Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Psychedelic drugs: neurobiology and potential for treatment of psychiatric disorders


Renewed interest in the use of psychedelics in the treatment of psychiatric disorders warrants a better understanding of the neurobiological mechanisms underlying the effects of these substances. After a hiatus of about 50 years, state-of-the art studies have recently begun to close important knowledge gaps by elucidating the mechanisms of action of psychedelics with regard to their effects on receptor subsystems, systems-level brain activity and connectivity, and cognitive and emotional processing. In addition, functional studies have shown that changes in self-experience, emotional processing and social cognition may contribute to the potential therapeutic effects of psychedelics. These discoveries provide a scientific road map for the investigation and application of psychedelic substances in psychiatry.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Effects of psychedelic drugs on cortico-cortical and cortico-thalamic circuits.
Fig. 2: A working hypothesis of psychedelic-induced changes in brain connectivity.
Fig. 3: Functional psychedelic-induced alterations that may underlie therapeutic effects.


  1. 1.

    Grinspoon, L. & Bakalar, J. B. Psychedelic Drugs Reconsidered (Basic Books, 1979).

  2. 2.

    Mascher, E. in Neuro-Psychopharmacology (ed. Brill, H.) 441–444 (Excerpta-Medica, 1967).

  3. 3.

    Rucker, J. J., Jelen, L. A., Flynn, S., Frowde, K. D. & Young, A. H. Psychedelics in the treatment of unipolar mood disorders: a systematic review. J. Psychopharmacol. 30, 1220–1229 (2016).

    CAS  PubMed  Google Scholar 

  4. 4.

    Leuner, H. in 50 Years of LSD: Current Status and Perspectives of Hallucinogens: a Symposium of the Swiss Academy of Medical Sciences (eds Pletscher, A. & Ladewig, D.) 175–189 (Parthenon Publisher Group Ltd, 1994).

  5. 5.

    Krebs, T. S. & Johansen, P. O. Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. J. Psychopharmacol. 26, 994–1002 (2012).

    PubMed  Google Scholar 

  6. 6.

    Pletscher, A. & Ladewig, D. 50 Years of LSD: Current Status and Perspectives of Hallucinogens: A Symposium of the Swiss Academy of Medical Sciences (Parthenon Publisher Group Ltd, 1994).

  7. 7.

    Vollenweider, F. X. & Kometer, M. The neurobiology of psychedelic drugs: implications for the treatment of mood disorders. Nat. Rev. Neurosci. 11, 642–651 (2010).

    CAS  PubMed  Google Scholar 

  8. 8.

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

    CAS  PubMed  Google Scholar 

  9. 9.

    Halberstadt, A. L. Recent advances in the neuropsychopharmacology of serotonergic hallucinogens. Behav. Brain Res. 277, 99–120 (2015).

    CAS  PubMed  Google Scholar 

  10. 10.

    Halberstadt, A. L., Chatha, M., Klein, A. K., Wallach, J. & Brandt, S. D. Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. Neuropharmacology 167, 107933 (2020).

    CAS  PubMed  Google Scholar 

  11. 11.

    Preller, K. H. et al. The fabric of meaning and subjective effects in LSD-induced states depend on serotonin 2A receptor activation. Curr. Biol. 27, 451–457 (2017).

    CAS  PubMed  Google Scholar 

  12. 12.

    Preller, K. H. et al. Role of the 5-HT2A receptor in self- and other-initiated social interaction in lysergic acid diethylamide-induced states: a pharmacological fMRI study. J. Neurosci. 38, 3603–3611 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Kraehenmann, R. et al. LSD increases primary process thinking via serotonin 2A receptor activation. Front. Pharmacol. 8, 814 (2017).

    PubMed  PubMed Central  Google Scholar 

  14. 14.

    Kraehenmann, R. et al. Dreamlike effects of LSD on waking imagery in humans depend on serotonin 2A receptor activation. Psychopharmacology 234, 2031–2046 (2017).

    CAS  PubMed  Google Scholar 

  15. 15.

    Vollenweider, F. X., Vollenweider-Scherpenhuyzen, M. F., Babler, A., Vogel, H. & Hell, D. Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Neuroreport 9, 3897–3902 (1998).

    CAS  PubMed  Google Scholar 

  16. 16.

    Winter, J. C., Rice, K. C., Amorosi, D. J. & Rabin, R. A. Psilocybin-induced stimulus control in the rat. Pharmacol. Biochem. Behav. 87, 472–480 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Benneyworth, M. A., Smith, R. L., Barrett, R. J. & Sanders-Bush, E. Complex discriminative stimulus properties of (+)lysergic acid diethylamide (LSD) in C57Bl/6J mice. Psychopharmacology 179, 854–862 (2005).

    CAS  PubMed  Google Scholar 

  18. 18.

    Leysen, J. E. in Neuromethods (eds Boulton, A. A., Baker, G. B. & Butterworth, R.) 299–350 (Springer, 1989).

  19. 19.

    Titeler, M., Lyon, R. A. & Glennon, R. A. Radioligand binding evidence implicates the brain 5-HT2 receptor as a site of action for LSD and phenylisopropylamine hallucinogens. Psychopharmacology 94, 213–216 (1988).

    CAS  PubMed  Google Scholar 

  20. 20.

    Preller, K. H. et al. Effects of serotonin 2A/1A receptor stimulation on social exclusion processing. Proc. Natl Acad. Sci. USA 113, 5119–5124 (2016).

    CAS  PubMed  Google Scholar 

  21. 21.

    Valle, M. et al. Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans. Eur. Neuropsychopharm 26, 1161–1175 (2016).

    CAS  Google Scholar 

  22. 22.

    Quednow, B., Geyer, M. A. & Halberstadt, A. L. in Handbook of Behavioral Neurobiology of Serotonin (eds Müller, C. P. & Cunningham, K. A.) 585–619 (Elsevier, 2010).

  23. 23.

