Sachin Patel, MD, PhD

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Research Description

Psychosocial stress is a key trigger for the development and exacerbation of a variety of psychiatric disorders including depression, addiction, schizophrenia, and post-traumatic stress disorder. By understanding the molecular, structural, and physiological adaptations in endocannabinoid signaling that occur in response to stress, we hope uncover novel bio-markers and pharmacological targets for drug development. In addition, we hope these investigations will provide insight into the pathophysiology of stress-related neuropsychiatric disorders. We use a variety of techniques including electrophysiology, mass spectrometry, protein biochemistry, genetic models, and functional anatomical studies, to understand the role of endocannabinoids in the brain's response to stress.

Clinical Interest

My clinical work focuses on acute inpatient care of patients with dual mood/anxiety disorders and addiction.

Selected Publications

• Bedse G, Hartley ND, Neale E, Gaulden AD, Patrick TA, Kingsley PJ, Uddin MJ, Plath N, Marnett LJ, Patel S. Functional Redundancy Between Canonical Endocannabinoid Signaling Systems in the Modulation of Anxiety. Biol. Psychiatry [print-electronic]. 2017 Mar 3/15/2017; PMID: 28438413, PII: S0006-3223(17)31357-4, DOI: 10.1016/j.biopsych.2017.03.002, ISSN: 1873-2402.

  Bluett RJ, Báldi R, Haymer A, Gaulden AD, Hartley ND, Parrish WP, Baechle J, Marcus DJ, Mardam-Bey R, Shonesy BC, Uddin MJ, Marnett LJ, Mackie K, Colbran RJ, Winder DG, Patel S. Endocannabinoid signalling modulates susceptibility to traumatic stress exposure. Nat Commun. 2017 Mar 3/28/2017; 8: 14782. PMID: 28348378, PMCID: PMC5379055, PII: ncomms14782, DOI: 10.1038/ncomms14782, ISSN: 2041-1723.

  Patel S, Hill MN, Cheer JF, Wotjak CT, Holmes A. The endocannabinoid system as a target for novel anxiolytic drugs. Neurosci Biobehav Rev. 2017 May; 76(Pt A): 56-66. PMID: 28434588, PMCID: PMC5407316, PII: S0149-7634(16)30469-9, DOI: 10.1016/j.neubiorev.2016.12.033, ISSN: 1873-7528.

  Patel S, Williams JW, Wallace RB. What We Do (and Don't) Know About the Health Effects of Cannabis and Whether Marijuana Is Medicine. Ann. Intern. Med [print-electronic]. 2017 May 5/16/2017; 166(10): 747-8. PMID: 28384665, PII: 2615815, DOI: 10.7326/M17-0501, ISSN: 1539-3704.

  Patel S. Cannabis for Pain and Posttraumatic Stress Disorder: More Consensus Than Controversy or Vice Versa?. Ann. Intern. Med [print-electronic]. 2017 Aug 8/15/2017; PMID: 28806789, PII: 2648597, DOI: 10.7326/M17-1713, ISSN: 1539-3704.

• Morena M, Patel S, Bains JS, Hill MN. Neurobiological Interactions Between Stress and the Endocannabinoid System. Neuropsychopharmacology [print-electronic]. 2016 Jan; 41(1): 80-102. PMID: 26068727, PMCID: PMC4677118, PII: npp2015166, DOI: 10.1038/npp.2015.166, ISSN: 1740-634X.

  Hartley ND, Gunduz-Cinar O, Halladay L, Bukalo O, Holmes A, Patel S. 2-arachidonoylglycerol signaling impairs short-term fear extinction. Transl Psychiatry. 2016 Mar 3/1/2016; 6: e749. PMID: 26926885, PMCID: PMC4872450, PII: tp201626, DOI: 10.1038/tp.2016.26, ISSN: 2158-3188.

  Gray JM, Wilson CD, Lee TT, Pittman QJ, Deussing JM, Hillard CJ, McEwen BS, Schulkin J, Karatsoreos IN, Patel S, Hill MN. Sustained glucocorticoid exposure recruits cortico-limbic CRH signaling to modulate endocannabinoid function. Psychoneuroendocrinology [print-electronic]. 2016 Apr; 66: 151-8. PMID: 26821211, PMCID: PMC4788523, PII: S0306-4530(16)30003-8, DOI: 10.1016/j.psyneuen.2016.01.004, ISSN: 1873-3360.

