Advertisement

Psychopharmacology

, Volume 230, Issue 3, pp 415–424 | Cite as

Acute effects of ayahuasca on neuropsychological performance: differences in executive function between experienced and occasional users

  • José Carlos Bouso
  • Josep Maria Fábregas
  • Rosa Maria Antonijoan
  • Antoni Rodríguez-Fornells
  • Jordi Riba
Original Investigation

Abstract

Background

Ayahuasca, a South American psychotropic plant tea containing the psychedelic 5-HT2A receptor agonist N,N-dimethyltryptamine, has been shown to increase regional cerebral blood flow in prefrontal brain regions after acute administration to humans. Despite interactions at this level, neuropsychological studies have not found cognitive deficits in abstinent long-term users.

Objectives

Here, we wished to investigate the effects of acute ayahuasca intake on neuropsychological performance, specifically on working memory and executive function.

Methods

Twenty-four ayahuasca users (11 long-term experienced users and 13 occasional users) were assessed in their habitual setting using the Stroop, Sternberg, and Tower of London tasks prior to and following ayahuasca intake.

Results

Errors in the Sternberg task increased, whereas reaction times in the Stroop task decreased and accuracy was maintained for the whole sample following ayahuasca intake. Interestingly, results in the Tower of London showed significantly increased execution and resolution times and number of movements for the occasional but not the experienced users. Additionally, a correlation analysis including all subjects showed that impaired performance in the Tower of London was inversely correlated with lifetime ayahuasca use.

Conclusions

Acute ayahuasca administration impaired working memory but decreased stimulus–response interference. Interestingly, detrimental effects on higher cognition were only observed in the less experienced group. Rather than leading to increased impairment, greater prior exposure to ayahuasca was associated with reduced incapacitation. Compensatory or neuromodulatory effects associated with long-term ayahuasca intake could underlie preserved executive function in experienced users.

Keywords

Psychedelics Ayahuasca Neuropsychology Executive functions 

Notes

Acknowledgments

We wish to thank the study volunteers for their participation. The present study was funded in part by a grant from the Spanish Plan Nacional Sobre Drogas PNSD 2006/074.

