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Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers

  • Rainer Kraehenmann
    Correspondence
    Address correspondence to Rainer Kraehenmann, M.D., University of Zürich, Department of Psychiatry, Psychotherapy and Psychosomatics, Neuropsychopharmacology and Brain Imaging, Psychiatric Hospital, Lenggstrasse 31, Zürich, ZH 8032, Switzerland
    Affiliations
    Department of Psychiatry, Psychotherapy and Psychosomatics, University of Zurich and Swiss Federal Institute of Technology, Zurich, Switzerland

    Department of Neuropsychopharmacology and Brain Imaging, University of Zurich and Swiss Federal Institute of Technology, Zurich, Switzerland
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  • Katrin H. Preller
    Affiliations
    Department of Neuropsychopharmacology and Brain Imaging, University of Zurich and Swiss Federal Institute of Technology, Zurich, Switzerland
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  • Milan Scheidegger
    Affiliations
    Department of Psychiatry, Psychotherapy and Psychosomatics, University of Zurich and Swiss Federal Institute of Technology, Zurich, Switzerland

    Department of Neuropsychopharmacology and Brain Imaging, University of Zurich and Swiss Federal Institute of Technology, Zurich, Switzerland

    Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich; and Institute for Biomedical Engineering, University of Zurich and Swiss Federal Institute of Technology, Zurich, Switzerland
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  • Thomas Pokorny
    Affiliations
    Department of Neuropsychopharmacology and Brain Imaging, University of Zurich and Swiss Federal Institute of Technology, Zurich, Switzerland
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  • Oliver G. Bosch
    Affiliations
    Department of Psychiatry, Psychotherapy and Psychosomatics, University of Zurich and Swiss Federal Institute of Technology, Zurich, Switzerland
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  • Erich Seifritz
    Affiliations
    Department of Psychiatry, Psychotherapy and Psychosomatics, University of Zurich and Swiss Federal Institute of Technology, Zurich, Switzerland
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  • Franz X. Vollenweider
    Affiliations
    Department of Neuropsychopharmacology and Brain Imaging, University of Zurich and Swiss Federal Institute of Technology, Zurich, Switzerland
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      Abstract

      Background

      The amygdala is a key structure in serotonergic emotion-processing circuits. In healthy volunteers, acute administration of the serotonin 1A/2A/2C receptor agonist psilocybin reduces neural responses to negative stimuli and induces mood changes toward positive states. However, it is little-known whether psilocybin reduces amygdala reactivity to negative stimuli and whether any change in amygdala reactivity is related to mood change.

      Methods

      This study assessed the effects of acute administration of the hallucinogen psilocybin (.16 mg/kg) versus placebo on amygdala reactivity to negative stimuli in 25 healthy volunteers using blood oxygen level-dependent functional magnetic resonance imaging. Mood changes were assessed using the Positive and Negative Affect Schedule and the state portion of the State-Trait Anxiety Inventory. A double-blind, randomized, cross-over design was used with volunteers counterbalanced to receive psilocybin and placebo in two separate sessions at least 14 days apart.

      Results

      Amygdala reactivity to negative and neutral stimuli was lower after psilocybin administration than after placebo administration. The psilocybin-induced attenuation of right amygdala reactivity in response to negative stimuli was related to the psilocybin-induced increase in positive mood state.

      Conclusions

      These results demonstrate that acute treatment with psilocybin decreased amygdala reactivity during emotion processing and that this was associated with an increase of positive mood in healthy volunteers. These findings may be relevant to the normalization of amygdala hyperactivity and negative mood states in patients with major depression.

