannabinoid following its ‘autoprotective’ endogenous release. For inhibition of endocannabinoid metabolism, research has focused particularly on two highly investigated endocannabinoids, anandamide and 2-arachidonoyl glycerol, and hence on inhibitors of the main anandamide-metabolising enzyme, fatty acid amide hydrolase (FAAH), and of the main 2-arachidonoyl glycerol-metabolising enzyme, monoacylglycerol (MAG) lipase. The resulting data have provided strong preclinical evidence that selective FAAH and MAG lipase inhibitors would ameliorate the unwanted effects of several disorders, when administered alone or with a cyclooxygenase inhibitor, and that the benefit-to-risk ratio of a FAAH inhibitor would exceed that of a MAG lipase inhibitor or dual inhibitor of FAAH and MAG lipase. Promising preclinical data have also been obtained with inhibitors of endocannabinoid cellular uptake. There is now an urgent need for clinical research with these enzyme and uptake inhibitors.

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Copyright

Corresponding author

Corresponding author: Professor R. G. Pertwee, fax 01224 437465, email rgp@abdn.ac.uk

References

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1. Pertwee, RG, Howlett, AC, Abood, ME et al. (2010) International union of basic and clinical pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB1 and CB2 . Pharmacol Rev 62, 588631.
2. Pertwee, RG (2005) The therapeutic potential of drugs that target cannabinoid receptors or modulate the tissue levels or actions of endocannabinoids. AAPS J 7, E625E654.
3. Pertwee, RG (2012) Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities. Phil Trans R Soc B 367, 33533363.
4. Alvarez-Jaimes, LJ & Palmer, JA (2011) The role of endocannabinoids in pain modulation and the therapeutic potential of inhibiting their enzymatic degradation. Curr Pharm Biotechnol 12, 16441659.
5. Zhao, P & Abood, ME (2013) GPR55 and GPR35 and their relationship to cannabinoid and lysophospholipid receptors. Life Sci 92, 453457.
6. Blankman, JL, Simon, GM & Cravatt, BF (2007) A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol. Chem Biol 14, 13471356.
7. Savinainen, JR, Saario, SM & Laitinen, JT (2012) The serine hydrolases MAGL, ABHD6 and ABHD12 as guardians of 2-arachidonoylglycerol signalling through cannabinoid receptors. Acta Physiol 204, 267276.
8. Kuc, C, Jenkins, A & Van Dross, RT (2012) Arachidonoyl ethanolamide (AEA)-induced apoptosis is mediated by J-series prostaglandins and is enhanced by fatty acid amide hydrolase (FAAH) blockade. Mol Carcinog 51, 139149.
9. Hu, SS-J, Bradshaw, HB, Chen, JS-C et al. (2008) Prostaglandin E2 glycerol ester, an endogenous COX-2 metabolite of 2-arachidonoylglycerol, induces hyperalgesia and modulates NFκB activity. Br J Pharmacol 153, 15381549.
10. Di Marzo, V (2008) Targeting the endocannabinoid system: to enhance or reduce? Nat Rev Drug Discov 7, 438455.
11. Martin, BR, Beletskaya, I, Patrick, G et al. (2000) Cannabinoid properties of methylfluorophosphonate analogs. J Pharmacol Exp Ther 294, 12091218.
12. Pertwee, RG (2008) Ligands that target cannabinoid receptors in the brain: from THC to anandamide and beyond. Addict Biol 13, 147159.
13. Petrosino, S & Di Marzo, V (2010) FAAH and MAGL inhibitors: therapeutic opportunities from regulating endocannabinoid levels. Curr Opin Investig Drugs 11, 5162.
14. Godlewski, G, Alapafuja, SO, Bátkai, S et al. (2010) Inhibitor of fatty acid amide hydrolase normalizes cardiovascular function in hypertension without adverse metabolic effects. Chem Biol 17, 12561266.
15. Naidoo, V, Nikas, SP, Karanian, DA et al. (2011) A new generation fatty acid amide hydrolase inhibitor protects against kainate-induced excitotoxicity. J Mol Neurosci 43, 493502.
16. Gattinoni, S, De Simone, C, Dallavalle, S et al. (2010) Enol carbamates as inhibitors of fatty acid amide hydrolase (FAAH) endowed with high selectivity for FAAH over the other targets of the endocannabinoid system. ChemMedChem 5, 357360.
17. Caprioli, A, Coccurello, R, Rapino, C et al. (2012) The novel reversible fatty acid amide hydrolase inhibitor ST4070 increases endocannabinoid brain levels and counteracts neuropathic pain in different animal models. J Pharmacol Exp Ther 342, 188195.
