Opinion | Published:

The neurobiology of psychedelic drugs: implications for the treatment of mood disorders

Nature Reviews Neuroscience volume 11, pages 642651 (2010) | Download Citation

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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    & Plants of the Gods (McGraw-Hill Book Company, Maidenhead, UK, 1979).

  2. 2.

    in Chemical Constitution and Pharmacodynamic Actions (ed. Burger, A.) 169–235 (M.Dekker, New York, 1968).

  3. 3.

    , & The joint French–US seminar on phencyclidine and related arylcyclohexylamines. Trends Pharmacol. Sci. 9, 363–367 (1983).

  4. 4.

    , , , & Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose-effect study. Psychopharmacology 172, 145–156 (2004).

  5. 5.

    in 50 Years of LSD. Current Status and Perspectives of Hallucinogens (eds Pletscher, A. & Ladewig, D.) 101–118 (Parthenon, New York, 1994).

  6. 6.

    , , & Personality structure as the main determinant of drug induced (model) psychoses. Nature 218, 296–298 (1968).

  7. 7.

    Die Experimentelle Psychose (Springer, Berlin Göttingen Heidelberg, 1962).

  8. 8.

    , & Effects of mescaline and lysergic acid (d-LSD-25). Am. J. Psychiatry 108, 579–584 (1952).

  9. 9.

    The early symptoms of schizophrenia. Br. J. Psychiatry 112, 225–251 (1966).

  10. 10.

    et al. Hallucinogenic drug induced states resemble acute endogenous psychoses: results of an empirical study. Eur. Psychiatry 13, 399–406 (1998).

  11. 11.

    & Serotonin research: contributions to understanding psychoses. Trends Pharmacol. Sci. 29, 445–453 (2008).

  12. 12.

    Hallucinogens. Pharmacol. Ther. 101, 131–181 (2004).

  13. 13.

    et al. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Arch. Gen. Psychiatry 51, 199–214 (1994).

  14. 14.

    , , & The dissociative anesthetics, ketamine and phencyclidine selective reduce excitation of central mammalian neurons by N-methyl-D-aspartate. Br. J. Pharmacol. 79, 565–575 (1983).

  15. 15.

    Psychological aspects of the LSD treatment of neuroses. J. Ment Sci. 100, 508–515 (1954).

  16. 16.

    LSD as a therapeutic tool. J. Med. Soc. N.J. 60, 203–207 (1963).

  17. 17.

    Acute adverse reactions to LSD in clinical and experimental use in the United Kingdom. Br. J. Psychiatry 118, 229–230 (1971).

  18. 18.

    in The Uses and Implications of Hallucinogenic Drugs (eds Aaronson, B. & Osmond, H.) 357–366 (Hogarth Press, London, 1970).

  19. 19.

    The use of LSD in Psychotherapy and Alcoholism (Bobbs-Merrill, New York, 1967).

  20. 20.

    in LSD: The Consciousness Expanding Drug (ed. Solomon, D.) 241–256 (G.P. Putman, New York, 1964).

  21. 21.

    , , & LSD-assisted psychotherapy with terminal cancer patients. Curr. Psychiatr. Ther. 9, 144–152 (1969).

  22. 22.

    in 50 Years of LSD: Current Status and Perspectives of Hallucinogen Research (eds Pletscher, A. & Ladewig, D.) 175–189 (Parthenon, New York, 1994).

  23. 23.

    , , & Psychedelic therapy utilizing LSD in the treatment of the alcoholic patient: a preliminary report. Am. J. Psychiatry 123, 1202–1209 (1967).

  24. 24.

    , & Glutamate-based antidepressants: 20 years on. Trends Pharmacol. Sci. 30, 563–569 (2009).

  25. 25.

    et al. Antidepressant effects of ketamine in depressed patients. Biol. Psychiatry 47, 351–354 (2000).

  26. 26.

    et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch. Gen. Psychiatry 63, 856–864 (2006).

  27. 27.

    et al. Family history of alcohol dependence and initial antidepressant response to an N-methyl-D-aspartate antagonist. Biol. Psychiatry 65, 181–184 (2009).

  28. 28.

    , , & Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression. Biol. Psychiatry 66, 522–526 (2009).

  29. 29.

    et al. Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression. Biol. Psychiatry 67, 139–145 (2010).

  30. 30.

    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).

  31. 31.

    How can we realize the promise of personalized antidepressant medicines? Nature Rev. Neurosci. 9, 638–646 (2008).

  32. 32.

    et al. Anterior cingulate desynchronization and functional connectivity with the amygdala during a working memory task predict rapid antidepressant response to ketamine. Neuropsychopharmacology 35, 1415–1422 (2010).

  33. 33.

    et al. Increased anterior cingulate cortical activity in response to fearful faces: a neurophysiological biomarker that predicts rapid antidepressant response to ketamine. Biol. Psychiatry 65, 289–295 (2009).

  34. 34.

    , , & Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nature Rev. Drug Discov. 7, 426–437 (2008).

  35. 35.

    & NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders. Nature Rev. Neurosci. 8, 413–426 (2007).

  36. 36.

    et al. Ketamine psychotherapy for heroin addiction: immediate effects and two-year follow-up. J. Subst. Abuse Treatment 23, 273–283 (2002).

  37. 37.

    , , & Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. J. Clin. Psychiatry 67, 1735–1740 (2006).

  38. 38.

    & LSD treatment in a severe case of compulsive neurosis. Acta Psychiatr. Scand. 55, 127–141 (1977).

  39. 39.

    & Relief of obsessive–compulsive symptoms by LSD and psilocin. Am. J. Psychiatry 144, 1239–1240 (1987).

  40. 40.

    & Hallucinogen-induced relief of obsessions and compulsions. Am. J. Psychiatry 154, 1037–1038 (1997).

  41. 41.

    , & Response of cluster headache to psilocybin and LSD. Neurology 66, 1920–1922 (2006).

  42. 42.

    & Agonist-trafficking and hallucinogens. Curr. Med. Chem. 16, 1017–1027 (2009).

  43. 43.

    Hallucinogens as discriminative stimuli in animals: LSD, phenethylamines, and tryptamines. Psychopharmacology (Berlin) 203, 251–263 (2009).

  44. 44.

    Do NMDA receptor antagonist models of schizophrenia predict the clinical efficacy of antipsychotic drugs? J. Psychopharmacol. 21, 283–301 (2007).

  45. 45.

    , , , & A defined network of fast-spiking interneurons in orbitofrontal cortex: responses to behavioral contingencies and ketamine administration. Front. Syst. Neurosci. 3, 13 (2009).

  46. 46.

    , & Cognitive therapy versus medication for depression: treatment outcomes and neural mechanisms. Nature Rev. Neurosci. 9, 788–796 (2008).

  47. 47.

    , & Neurocognitive mechanisms in depression: implications for treatment. Annu. Rev. Neurosci. 32, 57–74 (2009).

  48. 48.

    , & in Encyclopedia of Neuroscience (ed. Squire, L. R.) 741–748 (Academic Press, Oxford, 2009).

  49. 49.

    , & 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).

  50. 50.

    , & Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sci. 35, 2505–2511 (1984).

  51. 51.

    & Serotonin induces excitatory postsynaptic potentials in apical dendrites of neocortical pyramidal cells. Neuropsychopharmacology 36, 589–599 (1997).

  52. 52.

    & 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).

  53. 53.

    , & 5HT-2 mediation of acute behavioral effects of hallucinogens in rats. Psychopharmacology 100, 417–425 (1990).

  54. 54.

    & 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).

  55. 55.

    et al. Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior. Neuron 53, 439–452 (2007).

  56. 56.

    , , , & Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Neuroreport 9, 3897–3902 (1998).

  57. 57.

    , & Agonist-directed signaling of the serotonin 2A receptor depends on b-arrestin-2 interactions in vivo. Proc. Natl Acad. Sci. USA 105, 1079–1084 (2008).

  58. 58.

    , , & In vivo modulation of the activity of pyramidal neurons in the rat medial prefrontal cortex by 5-HT2A receptors: relationship to thalamocortical afferents. Cereb. Cortex 13, 870–882 (2003).

  59. 59.