  Báldi R, Ghosh D, Grueter BA, Patel S. Electrophysiological Measurement of Cannabinoid-Mediated Synaptic Modulation in Acute Mouse Brain Slices. Curr Protoc Neurosci. 2016 Apr 4/8/2016; 75: 6.29.1-6.29.19. PMID: 27063786, PMCID: PMC4866814, DOI: 10.1002/cpns.8, ISSN: 1934-8576.

  Gunduz-Cinar O, Flynn S, Brockway E, Kaugars K, Baldi R, Ramikie TS, Cinar R, Kunos G, Patel S, Holmes A. Fluoxetine Facilitates Fear Extinction Through Amygdala Endocannabinoids. Neuropsychopharmacology [print-electronic]. 2016 May; 41(6): 1598-609. PMID: 26514583, PMCID: PMC4832021, PII: npp2015318, DOI: 10.1038/npp.2015.318, ISSN: 1740-634X.

  Gamble-George JC, Baldi R, Halladay L, Kocharian A, Hartley N, Silva CG, Roberts H, Haymer A, Marnett LJ, Holmes A, Patel S. Cyclooxygenase-2 inhibition reduces stress-induced affective pathology. Elife. 2016 May 5/10/2016; 5: PMID: 27162170, PMCID: PMC4862754, DOI: 10.7554/eLife.14137, ISSN: 2050-084X.

  Patel S, Shonesy BC, Bluett RJ, Winder DG, Colbran RJ. The Anxiolytic Actions of 2-Arachidonoylglycerol: Converging Evidence From Two Recent Genetic Endocannabinoid Deficiency Models [letter]. Biol. Psychiatry [print-electronic]. 2016 May 5/15/2016; 79(10): e78-9. PMID: 26212898, PII: S0006-3223(15)00532-6, DOI: 10.1016/j.biopsych.2015.04.028, ISSN: 1873-2402.

  Reddy IA, Pino JA, Weikop P, Osses N, Sørensen G, Bering T, Valle C, Bluett RJ, Erreger K, Wortwein G, Reyes JG, Graham D, Stanwood GD, Hackett TA, Patel S, Fink-Jensen A, Torres GE, Galli A. Glucagon-like peptide 1 receptor activation regulates cocaine actions and dopamine homeostasis in the lateral septum by decreasing arachidonic acid levels. Transl Psychiatry. 2016 May 5/17/2016; 6: e809. PMID: 27187231, PMCID: PMC5070047, PII: tp201686, DOI: 10.1038/tp.2016.86, ISSN: 2158-3188.

  Holleran KM, Wilson HH, Fetterly TL, Bluett RJ, Centanni SW, Gilfarb RA, Rocco LE, Patel S, Winder DG. Ketamine and MAG Lipase Inhibitor-Dependent Reversal of Evolving Depressive-Like Behavior During Forced Abstinence From Alcohol Drinking. Neuropsychopharmacology [print-electronic]. 2016 Jul; 41(8): 2062-71. PMID: 26751284, PMCID: PMC4908652, PII: npp20163, DOI: 10.1038/npp.2016.3, ISSN: 1740-634X.

  Foster DJ, Wilson JM, Remke DH, Mahmood MS, Uddin MJ, Wess J, Patel S, Marnett LJ, Niswender CM, Jones CK, Xiang Z, Lindsley CW, Rook JM, Conn PJ. Antipsychotic-like Effects of M4 Positive Allosteric Modulators Are Mediated by CB2 Receptor-Dependent Inhibition of Dopamine Release. Neuron [print-electronic]. 2016 Sep 9/21/2016; 91(6): 1244-52. PMID: 27618677, PMCID: PMC5033724, PII: S0896-6273(16)30509-8, DOI: 10.1016/j.neuron.2016.08.017, ISSN: 1097-4199.