References

  1. Abdullaev Y, Posner MI, Nunnally R, Dishion TJ (2010) Functional MRI evidence for inefficient attentional control in adolescent chronic cannabis abuse. Behav Brain Res 215:45–57PubMedCrossRefGoogle Scholar
  2. Aghajanian GK, Marek GJ (1997) Serotonin induces excitatory postsynaptic potentials in apical dendrites of neocortical pyramidal cells. Neuropharmacol 36:589–599CrossRefGoogle Scholar
  3. Béïque JC, Imad M, Mladenovic L, Gingrich JA, Andrade R (2007) Mechanism of the 5-hydroxytryptamine 2A receptor-mediated facilitation of synaptic activity in prefrontal cortex. Proc Natl Acad Sci U S A 104:9870–9875PubMedCrossRefGoogle Scholar
  4. Bouso JC, González D, Fondevila S, Cutchet M, Fernández X, Ribeiro Barbosa PC, Alcázar-Córcoles MÁ, Araújo WS, Barbanoj MJ, Fábregas JM, Riba J (2012) Personality, psychopathology, life attitudes, and neuropsychological performance among ritual users of ayahuasca: a longitudinal study. PLOS ONE 7:e42421Google Scholar
  5. Bramham CR, Messaoudi E (2005) BDNF function in adult synaptic plasticity: the synaptic consolidation hypothesis. Prog Neurobiol 76:99–125PubMedCrossRefGoogle Scholar
  6. Carhart-Harris RL, Leech R, Erritzoe D, Williams TM, Stone JM, Evans J, Sharp DJ, Feilding A, Wise RG, Nutt DJ (2012a) Functional connectivity measures after psilocybin inform a novel hypothesis of early psychosis. Schizophr Bull. doi: 10.1093/schbul/sbs117 PubMedGoogle Scholar
  7. Carhart-Harris RL, Erritzoe D, Williams T, Stone JM, Reed LJ, Colasanti A, Tyacke RJ, Leech R, Malizia AL, Murphy K, Hobden P, Evans J, Feilding A, Wise RG, Nutt DJ (2012b) Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proc Natl Acad Sci USA 109(6):2138–2143PubMedCrossRefGoogle Scholar
  8. Carter CS, van Veen V (2007) Anterior cingulate cortex and conflict detection: an update of theory and data. Cogn Affect Behav Neurosci 7:367–379PubMedCrossRefGoogle Scholar
  9. Carter OL, Pettigrew JD, Burr DC, Alais D, Hasler F, Vollenweider FX (2004) Psilocybin impairs high-level but not low-level motion perception. Neuroreport 15:1947–1951PubMedCrossRefGoogle Scholar
  10. Carter OL, Burr DC, Pettigrew JD, Wallis GM, Hasler F, Vollenweider FX (2005a) Using psilocybin to investigate the relationship between attention, working memory, and the serotonin 1A and 2A receptors. J Cogn Neurosci 17:1497–1508PubMedCrossRefGoogle Scholar
  11. Carter OL, Pettigrew JD, Hasler F, Wallis GM, Liu GB, Hell D, Vollenweider FX (2005b) Modulating the rate and rhythmicity of perceptual rivalry alternations with the mixed 5-HT2A and 5-HT1A agonist psilocybin. Neuropsychopharmacology 30:1154–1162PubMedCrossRefGoogle Scholar
  12. Carter OL, Hasler F, Pettigrew JD, Wallis GM, Liu GB, Vollenweider FX (2007) Psilocybin links binocular rivalry switch rate to attention and subjective arousal levels in humans. Psychopharmacology (Berl) 195:415–424CrossRefGoogle Scholar
  13. Daumann J, Heekeren K, Neukirch A, Thiel CM, Möller-Hartmann W, Gouzoulis-Mayfrank E (2008) Pharmacological modulation of the neural basis underlying inhibition of return (IOR) in the human 5-HT2A agonist and NMDA antagonist model of psychosis. Psychopharmacology (Berl) 200:573–583CrossRefGoogle Scholar
  14. Daumann J, Wagner D, Heekeren K, Neukirch A, Thiel CM, Gouzoulis-Mayfrank E (2010) Neuronal correlates of visual and auditory alertness in the DMT and ketamine model of psychosis. J Psychopharmacol 24:1515–1524PubMedCrossRefGoogle Scholar
  15. de Almeida J, Mengod G (2007) Quantitative analysis of glutamatergic and GABAergic neurons expressing 5-HT(2A) receptors in human and monkey prefrontal cortex. J Neurochem 103:475–486PubMedCrossRefGoogle Scholar