    , , , & Mechanism of the 5-hydroxytryptamine 2A receptor-mediated facilitation of synaptic activity in prefrontal cortex. Proc. Natl Acad. Sci. USA 104, 9870–9875 (2007).

  60. 60.

    & Serotonin and hallucinogens. Neuropsychopharmacology 21, 16S–23S (1999).

  61. 61.

    , , & A major role for thalamocortical afferents in serotonergic hallucinogen receptor function in the rat neocortex. Neuroscience 105, 379–392 (2001).

  62. 62.

    Modeling 'psychosis' in vitro by inducing disordered neuronal network activity in cortical brain slices. Psychopharmacology (Berlin) 206, 575–585 (2009).

  63. 63.

    & AMPA receptor involvement in 5-hydroxytryptamine2A receptor-mediated pre-frontal cortical excitatory synaptic currents and DOI-induced head shakes. Prog. Neuropsychopharmacol. Biol. Psychiatry 32, 62–71 (2008).

  64. 64.

    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).

  65. 65.

    & Hallucinogen-induced UP states in the brain slice of rat prefrontal cortex: role of glutamate spillover and NR2B-NMDA receptors. Neuropsychopharmacology 31, 1682–1689 (2006).

  66. 66.

    , , , & 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).

  67. 67.

    , & Pyramidal neurons in rat prefrontal cortex projecting to ventral tegmental area and dorsal raphe nucleus express 5-HT2A receptors. Cereb. Cortex 19, 1678–1686 (2009).

  68. 68.

    , , & 5-HT modulation of dopamine release in basal ganglia in psilocybin-induced psychosis in man: A PET study with [11C]raclopride. Neuropsychopharmacology 20, 424–433 (1999).

  69. 69.

    et al. Rapid modulation of spine morphology by the 5-HT2A serotonin receptor through kalirin-7 signaling. Proc. Natl Acad. Sci. USA 106, 19575–19580 (2009).

  70. 70.

    , , & Lysergic acid diethylamide (LSD) administration selectively downregulates serotonin2 receptors in rat brain. Neuropsychopharmacology 3, 137–148 (1990).

  71. 71.

    , , & Behavioral tolerance to lysergic acid diethylamide is associated with reduced serotonin-2A receptor signaling in rat cortex. Neuropsychopharmacology 30, 1693–1702 (2005).

  72. 72.

    , , & Elevated 5-HT 2A receptors in postmortem prefrontal cortex in major depression is associated with reduced activity of protein kinase, A. Neuroscience 158, 1406–1415 (2008).

  73. 73.

    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. Psychiatry 163, 1580–1587 (2006).

  74. 74.

    et al. Dysfunctional attitudes and 5-HT2 receptors during depression and self-harm. Am. J. Psychiatry 160, 90–99 (2003).

  75. 75.

    et al. Antisense inhibition of 5-hydroxytryptamine2a receptor induces an antidepressant-like effect in mice. Mol. Pharmacol. 52, 1056–1063 (1997).

  76. 76.

    , , & Desensitization of 5-HT2A receptor function by chronic administration of selective serotonin reuptake inhibitors. Brain Res. 1067, 164–169 (2006).

  77. 77.

    et al. Decrease of the platelet 5-HT2A receptor function by long-term imipramine treatment in endogenous depression. Hum. Psychopharmacol. 19, 251–258 (2004).

  78. 78.

    Anxiolytic effect and memory improvement in rats by antisense oligodeoxynucleotide to 5-hydroxytryptamine-2A precursor protein. Depress. Anxiety. 22, 84–93 (2005).

  79. 79.

    et al. Cortical 5-HT2A receptor signaling modulates anxiety-like behaviors in mice. Science 313, 536–540 (2006).

  80. 80.

    , & Experiential and genetic contributions to depressive- and anxiety-like disorders: clinical and experimental studies. Neurosci. Biobehav. Rev. 32, 1185–1206 (2008).

  81. 81.

    , , , & 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).

  82. 82.

    & Corticotropin-releasing factor receptors 1 and 2 in anxiety and depression. Curr. Opin. Pharmacol. 2, 23–33 (2002).

