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The neurobiology of psychedelic drugs: implications for the treatment of mood disorders
Nature Reviews Neurosciencevolume 11, pages642–651 (2010)Cite this article
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Abstract
After a pause of nearly 40 years in research into the effects of psychedelic drugs, recent advances in our understanding of the neurobiology of psychedelics, such as lysergic acid diethylamide (LSD), psilocybin and ketamine have led to renewed interest in the clinical potential of psychedelics in the treatment of various psychiatric disorders. Recent behavioural and neuroimaging data show that psychedelics modulate neural circuits that have been implicated in mood and affective disorders, and can reduce the clinical symptoms of these disorders. These findings raise the possibility that research into psychedelics might identify novel therapeutic mechanisms and approaches that are based on glutamate-driven neuroplasticity.
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References
Hofmann, A. & Schultes, R. E.Plants of the Gods (McGraw-Hill Book Company, Maidenhead, UK, 1979).
Hofmann, A. inChemical Constitution and Pharmacodynamic Actions (ed. Burger, A.) 169–235 (M.Dekker, New York, 1968).
Domino, E. F., Kamenka, J. M. & Gneste, P. The joint French–US seminar on phencyclidine and related arylcyclohexylamines.Trends Pharmacol. Sci.9, 363–367 (1983).
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.Psychopharmacology172, 145–156 (2004).
Dittrich, A. in50 Years of LSD. Current Status and Perspectives of Hallucinogens (eds Pletscher, A. & Ladewig, D.) 101–118 (Parthenon, New York, 1994).
Fischer, R., Marks, P. A., Hill, R. M. & Rockey, M. A. Personality structure as the main determinant of drug induced (model) psychoses.Nature218, 296–298 (1968).
Leuner, H.Die Experimentelle Psychose (Springer, Berlin Göttingen Heidelberg, 1962).
Hoch, P. H., Cattell, J. P. & Pennes, H. H. Effects of mescaline and lysergic acid (d-LSD-25).Am. J. Psychiatry108, 579–584 (1952).
Chapman, J. The early symptoms of schizophrenia.Br. J. Psychiatry112, 225–251 (1966).
Gouzoulis-Mayfrank, E. et al. Hallucinogenic drug induced states resemble acute endogenous psychoses: results of an empirical study.Eur. Psychiatry13, 399–406 (1998).
Geyer, M. A. & Vollenweider, F. X. Serotonin research: contributions to understanding psychoses.Trends Pharmacol. Sci.29, 445–453 (2008).
Nichols, D. E. Hallucinogens.Pharmacol. Ther.101, 131–181 (2004).
Krystal, J. H. et al. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans.Arch. Gen. Psychiatry51, 199–214 (1994).
Anis, N. A., Berry, S. C., Burton, N. R. & Lodge, D. The dissociative anesthetics, ketamine and phencyclidine selective reduce excitation of central mammalian neurons byN-methyl-D-aspartate.Br. J. Pharmacol.79, 565–575 (1983).
Sandison, R. A. Psychological aspects of the LSD treatment of neuroses.J. Ment Sci.100, 508–515 (1954).
Schmiege, G. R. Jr. LSD as a therapeutic tool.J. Med. Soc. N.J.60, 203–207 (1963).
Malleson, N. Acute adverse reactions to LSD in clinical and experimental use in the United Kingdom.Br. J. Psychiatry118, 229–230 (1971).
Hoffer, A. inThe Uses and Implications of Hallucinogenic Drugs (eds Aaronson, B. & Osmond, H.) 357–366 (Hogarth Press, London, 1970).
Abramson, H.The use of LSD in Psychotherapy and Alcoholism (Bobbs-Merrill, New York, 1967).
Kast, E. inLSD: The Consciousness Expanding Drug (ed. Solomon, D.) 241–256 (G.P. Putman, New York, 1964).
Pahnke, W. N., Kurland, A. A., Goodman, L. E. & Richards, W. A. LSD-assisted psychotherapy with terminal cancer patients.Curr. Psychiatr. Ther.9, 144–152 (1969).
Leuner, H. in50 Years of LSD: Current Status and Perspectives of Hallucinogen Research (eds Pletscher, A. & Ladewig, D.) 175–189 (Parthenon, New York, 1994).