  16. D’Esposito M, Postle BR, Rypma B (2000) Prefrontal cortical contributions to working memory: evidence from event-related fMRI studies. Exp Brain Res 133:3–11PubMedCrossRefGoogle Scholar
  17. del Ser T, García-Montalvo JI, Martínez Espinosa S, Delgado-Villapalos C, Bermejo F (1997) The estimation of premorbid intelligence in Spanish people with the «Word Accentuation Test» and its application to the diagnosis of dementia. Brain Cogn 33:343–356PubMedCrossRefGoogle Scholar
  18. Dockery CA, Hueckel-Weng R, Birbaumer N, Plewnia C (2009) Enhancement of planning ability by transcranial direct current stimulation. J Neurosci 29:7271–7277PubMedCrossRefGoogle Scholar
  19. dos Santos R, Valle M, Bouso JC, Nomdedéu JF, Rodríguez-Espinosa J, McIlhenny EH, Barker SA, Barbanoj MJ, Riba J (2011) Autonomic, neuroendocrine, and immunological effects of ayahuasca: a comparative study with d-amphetamine. J Clin Psychopharmacol 31:717–726PubMedCrossRefGoogle Scholar
  20. dos Santos RG, Grasa E, Valle M, Ballester MR, Bouso JC, Nomdedéu JF, Homs R, Barbanoj MJ, Riba J (2012) Pharmacology of ayahuasca administered in two repeated doses. Psychopharmacology (Berl) 219:1039–1053CrossRefGoogle Scholar
  21. Frankel PS, Cunningham KA (2002) The hallucinogen d-lysergic acid diethylamide (d-LSD) induces the immediate-early gene c-Fos in rat forebrain. Brain Res 958:251–260PubMedCrossRefGoogle Scholar
  22. Frecska E, White KD, Luna LE (2004) Effects of ayahuasca on binocular rivalry with dichoptic stimulus alternation. Psychopharmacology (Berl) 173:79–87CrossRefGoogle Scholar
  23. Geyer MA, Vollenweider FX (2008) Serotonin research: contributions to understanding psychoses. Trends Pharmacol Sci 29:445–453PubMedCrossRefGoogle Scholar
  24. Gewirtz JC, Chen AC, Terwilliger R, Duman RC, Marek GJ (2002) Modulation of DOI-induced increases in cortical BDNF expression by group II mGlu receptors. Pharmacol Biochem Behav 73:317–326PubMedCrossRefGoogle Scholar
  25. Golden CJ (1978) Stroop color and word test. A manual for clinical and experimental uses. Illinois: Stoelting Co, Wood DaleGoogle Scholar
  26. González-Maeso J, Sealfon SC (2009a) Psychedelics and schizophrenia. Trends Neurosci 32:225–232PubMedCrossRefGoogle Scholar
  27. González-Maeso J, Sealfon SC (2009b) Agonist-trafficking and hallucinogens. Curr Med Chem 16:1017–1027PubMedCrossRefGoogle Scholar
  28. Gouzoulis-Mayfrank E, Habermeyer E, Hermle L, Steinmeyer A, Kunert H, Sass H (1998a) Hallucinogenic drug-induced states resemble acute endogenous psychoses: results of an empirical study. Eur Psychiatry 13:399–406PubMedCrossRefGoogle Scholar
  29. Gouzoulis-Mayfrank E, Heekeren K, Thelen B, Lindenblatt H, Kovar KA, Sass H, Geyer MA (1998b) Effects of the hallucinogen psilocybin on habituation and prepulse inhibition of the startle reflex in humans. Behav Pharmacol 9:561–566PubMedCrossRefGoogle Scholar
  30. Gouzoulis-Mayfrank E, Schreckenberger M, Sabri O, Arning C, Thelen B, Spitzer M, Kovar KA, Hermle L, Büll U, Sass H. (1999a) 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 20:565-81Google Scholar
  31. Gouzoulis-Mayfrank E, Thelen B, Habermeyer E, Kunert HJ, Kovar KA, Lindenblatt H, Hermle L, Spitzer M, Sass H (1999b) Psychopathological, neuroendocrine, and autonomic effects of 3,4-methylenedioxyethylamphetamine (MDE), psilocybin and d-methamphetamine in healthy volunteers. Results of an experimental double-blind placebo-controlled study. Psychopharmacology (Berl) 142:41–50CrossRefGoogle Scholar