  83. 83.

    et al. CRF receptor 1 regulates anxiety behavior via sensitization of 5-HT2 receptor signaling. Nature Neurosci. 13, 622–629 (2010).

  84. 84.

    et al. Frontolimbic serotonin 2A receptor binding in healthy subjects is associated with personality risk factors for affective disorder. Biol. Psychiatry 63, 569–576 (2008).

  85. 85.

    et al. Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus. Nature Neurosci. 8, 365–371 (2005).

  86. 86.

    et al. A PET [18F]altanserin study of 5-HT12A receptor binding in the human brain and responses to painful heat stimulation. Neuroimage 44, 1001–1007 (2009).

  87. 87.

    , & Effects of ketamine on sensory perception: Evidence for a role of N-methyl-D-aspartate receptors. J. Pharmac. Exp. Ther. 260, 1209–1213 (1992).

  88. 88.

    , , & 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).

  89. 89.

    et al. Clozapine and haloperidol differently suppress the MK-801-increased glutamatergic and serotonergic transmission in the medial prefrontal cortex of the rat. Neuropsychopharmacology 32, 2087–2097 (2007).

  90. 90.

    , & NMDA receptor hypofunction produces concomitant firing rate potentiation and burst activity reduction in the prefrontal cortex. Proc. Natl Acad. Sci. USA 101, 8467–8472 (2004).

  91. 91.

    & NMDA receptor hypofunction produces opposite effects on prefrontal cortex interneurons and pyramidal neurons. J. Neurosci. 27, 11496–11500 (2007).

  92. 92.

    et al. Activation of medial prefrontal cortex by phencyclidine is mediated via a hippocampo-prefrontal pathway. Cereb. Cortex 15, 663–669 (2005).

  93. 93.

    & Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats. Science 281, 1349–1352 (1998).

  94. 94.

    et al. An innovative design to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-D-aspartate antagonist, CP-101,606, in patients with treatment-refractory major depressive disorder. J. Clin. Psychopharmacol. 28, 631–637 (2008).

  95. 95.

    et al. Cellular mechanisms underlying the antidepressant effects of ketamine: role of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biol. Psychiatry 63, 349–352 (2008).

  96. 96.

    et al. Attenuation of the neuropsychiatric effects of ketamine with lamotrigine: support for hyperglutamatergic effects of N-methyl-D-aspartate receptor antagonists. Arch. Gen. Psychiatry 57, 270–276 (2000).

  97. 97.

    , , & Prefrontal cortical involvement in phencyclidine-induced activation of the mesolimbic dopamine system: behavioral and neurochemical evidence. Psychopharmacology (Berlin) 138, 89–95 (1998).

  98. 98.

    et al. Effects of NMDA antagonism on striatal dopamine release in healthy subjects — application of a novel PET approach. Synapse 29, 142–147 (1998).

  99. 99.

    , , & Effects of S-ketamine on striatal dopamine release: a [11C] raclopride PET study of a model psychosis in humans. J. Psych. Res. 34, 35–43 (2000).

  100. 100.

    et al. Interactive effects of subanesthetic ketamine and haloperidol in healthy humans. Psychopharmacology 145, 193–204 (1999).

  101. 101.

    , & M100907, a serotonin 5-HT2A receptor antagonist and putative antipsychotic, blocks dizocilpine-induced prepulse inhibition deficits in sprague-dawley and wistar rats. Neuropsychopharmacology 20, 311–321 (1999).

  102. 102.

    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).

  103. 103.

    , & The hallucinogen 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) increases cortical extracellular glutamate levels in rats. Neurosci. Lett. 346, 137–140 (2003).

  104. 104.

    , , , & Lysergic acid diethylamide and [-]-2,5-dimethoxy-4-methylamphetamine increase extracellular glutamate in rat prefrontal cortex. Brain Res. 1023, 134–140 (2004).

  105. 105.

    , , , & Antipsychotic drugs reverse the disruption in prefrontal cortex function produced by NMDA receptor blockade with phencyclidine. Proc. Natl Acad. Sci. USA 104, 14843–14848 (2007).

  106. 106.

    & Dendritic glutamate-induced bursting in the prefrontal cortex: further characterization and effects of phencyclidine. J. Pharmacol. Exp. Ther. 305, 680–687 (2003).