Kurland, A. A., Unger, S., Shaffer, J. W. & Savage, C. Psychedelic therapy utilizing LSD in the treatment of the alcoholic patient: a preliminary report.Am. J. Psychiatry123, 1202–1209 (1967).
Skolnick, P., Popik, P. & Trullas, R. Glutamate-based antidepressants: 20 years on.Trends Pharmacol. Sci.30, 563–569 (2009).
Berman, R. M. et al. Antidepressant effects of ketamine in depressed patients.Biol. Psychiatry47, 351–354 (2000).
Zarate, C. A. Jr et al. A randomized trial of anN-methyl-D-aspartate antagonist in treatment-resistant major depression.Arch. Gen. Psychiatry63, 856–864 (2006).
Phelps, L. E. et al. Family history of alcohol dependence and initial antidepressant response to anN-methyl-D-aspartate antagonist.Biol. Psychiatry65, 181–184 (2009).
Price, R. B., Nock, M. K., Charney, D. S. & Mathew, S. J. Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression.Biol. Psychiatry66, 522–526 (2009).
Aan het Rot, M. et al. Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression.Biol. Psychiatry67, 139–145 (2010).
Mathew, S. J. et al. Riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression: a pilot randomized, placebo-controlled continuation trial.Int. J. Neuropsychopharmacol.13, 71–82 (2010).
Holsboer, F. How can we realize the promise of personalized antidepressant medicines?Nature Rev. Neurosci.9, 638–646 (2008).
Salvadore, G. et al. Anterior cingulate desynchronization and functional connectivity with the amygdala during a working memory task predict rapid antidepressant response to ketamine.Neuropsychopharmacology35, 1415–1422 (2010).
Salvadore, G. et al. Increased anterior cingulate cortical activity in response to fearful faces: a neurophysiological biomarker that predicts rapid antidepressant response to ketamine.Biol. Psychiatry65, 289–295 (2009).
Sanacora, G., Zarate, C. A., Krystal, J. H. & Manji, H. K. Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders.Nature Rev. Drug Discov.7, 426–437 (2008).
Lau, C. G. & Zukin, R. S. NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders.Nature Rev. Neurosci.8, 413–426 (2007).
Krupitsky, E. et al. Ketamine psychotherapy for heroin addiction: immediate effects and two-year follow-up.J. Subst. Abuse Treatment23, 273–283 (2002).
Moreno, F. A., Wiegand, C. B., Taitano, E. K. & Delgado, P. L. Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder.J. Clin. Psychiatry67, 1735–1740 (2006).
Brandrup, E. & Vanggaard, T. LSD treatment in a severe case of compulsive neurosis.Acta Psychiatr. Scand.55, 127–141 (1977).
Leonard, H. L. & Rapoport, J. L. Relief of obsessive–compulsive symptoms by LSD and psilocin.Am. J. Psychiatry144, 1239–1240 (1987).
Moreno, F. A. & Delgado, P. L. Hallucinogen-induced relief of obsessions and compulsions.Am. J. Psychiatry154, 1037–1038 (1997).
Sewell, R. A., Halpern, J. H. & Pope, H. G. Jr. Response of cluster headache to psilocybin and LSD.Neurology66, 1920–1922 (2006).
Gonzalez-Maeso, J. & Sealfon, S. C. Agonist-trafficking and hallucinogens.Curr. Med. Chem.16, 1017–1027 (2009).
Winter, J. C. Hallucinogens as discriminative stimuli in animals: LSD, phenethylamines, and tryptamines.Psychopharmacology (Berlin)203, 251–263 (2009).
Large, C. H. Do NMDA receptor antagonist models of schizophrenia predict the clinical efficacy of antipsychotic drugs?J. Psychopharmacol.21, 283–301 (2007).
Quirk, M. C., Sosulski, D. L., Feierstein, C. E., Uchida, N. & Mainen, Z. F. A defined network of fast-spiking interneurons in orbitofrontal cortex: responses to behavioral contingencies and ketamine administration.Front. Syst. Neurosci.3, 13 (2009).
DeRubeis, R. J., Siegle, G. J. & Hollon, S. D. Cognitive therapy versus medication for depression: treatment outcomes and neural mechanisms.Nature Rev. Neurosci.9, 788–796 (2008).