      Keywords

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      References

        • DeRubeis R.J.
        • Siegle G.J.
        • Hollon S.D.
        Cognitive therapy versus medication for depression: Treatment outcomes and neural mechanisms.
        Nat Rev Neurosci. 2008; 9: 788-796
        • Phelps E.A.
        • LeDoux J.E.
        Contributions of the amygdala to emotion processing: From animal models to human behavior.
        Neuron. 2005; 48: 175-187
        • Ramel W.
        • Goldin P.R.
        • Eyler L.T.
        • Brown G.G.
        • Gotlib I.H.
        • McQuaid J.R.
        Amygdala reactivity and mood-congruent memory in individuals at risk for depressive relapse.
        Biol Psychiatry. 2007; 61: 231-239
        • Siegle G.J.
        • Steinhauer S.R.
        • Thase M.E.
        • Stenger V.A.
        • Carter C.S.
        Canʼt shake that feeling: Event-related fMRI assessment of sustained amygdala activity in response to emotional information in depressed individuals.
        Biol Psychiatry. 2002; 51: 693-707
        • Stuhrmann A.
        • Dohm K.
        • Kugel H.
        • Zwanzger P.
        • Redlich R.
        • Grotegerd D.
        • et al.
        Mood-congruent amygdala responses to subliminally presented facial expressions in major depression: Associations with anhedonia.
        J Psychiatry Neurosci. 2013; 38: 249-258
        • Fu C.H.
        • Williams S.C.
        • Cleare A.J.
        • Brammer M.J.
        • Walsh N.D.
        • Kim J.
        • et al.
        Attenuation of the neural response to sad faces in major depression by antidepressant treatment: A prospective, event-related functional magnetic resonance imaging study.
        Arch Gen Psychiatry. 2004; 61: 877-889
        • Victor T.A.
        • Furey M.L.
        • Fromm S.J.
        • Ohman A.
        • Drevets W.C.
        Relationship between amygdala responses to masked faces and mood state and treatment in major depressive disorder.
        Arch Gen Psychiatry. 2010; 67: 1128-1138
        • Hariri A.R.
        • Mattay V.S.
        • Tessitore A.
        • Kolachana B.
        • Fera F.
        • Goldman D.
        • et al.
        Serotonin transporter genetic variation and the response of the human amygdala.
        Science. 2002; 297: 400-403
        • Hariri A.R.
        • Drabant E.M.
        • Munoz K.E.
        • Kolachana B.S.
        • Mattay V.S.
        • Egan M.F.
        • et al.
        A susceptibility gene for affective disorders and the response of the human amygdala.
        Arch Gen Psychiatry. 2005; 62: 146-152
        • Murphy S.E.
        • Norbury R.
        • Godlewska B.R.
        • Cowen P.J.
        • Mannie Z.M.
        • Harmer C.J.
        • Munafò M.R.
        The effect of the serotonin transporter polymorphism (5-HTTLPR) on amygdala function: A meta-analysis.
        Mol Psychiatry. 2013; 18: 512-520
        • Wong M.L.
        • Licinio J.
        Research and treatment approaches to depression.
        Nat Rev Neurosci. 2001; 2: 343-351
        • Hamilton J.P.
        • Etkin A.
        • Furman D.J.
        • Lemus M.G.
        • Johnson R.F.
        • Gotlib I.H.
        Functional neuroimaging of major depressive disorder: A meta-analysis and new integration of base line activation and neural response data.
        Am J Psychiatry. 2012; 169: 693-703
        • Drevets W.C.
        Neuroimaging abnormalities in the amygdala in mood disorders.
        Ann N Y Acad Sci. 2003; 985: 420-444
        • Hahn A.
        • Lanzenberger R.
        • Wadsak W.
        • Spindelegger C.
        • Moser U.
        • Mien L.
        • et al.
        Escitalopram enhances the association of serotonin-1A autoreceptors to heteroreceptors in anxiety disorders.
        J Neurosci. 2010; 30: 14482-14489
        • Hasler F.
        • Grimberg U.
        • Benz M.A.
        • Huber T.
        • Vollenweider F.X.
        Acute psychological and physiological effects of psilocybin in healthy humans: A double-blind, placebo-controlled dose-effect study.
        Psychopharmacology (Berl). 2004; 172: 145-156
        • Nichols D.E.
        Hallucinogens.
        Pharmacol Ther. 2004; 101: 131-181
        • González-Maeso J.
        • Weisstaub N.V.
        • Zhou M.
        • Chan P.