18. Ahn, K, Johnson, DS, Mileni, M et al. (2009) Discovery and characterization of a highly selective FAAH inhibitor that reduces inflammatory pain. Chem Biol 16, 411420.
19. Johnson, DS, Stiff, C, Lazerwith, SE et al. (2011) Discovery of PF-04457845: a highly potent, orally bioavailable, and selective urea FAAH inhibitor. ACS Med Chem Lett 2, 9196.
20. Busquets-Garcia, A, Puighermanal, E, Pastor, A et al. (2011) Differential role of anandamide and 2-arachidonoylglycerol in memory and anxiety-like responses. Biol Psychiatry 70, 479486.
21. Kinsey, SG, Long, JZ, Cravatt, BF et al. (2010) Fatty acid amide hydrolase and monoacylglycerol lipase inhibitors produce anti-allodynic effects in mice through distinct cannabinoid receptor mechanisms. J Pain 11, 14201428.
22. Kinsey, SG, Long, JZ, O'Neal, ST et al. (2009) Blockade of endocannabinoid-degrading enzymes attenuates neuropathic pain. J Pharmacol Exp Ther 330, 902910.
23. Miller, LL, Picker, MJ, Umberger, MD et al. (2012) Effects of alterations in cannabinoid signaling, alone and in combination with morphine, on pain-elicited and pain-suppressed behavior in mice. J Pharmacol Exp Ther 342, 177187.
24. Okine, BN, Norris, LM, Woodhams, S et al. (2012) Lack of effect of chronic pre-treatment with the FAAH inhibitor URB597 on inflammatory pain behaviour: evidence for plastic changes in the endocannabinoid system. Br J Pharmacol 167, 627640.
25. Schuelert, N, Johnson, MP, Oskins, JL et al. (2011) Local application of the endocannabinoid hydrolysis inhibitor URB597 reduces nociception in spontaneous and chemically induced models of osteoarthritis. Pain 152, 975981.
26. Merriam, FV, Wang, Z-Y, Hillard, CJ et al. (2011) Inhibition of fatty acid amide hydrolase suppresses referred hyperalgesia induced by bladder inflammation. BJU Int 108, 11451149.
27. Johnston, TH, Huot, P, Fox, SH et al. (2011) Fatty acid amide hydrolase (FAAH) inhibition reduces L-3,4-dihydroxyphenylalanine-induced hyperactivity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned non-human primate model of Parkinson's disease. J Pharmacol Exp Ther 336, 423430.
28. Naderi, N, Ahmad-Molaei, L, Mazar-Atabaki, A et al. (2012) L-type calcium channel mediates anticonvulsant effect of cannabinoids in acute and chronic murine models of seizure. Neurochem Res 37, 279287.
29. Alhouayek, M & Muccioli, GG (2012) The endocannabinoid system in inflammatory bowel diseases: from pathophysiology to therapeutic opportunity. Trends Mol Med 18, 615625.
30. Andrzejak, V, Muccioli, GG, Body-Malapel, M et al. (2011) New FAAH inhibitors based on 3-carboxamido-5-aryl-isoxazole scaffold that protect against experimental colitis. Bioorg Med Chem 19, 37773786.
31. Bashashati, M, Storr, MA, Nikas, SP et al. (2012) Inhibiting fatty acid amide hydrolase normalizes endotoxin-induced enhanced gastrointestinal motility in mice. Br J Pharmacol 165, 15561571.
32. Fowler, CJ (2012) NSAIDs: eNdocannabinoid stimulating anti-inflammatory drugs? Trends Pharmacol Sci 33, 468473.
33. Naidu, PS, Booker, L, Cravatt, BF et al. (2009) Synergy between enzyme inhibitors of fatty acid amide hydrolase and cyclooxygenase in visceral nociception. J Pharmacol Exp Ther 329, 4856.
34. Sasso, O, Bertorelli, R, Bandiera, T et al. (2012) Peripheral FAAH inhibition causes profound antinociception and protects against indomethacin-induced gastric lesions. Pharmacol Res 65, 553563.
35. Schlosburg, JE, Boger, DL, Cravatt, BF et al. (2009) Endocannabinoid modulation of scratching response in an acute allergenic model: a new prospective neural therapeutic target for pruritus. J Pharmacol Exp Ther 329, 314323.
36. Spradley, JM, Davoodi, A, Gee, LB et al. (2012) Differences in peripheral endocannabinoid modulation of scratching behavior in facial vs. spinally-innervated skin. Neuropharmacology 63, 743749.