Clark, L., Chamberlain, S. R. & Sahakian, B. J. Neurocognitive mechanisms in depression: implications for treatment.Annu. Rev. Neurosci.32, 57–74 (2009).
Geyer, M. A., Nichols, D. E. & Vollenweider, F. X. inEncyclopedia of Neuroscience (ed. Squire, L. R.) 741–748 (Academic Press, Oxford, 2009).
Marona-Lewicka, D., Thisted, R. A. & Nichols, D. E. Distinct temporal phases in the behavioral pharmacology of LSD: dopamine D2 receptor-mediated effects in the rat and implications for psychosis.Psychopharmacologia (Berlin)180, 427–435 (2005).
Glennon, R. A., Titeler, M. & McKenney, J. D. Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents.Life Sci.35, 2505–2511 (1984).
Aghajanian, G. K. & Marek, G. J. Serotonin induces excitatory postsynaptic potentials in apical dendrites of neocortical pyramidal cells.Neuropsychopharmacology36, 589–599 (1997).
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.825, 161–171 (1999).
Wing, L. L., Tapson, G. S. & Geyer, M. A. 5HT-2 mediation of acute behavioral effects of hallucinogens in rats.Psychopharmacology100, 417–425 (1990).
Sipes, T. E. & Geyer, M. A. DOI disruption of prepulse inhibition of startle in the rat is mediated by 5-HT2A and not by 5-HT2C receptors.Behav. Pharmacol.6, 839–842 (1995).
Gonzalez-Maeso, J. et al. Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior.Neuron53, 439–452 (2007).
Vollenweider, F. X., Vollenweider-Scherpenhuyzen, M. F. I., Bäbler, A., Vogel, H. & Hell, D. Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action.Neuroreport9, 3897–3902 (1998).
Schmid, C. L., Raehal, K. M. & Bohn, L. M. Agonist-directed signaling of the serotonin 2A receptor depends on b-arrestin-2 interactionsin vivo.Proc. Natl Acad. Sci. USA105, 1079–1084 (2008).
Puig, M. V., Celada, P., az-Mataix, L. & Artigas, F.In vivo modulation of the activity of pyramidal neurons in the rat medial prefrontal cortex by 5-HT2A receptors: relationship to thalamocortical afferents.Cereb. Cortex13, 870–882 (2003).
Beique, J. C., Imad, M., Mladenovic, L., Gingrich, J. A. & Andrade, R. Mechanism of the 5-hydroxytryptamine 2A receptor-mediated facilitation of synaptic activity in prefrontal cortex.Proc. Natl Acad. Sci. USA104, 9870–9875 (2007).
Aghajanian, G. K. & Marek, G. J. Serotonin and hallucinogens.Neuropsychopharmacology21, 16S–23S (1999).
Marek, G. J., Wright, R. A., Gewirtz, J. C. & Schoepp, D. D. A major role for thalamocortical afferents in serotonergic hallucinogen receptor function in the rat neocortex.Neuroscience105, 379–392 (2001).
Aghajanian, G. K. Modeling 'psychosis'in vitro by inducing disordered neuronal network activity in cortical brain slices.Psychopharmacology (Berlin)206, 575–585 (2009).
Zhang, C. & Marek, G. J. AMPA receptor involvement in 5-hydroxytryptamine2A receptor-mediated pre-frontal cortical excitatory synaptic currents and DOI-induced head shakes.Prog. Neuropsychopharmacol. Biol. Psychiatry32, 62–71 (2008).
Benneyworth, M. A. et al. A selective positive allosteric modulator of metabotropic glutamate receptor subtype 2 blocks a hallucinogenic drug model of psychosis.Mol. Pharmacol.72, 477–484 (2007).
Lambe, E. K. & Aghajanian, G. K. Hallucinogen-induced UP states in the brain slice of rat prefrontal cortex: role of glutamate spillover and NR2B-NMDA receptors.Neuropsychopharmacology31, 1682–1689 (2006).
Celada, P., Puig, M. V., Casanovas, J. M., Guillazo, G. & Artigas, F. Control of dorsal raphe serotonergic neurons by the medial prefrontal cortex: Involvement of serotonin-1A, GABA(A), and glutamate receptors.J. Neurosci.21, 9917–9929 (2001).
Vazquez-Borsetti, P., Cortes, R. & Artigas, F. Pyramidal neurons in rat prefrontal cortex projecting to ventral tegmental area and dorsal raphe nucleus express 5-HT2A receptors.Cereb. Cortex19, 1678–1686 (2009).