  32. Gouzoulis-Mayfrank E, Thelen B, Maier S, Heekeren K, Kovar KA, Sass H, Spitzer M (2002) Effects of the hallucinogen psilocybin on covert orienting of visual attention in humans. Neuropsychobiology 45:205–212PubMedCrossRefGoogle Scholar
  33. Gouzoulis-Mayfrank E, Heekeren K, Neukirch A, Stoll M, Stock C, Daumann J, Obradovic M, Kovar KA (2006) Inhibition of return in the human 5HT2A agonist and NMDA antagonist model of psychosis. Neuropsychopharmacology 31:431–441PubMedCrossRefGoogle Scholar
  34. Gresch PJ, Strickland LV, Sanders-Bush E (2002) Lysergic acid diethylamide-induced Fos expression in rat brain: role of serotonin-2A receptors. Neuroscience 114:707–713PubMedCrossRefGoogle Scholar
  35. Halberstadt AL, Koedood L, Powell SB, Geyer MA (2011) Differential contributions of serotonin receptors to the behavioral effects of indoleamine hallucinogens in mice. J Psychopharmacol 25:1548–1561PubMedCrossRefGoogle Scholar
  36. Hannon J, Hoyer D (2008) Molecular biology of 5-HT receptors. Behav Brain Res 195:198–213PubMedCrossRefGoogle Scholar
  37. Harding IH, Solowij N, Harrison BJ, Takagi M, Lorenzetti V, Lubman DI, Seal ML, Pantelis C, Yücel M (2012) Functional connectivity in brain networks underlying cognitive control in chronic cannabis users. Neuropsychopharmacology 37:1923–1933PubMedCrossRefGoogle Scholar
  38. Hart CL, van Gorp W, Haney M, Foltin RW, Fischman MW (2001) Effects of acute smoked marijuana on complex cognitive performance. Neuropsychopharmacology 25:757–765PubMedCrossRefGoogle Scholar
  39. Hart CL, Ilan AB, Gevins A, Gunderson EW, Role K, Colley J, Foltin RW (2010) Neurophysiological and cognitive effects of smoked marijuana in frequent users. Pharmacol Biochem Behav 96:333–341PubMedCrossRefGoogle Scholar
  40. Hasler F, Grimberg U, Benz MA, Huber T, Vollenweider FX (2004) Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose-effect study. Psychopharmacology (Berl) 172:145–156CrossRefGoogle Scholar
  41. Heekeren K, Daumann J, Neukirch A, Stock C, Kawohl W, Norra C, Waberski TD, Gouzoulis-Mayfrank E (2008) Mismatch negativity generation in the human 5HT2A agonist and NMDA antagonist model of psychosis. Psychopharmacology (Berl) 199:77–88CrossRefGoogle Scholar
  42. Hermle L, Fünfgeld M, Oepen G, Botsch H, Borchardt D, Gouzoulis E, Fehrenbach RA, Spitzer M (1992) Mescaline-induced psychopathological, neuropsychological, and neurometabolic effects in normal subjects: experimental psychosis as a tool for psychiatric. Biol Psychiatry 32:976–991PubMedCrossRefGoogle Scholar
  43. Jocham G, Ullsperger M (2009) Neuropharmacology of performance monitoring. Neurosci Biobehav Rev 33:48–60PubMedCrossRefGoogle Scholar
  44. Kirschen MP, Chen SH, Desmond JE (2010) Modality specific cerebrocerebellar activations in verbal working memory: an fMRI study. Behav Neurol 23:51–63PubMedGoogle Scholar
  45. Klodzinska A, Bijak M, Tokarski K, Pilc A (2002) Group II mGlu receptor agonists inhibit behavioral and electrophysiological effects of DOI in mice. Pharmacol Biochem Behav 73:327–332PubMedCrossRefGoogle Scholar
  46. Kometer M, Cahn BR, Andel D, Carter OL, Vollenweider FX (2011) The 5-HT2A/1A agonist psilocybin disrupts modal object completion associated with visual hallucinations. Biol Psychiatry 69:399–406PubMedCrossRefGoogle Scholar
  47. Lazaron RHC, Rombouts SARB, Machielsen WCM, Scheltens P, Menno P, Witter Uylings HBM, Barkhof F (2000) Visualizing brain activation during planning: The Tower of London Test adapted for functional MR imaging, AJNR Am. J Neuroradiol 21:1407–1414Google Scholar