• Gray JM, Vecchiarelli HA, Morena M, Lee TT, Hermanson DJ, Kim AB, McLaughlin RJ, Hassan KI, Kühne C, Wotjak CT, Deussing JM, Patel S, Hill MN. Corticotropin-releasing hormone drives anandamide hydrolysis in the amygdala to promote anxiety. J. Neurosci. 2015 Mar 3/4/2015; 35(9): 3879-92. PMID: 25740517, PMCID: PMC4348185, PII: 35/9/3879, DOI: 10.1523/JNEUROSCI.2737-14.2015, ISSN: 1529-2401.

  Patel S, Cone RD. Neuroscience: a cellular basis for the munchies. Nature [print-electronic]. 2015 Mar 3/5/2015; 519(7541): 38-40. PMID: 25707800, PII: nature14206, DOI: 10.1038/nature14206, ISSN: 1476-4687.

  Bukalo O, Pinard CR, Silverstein S, Brehm C, Hartley ND, Whittle N, Colacicco G, Busch E, Patel S, Singewald N, Holmes A. Prefrontal inputs to the amygdala instruct fear extinction memory formation. Sci Adv [print-electronic]. 2015 Jul; 1(6): PMID: 26504902, PMCID: PMC4618669, DOI: 10.1126/sciadv.1500251, ISSN: 2375-2548.

  Brown JA, Ramikie TS, Schmidt MJ, Báldi R, Garbett K, Everheart MG, Warren LE, Gellért L, Horváth S, Patel S, Mirnics K. Inhibition of parvalbumin-expressing interneurons results in complex behavioral changes. Mol. Psychiatry [print-electronic]. 2015 Dec; 20(12): 1499-507. PMID: 25623945, PMCID: PMC4516717, PII: mp2014192, DOI: 10.1038/mp.2014.192, ISSN: 1476-5578.

• Bluett RJ, Gamble-George JC, Hermanson DJ, Hartley ND, Marnett LJ, Patel S. Central anandamide deficiency predicts stress-induced anxiety: behavioral reversal through endocannabinoid augmentation. Transl Psychiatry. 2014; 4: e408. PMID: 25004388, PMCID: PMC4119220, PII: tp201453, DOI: 10.1038/tp.2014.53, ISSN: 2158-3188.

  Ramikie TS, Nyilas R, Bluett RJ, Gamble-George JC, Hartley ND, Mackie K, Watanabe M, Katona I, Patel S. Multiple mechanistically distinct modes of endocannabinoid mobilization at central amygdala glutamatergic synapses. Neuron. 2014 Mar 3/5/2014; 81(5): 1111-25. PMID: 24607231, PMCID: PMC3955008, PII: S0896-6273(14)00017-8, DOI: 10.1016/j.neuron.2014.01.012, ISSN: 1097-4199.

  Hermanson DJ, Gamble-George JC, Marnett LJ, Patel S. Substrate-selective COX-2 inhibition as a novel strategy for therapeutic endocannabinoid augmentation. Trends Pharmacol. Sci [print-electronic]. 2014 Jul; 35(7): 358-67. PMID: 24845457, PMCID: PMC4074568, PII: S0165-6147(14)00068-6, DOI: 10.1016/j.tips.2014.04.006, ISSN: 1873-3735.

  Tchantchou F, Tucker LB, Fu AH, Bluett RJ, McCabe JT, Patel S, Zhang Y. The fatty acid amide hydrolase inhibitor PF-3845 promotes neuronal survival, attenuates inflammation and improves functional recovery in mice with traumatic brain injury. Neuropharmacology [print-electronic]. 2014 Oct; 85: 427-39. PMID: 24937045, PMCID: PMC4437642, PII: S0028-3908(14)00228-7, DOI: 10.1016/j.neuropharm.2014.06.006, ISSN: 1873-7064.

  Shonesy BC, Bluett RJ, Ramikie TS, Báldi R, Hermanson DJ, Kingsley PJ, Marnett LJ, Winder DG, Colbran RJ, Patel S. Genetic disruption of 2-arachidonoylglycerol synthesis reveals a key role for endocannabinoid signaling in anxiety modulation. Cell Rep [print-electronic]. 2014 Dec 12/11/2014; 9(5): 1644-53. PMID: 25466252, PMCID: PMC4268380, PII: S2211-1247(14)00955-3, DOI: 10.1016/j.celrep.2014.11.001, ISSN: 2211-1247.