    Madsen, M. K. et al. Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels. Neuropsychopharmacology 44, 1328–1334 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Pokorny, T., Preller, K. H., Kraehenmann, R. & Vollenweider, F. X. Modulatory effect of the 5-HT1A agonist buspirone and the mixed non-hallucinogenic 5-HT1A/2A agonist ergotamine on psilocybin-induced psychedelic experience. Eur. Neuropsychopharmacol. 26, 756–766 (2016).

    CAS  PubMed  Google Scholar 

  25. 25.

    Carter, O. L. et al. Modulating the rate and rhythmicity of perceptual rivalry alternations with the mixed 5-HT2A and 5-HT1A agonist psilocybin. Neuropsychopharmacology 30, 1154–1162 (2005).

    CAS  PubMed  Google Scholar 

  26. 26.

    Gonzalez-Maeso, J. et al. Hallucinogens recruit specific cortical 5-HT2A receptor-mediated signaling pathways to affect behavior. Neuron 53, 439–452 (2007).

    CAS  PubMed  Google Scholar 

  27. 27.

    Gonzalez-Maeso, J. et al. Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature 452, 93–97 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28.

    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 [C-11]raclopride. Neuropsychopharmacology 20, 424–433 (1999).

    CAS  PubMed  Google Scholar 

  29. 29.

    Ichikawa, J. & Meltzer, H. Y. The effect of serotonin(1A) receptor agonism on antipsychotic drug-induced dopamine release in rat striatum and nucleus accumbens. Brain Res. 858, 252–263 (2000).

    CAS  PubMed  Google Scholar 

  30. 30.

    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 180, 427–435 (2005).

    CAS  Google Scholar 

  31. 31.

    Preller, K. H. et al. Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor. eLife 7, e35082 (2018).

    PubMed  PubMed Central  Google Scholar 

  32. 32.

    Hall, H., Farde, L., Halldin, C., Lundkvist, C. & Sedvall, G. Autoradiographic localization of 5-HT2A receptors in the human brain using [3H]M100907 and [11C]M100907. Synapse 38, 421–431 (2000).

    CAS  PubMed  Google Scholar 

  33. 33.

    Saulin, A., Savli, M. & Lanzenberger, R. Serotonin and molecular neuroimaging in humans using PET. Amino Acids 42, 2039–2057 (2012).

    CAS  PubMed  Google Scholar 

  34. 34.

    Celada, P., Puig, M. V. & Artigas, F. Serotonin modulation of cortical neurons and networks. Front. Integr. Neurosci. 7, 25 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Marek, G. J. Interactions of hallucinogens with the glutamatergic system: permissive network effects mediated through cortical layer V pyramidal neurons. Curr. Top. Behav. Neurosci. 36, 107–135 (2018).

    CAS  PubMed  Google Scholar 

  36. 36.

    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).

    CAS  PubMed  Google Scholar 

  37. 37.

    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. Cortex 13, 870–882 (2003).

    PubMed  Google Scholar 

  38. 38.

    Wood, J., Kim, Y. & Moghaddam, B. Disruption of prefrontal cortex large scale neuronal activity by different classes of psychotomimetic drugs. J. Neurosci. 32, 3022–3031 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Llado-Pelfort, L. et al. Effects of hallucinogens on neuronal activity. Curr. Top. Behav. Neurosci. 36, 75–105 (2018).

    CAS  PubMed  Google Scholar 

  40. 40.

    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. USA 104, 9870–9875 (2007).

    PubMed  Google Scholar 

  41. 41.

    Zhang, C. & Marek, G. J. AMPA receptor involvement in 5-hydroxytryptamine 2A receptor-mediated pre-frontal cortical excitatory synaptic currents and DOI-induced head shakes. Prog. Neuropsychopharmacol. Biol. Psychiatry 32, 62–71 (2008).

    PubMed  Google Scholar 

  42. 42.

    Aru, J., Suzuki, M., Rutiku, R., Larkum, M. E. & Bachmann, T. Coupling the state and contents of consciousness. Front. Syst. Neurosci. 13, 43 (2019).

    PubMed  PubMed Central  Google Scholar 

  43. 43.

    Barre, A. et al. Presynaptic serotonin 2A receptors modulate thalamocortical plasticity and associative learning. Proc. Natl Acad. Sci. USA 113, E1382–E1391 (2016).

    CAS  PubMed  Google Scholar 

  44. 44.

    Larkum, M. E., Zhu, J. J. & Sakmann, B. A new cellular mechanism for coupling inputs arriving at different cortical layers. Nature 398, 338–341 (1999).

    CAS  PubMed  Google Scholar 

  45. 45.

    Larkum, M. A cellular mechanism for cortical associations: an organizing principle for the cerebral cortex. Trends Neurosci. 36, 141–151 (2013).

    CAS  PubMed  Google Scholar 

  46. 46.

    Disner, S. G., Beevers, C. G., Haigh, E. A. & Beck, A. T. Neural mechanisms of the cognitive model of depression. Nat. Rev. Neurosci. 12, 467–477 (2011).

    CAS  PubMed  Google Scholar 

  47. 47.

    Fisher, P. M. & Hariri, A. R. Identifying serotonergic mechanisms underlying the corticolimbic response to threat in humans. Philos. Trans. R. Soc. Lond. B Biol. Sci. 368, 20120192 (2013).

    PubMed  PubMed Central  Google Scholar 

  48. 48.

    Meltzer, H. Y. Serotonergic mechanisms as targets for existing and novel antipsychotics. Handb. Exp. Pharmacol. 212, 87–124 (2012).

    CAS  Google Scholar 

  49. 49.

    Northoff, G. Self and brain: what is self-related processing? Trends Cogn. Sci. 15, 186–187 (2011).

    PubMed  Google Scholar 

  50. 50.

    Carhart-Harris, R. L., Brugger, S., Nutt, D. J. & Stone, J. M. Psychiatry’s next top model: cause for a re-think on drug models of psychosis and other psychiatric disorders. J. Psychopharmacol. 27, 771–778 (2013).