  48. Lane HY, Liu YC, Huang CL, Hsieh CL, Chang YL, Chang L, Chang YC, Chang WH (2008) Prefrontal executive function and D1, D3, 5-HT2A, and 5-HT6 receptor gene variations in healthy adults. J Psychiatry Neurosci 33:47–53PubMedGoogle Scholar
  49. Miller EK, Cohen JD (2001) An integrative theory of prefrontal cortex function. Annu Rev Neurosci 24:167–202PubMedCrossRefGoogle Scholar
  50. Nelson H, O’Connell A (1978) Dementia: the estimation of premorbid intelligence levels using the new Adult Reading Test. Cortex 14:234–244PubMedCrossRefGoogle Scholar
  51. Passetti F, Dalley JW, Robbins TW (2003) Double dissociation of serotonergic and dopaminergic mechanisms on attentional performance using a rodent five-choice reaction time task. Psychopharmacology (Berl) 165:136–145Google Scholar
  52. Riba J (2003) Human Pharmacology of Ayahuasca, doctoral thesis, Universitat Autònoma de Barcelona, 2003. http://www.tdx.cat/handle/10803/5378 [23 January 2013].
  53. Riba J, Rodríguez-Fornells A, Urbano G, Morte A, Antonijoan R, Montero M, Callaway JC, Barbanoj MJ (2001) Subjective effects and tolerability of the South American psychoactive beverage ayahuasca in healthy volunteers. Psychopharmacology 154:85–95Google Scholar
  54. Riba J, Anderer P, Morte A, Urbano G, Jane F, Saletu B, Barbanoj MJ (2002) Topographic pharmaco-EEG mapping of the effects of the South American psychoactive beverage ayahuasca in healthy volunteers. Br J Clin Pharmacol 53:613–628PubMedCrossRefGoogle Scholar
  55. Riba J, Valle M, Urbano G, Yritia M, Morte A, Barbanoj MJ (2003) Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics. J Pharmacol Exp Ther 306:73–83PubMedCrossRefGoogle Scholar
  56. Riba J, Romero S, Grasa E, Mena E, Carrió I, Barbanoj MJ (2006) Increased frontal and paralimbic activation following ayahuasca, the pan-Amazonian inebriant. Psychopharmacology (Berl) 186:93–98CrossRefGoogle Scholar
  57. Robbins TW, Arnsten AF (2009) The neuropsychopharmacology of fronto-executive function: monoaminergic modulation. Annu Rev Neurosci 32:267–287PubMedCrossRefGoogle Scholar
  58. Schall U et al (2003) Functional brain maps of Tower of London performance: a positron emission tomography and functional magnetic resonance imaging study. NeuroImage 20:1154–1161PubMedCrossRefGoogle Scholar
  59. Shallice T (1982) Specific impairments of planning. Phil Trans R Soc Lond 298:199–209CrossRefGoogle Scholar
  60. Soulé J, Messaoudi E, Bramham CR (2006) Brain-derived neurotrophic factor and control of synaptic consolidation in the adult brain. Biochem Soc Trans 34:600–604PubMedCrossRefGoogle Scholar
  61. Spitzer M, Thimm M, Hermle L, Holzmann P, Kovar KA, Heimann H, Gouzoulis-Mayfrank E, Kischka U, Schneider F (1996) Increased activation of indirect semantic associations under psilocybin. Biol Psychiatry 39:1055–1057PubMedCrossRefGoogle Scholar
  62. Sternberg S (1966) High-speed scanning in human memory. Science 153:652–654PubMedCrossRefGoogle Scholar
  63. Strassman RJ, Qualls CR, Uhlenhuth EH, Kellner R (1994) Dose–response study of N, N-dimethyltryptamine in humans, II. Subjective effects and preliminary results of a new rating scale. Arch Gen Psychiatry 51:98–108PubMedCrossRefGoogle Scholar
  64. Studerus E, Kometer M, Hasler F, Vollenweider FX (2011) Acute, subacute, and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies. J Psychopharmacol 25:1434–1452PubMedCrossRefGoogle Scholar
  65. Strauss E, Sherman EMS, Spreen O (2006) A compendium of neuropsychological tests: administration, norms, and commentary. Oxford University Press, Oxford; New YorkGoogle Scholar