37. Gomes, FV, Casarotto, PC, Resstel, LBM et al. (2011) Facilitation of CB1 receptor-mediated neurotransmission decreases marble burying behavior in mice. Prog Neuro-Psychopharmacol Biol Psychiatry 35, 434438.
38. Kinsey, SG, O'Neal, ST, Long, JZ et al. (2011) Inhibition of endocannabinoid catabolic enzymes elicits anxiolytic-like effects in the marble burying assay. Pharmacol Biochem Behav 98, 2127.
39. Forget, B, Coen, KM & Le Foll, B (2009) Inhibition of fatty acid amide hydrolase reduces reinstatement of nicotine seeking but not break point for nicotine self-administration – comparison with CB1 receptor blockade. Psychopharmacology 205, 613624.
40. Scherma, M, Panlilio, LV, Fadda, P et al. (2008) Inhibition of anandamide hydrolysis by cyclohexyl carbamic acid 3′-carbamoyl-3-yl ester (URB597) reverses abuse-related behavioral and neurochemical effects of nicotine in rats. J Pharmacol Exp Ther 327, 482490.
41. Ramesh, D, Ross, GR, Schlosburg, JE et al. (2011) Blockade of endocannabinoid hydrolytic enzymes attenuates precipitated opioid withdrawal symptoms in mice. J Pharmacol Exp Ther 339, 173185.
42. Shahidi, S & Hasanein, P (2011) Behavioral effects of fatty acid amide hydrolase inhibition on morphine withdrawal symptoms. Brain Res Bull 86, 118122.
43. Mulvihill, MM & Nomura, DK (2013) Therapeutic potential of monoacylglycerol lipase inhibitors. Life Sci 92, 492497.
44. Cippitelli, A, Astarita, G, Duranti, A et al. (2011) Endocannabinoid regulation of acute and protracted nicotine withdrawal: effect of FAAH inhibition. PLoS ONE 6, e28142.
45. Parker, LA, Rock, EM & Limebeer, CL (2011) Regulation of nausea and vomiting by cannabinoids. Br J Pharmacol 163, 14111422.
46. Endsley, MP, Thill, R, Choudhry, I et al. (2008) Expression and function of fatty acid amide hydrolase in prostate cancer. Int J Cancer 123, 13181326.
47. Malfitano, AM, Ciaglia, E, Gangemi, G et al. (2011) Update on the endocannabinoid system as an anticancer target. Expert Opin Ther Targets 15, 297308.
48. Proto, MC, Gazzerro, P, Di Croce, L et al. (2012) Interaction of endocannabinoid system and steroid hormones in the control of colon cancer cell growth. J Cell Physiol 227, 250258.
49. Piscitelli, F & Di Marzo, V (2012) “Redundancy” of endocannabinoid inactivation: new challenges and opportunities for pain control. ACS Chem Neurosci 3, 356363.
50. Khasabova, IA, Khasabov, S, Paz, J et al. (2012) Cannabinoid type-1 receptor reduces pain and neurotoxicity produced by chemotherapy. J Neurosci 32, 70917101.
51. Starowicz, K, Makuch, W, Osikowicz, M et al. (2012) Spinal anandamide produces analgesia in neuropathic rats: possible CB1- and TRPV1-mediated mechanisms. Neuropharmacology 62, 17461755.
52. Booker, L, Kinsey, SG, Abdullah, RA et al. (2012) The fatty acid amide hydrolase (FAAH) inhibitor PF-3845 acts in the nervous system to reverse LPS-induced tactile allodynia in mice. Br J Pharmacol 165, 24852496.
53. Bisogno, T, Ortar, G, Petrosino, S et al. (2009) Development of a potent inhibitor of 2-arachidonoylglycerol hydrolysis with antinociceptive activity in vivo . Biochim Biophys Acta 1791, 5360.
54. Comelli, F, Giagnoni, G, Bettoni, I et al. (2007) The inhibition of monoacylglycerol lipase by URB602 showed an anti-inflammatory and anti-nociceptive effect in a murine model of acute inflammation. Br J Pharmacol 152, 787794.
55. Fowler, CJ (2012) Monoacylglycerol lipase – a target for drug development? Br J Pharmacol 166, 15681585.
56. Ghosh, S, Wise, LE, Chen, Y et al. (2013) The monoacylglycerol lipase inhibitor JZL184 suppresses inflammatory pain in the mouse carrageenan model. Life Sci 92, 498505.
57. Long, JZ, Li, W, Booker, L et al. (2009) Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects. Nat Chem Biol 5, 3744.