• Shonesy BC, Wang X, Rose KL, Ramikie TS, Cavener VS, Rentz T, Baucum AJ, Jalan-Sakrikar N, Mackie K, Winder DG, Patel S, Colbran RJ. CaMKII regulates diacylglycerol lipase-a and striatal endocannabinoid signaling. Nat. Neurosci [print-electronic]. 2013 Apr; 16(4): 456-63. PMID: 23502535, PMCID: PMC3636998, PII: nn.3353, DOI: 10.1038/nn.3353, ISSN: 1546-1726.

  Gamble-George JC, Conger JR, Hartley ND, Gupta P, Sumislawski JJ, Patel S. Dissociable effects of CB1 receptor blockade on anxiety-like and consummatory behaviors in the novelty-induced hypophagia test in mice. Psychopharmacology (Berl.) [print-electronic]. 2013 Aug; 228(3): 401-9. PMID: 23483200, PMCID: PMC3707973, DOI: 10.1007/s00213-013-3042-8, ISSN: 1432-2072.

  Hermanson DJ, Hartley ND, Gamble-George J, Brown N, Shonesy BC, Kingsley PJ, Colbran RJ, Reese J, Marnett LJ, Patel S. Substrate-selective COX-2 inhibition decreases anxiety via endocannabinoid activation. Nat. Neurosci [print-electronic]. 2013 Sep; 16(9): 1291-8. PMID: 23912944, PMCID: PMC3788575, PII: nn.3480, DOI: 10.1038/nn.3480, ISSN: 1546-1726.

• Ramikie TS, Patel S. Endocannabinoid signaling in the amygdala: anatomy, synaptic signaling, behavior, and adaptations to stress. Neuroscience [print-electronic]. 2012 Mar 3/1/2012; 204: 38-52. PMID: 21884761, PMCID: PMC3236282, PII: S0306-4522(11)00979-1, DOI: 10.1016/j.neuroscience.2011.08.037, ISSN: 1873-7544.

• Sumislawski JJ, Ramikie TS, Patel S. Reversible gating of endocannabinoid plasticity in the amygdala by chronic stress: a potential role for monoacylglycerol lipase inhibition in the prevention of stress-induced behavioral adaptation. Neuropsychopharmacology [print-electronic]. 2011 Dec; 36(13): 2750-61. PMID: 21849983, PMCID: PMC3230498, PII: npp2011166, DOI: 10.1038/npp.2011.166, ISSN: 1740-634X.

• McElligott ZA, Klug JR, Nobis WP, Patel S, Grueter BA, Kash TL, Winder DG. Distinct forms of Gq-receptor-dependent plasticity of excitatory transmission in the BNST are differentially affected by stress. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2010 Feb 2/2/2010; 107(5): 2271-6. PMID: 20133871, PMCID: PMC2836642, PII: 0905568107, DOI: 10.1073/pnas.0905568107, ISSN: 1091-6490.

  Ho WS, Patel S, Thompson JR, Roberts CJ, Stuhr KL, Hillard CJ. Endocannabinoid modulation of hyperaemia evoked by physiologically relevant stimuli in the rat primary somatosensory cortex. Br. J. Pharmacol. 2010 Jun; 160(3): 736-46. PMID: 20590576, PMCID: PMC2931572, PII: BPH772, DOI: 10.1111/j.1476-5381.2010.00772.x, ISSN: 1476-5381.

• Hill MN, Hillard CJ, Bambico FR, Patel S, Gorzalka BB, Gobbi G. The therapeutic potential of the endocannabinoid system for the development of a novel class of antidepressants. Trends Pharmacol. Sci [print-electronic]. 2009 Sep; 30(9): 484-93. PMID: 19732971, PII: S0165-6147(09)00121-7, DOI: 10.1016/j.tips.2009.06.006, ISSN: 1873-3735.