Vollenweider, F. X., Vontobel, P., Hell, D. & Leenders, K. L. 5-HT modulation of dopamine release in basal ganglia in psilocybin-induced psychosis in man: A PET study with [11C]raclopride.Neuropsychopharmacology20, 424–433 (1999).
Jones, K. A. et al. Rapid modulation of spine morphology by the 5-HT2A serotonin receptor through kalirin-7 signaling.Proc. Natl Acad. Sci. USA106, 19575–19580 (2009).
Buckholtz, N. S., Zhou, D. F., Freedman, D. X. & Potter, W. Z. Lysergic acid diethylamide (LSD) administration selectively downregulates serotonin2 receptors in rat brain.Neuropsychopharmacology3, 137–148 (1990).
Gresch, P. J., Smith, R. L., Barrett, R. J. & Sanders-Bush, E. Behavioral tolerance to lysergic acid diethylamide is associated with reduced serotonin-2A receptor signaling in rat cortex.Neuropsychopharmacology30, 1693–1702 (2005).
Shelton, R. C., Sanders-Bush, E., Manier, D. H. & Lewis, D. A. Elevated 5-HT 2A receptors in postmortem prefrontal cortex in major depression is associated with reduced activity of protein kinase, A.Neuroscience158, 1406–1415 (2008).
Bhagwagar, Z. et al. Increased 5-HT2A receptor binding in euthymic, medication-free patients recovered from depression: a positron emission study with [11C]MDL 100,907.Am. J. Psychiatry163, 1580–1587 (2006).
Meyer, J. H. et al. Dysfunctional attitudes and 5-HT2 receptors during depression and self-harm.Am. J. Psychiatry160, 90–99 (2003).
Sibille, E. et al. Antisense inhibition of 5-hydroxytryptamine2a receptor induces an antidepressant-like effect in mice.Mol. Pharmacol.52, 1056–1063 (1997).
Yamauchi, M., Miyara, T., Matsushima, T. & Imanishi, T. Desensitization of 5-HT2A receptor function by chronic administration of selective serotonin reuptake inhibitors.Brain Res.1067, 164–169 (2006).
Gomez-Gil, E. et al. Decrease of the platelet 5-HT2A receptor function by long-term imipramine treatment in endogenous depression.Hum. Psychopharmacol.19, 251–258 (2004).
Cohen, H. Anxiolytic effect and memory improvement in rats by antisense oligodeoxynucleotide to 5-hydroxytryptamine-2A precursor protein.Depress. Anxiety.22, 84–93 (2005).
Weisstaub, N. V. et al. Cortical 5-HT2A receptor signaling modulates anxiety-like behaviors in mice.Science313, 536–540 (2006).
Anisman, H., Merali, Z. & Stead, J. D. Experiential and genetic contributions to depressive- and anxiety-like disorders: clinical and experimental studies.Neurosci. Biobehav. Rev.32, 1185–1206 (2008).
Lukkes, J., Vuong, S., Scholl, J., Oliver, H. & Forster, G. Corticotropin-releasing factor receptor antagonism within the dorsal raphe nucleus reduces social anxiety-like behavior after early-life social isolation.J. Neurosci.29, 9955–9960 (2009).
Reul, J. M. & Holsboer, F. Corticotropin-releasing factor receptors 1 and 2 in anxiety and depression.Curr. Opin. Pharmacol.2, 23–33 (2002).
Magalhaes, A. C. et al. CRF receptor 1 regulates anxiety behavior via sensitization of 5-HT2 receptor signaling.Nature Neurosci.13, 622–629 (2010).
Frokjaer, V. G. et al. Frontolimbic serotonin 2A receptor binding in healthy subjects is associated with personality risk factors for affective disorder.Biol. Psychiatry63, 569–576 (2008).
Amat, J. et al. Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus.Nature Neurosci.8, 365–371 (2005).
Kupers, R. et al. A PET [18F]altanserin study of 5-HT12A receptor binding in the human brain and responses to painful heat stimulation.Neuroimage44, 1001–1007 (2009).
Oye, I., Paulsen, O. & Maurset, A. Effects of ketamine on sensory perception: Evidence for a role ofN-methyl-D-aspartate receptors.J. Pharmac. Exp. Ther.260, 1209–1213 (1992).