    CAS  PubMed  Google Scholar 

  51. 51.

    Geyer, M. A. & Vollenweider, F. X. Serotonin research: contributions to understanding psychoses. Trends Pharmacol. Sci. 29, 445–453 (2008).

    CAS  PubMed  Google Scholar 

  52. 52.

    Zhang, G. et al. Stimulation of serotonin 2A receptors facilitates consolidation and extinction of fear memory in C57BL/6J mice. Neuropharmacology 64, 403–413 (2013).

    CAS  PubMed  Google Scholar 

  53. 53.

    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. 228, 481–491 (2013).

    CAS  PubMed  Google Scholar 

  54. 54.

    Ly, C. et al. Psychedelics promote structural and functional neural plasticity. Cell Rep. 23, 3170–3182 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. 55.

    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).

    CAS  PubMed  Google Scholar 

  56. 56.

    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).

    CAS  PubMed  Google Scholar 

  57. 57.

    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).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Jourdi, H. et al. Positive AMPA receptor modulation rapidly stimulates BDNF release and increases dendritic mRNA translation. J. Neurosci. 29, 8688–8697 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. 59.

    Rex, C. S. et al. Restoration of long-term potentiation in middle-aged hippocampus after induction of brain-derived neurotrophic factor. J. Neurophysiol. 96, 677–685 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Goff, D. C. et al. A placebo-controlled add-on trial of the Ampakine, CX516, for cognitive deficits in schizophrenia. Neuropsychopharmacology 33, 465–472 (2008).

    CAS  PubMed  Google Scholar 

  61. 61.

    Berthoux, C., Barre, A., Bockaert, J., Marin, P. & Becamel, C. Sustained activation of postsynaptic 5-HT2A receptors gates plasticity at prefrontal cortex synapses. Cereb. Cortex 29, 1659–1669 (2019).

    PubMed  Google Scholar 

  62. 62.

    Vollenweider, F. X. & Geyer, M. A. A systems model of altered consciousness: integrating natural and drug-induced psychoses. Brain Res. Bull. 56, 495–507 (2001).

    CAS  PubMed  Google Scholar 

  63. 63.

    Swerdlow, N. R., Geyer, M. A. & Braff, D. L. Neural circuit regulation of prepulse inhibition of startle in the rat: current knowledge and future challenges. Psychopharmacology 156, 194–215 (2001).

    CAS  PubMed  Google Scholar 

  64. 64.

    Carhart-Harris, R. L. & Friston, K. J. REBUS and the anarchic brain: toward a unified model of the brain action of psychedelics. Pharmacol. Rev. 71, 316–344 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Sipes, T. E. & Geyer, M. A. DOI disrupts prepulse inhibition of startle in rats via 5-HT2A receptors in the ventral pallidum. Brain Res. 761, 97–104 (1997).

    CAS  PubMed  Google Scholar 

  66. 66.

    Vollenweider, F. X., Csomor, P. A., Knappe, B., Geyer, M. A. & Quednow, B. B. The effects of the preferential 5-HT2A agonist psilocybin on prepulse inhibition of startle in healthy human volunteers depend on interstimulus interval. Neuropsychopharmacology 32, 1876–1887 (2007).

    CAS  PubMed  Google Scholar 

  67. 67.

    Quednow, B. B., Kometer, M., Geyer, M. A. & Vollenweider, F. X. Psilocybin-induced deficits in automatic and controlled inhibition are attenuated by ketanserin in healthy human volunteers. Neuropsychopharmacology 37, 630–640 (2012).

    CAS  PubMed  Google Scholar 

  68. 68.

    Schmid, Y. et al. Acute effects of lysergic acid diethylamide in healthy subjects. Biol. Psychiatry 78, 544–553 (2015).

    CAS  PubMed  Google Scholar 

  69. 69.

    Riba, J., Rodriguez-Fornells, A. & Barbanoj, M. J. Effects of ayahuasca on sensory and sensorimotor gating in humans as measured by P50 suppression and prepulse inhibition of the startle reflex, respectively. Psychopharmacology 165, 18–28 (2002).

    CAS  PubMed  Google Scholar 

  70. 70.

    Muller, F. et al. Increased thalamic resting-state connectivity as a core driver of LSD-induced hallucinations. Acta Psychiatr. Scand. 136, 648–657 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. 71.

    Preller, K. H. et al. Effective connectivity changes in LSD-induced altered states of consciousness in humans. Proc. Natl Acad. Sci. USA 116, 2743–2748 (2019).

    PubMed  Google Scholar 

  72. 72.

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

    CAS  PubMed  Google Scholar 

  73. 73.

    Gouzoulis-Mayfrank, E. 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).

    CAS  PubMed  Google Scholar 

  74. 74.

    Vollenweider, F. X. Advances and pathophysiological models of hallucinogenic drug actions in humans: a preamble to schizophrenia research. Pharmacopsychiatry 31 (Suppl. 2), 92–103 (1998).

    CAS  PubMed  Google Scholar 

  75. 75.

    Riba, J. et al. Increased frontal and paralimbic activation following ayahuasca, the pan-Amazonian inebriant. Psychopharmacology 186, 93–98 (2006).

    CAS  PubMed  Google Scholar 

  76. 76.

    Hermle, L. et al. Mescaline-induced psychopathological, neuropsychological, and neurometabolic effects in normal subjects — experimental psychosis as a tool for psychiatric research. Biol. Psychiat 32, 976–991 (1992).

    CAS  PubMed  Google Scholar 

  77. 77.

    Lewis, C. R. et al. Two dose investigation of the 5-HT-agonist psilocybin on relative and global cerebral blood flow. Neuroimage 159, 70–78 (2017).

    CAS  PubMed  Google Scholar 

  78. 78.

    Carhart-Harris, R. L. et al. Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proc. Natl Acad. Sci. USA 109, 2138–2143 (2012).