        • Ivic L.
        • Ang R.
        • et al.
        Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior.
        Neuron. 2007; 53: 439-452
        • Vollenweider F.X.
        • Kometer M.
        The neurobiology of psychedelic drugs: Implications for the treatment of mood disorders.
        Nat Rev Neurosci. 2010; 11: 642-651
        • Kometer M.
        • Schmidt A.
        • Bachmann R.
        • Studerus E.
        • Seifritz E.
        • Vollenweider F.X.
        Psilocybin biases facial recognition, goal-directed behavior, and mood state toward positive relative to negative emotions through different serotonergic subreceptors.
        Biol Psychiatry. 2012; 72: 898-906
        • Schmidt A.
        • Kometer M.
        • Bachmann R.
        • Seifritz E.
        • Vollenweider F.
        The NMDA antagonist ketamine and the 5-HT agonist psilocybin produce dissociable effects on structural encoding of emotional face expressions.
        Psychopharmacology (Berl). 2013; 225: 227-239
        • Bernasconi F.
        • Schmidt A.
        • Pokorny T.
        • Kometer M.
        • Seifritz E.
        • Vollenweider F.X.
        Spatiotemporal brain dynamics of emotional face processing modulations induced by the serotonin 1A/2A receptor agonist psilocybin [published online ahead of print July 16].
        Cereb Cortex. 2013;
        • Carhart-Harris R.L.
        • Erritzoe D.
        • Williams T.
        • Stone J.M.
        • Reed L.J.
        • Colasanti A.
        • et al.
        Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin.
        Proc Natl Acad Sci U S A. 2012; 109: 2138-2143
        • Carhart-Harris R.L.
        • Leech R.
        • Williams T.M.
        • Erritzoe D.
        • Abbasi N.
        • Bargiotas T.
        • et al.
        Implications for psychedelic-assisted psychotherapy: Functional magnetic resonance imaging study with psilocybin.
        Br J Psychiatry. 2012; 200: 238-244
        • Sercl M.
        • Kovarik J.
        • Jaros O.
        [Clinical experiences with psilocybin (CY 39 Sandoz)].
        Psychiatr Neurol (Basel). 1961; 142: 137-146
        • Riedlinger T.J.
        • Riedlinger J.E.
        Psychedelic and entactogenic drugs in the treatment of depression.
        J Psychoactive Drugs. 1994; 26: 41-55
        • Leuner H.
        [Psychotherapy with the aid of hallucinogenic drugs] [German].
        Arzneimittelforschung. 1966; 16: 253-255
        • Grob C.S.
        • Danforth A.L.
        • Chopra G.S.
        • Hagerty M.
        • McKay C.R.
        • Halberstadt A.L.
        • Greer G.R.
        Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer.
        Arch Gen Psychiatry. 2011; 68: 71-78
        • Dannlowski U.
        • Ohrmann P.
        • Bauer J.
        • Kugel H.
        • Baune B.T.
        • Hohoff C.
        • et al.
        Serotonergic genes modulate amygdala activity in major depression.
        Genes Brain Behav. 2007; 6: 672-676
        • Watson D.
        • Clark L.A.
        • Tellegen A.
        Development and validation of brief measures of positive and negative affect: The PANAS scales.
        J Pers Soc Psychol. 1988; 54: 1063-1070
        • Spielberger C.D.
        • Gorsuch R.L.
        Manual for the State-Trait Anxiety Inventory (Form Y) (“Self-Evaluation Questionnaire”).
        Consulting Psychologists Press, Palo Alto, CA1983
        • Hariri A.R.
        • Tessitore A.
        • Mattay V.S.
        • Fera F.
        • Weinberger D.R.
        The amygdala response to emotional stimuli: A comparison of faces and scenes.
        Neuroimage. 2002; 17: 317-323
        • Hariri A.R.
        • Mattay V.S.
        • Tessitore A.
        • Fera F.
        • Weinberger D.R.
        Neocortical modulation of the amygdala response to fearful stimuli.
        Biol Psychiatry. 2003; 53: 494-501
        • Kirsch P.
        • Esslinger C.
        • Chen Q.
        • Mier D.
        • Lis S.
        • Siddhanti S.
        • et al.
        Oxytocin modulates neural circuitry for social cognition and fear in humans.
        J Neurosci. 2005; 25: 11489-11493
        • Patin A.
        • Hurlemann R.
        Modulating amygdala responses to emotion: Evidence from pharmacological fMRI.
        Neuropsychologia. 2011; 49: 706-717
        • Hariri A.R.