Moghaddam, B., Adams, B., Verma, A. & Daly, D. Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex.J. Neurosci.17, 2921–2927 (1997).
Lopez-Gil, X. et al. Clozapine and haloperidol differently suppress the MK-801-increased glutamatergic and serotonergic transmission in the medial prefrontal cortex of the rat.Neuropsychopharmacology32, 2087–2097 (2007).
Jackson, M. E., Homayoun, H. & Moghaddam, B. NMDA receptor hypofunction produces concomitant firing rate potentiation and burst activity reduction in the prefrontal cortex.Proc. Natl Acad. Sci. USA101, 8467–8472 (2004).
Homayoun, H. & Moghaddam, B. NMDA receptor hypofunction produces opposite effects on prefrontal cortex interneurons and pyramidal neurons.J. Neurosci.27, 11496–11500 (2007).
Jodo, E. et al. Activation of medial prefrontal cortex by phencyclidine is mediated via a hippocampo-prefrontal pathway.Cereb. Cortex15, 663–669 (2005).
Moghaddam, B. & Adams, B. W. Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats.Science281, 1349–1352 (1998).
Preskorn, S. H. et al. An innovative design to establish proof of concept of the antidepressant effects of the NR2B subunit selectiveN-methyl-D-aspartate antagonist, CP-101,606, in patients with treatment-refractory major depressive disorder.J. Clin. Psychopharmacol.28, 631–637 (2008).
Maeng, S. et al. Cellular mechanisms underlying the antidepressant effects of ketamine: role of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors.Biol. Psychiatry63, 349–352 (2008).
Anand, A. et al. Attenuation of the neuropsychiatric effects of ketamine with lamotrigine: support for hyperglutamatergic effects ofN-methyl-D-aspartate receptor antagonists.Arch. Gen. Psychiatry57, 270–276 (2000).
Jentsch, J. D., Tran, A., Taylor, J. R. & Roth, R. H. Prefrontal cortical involvement in phencyclidine-induced activation of the mesolimbic dopamine system: behavioral and neurochemical evidence.Psychopharmacology (Berlin)138, 89–95 (1998).
Breier, A. et al. Effects of NMDA antagonism on striatal dopamine release in healthy subjects — application of a novel PET approach.Synapse29, 142–147 (1998).
Vollenweider, F. X., Vontobel, P., Leenders, K. L. & Hell, D. Effects ofS-ketamine on striatal dopamine release: a [11C] raclopride PET study of a model psychosis in humans.J. Psych. Res.34, 35–43 (2000).
Krystal, J. H. et al. Interactive effects of subanesthetic ketamine and haloperidol in healthy humans.Psychopharmacology145, 193–204 (1999).
Varty, G. B., Bakshi, V. P. & Geyer, M. A. M100907, a serotonin 5-HT2A receptor antagonist and putative antipsychotic, blocks dizocilpine-induced prepulse inhibition deficits in sprague-dawley and wistar rats.Neuropsychopharmacology20, 311–321 (1999).
Snigdha, S. et al. Attenuation of phencyclidine-induced object recognition deficits by the combination of atypical antipsychotic drugs and pimavanserin (ACP 103), a 5-hydroxytryptamine(2A) receptor inverse agonist.J. Pharmacol. Exp. Ther.332, 622–631 (2010).
Scruggs, J. L., Schmidt, D. & Deutch, A. Y. The hallucinogen 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) increases cortical extracellular glutamate levels in rats.Neurosci. Lett.346, 137–140 (2003).
Muschamp, J. W., Regina, M. J., Hull, E. M., Winter, J. C. & Rabin, R. A. Lysergic acid diethylamide and [-]-2,5-dimethoxy-4-methylamphetamine increase extracellular glutamate in rat prefrontal cortex.Brain Res.1023, 134–140 (2004).
Kargieman, L., Santana, N., Mengod, G., Celada, P. & Artigas, F. Antipsychotic drugs reverse the disruption in prefrontal cortex function produced by NMDA receptor blockade with phencyclidine.Proc. Natl Acad. Sci. USA104, 14843–14848 (2007).
Shi, W. X. & Zhang, X. X. Dendritic glutamate-induced bursting in the prefrontal cortex: further characterization and effects of phencyclidine.J. Pharmacol. Exp. Ther.305, 680–687 (2003).