  66. Tapert SF, Schweinsburg AD, Drummond SP, Paulus MP, Brown SA, Yang TT, Frank LR (2007) Functional MRI of inhibitory processing in abstinent adolescent marijuana users. Psychopharmacology (Berl) 194:173–183CrossRefGoogle Scholar
  67. Umbricht D, Vollenweider FX, Schmid L, Grübel C, Skrabo A, Huber T, Koller R (2003) 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 28:170–181PubMedCrossRefGoogle Scholar
  68. Vaidya VA, Marek GJ, Aghajanian GK, Duman RS (1997) 5-HT2A receptor-mediated regulation of brain-derived neurotrophic factor mRNA in the hippocampus and the neocortex. J Neurosci 17:2785–2795PubMedGoogle Scholar
  69. Vollenweider FX, Kometer M (2010) The neurobiology of psychedelic drugs: implications for the treatment of mood disorders. Nat Rev Neurosci 11:642–651PubMedCrossRefGoogle Scholar
  70. Vollenweider FX, Leenders KL, Scharfetter C, Maguire P, Stadelmann O, Angst J (1997) Positron emission tomography and fluorodeoxyglucose studies of metabolic hyperfrontality and psychopathology in the psilocybin model of psychosis. Neuropsychopharmacology 16:357–372PubMedCrossRefGoogle Scholar
  71. Vollenweider FX, Vollenweider-Scherpenhuyzen MF, Bäbler A, Vogel H, Hell D (1998) Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Neuroreport 9:3897–3902PubMedCrossRefGoogle Scholar
  72. Vollenweider FX, Csomor PA, Knappe B, Geyer MA, Quednow BB (2007) The effects of the preferential 5-HT2A agonist psilocybin on prepulse inhibition of startle in healthy human volunteers depend on interstimulus interval. Neuropsychopharmacology 32:1876–1887PubMedCrossRefGoogle Scholar
  73. Wackermann J, Wittmann M, Hasler F, Vollenweider FX (2008) Effects of varied doses of psilocybin on time interval reproduction in human subjects. Neurosci Lett 435:51–55PubMedCrossRefGoogle Scholar
  74. Wechsler D (1997) Wechsler Adult Intelligence Scale-III (WAIS-III). The Psychological Corporation, San Antonio, TXGoogle Scholar
  75. Williams GV, Srinivas GR, Goldman-Rakic PS (2002) The pshysiological role of the 5-HT2A in working memory. J Neurosci 22:2843–2854PubMedGoogle Scholar
  76. Wittmann M, Carter O, Hasler F, Cahn BR, Grimberg U, Spring P, Hell D, Flohr H, Vollenweider FX (2007) Effects of psilocybin on time perception and temporal control of behavior in humans. J Psychopharmacol 21:50–64PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • José Carlos Bouso
    • 1
    • 2
    • 3
    • 5
  • Josep Maria Fábregas
    • 6
    • 7
  • Rosa Maria Antonijoan
    • 2
    • 3
    • 4
  • Antoni Rodríguez-Fornells
    • 8
    • 9
    • 10
  • Jordi Riba
    • 1
    • 2
    • 3
    • 4
  1. 1.Human Experimental NeuropsychopharmacologySant Pau Institute of Biomedical Research (IIB-Sant Pau)BarcelonaSpain
  2. 2.Centre d’Investigació de Medicaments. Servei de Farmacologia ClínicaHospital de la Santa Creu i Sant PauBarcelonaSpain
  3. 3.Departament de Farmacologia i TerapèuticaUniversitat Autònoma de BarcelonaCataloniaSpain
  4. 4.Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM
  5. 5.ICEERS—International Center for Ethnobotanical Education, Research, and ServiceHalsterenThe Netherlands
  6. 6.Centre d’Investigació i Tractament d’Addiccions (CITA)BarcelonaSpain
  7. 7.Institut d’Etnospicologia Amazonica AplicadaAmazonasBrazil
  8. 8.Cognition and Brain Plasticity GroupBellvitge Biomedical Research Institute (IDIBELL)BarcelonaSpain
  9. 9.Department of Basic PsychologyUniversity of BarcelonaBarcelonaSpain
  10. 10.Catalan Institution for Research and Advanced StudiesICREABarcelonaSpain

Personalised recommendations