  107. 107.

    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).

  108. 108.

    et al. Positron emission tomography and fluorodeoxyglucose studies of metabolic hyperfrontality and psychopathology in the psilocybin model of psychosis. Neuropsychopharmacology 16, 357–372 (1997).

  109. 109.

    , , , & 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).

  110. 110.

    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).

  111. 111.

    et al. Neurometabolic effects of psilocybin, 3,4-methylenedioxyethylamphetamine (MDE) and D-methamphetamine in healthy volunteers. A double-blind, placebo-controlled PET study with [18F]FDG. Neuropsychopharmacology 20, 565–581 (1999).

  112. 112.

    et al. The relationship between aberrant neuronal activation in the pregenual anterior cingulate, altered glutamatergic metabolism, and anhedonia in major depression. Arch. Gen. Psychiatry 66, 478–486 (2009).

  113. 113.

    et al. Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. Arch. Gen. Psychiatry 64, 193–200 (2007).

  114. 114.

    Trait anxiety and impoverished prefrontal control of attention. Nature Neurosci. 12, 92–98 (2009).

  115. 115.

    Neural mechanisms underlying selective attention to threat. Ann. NY Acad. Sci. 1129, 141–152 (2008).

  116. 116.

    , , , & Failure to regulate: counterproductive recruitment of top-down prefrontal-subcortical circuitry in major depression. J. Neurosci. 27, 8877–8884 (2007).

  117. 117.

    et al. Functional coupling of the amygdala in depressed patients treated with antidepressant medication. Neuropsychopharmacology 33, 1909–1918 (2008).

  118. 118.

    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 61, 877–889 (2004).

  119. 119.

    et al. Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study. Biol. Psychiatry 50, 651–658 (2001).

  120. 120.

    , & New insights into BDNF function in depression and anxiety. Nature Neurosci. 10, 1089–1093 (2007).

  121. 121.

    et al. Neuroplasticity as a target for the pharmacotherapy of anxiety disorders, mood disorders, and schizophrenia. Drug Discov. Today 14, 690–697 (2009).

  122. 122.

    , , & Ketamine and the next generation of antidepressants with a rapid onset of action. Pharmacol. Ther. 123, 143–150 (2009).

  123. 123.

    , , & 5-HT2A receptor-mediated regulation of brain-derived neurotrophic factor mRNA in the hippocampus and the neocortex. J. Neurosci. 17, 2785–2795 (1997).

  124. 124.

    & Influence of estradiol, stress, and 5-HT2A agonist treatment on brain-derived neurotrophic factor expression in female rats. Biol. Psychiatry 54, 59–69 (2003).

  125. 125.

    et al. Ketamine treatment reverses behavioral and physiological alterations induced by chronic mild stress in rats. Prog. Neuropsychopharmacol. Biol. Psychiatry 33, 450–455 (2009).

  126. 126.

    , , & Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies. J. Psychopharmacology (in the press).

  127. 127.

    et al. Psychiatric safety of ketamine in psychopharmacology research. Psychopharmacology (Berlin) 192, 253–260 (2007).

  128. 128.

    , , & LSD: Therapeutic effects of the psychedelic experience. Psychol. Rep. 14, 111–120 (1964).

  129. 129.

    , , , & The experimental use of psychedelic (LSD) psychotherapy. JAMA 212, 1856–1863 (1970).

  130. 130.

    , & LSD in the treatment of alcoholics. Pharmakopsychiatr. Neuropsychopharmakol. 4, 83–94 (1971).

  131. 131.

    , , , & Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. J. Psychopharmacol. 22, 621–632 (2008).

  132. 132.

    , , & Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology (Berlin) 187, 268–283 (2006).

  133. 133.

    The standardized psychometric assessment of altered states of consciousness (ASCs) in humans. Pharmacopsychiatry 31, 80–84 (1998).

  134. 134.

    Advances and pathophysiological models of hallucinogen drug actions in humans: a preamble to schizophrenia research. Pharmacopsychiatry 31, 92–103 (1998).

  135. 135.