Vollenweider, F. X. et al. Metabolic hyperfrontality and psychopathology in the ketamine model of psychosis using positron emission tomography (PET) and [F-18]-fluorodeoxyglocose (FDG).Eur. Neuropsychopharmacol.7, 9–24 (1997).
Vollenweider, F. X. et al. Positron emission tomography and fluorodeoxyglucose studies of metabolic hyperfrontality and psychopathology in the psilocybin model of psychosis.Neuropsychopharmacology16, 357–372 (1997).
Vollenweider, F. X., Leenders, K. L., Oye, I., Hell, D. & Angst, J. Differential psychopathology and patterns of cerebral glucose utilisation produced by (S)- and (R)-ketamine in healthy volunteers measured by FDG-PET.Eur. Neuropsychopharmacol.7, 25–38 (1997).
Schreckenberger, M. et al. The psilocybin psychosis as a model psychosis paradigma for acute schizophrenia: a PET study with 18-FDG.Eur. J. Nucl. Med.25, 877 (1998).
Gouzoulis-Mayfrank, E. et al. Neurometabolic effects of psilocybin, 3,4-methylenedioxyethylamphetamine (MDE) andD-methamphetamine in healthy volunteers. A double-blind, placebo-controlled PET study with [18F]FDG.Neuropsychopharmacology20, 565–581 (1999).
Walter, M. et al. The relationship between aberrant neuronal activation in the pregenual anterior cingulate, altered glutamatergic metabolism, and anhedonia in major depression.Arch. Gen. Psychiatry66, 478–486 (2009).
Hasler, G. et al. Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy.Arch. Gen. Psychiatry64, 193–200 (2007).
Bishop, S. J. Trait anxiety and impoverished prefrontal control of attention.Nature Neurosci.12, 92–98 (2009).
Bishop, S. J. Neural mechanisms underlying selective attention to threat.Ann. NY Acad. Sci.1129, 141–152 (2008).
Johnstone, T., van Reekum, C. M., Urry, H. L., Kalin, N. H. & Davidson, R. J. Failure to regulate: counterproductive recruitment of top-down prefrontal-subcortical circuitry in major depression.J. Neurosci.27, 8877–8884 (2007).
Chen, C. H. et al. Functional coupling of the amygdala in depressed patients treated with antidepressant medication.Neuropsychopharmacology33, 1909–1918 (2008).
Fu, C. H. 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. Psychiatry61, 877–889 (2004).
Sheline, Y. I. et al. Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study.Biol. Psychiatry50, 651–658 (2001).
Martinowich, K., Manji, H. & Lu, B. New insights into BDNF function in depression and anxiety.Nature Neurosci.10, 1089–1093 (2007).
Krystal, J. H. et al. Neuroplasticity as a target for the pharmacotherapy of anxiety disorders, mood disorders, and schizophrenia.Drug Discov. Today14, 690–697 (2009).
Machado-Vieira, R., Salvadore, G., DiazGranados, N. & Zarate, C. A. Jr. Ketamine and the next generation of antidepressants with a rapid onset of action.Pharmacol. Ther.123, 143–150 (2009).
Vaidya, V. A., Marek, G. J., Aghajanian, G. K. & Duman, R. S. 5-HT2A receptor-mediated regulation of brain-derived neurotrophic factor mRNA in the hippocampus and the neocortex.J. Neurosci.17, 2785–2795 (1997).
Cavus, I. & Duman, R. S. Influence of estradiol, stress, and 5-HT2A agonist treatment on brain-derived neurotrophic factor expression in female rats.Biol. Psychiatry54, 59–69 (2003).
Garcia, L. S. et al. Ketamine treatment reverses behavioral and physiological alterations induced by chronic mild stress in rats.Prog. Neuropsychopharmacol. Biol. Psychiatry33, 450–455 (2009).
Studerus, E., Kometer, M., Hasler, F. & Vollenweider, F. X. Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies.J. Psychopharmacology (in the press).
Perry, E. B. Jr et al. Psychiatric safety of ketamine in psychopharmacology research.Psychopharmacology (Berlin)192, 253–260 (2007).
Savage, C., Savage, E., Fadiman, J. & Harman, W. W. LSD: Therapeutic effects of the psychedelic experience.Psychol. Rep.14, 111–120 (1964).