    CAS  PubMed  Google Scholar 

  79. 79.

    Carhart-Harris, R. L. et al. Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proc. Natl Acad. Sci. USA 113, 4853–4858 (2016).

    CAS  PubMed  Google Scholar 

  80. 80.

    Anticevic, A. et al. Association of thalamic dysconnectivity and conversion to psychosis in youth and young adults at elevated clinical risk. JAMA Psychiat 72, 882–891 (2015).

    Google Scholar 

  81. 81.

    McAlonan, K., Cavanaugh, J. & Wurtz, R. H. Guarding the gateway to cortex with attention in visual thalamus. Nature 456, 391–394 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. 82.

    Kometer, M., Pokorny, T., Seifritz, E. & Vollenweider, F. X. Psilocybin-induced spiritual experiences and insightfulness are associated with synchronization of neuronal oscillations. Psychopharmacology 232, 3663–3676 (2015).

    CAS  PubMed  Google Scholar 

  83. 83.

    Muller, F., Dolder, P. C., Schmidt, A., Liechti, M. E. & Borgwardt, S. Altered network hub connectivity after acute LSD administration. Neuroimage Clin. 18, 694–701 (2018).

    PubMed  PubMed Central  Google Scholar 

  84. 84.

    Carhart-Harris, R. L. et al. Functional connectivity measures after psilocybin inform a novel hypothesis of early psychosis. Schizophr. Bull. 39, 1343–1351 (2013).

    PubMed  Google Scholar 

  85. 85.

    Roseman, L., Leech, R., Feilding, A., Nutt, D. J. & Carhart-Harris, R. L. The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers. Front. Hum. Neurosci. 8, 204 (2014).

    PubMed  PubMed Central  Google Scholar 

  86. 86.

    Palhano-Fontes, F. et al. The psychedelic state induced by ayahuasca modulates the activity and connectivity of the default mode network. PLoS ONE 10, e0118143 (2015).

    PubMed  PubMed Central  Google Scholar 

  87. 87.

    Preller, K. H. et al. Psilocybin induces time-dependent changes in global functional connectivity. Biol. Psychiatry 88, 197–207 (2020).

    CAS  PubMed  Google Scholar 

  88. 88.

    Komorowski, A. et al. Association of protein distribution and gene expression revealed by PET and post-mortem quantification in the serotonergic system of the human brain. Cereb. Cortex 27, 117–130 (2017).

    CAS  PubMed  Google Scholar 

  89. 89.

    Lord, L. D. et al. Dynamical exploration of the repertoire of brain networks at rest is modulated by psilocybin. Neuroimage 199, 127–142 (2019).

    CAS  PubMed  Google Scholar 

  90. 90.

    Tagliazucchi, E. et al. Increased global functional connectivity correlates with LSD-induced ego dissolution. Curr. Biol. 26, 1043–1050 (2016).

    CAS  PubMed  Google Scholar 

  91. 91.

    Muller, F., Liechti, M. E., Lang, U. E. & Borgwardt, S. Advances and challenges in neuroimaging studies on the effects of serotonergic hallucinogens: contributions of the resting brain. Prog. Brain Res. 242, 159–177 (2018).

    PubMed  Google Scholar 

  92. 92.

    Fox, M. D. et al. The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc. Natl Acad. Sci. USA 102, 9673–9678 (2005).

    CAS  PubMed  Google Scholar 

  93. 93.

    Turner, B. O., Paul, E. J., Miller, M. B. & Barbey, A. K. Small sample sizes reduce the replicability of task-based fMRI studies. Commun. Biol. 1, 62 (2018).

    PubMed  PubMed Central  Google Scholar 

  94. 94.

    Mumford, J. A. & Nichols, T. E. Power calculation for group fMRI studies accounting for arbitrary design and temporal autocorrelation. Neuroimage 39, 261–268 (2008).

    PubMed  Google Scholar 

  95. 95.

    Zandbelt, B. B. et al. Within-subject variation in BOLD-fMRI signal changes across repeated measurements: quantification and implications for sample size. Neuroimage 42, 196–206 (2008).

    PubMed  Google Scholar 

  96. 96.

    Muthukumaraswamy, S. D. et al. Broadband cortical desynchronization underlies the human psychedelic state. J. Neurosci. 33, 15171–15183 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. 97.

    Klaassens, B. L. et al. Single-dose serotonergic stimulation shows widespread effects on functional brain connectivity. Neuroimage 122, 440–450 (2015).

    PubMed  Google Scholar 

  98. 98.

    Mathys, C. D. et al. Uncertainty in perception and the hierarchical Gaussian filter. Front. Hum. Neurosci. 8, 825 (2014).

    PubMed  PubMed Central  Google Scholar 

  99. 99.

    Carhart-Harris, R. L. et al. The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs. Front. Hum. Neurosci. 8, 20 (2014).

    PubMed  PubMed Central  Google Scholar 

  100. 100.

    Carhart-Harris, R. L. The entropic brain — revisited. Neuropharmacology 142, 167–178 (2018).

    CAS  PubMed  Google Scholar 

  101. 101.

    Schartner, M. M., Carhart-Harris, R. L., Barrett, A. B., Seth, A. K. & Muthukumaraswamy, S. D. Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin. Sci. Rep. 7, 46421 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. 102.

    Timmermann, C. et al. Neural correlates of the DMT experience assessed with multivariate EEG. Sci. Rep. 9, 16324 (2019).

    PubMed  PubMed Central  Google Scholar 

  103. 103.

    Lebedev, A. V. et al. LSD-induced entropic brain activity predicts subsequent personality change. Hum. Brain Mapp. 37, 3203–3213 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. 104.

    Atasoy, S. et al. Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD. Sci. Rep. 7, 17661 (2017).

    PubMed  PubMed Central  Google Scholar 

  105. 105.