    A cartography of the ecstatic and meditative states. Science 174, 897–904 (1971).

  136. 136.

    A review of the clinical effects of psychotomimetic agents. Ann. NY Acad. Sci. 66, 418–434 (1957).

  137. 137.

    LSD in the supportive care of the terminally ill cancer patient. J. Psychoactive Drugs 17, 279–290 (1985).

  138. 138.

    The Use of LSD in Psychotherapy and Alcoholism (Bobbs-Merrill, Indianapolis, 1967).

  139. 139.

    , & A controlled comparison of lysergic acid diethylamide (LSD) and dextroamphetmine in alcoholics. Am. J. Psychiatry 125, 1352–1357 (1969).

  140. 140.

    & Residential psychedelic (LSD) therapy for the narcotic addict. A controlled study. Arch. Gen. Psychiatry 28, 808–814 (1973).

  141. 141.

    , , & LSD-assisted psychotherapy in patients with terminal cancer. Int. Pharmacopsychiatry 8, 129–144 (1973).

  142. 142.

    Psychedelic drugs and mystical experience. Int. Psychiatry Clin. 5, 149–162 (1969).

  143. 143.

    & Psychedelic Drugs Reconsidered (Basic Books., New York, 1979).

  144. 144.

    , & in Proc. R. Med–Psychol. Assoc. (Lewis & Co., London, 1963).

  145. 145.

    in Ethnopsychotherapie (eds Dittrich, A. & Scharfetter, C.) 151–161 (Enke, Stuttgard, 1987)

  146. 146.

    Further observations regarding hallucinogenic treatment. Acta Psychiatr. Scand. 203 (Suppl.), 195–200 (1968).

  147. 147.

    & The use of ketamine in psychiatry. Psychosomatics 14, 344–346 (1973).

  148. 148.

    in Neuro-Psychopharmacology (eds Brill, H., Cole, J. O., Denker, P., Hippins, H. & Bradley, P. B.) 441–444 (Excerpta-Medica, Amsterdam, 2010).

  149. 149.

    Brain mechanisms of hallucinogens and entactogens. Dialogues Clin. Neurosci. 3, 265–279 (2001).

Download references

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.

Author information

Affiliations

  1. 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
  2. Franz X. Vollenweider is also at the School of Medicine, University of Zurich, Switzerland.

    • Franz X. Vollenweider

Authors

  1. Search for Franz X. Vollenweider in:

  2. Search for Michael Kometer in:

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Franz X. Vollenweider.

Glossary

Cluster period

A period of time during which cluster headache attacks occur regularly.

Enantiomers

Two stereoisomeric molecules that are mirror images of each other and are not superimposable.

Existentially oriented psychotherapy

A form of therapy that emphasizes the development of a sense of self-direction through choice and of awareness in resolving existential conflicts (such as the inevitability of death, isolation and meaninglessness).

Neurosis

A former term for a category of mental disorders characterized by anxiety and a sense of distress. This category includes disorders now classified as mood disorders, anxiety disorders, dissociative disorders, sexual disorders and somatoform disorders.

Psychoanalytically oriented psychotherapy

A therapy based on Freudian psychoanalysis in which unconscious conflicts that are thought to cause the patient's symptoms are brought into consciousness to create insight for the resolution of the problems.

Regression

In Freudian psychoanalytic theory this term describes a psychological strategy to cope with reality by means of a temporary reversion of the ego to an earlier stage of development.

Riluzole

A drug used to treat amyotrophic lateral sclerosis and that has NMDA (N-methyl-D-aspartate) receptor blocking properties similar to those of ketamine.

Schedule 1

A legislative category containing controlled drugs that have a high potential for abuse, a lack of accepted safety and no currently accepted medical use in treatments.

Selective serotonin reuptake inhibitors

A class of compounds typically used as antidepressants.

Self-actualization

The motivation to realize all of one's potential.

Structure–activity relationship

(Often abbreviated to SAR.) This is the relationship between the chemical structure of a molecule and its biological activity.

Transference

A phenomenon in psychoanalysis characterized by unconscious redirection of feelings or desires from one person to another.

About this article

Publication history

Published

DOI

https://doi.org/10.1038/nrn2884