Pahnke, W. N., Kurland, A. A., Unger, S., Savage, C. & Grof, S. The experimental use of psychedelic (LSD) psychotherapy.JAMA212, 1856–1863 (1970).
Kurland, A. A., Grof, S. & Panke, W. N. G. L. E. LSD in the treatment of alcoholics.Pharmakopsychiatr. Neuropsychopharmakol.4, 83–94 (1971).
Griffiths, R. R., Richards, W., Johnson, M., McCann, U. & Jesse, R. Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later.J. Psychopharmacol.22, 621–632 (2008).
Griffiths, R. R., Richards, W. A., McCann, U. & Jesse, R. Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance.Psychopharmacology (Berlin)187, 268–283 (2006).
Dittrich, A. The standardized psychometric assessment of altered states of consciousness (ASCs) in humans.Pharmacopsychiatry31, 80–84 (1998).
Vollenweider, F. X. Advances and pathophysiological models of hallucinogen drug actions in humans: a preamble to schizophrenia research.Pharmacopsychiatry31, 92–103 (1998).
Fischer, R. A cartography of the ecstatic and meditative states.Science174, 897–904 (1971).
Osmond, H. A review of the clinical effects of psychotomimetic agents.Ann. NY Acad. Sci.66, 418–434 (1957).
Kurland, A. A. LSD in the supportive care of the terminally ill cancer patient.J. Psychoactive Drugs17, 279–290 (1985).
Abramson, H. A.The Use of LSD in Psychotherapy and Alcoholism (Bobbs-Merrill, Indianapolis, 1967).
Hollister, L. E., Shelton, J. & Krieger, G. A controlled comparison of lysergic acid diethylamide (LSD) and dextroamphetmine in alcoholics.Am. J. Psychiatry125, 1352–1357 (1969).
Savage, C. & McCabe, O. L. Residential psychedelic (LSD) therapy for the narcotic addict. A controlled study.Arch. Gen. Psychiatry28, 808–814 (1973).
Grof, S., Goodman, L. E., Richards, W. A. & Kurland, A. A. LSD-assisted psychotherapy in patients with terminal cancer.Int. Pharmacopsychiatry8, 129–144 (1973).
Pahnke, W. N. Psychedelic drugs and mystical experience.Int. Psychiatry Clin.5, 149–162 (1969).
Grinspoon, L. & Bakalar, J. B.Psychedelic Drugs Reconsidered (Basic Books., New York, 1979).
Crocket, R., Sandison, R. A. & Walk, A. inProc. R. Med–Psychol. Assoc. (Lewis & Co., London, 1963).
Leuner H.in Ethnopsychotherapie (eds Dittrich, A. & Scharfetter, C.) 151–161 (Enke, Stuttgard, 1987)
Geert-Jorgensen, E. Further observations regarding hallucinogenic treatment.Acta Psychiatr. Scand.203 (Suppl.), 195–200 (1968).
Khorramzadeh, E. & Lotfy, A. O. The use of ketamine in psychiatry.Psychosomatics14, 344–346 (1973).
Mascher, E. inNeuro-Psychopharmacology (eds Brill, H., Cole, J. O., Denker, P., Hippins, H. & Bradley, P. B.) 441–444 (Excerpta-Medica, Amsterdam, 2010).
Vollenweider, F. X. Brain mechanisms of hallucinogens and entactogens.Dialogues Clin. Neurosci.3, 265–279 (2001).
Acknowledgements
The authors would like to acknowledge the financial support of the Swiss Neuromatrix Foundation (to F.X.V. and M.K.), and of the Heffter Research Institute (to F.X.V.). The authors thank D. Nichols for critical comments on the manuscript.
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Franz X. Vollenweider and Michael Kometer are at the Neuropsychopharmacology and Brain Imaging Research Unit, University Hospital of Psychiatry, Zurich, Switzerland.,
Franz X. Vollenweider & Michael Kometer
Franz X. Vollenweider is also at the School of Medicine, University of Zurich, Switzerland.,
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Vollenweider, F., Kometer, M. The neurobiology of psychedelic drugs: implications for the treatment of mood disorders.Nat Rev Neurosci11, 642–651 (2010). https://doi.org/10.1038/nrn2884
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