Sachin Patel, Ph.D., M.D.

Associate Professor

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Faculty Appointments
Associate Professor of Psychiatry and Behavioral Sciences Associate Professor of Molecular Physiology & BiophysicsJames G. Blakemore Chair in Psychiatry
M.D., Psychiatry, Medical College of Wisconsin, Milwaukee, WisconsinPh.D., Pharmacology , Medical College of Wisconsin, Milwaukee, WisconsinB.S., University of California, Santa Barbara, California
Office Address
a?? 702 Robinson Research Building
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 Description
My clinical work focuses on acute inpatient care of patients with dual mood/anxiety dividers and addiction.
Research Keywords
Our research program focuses on the role of endocannabinoids in stress-induced neuroadaptation.
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.

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.

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.

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.

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.

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.

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.

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/, ISSN: 1873-3735.

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.

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.

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.

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.

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.

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.

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.

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.

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, 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/, ISSN: 1873-3735.

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.

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. 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.

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.

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.

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.

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.

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, 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.

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.

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.

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.

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, 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.

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, 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.

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.