        • Mattay V.S.
        • Tessitore A.
        • Fera F.
        • Smith W.G.
        • Weinberger D.R.
        Dextroamphetamine modulates the response of the human amygdala.
        Neuropsychopharmacology. 2002; 27: 1036-1040
        • Muñoz K.E.
        • Meyer-Lindenberg A.
        • Hariri A.R.
        • Mervis C.B.
        • Mattay V.S.
        • Morris C.A.
        • Berman K.F.
        Abnormalities in neural processing of emotional stimuli in Williams syndrome vary according to social vs. non-social content.
        Neuroimage. 2010; 50: 340-346
        • Tzourio-Mazoyer N.
        • Landeau B.
        • Papathanassiou D.
        • Crivello F.
        • Etard O.
        • Delcroix N.
        • et al.
        Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain.
        Neuroimage. 2002; 15: 273-289
        • Maldjian J.A.
        • Laurienti P.J.
        • Kraft R.A.
        • Burdette J.H.
        An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets.
        Neuroimage. 2003; 19: 1233-1239
        • Worsley K.J.
        • Marrett S.
        • Neelin P.
        • Vandal A.C.
        • Friston K.J.
        • Evans A.C.
        A unified statistical approach for determining significant signals in images of cerebral activation.
        Hum Brain Mapp. 1996; 4: 58-73
        • Aghajanian G.K.
        • Marek G.J.
        Serotonin, via 5-HT2A receptors, increases EPSCs in layer V pyramidal cells of prefrontal cortex by an asynchronous mode of glutamate release.
        Brain Res. 1999; 825: 161-171
        • Dale A.M.
        • Halgren E.
        Spatiotemporal mapping of brain activity by integration of multiple imaging modalities.
        Curr Opin Neurobiol. 2001; 11: 202-208
        • Wager T.D.
        • Phan K.L.
        • Liberzon I.
        • Taylor S.F.
        Valence, gender, and lateralization of functional brain anatomy in emotion: A meta-analysis of findings from neuroimaging.
        Neuroimage. 2003; 19: 513-531
        • Sergerie K.
        • Chochol C.
        • Armony J.L.
        The role of the amygdala in emotional processing: A quantitative meta-analysis of functional neuroimaging studies.
        Neurosci Biobehav Rev. 2008; 32: 811-830
        • Baas D.
        • Aleman A.
        • Kahn R.S.
        Lateralization of amygdala activation: A systematic review of functional neuroimaging studies.
        Brain Res Brain Res Rev. 2004; 45: 96-103
        • Oliveri M.
        • Calvo G.
        Increased visual cortical excitability in ecstasy users: A transcranial magnetic stimulation study.
        J Neurol Neurosurg Psychiatry. 2003; 74: 1136-1138
        • Merabet L.B.
        • Kobayashi M.
        • Barton J.
        • Pascual-Leone A.
        Suppression of complex visual hallucinatory experiences by occipital transcranial magnetic stimulation: A case report.
        Neurocase. 2003; 9: 436-440
        • Boroojerdi B.
        • Bushara K.O.
        • Corwell B.
        • Immisch I.
        • Battaglia F.
        • Muellbacher W.
        • Cohen L.G.
        Enhanced excitability of the human visual cortex induced by short-term light deprivation.
        Cereb Cortex. 2000; 10: 529-534
        • Ffytche D.H.
        • Howard R.J.
        • Brammer M.J.
        • David A.
        • Woodruff P.
        • Williams S.
        The anatomy of conscious vision: An fMRI study of visual hallucinations.
        Nat Neurosci. 1998; 1: 738-742
        • Kometer M.
        • Cahn B.R.
        • Andel D.
        • Carter O.L.
        • Vollenweider F.X.
        The 5-HT2A/1A agonist psilocybin disrupts modal object completion associated with visual hallucinations.
        Biol Psychiatry. 2011; 69: 399-406
        • Kometer M.
        • Schmidt A.
        • Jäncke L.
        • Vollenweider F.X.
        Activation of serotonin 2A receptors underlies the psilocybin-induced effects on α oscillations, N170 visual-evoked potentials, and visual hallucinations.
        J Neurosci. 2013; 33: 10544-10551
        • Amaral D.G.
        • Behniea H.
        • Kelly J.L.
        Topographic organization of projections from the amygdala to the visual cortex in the macaque monkey.
        Neuroscience. 2003; 118: 1099-1120
        • Vuilleumier P.
        • Richardson M.P.
        • Armony J.L.