58. Guindon, J, Desroches, J & Beaulieu, P (2007) The antinociceptive effects of intraplantar injections of 2-arachidonoyl glycerol are mediated by cannabinoid CB2 receptors. Br J Pharmacol 150, 693701.
59. Woodhams, SG, Wong, A, Barrett, DA et al. (2012) Spinal administration of the monoacylglycerol lipase inhibitor JZL184 produces robust inhibitory effects on nociceptive processing and the development of central sensitization in the rat. Br J Pharmacol 167, 16091619.
60. Guindon, J, Guijarro, A, Piomelli, D et al. (2011) Peripheral antinociceptive effects of inhibitors of monoacylglycerol lipase in a rat model of inflammatory pain. Br J Pharmacol 163, 14641478.
61. Alhouayek, M, Lambert, DM, Delzenne, NM et al. (2011) Increasing endogenous 2-arachidonoylglycerol levels counteracts colitis and related systemic inflammation. FASEB J 25, 27112721.
62. Kinsey, SG, Nomura, DK, O'Neal, ST et al. (2011) Inhibition of monoacylglycerol lipase attenuates nonsteroidal anti-inflammatory drug-induced gastric hemorrhages in mice. J Pharmacol Exp Ther 338, 795802.
63. Aliczki, M, Balogh, Z, Tulogdi, A et al. (2012) The temporal dynamics of the effects of monoacylglycerol lipase blockade on locomotion, anxiety, and body temperature. Behav Pharmacol 23, 348357.
64. Sticht, MA, Long, JZ, Rock, EM et al. (2012) Inhibition of monoacylglycerol lipase attenuates vomiting in Suncus murinus and 2-arachidonoyl glycerol attenuates nausea in rats. Br J Pharmacol 165, 24252435.
65. Nomura, DK, Lombardi, DP, Chang, JW et al. (2011) Monoacylglycerol lipase exerts dual control over endocannabinoid and fatty acid pathways to support prostate cancer. Chem Biol 18, 846856.
66. Chen, X, Zhang, J & Chen, C (2011) Endocannabinoid 2-arachidonoylglycerol protects neurons against β-amyloid insults. Neuroscience 178, 159168.
67. Chen, R, Zhang, J, Wu, Y et al. (2012) Monoacylglycerol lipase is a therapeutic target for Alzheimer's disease. Cell Rep 2, 13291339.
68. Piro, JR, Benjamin, DI, Duerr, JM et al. (2012) A dysregulated endocannabinoid-eicosanoid network supports pathogenesis in a mouse model of Alzheimer's disease. Cell Rep 1, 617623.
69. Sigel, E, Baur, R, Rácz, I et al. (2011) The major central endocannabinoid directly acts at GABAA receptors. Proc Natl Acad Sci USA 108, 1815018155.
70. Cravatt, BF & Lichtman, AH (2004) The endogenous cannabinoid system and its role in nociceptive behavior. J Neurobiol 61, 149160.
71. Kathuria, S, Gaetani, S, Fegley, D et al. (2003) Modulation of anxiety through blockade of anandamide hydrolysis. Nat Med 9, 7681.
72. Lichtman, AH, Leung, D, Shelton, CC et al. (2004) Reversible inhibitors of fatty acid amide hydrolase that promote analgesia: evidence for an unprecedented combination of potency and selectivity. J Pharmacol Exp Ther 311, 441448.
73. Schlosburg, JE, Blankman, JL, Long, JZ et al. (2010) Chronic monoacylglycerol lipase blockade causes functional antagonism of the endocannabinoid system. Nat Neurosci 13, 11131121.
74. Justinova, Z, Mangieri, RA, Bortolato, M et al. (2008) Fatty acid amide hydrolase inhibition heightens anandamide signaling without producing reinforcing effects in primates. Biol Psychiatry 64, 930937.
75. Nomura, DK, Blankman, JL, Simon, GM et al. (2008) Activation of the endocannabinoid system by organophosphorus nerve agents. Nat Chem Biol 4, 373378.
76. Long, JZ, Nomura, DK, Vann, RE et al. (2009) Dual blockade of FAAH and MAGL identifies behavioral processes regulated by endocannabinoid crosstalk in vivo . Proc Natl Acad Sci USA 106, 2027020275.
77. Wise, LE, Long, KA, Abdullah, RA et al. (2012) Dual fatty acid amide hydrolase and monoacylglycerol lipase blockade produces THC-like Morris water maze deficits in mice. ACS Chem Neurosci 3, 369378.
78. Naidoo, V, Karanian, DA, Vadivel, SK et al. (2012) Equipotent inhibition of fatty acid amide hydrolase and monoacylglycerol lipase – dual targets of the endocannabinoid system to protect against seizure pathology. Neurotherapeutics 9, 801813.