    Tagliazucchi, E., Carhart-Harris, R., Leech, R., Nutt, D. & Chialvo, D. R. Enhanced repertoire of brain dynamical states during the psychedelic experience. Hum. Brain Mapp. 35, 5442–5456 (2014).

    PubMed  PubMed Central  Google Scholar 

  106. 106.

    Viol, A., Palhano-Fontes, F., Onias, H., de Araujo, D. B. & Viswanathan, G. M. Shannon entropy of brain functional complex networks under the influence of the psychedelic ayahuasca. Sci. Rep. 7, 7388 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. 107.

    Timmermann, C. et al. LSD modulates effective connectivity and neural adaptation mechanisms in an auditory oddball paradigm. Neuropharmacology 142, 251–262 (2018).

    CAS  PubMed  Google Scholar 

  108. 108.

    Umbricht, D. et al. Effects of the 5-HT2A agonist psilocybin on mismatch negativity generation and AX-continuous performance task: implications for the neuropharmacology of cognitive deficits in schizophrenia. Neuropsychopharmacology 28, 170–181 (2003).

    CAS  PubMed  Google Scholar 

  109. 109.

    Schmidt, A. et al. Mismatch negativity encoding of prediction errors predicts S-ketamine-induced cognitive impairments. Neuropsychopharmacology 37, 865–875 (2012).

    CAS  PubMed  Google Scholar 

  110. 110.

    Sandison, R. A. & Whitelaw, J. D. Further studies in the therapeutic value of lysergic acid diethylamide in mental illness. J. Ment. Sci. 103, 332–343 (1957).

    CAS  PubMed  Google Scholar 

  111. 111.

    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. Psychopharmacol. 25, 1434–1452 (2011).

    CAS  PubMed  Google Scholar 

  112. 112.

    Roseman, L. et al. Emotional breakthrough and psychedelics: validation of the emotional breakthrough inventory. J. Psychopharmacol. 33, 1076–1087 (2019).

    PubMed  Google Scholar 

  113. 113.

    Carhart-Harris, R. L. et al. Implications for psychedelic-assisted psychotherapy: functional magnetic resonance imaging study with psilocybin. Br. J. Psychiatry 200, 238–244 (2012).

    CAS  PubMed  Google Scholar 

  114. 114.

    Dolder, P. C., Schmid, Y., Muller, F., Borgwardt, S. & Liechti, M. E. LSD acutely impairs fear recognition and enhances emotional empathy and sociality. Neuropsychopharmacology 41, 2638–2646 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. 115.

    Kometer, M. et al. Psilocybin biases facial recognition, goal-directed behavior, and mood state toward positive relative to negative emotions through different serotonergic subreceptors. Biol. Psychiatry 72, 898–906 (2012).

    CAS  PubMed  Google Scholar 

  116. 116.

    Bershad, A., Schepers, S., Bremmer, M. & de Wit, H. Subjective and behavioral effects of microdoses of LSD in healthy human volunteers. Biol. Psychiatry 85, S345–S345 (2019).

    Google Scholar 

  117. 117.

    Schmidt, A., Kometer, M., Bachmann, R., Seifritz, E. & Vollenweider, F. X. The NMDA antagonist ketamine and the 5-HT agonist psilocybin produce dissociable effects on structural encoding of emotional face expressions. Psychopharmacology 225, 227–239 (2013).

    CAS  PubMed  Google Scholar 

  118. 118.

    Bernasconi, F. et al. Spatiotemporal brain dynamics of emotional face processing modulations induced by the serotonin 1A/2A receptor agonist psilocybin. Cereb. Cortex 24, 3221–3231 (2014).

    PubMed  Google Scholar 

  119. 119.

    Mueller, F. et al. Acute effects of LSD on amygdala activity during processing of fearful stimuli in healthy subjects. Transl Psychiatry 7, e1084 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. 120.

    Kraehenmann, R. et al. Psilocybin-induced decrease in amygdala reactivity correlates with enhanced positive mood in healthy volunteers. Biol. Psychiatry 78, 572–581 (2015).

    CAS  PubMed  Google Scholar 

  121. 121.

    Kraehenmann, R. et al. The mixed serotonin receptor agonist psilocybin reduces threat-induced modulation of amygdala connectivity. Neuroimage Clin. 11, 53–60 (2016).

    PubMed  Google Scholar 

  122. 122.

    Grimm, O., Kraehenmann, R., Preller, K. H., Seifritz, E. & Vollenweider, F. X. Psilocybin modulates functional connectivity of the amygdala during emotional face discrimination. Eur. Neuropsychopharmacol. 28, 691–700 (2018).

    CAS  PubMed  Google Scholar 

  123. 123.

    Bershad, A. K. et al. Preliminary report on the effects of a low dose of LSD on resting-state amygdala functional connectivity. Biol. Psychiatry Cogn. Neurosci. Neuroimaging 5, 461–467 (2020).

    PubMed  Google Scholar 

  124. 124.

    Barrett, F. S., Doss, M. K., Sepeda, N. D., Pekar, J. J. & Griffiths, R. R. Emotions and brain function are altered up to one month after a single high dose of psilocybin. Sci. Rep. 10, 2214 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  125. 125.

    Stroud, J. B. et al. Psilocybin with psychological support improves emotional face recognition in treatment-resistant depression. Psychopharmacology 235, 459–466 (2018).

    CAS  PubMed  Google Scholar 

  126. 126.

    Roseman, L., Demetriou, L., Wall, M. B., Nutt, D. J. & Carhart-Harris, R. L. Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression. Neuropharmacology 142, 263–269 (2018).

    CAS  PubMed  Google Scholar 

  127. 127.

    Mertens, L. J. et al. Therapeutic mechanisms of psilocybin: changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression. J. Psychopharmacol. 34, 167–180 (2020).

    CAS  PubMed  Google Scholar 

  128. 128.

    Milliere, R., Carhart-Harris, R. L., Roseman, L., Trautwein, F. M. & Berkovich-Ohana, A. Psychedelics, meditation, and self-consciousness. Front. Psychol. 9, 1475 (2018).