        • Driver J.
        • Dolan R.J.
        Distant influences of amygdala lesion on visual cortical activation during emotional face processing.
        Nat Neurosci. 2004; 7: 1271-1278
        • Hornboll B.
        • Macoveanu J.
        • Rowe J.
        • Elliott R.
        • Paulson O.B.
        • Siebner H.R.
        • Knudsen G.M.
        Acute serotonin 2A receptor blocking alters the processing of fearful faces in the orbitofrontal cortex and amygdala.
        J Psychopharmacol. 2013; 27: 903-914
        • Vollenweider F.X.
        • Vollenweider-Scherpenhuyzen M.F.
        • Bäbler A.
        • Vogel H.
        • Hell D.
        Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action.
        Neuroreport. 1998; 9: 3897-3902
        • Blair J.B.
        • Kurrasch-Orbaugh D.
        • Marona-Lewicka D.
        • Cumbay M.G.
        • Watts V.J.
        • Barker E.L.
        • Nichols D.E.
        Effect of ring fluorination on the pharmacology of hallucinogenic tryptamines.
        J Med Chem. 2000; 43: 4701-4710
        • Sard H.
        • Kumaran G.
        • Morency C.
        • Roth B.L.
        • Toth B.A.
        • He P.
        • Shuster L.
        SAR of psilocybin analogs: Discovery of a selective 5-HT 2C agonist.
        Bioorg Med Chem Lett. 2005; 15: 4555-4559
        • Michelsen K.A.
        • Prickaerts J.
        • Steinbusch
        • Harry W.M.
        The dorsal raphe nucleus and serotonin: Implications for neuroplasticity linked to major depression and Alzheimerʼs disease.
        Prog Brain Res. 2008; 172: 233-264
        • Zhang G.
        • Ásgeirsdóttir H.N.
        • Cohen S.J.
        • Munchow A.H.
        • Barrera M.P.
        • Stackman R.W.
        Stimulation of serotonin 2A receptors facilitates consolidation and extinction of fear memory in C57BL/6J mice.
        Neuropharmacology. 2013; 64: 403-413
        • Savli M.
        • Bauer A.
        • Mitterhauser M.
        • Ding Y.
        • Hahn A.
        • Kroll T.
        • et al.
        Normative database of the serotonergic system in healthy subjects using multi-tracer PET.
        Neuroimage. 2012; 63: 447-459
        • Rammes G.
        • Eder M.
        • Dodt H.U.
        • Kochs E.
        • Zieglgänsberger W.
        Long-term depression in the basolateral amygdala of the mouse involves the activation of interneurons.
        Neuroscience. 2001; 107: 85-97
        • Vicente M.A.
        • Zangrossi H.
        Involvement of 5-HT2C and 5-HT1A receptors of the basolateral nucleus of the amygdala in the anxiolytic effect of chronic antidepressant treatment.
        Neuropharmacology. 2014; 79: 127-135
        • Rainnie D.G.
        Serotonergic modulation of neurotransmission in the rat basolateral amygdala.
        J Neurophysiol. 1999; 82: 69-85
        • Stutzmann G.E.
        • LeDoux J.E.
        GABAergic antagonists block the inhibitory effects of serotonin in the lateral amygdala: A mechanism for modulation of sensory inputs related to fear conditioning.
        J Neurosci. 1999; 19: RC8
        • Shen R.Y.
        • Andrade R.
        5-Hydroxytryptamine2 receptor facilitates GABAergic neurotransmission in rat hippocampus.
        J Pharmacol Exp Ther. 1998; 285: 805-812
        • Piñeyro G.
        • Blier P.
        Autoregulation of serotonin neurons: Role in antidepressant drug action.
        Pharmacol Rev. 1999; 51: 533-591
        • Fink K.B.
        • Go¨thert M.
        5-HT receptor regulation of neurotransmitter release.
        Pharmacol Rev. 2007; 59: 360-417
        • Meltzer C.C.
        • Price J.C.
        • Mathis C.A.
        • Butters M.A.
        • Ziolko S.K.
        • Moses-Kolko E.
        • et al.
        Serotonin 1A receptor binding and treatment response in late-life depression.
        Neuropsychopharmacology. 2004; 29: 2258-2265
        • Drevets W.C.
        • Frank E.
        • Price J.C.
        • Kupfer D.J.
        • Holt D.
        • Greer P.J.
        • et al.
        PET imaging of serotonin 1A receptor binding in depression.
        Biol Psychiatry. 1999; 46: 1375-1387
        • Drevets W.C.
        • Frank E.
        • Price J.C.
        • Kupfer D.J.
        • Greer P.J.
        • Mathis C.
        Serotonin type-1A receptor imaging in depression.
        Nucl Med Biol. 2000; 27: 499-507