  Patel S, Kingsley PJ, Mackie K, Marnett LJ, Winder DG. Repeated homotypic stress elevates 2-arachidonoylglycerol levels and enhances short-term endocannabinoid signaling at inhibitory synapses in basolateral amygdala. Neuropsychopharmacology [print-electronic]. 2009 Dec; 34(13): 2699-709. PMID: 19675536, PMCID: PMC2881681, PII: npp2009101, DOI: 10.1038/npp.2009.101, ISSN: 1740-634X.

• Hill MN, Carrier EJ, Ho WS, Shi L, Patel S, Gorzalka BB, Hillard CJ. Prolonged glucocorticoid treatment decreases cannabinoid CB1 receptor density in the hippocampus. Hippocampus. 2008; 18(2): 221-6. PMID: 18058925, DOI: 10.1002/hipo.20386, ISSN: 1098-1063.

  Patel S, Hillard CJ. Adaptations in endocannabinoid signaling in response to repeated homotypic stress: a novel mechanism for stress habituation. Eur. J. Neurosci. 2008 Jun; 27(11): 2821-9. PMID: 18588527, PMCID: PMC2593941, PII: EJN6266, DOI: 10.1111/j.1460-9568.2008.06266.x, ISSN: 1460-9568.

• Patel S, Hillard CJ. Pharmacological evaluation of cannabinoid receptor ligands in a mouse model of anxiety: further evidence for an anxiolytic role for endogenous cannabinoid signaling. J. Pharmacol. Exp. Ther [print-electronic]. 2006 Jul; 318(1): 304-11. PMID: 16569753, PII: jpet.106.101287, DOI: 10.1124/jpet.106.101287, ISSN: 0022-3565.

• Patel S, Roelke CT, Rademacher DJ, Hillard CJ. Inhibition of restraint stress-induced neural and behavioural activation by endogenous cannabinoid signalling. Eur. J. Neurosci. 2005 Feb; 21(4): 1057-69. PMID: 15787710, PII: EJN3916, DOI: 10.1111/j.1460-9568.2005.03916.x, ISSN: 0953-816X.

  Patel S, Carrier EJ, Ho WS, Rademacher DJ, Cunningham S, Reddy DS, Falck JR, Cravatt BF, Hillard CJ. The postmortal accumulation of brain N-arachidonylethanolamine (anandamide) is dependent upon fatty acid amide hydrolase activity. J. Lipid Res [print-electronic]. 2005 Feb; 46(2): 342-9. PMID: 15576840, PII: M400377-JLR200, DOI: 10.1194/jlr.M400377-JLR200, ISSN: 0022-2275.

  Patel S, Cravatt BF, Hillard CJ. Synergistic interactions between cannabinoids and environmental stress in the activation of the central amygdala. Neuropsychopharmacology. 2005 Mar; 30(3): 497-507. PMID: 15280883, PII: 1300535, DOI: 10.1038/sj.npp.1300535, ISSN: 0893-133X.

  Hill MN, Patel S, Carrier EJ, Rademacher DJ, Ormerod BK, Hillard CJ, Gorzalka BB. Downregulation of endocannabinoid signaling in the hippocampus following chronic unpredictable stress. Neuropsychopharmacology. 2005 Mar; 30(3): 508-15. PMID: 15525997, PII: 1300601, DOI: 10.1038/sj.npp.1300601, ISSN: 0893-133X.

  Rademacher DJ, Patel S, Ho WS, Savoie AM, Rusch NJ, Gauthier KM, Hillard CJ. U-46619 but not serotonin increases endocannabinoid content in middle cerebral artery: evidence for functional relevance. Am. J. Physiol. Heart Circ. Physiol [print-electronic]. 2005 Jun; 288(6): H2694-701. PMID: 15695564, PII: 00978.2004, DOI: 10.1152/ajpheart.00978.2004, ISSN: 0363-6135.

  Carrier EJ, Patel S, Hillard CJ. Endocannabinoids in neuroimmunology and stress. Curr Drug Targets CNS Neurol Disord. 2005 Dec; 4(6): 657-65. PMID: 16375683, ISSN: 1568-007X.

• Seagard JL, Dean C, Patel S, Rademacher DJ, Hopp FA, Schmeling WT, Hillard CJ. Anandamide content and interaction of endocannabinoid/GABA modulatory effects in the NTS on baroreflex-evoked sympathoinhibition. Am. J. Physiol. Heart Circ. Physiol [print-electronic]. 2004 Mar; 286(3): H992-1000. PMID: 14615281, PII: 00870.2003, DOI: 10.1152/ajpheart.00870.2003, ISSN: 0363-6135.

  Rademacher DJ, Kearn CS, Carrier EJ, Patel S, Delgado MA, Barkmeier A, Klick DE, Breese NM, Pfister SL, Nithipatikom K, Campbell WB, Hillard CJ. Production of hydroxyeicosatetraenoic acids and prostaglandins by a novel rat microglial cell line. J. Neuroimmunol. 2004 Apr; 149(1-2): 130-41. PMID: 15020073, PII: S0165572804000074, DOI: 10.1016/j.jneuroim.2003.12.022, ISSN: 0165-5728.

  Lu H, Patel S, Luo F, Li SJ, Hillard CJ, Ward BD, Hyde JS. Spatial correlations of laminar BOLD and CBV responses to rat whisker stimulation with neuronal activity localized by Fos expression. Magn Reson Med. 2004 Nov; 52(5): 1060-8. PMID: 15508149, DOI: 10.1002/mrm.20265, ISSN: 0740-3194.

  Patel S, Roelke CT, Rademacher DJ, Cullinan WE, Hillard CJ. Endocannabinoid signaling negatively modulates stress-induced activation of the hypothalamic-pituitary-adrenal axis. Endocrinology [print-electronic]. 2004 Dec; 145(12): 5431-8. PMID: 15331569, PII: en.2004-0638, DOI: 10.1210/en.2004-0638, ISSN: 0013-7227.

• Patel S, Hillard CJ. Cannabinoid-induced Fos expression within A10 dopaminergic neurons. Brain Res. 2003 Feb 2/14/2003; 963(1-2): 15-25. PMID: 12560108, PII: S0006899302037976, ISSN: 0006-8993.

  Rademacher DJ, Patel S, Hopp FA, Dean C, Hillard CJ, Seagard JL. Microinjection of a cannabinoid receptor antagonist into the NTS increases baroreflex duration in dogs. Am. J. Physiol. Heart Circ. Physiol [print-electronic]. 2003 May; 284(5): H1570-6. PMID: 12521935, PII: 00772.2002, DOI: 10.1152/ajpheart.00772.2002, ISSN: 0363-6135.

  Patel S, Wohlfeil ER, Rademacher DJ, Carrier EJ, Perry LJ, Kundu A, Falck JR, Nithipatikom K, Campbell WB, Hillard CJ. The general anesthetic propofol increases brain N-arachidonylethanolamine (anandamide) content and inhibits fatty acid amide hydrolase. Br. J. Pharmacol. 2003 Jul; 139(5): 1005-13. PMID: 12839875, PMCID: PMC1573928, DOI: 10.1038/sj.bjp.0705334, ISSN: 0007-1188.

  Patel S, Rademacher DJ, Hillard CJ. Differential regulation of the endocannabinoids anandamide and 2-arachidonylglycerol within the limbic forebrain by dopamine receptor activity. J. Pharmacol. Exp. Ther [print-electronic]. 2003 Sep; 306(3): 880-8. PMID: 12808005, PII: jpet.103.054270, DOI: 10.1124/jpet.103.054270, ISSN: 0022-3565.

• Patel S, Gerrits R, Muthian S, Greene AS, Hillard CJ. The CB1 receptor antagonist SR141716 enhances stimulus-induced activation of the primary somatosensory cortex of the rat. Neurosci. Lett. 2002 Dec 12/25/2002; 335(2): 95-8. PMID: 12459507, PII: S0304394002011709, ISSN: 0304-3940.

• Scruggs JL, Patel S, Bubser M, Deutch AY. DOI-Induced activation of the cortex: dependence on 5-HT2A heteroceptors on thalamocortical glutamatergic neurons. J. Neurosci. 2000 Dec 12/1/2000; 20(23): 8846-52. PMID: 11102493, PII: 20/23/8846, ISSN: 1529-2401.