    PubMed  PubMed Central  Google Scholar 

  129. 129.

    Northoff, G. & Bermpohl, F. Cortical midline structures and the self. Trends Cogn. Sci. 8, 102–107 (2004).

    PubMed  Google Scholar 

  130. 130.

    Kometer, M., Schmidt, A., Jancke, L. & Vollenweider, F. X. Activation of serotonin 2A receptors underlies the psilocybin-induced effects on alpha oscillations, N170 visual-evoked potentials, and visual hallucinations. J. Neurosci. 33, 10544–10551 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. 131.

    Lebedev, A. V. et al. Finding the self by losing the self: neural correlates of ego-dissolution under psilocybin. Hum. Brain Mapp. 36, 3137–3153 (2015).

    PubMed  PubMed Central  Google Scholar 

  132. 132.

    Nour, M. M. & Carhart-Harris, R. L. Psychedelics and the science of self-experience. Br. J. Psychiatry 210, 177–179 (2017).

    PubMed  Google Scholar 

  133. 133.

    Garcia-Romeu, A., Griffiths, R. R. & Johnson, M. W. Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction. Curr. Drug Abuse Rev. 7, 157–164 (2014).

    CAS  PubMed  Google Scholar 

  134. 134.

    Ross, S. et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J. Psychopharmacol. 30, 1165–1180 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  135. 135.

    Bogenschutz, M. P. et al. Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. J. Psychopharmacol. 29, 289–299 (2015).

    CAS  PubMed  Google Scholar 

  136. 136.

    Griffiths, R. R. et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J. Psychopharmacol. 30, 1181–1197 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  137. 137.

    Roseman, L., Nutt, D. J. & Carhart-Harris, R. L. Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression. Front. Pharmacol. 8, 974 (2017).

    PubMed  Google Scholar 

  138. 138.

    Pokorny, T., Preller, K. H., Kometer, M., Dziobek, I. & Vollenweider, F. X. Effect of psilocybin on empathy and moral decision-making. Int. J. Neuropsychopharmacol. 20, 747–757 (2017).

    PubMed  PubMed Central  Google Scholar 

  139. 139.

    Schilbach, L. Towards a second-person neuropsychiatry. Philos. Trans. R. Soc. Lond. B Biol. Sci. 371, 20150081 (2016).

    PubMed  PubMed Central  Google Scholar 

  140. 140.

    Millan, M. J. et al. Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. Nat. Rev. Drug. Discov. 11, 141–168 (2012).

    CAS  PubMed  Google Scholar 

  141. 141.

    Griffiths, R. R. et al. Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors. J. Psychopharmacol. 32, 49–69 (2018).

    CAS  PubMed  Google Scholar 

  142. 142.

    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).

    CAS  PubMed  PubMed Central  Google Scholar 

  143. 143.

    Griffiths, R. R. et al. Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology 218, 649–665 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  144. 144.

    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 187, 268–283 (2006).

    CAS  PubMed  Google Scholar 

  145. 145.

    Schmid, Y. & Liechti, M. E. Long-lasting subjective effects of LSD in normal subjects. Psychopharmacology 235, 535–545 (2018).

    CAS  PubMed  Google Scholar 

  146. 146.

    Smigielski, L., Scheidegger, M., Kometer, M. & Vollenweider, F. X. Psilocybin-assisted mindfulness training modulates self-consciousness and brain default mode network connectivity with lasting effects. Neuroimage 196, 207–215 (2019).

    CAS  PubMed  Google Scholar 

  147. 147.

    Smigielski, L. et al. Characterization and prediction of acute and sustained response to psychedelic psilocybin in a mindfulness group retreat. Sci. Rep. 9, 14914 (2019).

    PubMed  PubMed Central  Google Scholar 

  148. 148.

    Mason, N. L., Mischler, E., Uthaug, M. V. & Kuypers, K. P. C. Sub-acute effects of psilocybin on empathy, creative thinking, and subjective well-being. J. Psychoactive Drugs 51, 123–134 (2019).

    PubMed  Google Scholar 

  149. 149.

    Noorani, T., Garcia-Romeu, A., Swift, T. C., Griffiths, R. R. & Johnson, M. W. Psychedelic therapy for smoking cessation: qualitative analysis of participant accounts. J. Psychopharmacol. 32, 756–769 (2018).

    PubMed  Google Scholar 

  150. 150.

    Watts, R., Day, C., Krzanowski, J., Nutt, D. & Carhart-Harris, R. Patients’ accounts of increased “connectedness” and “acceptance” after psilocybin for treatment-resistant depression. J. Humanist. Psychol. 57, 520–564 (2017).

    Google Scholar 

  151. 151.

    Schenberg, E. E. et al. Acute biphasic effects of ayahuasca. PLoS ONE 10, e0137202 (2015).

    PubMed  PubMed Central  Google Scholar 

  152. 152.

    Pallavicini, C. et al. Spectral signatures of serotonergic psychedelics and glutamatergic dissociatives. Neuroimage 200, 281–291 (2019).

    CAS  PubMed  Google Scholar 

  153. 153.

    Kometer, M. & Vollenweider, F. X. Serotonergic hallucinogen-induced visual perceptual alterations. Curr. Top. Behav. Neurosci. 36, 257–282 (2018).

    CAS  PubMed  Google Scholar 

  154. 154.

    Roseman, L. et al. LSD alters eyes-closed functional connectivity within the early visual cortex in a retinotopic fashion. Hum. Brain Mapp. 37, 3031–3040 (2016).

    PubMed  PubMed Central  Google Scholar 

  155. 155.

    de Araujo, D. B. et al. Seeing with the eyes shut: neural basis of enhanced imagery following ayahuasca ingestion. Hum. Brain Mapp. 33, 2550–2560 (2012).

    PubMed  Google Scholar 

  156. 156.

    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 69, 399–406 (2011).