        • Lanzenberger R.
        • Wadsak W.
        • Spindelegger C.
        • Mitterhauser M.
        • Akimova E.
        • Mien L.
        • et al.
        Cortisol plasma levels in social anxiety disorder patients correlate with serotonin-1A receptor binding in limbic brain regions.
        Int J Neuropsychopharmacol. 2010; 13: 1129-1143
        • Sladky R.
        • Ho¨flich A.
        • Küblbo¨ck M.
        • Kraus C.
        • Baldinger P.
        • Moser E.
        • et al.
        Disrupted effective connectivity between the amygdala and orbitofrontal cortex in social anxiety disorder during emotion discrimination revealed by dynamic causal modeling for fMRI [published online ahead of print October 9].
        Cereb Cortex. 2013;
        • Hahn A.
        • Stein P.
        • Windischberger C.
        • Weissenbacher A.
        • Spindelegger C.
        • Moser E.
        • et al.
        Reduced resting-state functional connectivity between amygdala and orbitofrontal cortex in social anxiety disorder.
        Neuroimage. 2011; 56: 881-889
        • Spindelegger C.
        • Lanzenberger R.
        • Wadsak W.
        • Mien L.K.
        • Stein P.
        • Mitterhauser M.
        • et al.
        Influence of escitalopram treatment on 5-HT 1A receptor binding in limbic regions in patients with anxiety disorders.
        Mol Psychiatry. 2009; 14: 1040-1050
        • Dai J.
        • Han H.
        • Tian M.
        • Cao J.
        • Xiu J.
        • Song N.
        • et al.
        Enhanced contextual fear memory in central serotonin-deficient mice.
        Proc Natl Acad Sci U S A. 2008; 105: 11981-11986
        • Catlow B.J.
        • Song S.
        • Paredes D.A.
        • Kirstein C.L.
        • Sanchez-Ramos J.
        Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning.
        Exp Brain Res. 2013; 228: 481-491
        • Fisher P.M.
        • Meltzer C.C.
        • Ziolko S.K.
        • Price J.C.
        • Moses-Kolko E.L.
        • Berga S.L.
        • Hariri A.R.
        Capacity for 5-HT1A-mediated autoregulation predicts amygdala reactivity.
        Nat Neurosci. 2006; 9: 1362-1363
        • Griebel G.
        • Perrault G.
        • Sanger D.J.
        A comparative study of the effects of selective and non-selective 5-HT2 receptor subtype antagonists in rat and mouse models of anxiety.
        Neuropharmacology. 1997; 36: 793-802
        • Millan M.J.
        The neurobiology and control of anxious states.
        Prog Neurobiol. 2003; 70: 83-244
        • Li X.
        • Frye M.A.
        • Shelton R.C.
        Review of pharmacological treatment in mood disorders and future directions for drug development.
        Neuropsychopharmacology. 2012; 37: 77-101
        • Blier P.
        • Ward N.M.
        Is there a role for 5-HT1A agonists in the treatment of depression?.
        Biol Psychiatry. 2003; 53: 193-203
        • Outhred T.
        • Hawkshead B.E.
        • Wager T.D.
        • Das P.
        • Malhi G.S.
        • Kemp A.H.
        Acute neural effects of selective serotonin reuptake inhibitors versus noradrenaline reuptake inhibitors on emotion processing: Implications for differential treatment efficacy.
        Neurosci Biobehav Rev. 2013; 37: 1786-1800
        • Pringle A.
        • Browning M.
        • Cowen P.J.
        • Harmer C.J.
        A cognitive neuropsychological model of antidepressant drug action.
        Prog Neuropsychopharmacol Biol Psychiatry. 2011; 35: 1586-1592

      Linked Article

      • Lysergic Acid Diethylamide and Psilocybin Revisited
        Biological PsychiatryVol. 78Issue 8
        • Preview
          The past decade brought the beginnings of a renaissance in research on psychedelic drugs. Two articles in this issue of Biological Psychiatry signify that the resurrection of this long-ignored topic has begun to mature and bear at least the promise of fruit. In the early 1970s, the onset of the “War on Drugs” brought with it a near-total hiatus in serious research on psychedelic drugs, especially in the United States. The resumption of credible work in this area has come from Switzerland, where many of the original pioneering studies were initiated in the 1950s and 1960s.
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