79. Khasabova, IA, Chandiramani, A, Harding-Rose, C et al. (2011) Increasing 2-arachidonoyl glycerol signaling in the periphery attenuates mechanical hyperalgesia in a model of bone cancer pain. Pharmacol Res 64, 6067.
80. Moreno-Sanz, G, Barrera, B, Guijarro, A et al. (2011) The ABC membrane transporter ABCG2 prevents access of FAAH inhibitor URB937 to the central nervous system. Pharmacol Res 64, 359363.
81. Clapper, JR, Moreno-Sanz, G, Russo, R et al. (2010) Anandamide suppresses pain initiation through a peripheral endocannabinoid mechanism. Nat Neurosci 13, 12651270.
82. Li, WW, Blankman, JL & Cravatt, BF (2007) A functional proteomic strategy to discover inhibitors for uncharacterized hydrolases. J Am Chem Soc 129, 95949595.
83. Favia, AD, Habrant, D, Scarpelli, R et al. (2012) Identification and characterization of carprofen as a multitarget fatty acid amide hydrolase/cyclooxygenase inhibitor. J Med Chem 55, 88078826.
84. Lowin, T, Zhu, W, Dettmer-Wilde, K et al. (2012) Cortisol-mediated adhesion of synovial fibroblasts is dependent on the degradation of anandamide and activation of the endocannabinoid system. Arthritis Rheum 64, 38673876.
85. Hamtiaux, L, Masquelier, J, Muccioli, GG et al. (2012) The association of N-palmitoylethanolamine with the FAAH inhibitor URB597 impairs melanoma growth through a supra-additive action. BMC Cancer 12, 114.
86. Roques, BP, Fournié-Zaluski, M-C & Wurm, M (2012) Inhibiting the breakdown of endogenous opioids and cannabinoids to alleviate pain. Nat Rev Drug Discov 11, 292310.
87. Huggins, JP, Smart, TS, Langman, S et al. (2012) An efficient randomised, placebo-controlled clinical trial with the irreversible fatty acid amide hydrolase-1 inhibitor PF-04457845, which modulates endocannabinoids but fails to induce effective analgesia in patients with pain due to osteoarthritis of the knee. Pain 153, 18371846.
88. Li, GL, Winter, H, Arends, R et al. (2011) Assessment of the pharmacology and tolerability of PF-04457845, an irreversible inhibitor of fatty acid amide hydrolase-1, in healthy subjects. Br J Clin Pharmacol 73, 706716.
89. Gamaleddin, I, Guranda, M, Goldberg, SR et al. (2011) The selective anandamide transport inhibitor VDM11 attenuates reinstatement of nicotine seeking behaviour, but does not affect nicotine intake. Br J Pharmacol 164, 16521660.
90. Scherma, M, Justinová, Z, Zanettini, C et al. (2012) The anandamide transport inhibitor AM404 reduces the rewarding effects of nicotine and nicotine-induced dopamine elevations in the nucleus accumbens shell in rats. Br J Pharmacol 165, 25392548.
91. Reyes-Cabello, C, Alen, F, Gómez, R et al. (2012) Effects of the anandamide uptake blocker AM404 on food intake depend on feeding status and route of administration. Pharmacol Biochem Behav 101, 17.
92. Fu, J, Bottegoni, G, Sasso, O et al. (2012) A catalytically silent FAAH-1 variant drives anandamide transport in neurons. Nat Neurosci 15, 6469.
93. Marsicano, G & Chaouloff, F (2012) Moving bliss: a new anandamide transporter. Nat Neurosci 15, 56.
94. Berger, WT, Ralph, BP, Kaczocha, M et al. (2012) Targeting fatty acid binding protein (FABP) anandamide transporters – a novel strategy for development of anti-inflammatory and anti-nociceptive drugs. PLoS ONE 7, 112.
95. Pamplona, FA, Ferreira, J, Menezes-de-Lima, O et al. (2012) Anti-inflammatory lipoxin A4 is an endogenous allosteric enhancer of CB1 cannabinoid receptor. Proc Natl Acad Sci USA 109, 2113421139.
96. Pertwee, RG (2012) Lipoxin A4 is an allosteric endocannabinoid that strengthens anandamide-induced CB1 receptor activation. Proc Natl Acad Sci USA 109, 2078120782.
97. Bauer, M, Chicca, A, Tamborrini, M et al. (2012) Identification and quantification of a new family of peptide endocannabinoids (pepcans) showing negative allosteric modulation at CB1 receptors. J Biol Chem 287, 3694436967.
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