    CAS  PubMed  Google Scholar 

  157. 157.

    Sinke, C. et al. Genuine and drug-induced synesthesia: a comparison. Conscious. Cogn. 21, 1419–1434 (2012).

    PubMed  Google Scholar 

  158. 158.

    Kaelen, M. et al. LSD modulates music-induced imagery via changes in parahippocampal connectivity. Eur. Neuropsychopharmacol. 26, 1099–1109 (2016).

    CAS  PubMed  Google Scholar 

  159. 159.

    Reininghaus, U. et al. Stress sensitivity, aberrant salience, and threat anticipation in early psychosis: an experience sampling study. Schizophr. Bull. 43, 712–722 (2016).

    Google Scholar 

  160. 160.

    Moeller, S. J. & Goldstein, R. Z. Impaired self-awareness in human addiction: deficient attribution of personal relevance. Trends Cogn. Sci. 18, 635–641 (2014).

    PubMed  PubMed Central  Google Scholar 

  161. 161.

    Pyszczynski, T. & Greenberg, J. Self-regulatory perseveration and the depressive self-focusing style: a self-awareness theory of reactive depression. Psychol. Bull. 102, 122–138 (1987).

    CAS  PubMed  Google Scholar 

  162. 162.

    Seidl, E. et al. Response to ostracism in patients with chronic depression, episodic depression and borderline personality disorder a study using Cyberball. J. Affect. Disord. 260, 254–262 (2020).

    PubMed  Google Scholar 

  163. 163.

    Amargos-Bosch, M. et al. Co-expression and in vivo interaction of serotonin 1A and serotonin 2A receptors in pyramidal neurons of prefrontal cortex. Cereb. Cortex 14, 281–299 (2004).

    PubMed  Google Scholar 

  164. 164.

    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. Neuropsychopharmacology 31, 1682–1689 (2006).

    CAS  PubMed  Google Scholar 

  165. 165.

    Aghajanian, G. K. & Marek, G. J. Serotonin model of schizophrenia: emerging role of glutamate mechanisms. Brain Res. Rev. 31, 302–312 (2000).

    CAS  PubMed  Google Scholar 

  166. 166.

    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. Neuroscience 105, 379–392 (2001).

    CAS  PubMed  Google Scholar 

  167. 167.

    Llado-Pelfort, L., Santana, N., Ghisi, V., Artigas, F. & Celada, P. 5-HT1A receptor agonists enhance pyramidal cell firing in prefrontal cortex through a preferential action on GABA interneurons. Cereb. Cortex 22, 1487–1497 (2012).

    PubMed  Google Scholar 

  168. 168.

    Marek, G. J. & Aghajanian, G. K. LSD and the phenethylamine hallucinogen DOI are potent partial agonists at 5-HT2A receptors on interneurons in rat piriform cortex. J. Pharmacol. Exp. Ther. 278, 1373–1382 (1996).

    CAS  PubMed  Google Scholar 

  169. 169.

    Martin-Ruiz, R. et al. Control of serotonergic function in medial prefrontal cortex by serotonin-2A receptors through a glutamate-dependent mechanism. J. Neurosci. 21, 9856–9866 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  170. 170.

    Dittrich, A. The standardized psychometric assessment of altered states of consciousness (ASCs) in humans. Pharmacopsychiatry 31 (Suppl. 2), 80–84 (1998).

    PubMed  Google Scholar 

  171. 171.

    Studerus, E., Gamma, A. & Vollenweider, F. X. Psychometric evaluation of the altered states of consciousness rating scale (OAV). PLoS ONE 5, e12412 (2010).

    PubMed  PubMed Central  Google Scholar 

  172. 172.

    Dittrich, A., Lamparter, D. & Maurer, M. 5D-ABZ: Fragebogen zur Erfassung Aussergewöhnlicher Bewusstseinszustände. Eine kurze Einführung [5D-ASC: Questionnaire for the Assessment of Altered States of Consciousness. A Short Introduction] (PSIN Plus, 2006).

  173. 173.

    Liechti, M. E., Dolder, P. C. & Schmid, Y. Alterations of consciousness and mystical-type experiences after acute LSD in humans. Psychopharmacology 234, 1499–1510 (2017).

    CAS  PubMed  Google Scholar 

  174. 174.

    Murphy, K., Birn, R. M. & Bandettini, P. A. Resting-state fMRI confounds and cleanup. Neuroimage 80, 349–359 (2013).

    PubMed  PubMed Central  Google Scholar 

  175. 175.

    Murphy, K. & Fox, M. D. Towards a consensus regarding global signal regression for resting state functional connectivity MRI. Neuroimage 154, 169–173 (2017).

    PubMed  PubMed Central  Google Scholar 

  176. 176.

    Yang, G. J. et al. Altered global signal topography in schizophrenia. Cereb. Cortex 27, 5156–5169 (2017).

    PubMed  Google Scholar 

  177. 177.

    Almgren, H., Van de Steen, F., Razi, A., Friston, K. & Marinazzo, D. The effect of global signal regression on DCM estimates of noise and effective connectivity from resting state fMRI. Neuroimage 208, 116435 (2020).

    PubMed  PubMed Central  Google Scholar 

  178. 178.

    Wang, Z. Improving cerebral blood flow quantification for arterial spin labeled perfusion MRI by removing residual motion artifacts and global signal fluctuations. Magn. Reson. Imaging 30, 1409–1415 (2012).

    PubMed  PubMed Central  Google Scholar 

  179. 179.

    Viviani, R., Abler, B., Seeringer, A. & Stingl, J. C. Effect of paroxetine and bupropion on human resting brain perfusion: an arterial spin labeling study. Neuroimage 61, 773–779 (2012).

    CAS  PubMed  Google Scholar 

  180. 180.

    Handley, R. et al. Acute effects of single-dose aripiprazole and haloperidol on resting cerebral blood flow (rCBF) in the human brain. Hum. Brain Mapp. 34, 272–282 (2013).

    PubMed  Google Scholar 

  181. 181.

    Goldberg, S. B., Pace, B. T., Nicholas, C. R., Raison, C. L. & Hutson, P. R. The experimental effects of psilocybin on symptoms of anxiety and depression: a meta-analysis. Psychiatry Res. 284, 112749 (2020).

    CAS  PubMed  Google Scholar 

  182. 182.

    Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P. & Griffiths, R. R. Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. J. Psychopharmacol. 28, 983–992 (2014).

    PubMed  PubMed Central  Google Scholar 

  183. 183.

    Osorio Fde, L. et al. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report. Rev. Bras. Psiquiatr. 37, 13–20 (2015).

    PubMed  Google Scholar 

  184. 184.

    Sanches, R. F. et al. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a SPECT study. J. Clin. Psychopharmacol. 36, 77–81 (2016).

    CAS  PubMed  Google Scholar 

  185. 185.

    Carhart-Harris, R. L. et al. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry 3, 619–627 (2016).

    PubMed  Google Scholar 

  186. 186.

    Carhart-Harris, R. L. et al. Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology 235, 399–408 (2018).

    CAS  PubMed  Google Scholar 

  187. 187.

    Carhart-Harris, R. L. et al. Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Sci. Rep. 7, 13187 (2017).

    PubMed  PubMed Central  Google Scholar 

  188. 188.

    Brakowski, J. et al. Resting state brain network function in major depression — depression symptomatology, antidepressant treatment effects, future research. J. Psychiatr. Res. 92, 147–159 (2017).

    PubMed  Google Scholar 

  189. 189.

    Gasser, P. et al. Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases. J. Nerv. Ment. Dis. 202, 513–520 (2014).

    PubMed  PubMed Central  Google Scholar 

  190. 190.

    Palhano-Fontes, F. et al. Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial. Psychol. Med. 49, 655–663 (2019).

    PubMed  PubMed Central  Google Scholar 

  191. 191.

    Grob, C. S. et al. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch. Gen. Psychiatry 68, 71–78 (2011).

    CAS  PubMed  Google Scholar 

  192. 192.

    Gasser, P., Kirchner, K. & Passie, T. LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: a qualitative study of acute and sustained subjective effects. J. Psychopharmacol. 29, 57–68 (2015).

    PubMed  Google Scholar 

Download references


This work was supported by the Swiss National Science Foundation (to F.X.V. and K.H.P), the Swiss Neuromatrix Foundation (to F.X.V. and K.H.P.), the Heffter Research Institute (to F.X.V.) and the Carey and Claudia Turnbull Foundation N.Y. (to F.X.V.).

Author information




The authors contributed equally to all aspects of the article.

Corresponding author

Correspondence to Franz X. Vollenweider.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information

Nature Reviews Neuroscience thanks K. Friston, J. González-Maeso, M Johnson, M. Massimini and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


Substance-assisted psychotherapy

A therapy model that refers to the adjuvant use of one or a few doses of a classic psychedelic in combination with psychotherapeutic support. The process will commonly include a few drug-free preparation sessions, followed by a drug session and a few follow-up integration sessions of the psychedelic experience.

Positron emission tomography

A nuclear medicine functional imaging technique that uses radioligands to assess metabolic processes and receptor density and occupancy in the brain.

Excitatory postsynaptic potentials

Temporary depolarizations of the postsynaptic neuronal membrane potential that make it more likely that the neuron will exert an action potential.

Recurrent network activity

A self-generated network activity that arises from the recurrent synaptic architecture of the cortex. One form of such activity is the up state, in which neurons transiently receive bombardments of excitatory and inhibitory synaptic inputs that depolarize many neurons to the spike threshold before returning to a relatively quiescent down state.

Neuroplastic adaptions

The brain’s ability to reorganize itself by forming new neural connections throughout life. Neuroplasticity allows the neurons in the brain to compensate for injury and disease, and to adjust their activities in response to new situations or to changes in their environment.

Long-term depression

Long-lasting, activity-dependent decreases in synaptic strength.

Functional MRI

(fMRI). A neuroimaging technique that measures brain activity by detecting changes associated with blood flow.

Dynamic causal modelling

A framework for inferring the causal architecture of coupled or distributed dynamic systems, which allows the coupling between brain regions to be estimated.


The prior probability distributions in Bayesian statistical inference, which express one’s beliefs before some evidence is taken into account.

Arterial spin labelling

An imaging method used to quantify cerebral blood perfusion by magnetic labelling of arterial blood.

Blood oxygen level-dependent signal

A signal detected in functional MRI and used to investigate regional brain activity changes.

Intrinsic brain networks

Brain networks determined by their spatially independent and temporally correlated functional connectivity.

Default mode network

(DMN). A brain network consisting of various large regions, such as the posterior cingulate cortex, precuneus, medial prefrontal cortex and angular gyrus.

Selective serotonin reuptake inhibitors

A class of drugs increasing the level of serotonin by inhibiting the reuptake into the presynaptic cell, used to treat depression and anxiety disorders.

Predictive processing

A framework that views the brain as an organ of inference that is constantly generating and updating a mental model of the environment.


A measure of uncertainty about a dynamical phenomenon (in this context, neuronal fluctuations across time).


An imaging technique used to map brain activity by recording magnetic fields produced by electrical currents in the brain.


An electrophysiological imaging method that records the electrical activity of the brain using electrodes placed on the scalp.

Alpha oscillations

Neural oscillations in the frequency range of 8–12 Hz that can be measured using electroencephalography or magnetoencephalography.


A perceptual phenomenon in which stimulation of one sensory modality leads to experiences in a second sensory modality.

Pharmacological challenge studies

Studies involving the administration of a pharmacological substance.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Vollenweider, F.X., Preller, K.H. Psychedelic drugs: neurobiology and potential for treatment of psychiatric disorders. Nat Rev Neurosci 21, 611–624 (2020).

Download citation

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing