Psychopharmacology

, Volume 232, Issue 4, pp 785–794 | Cite as

LSD enhances suggestibility in healthy volunteers

  • R. L. Carhart-Harris
  • M. Kaelen
  • M. G. Whalley
  • M. Bolstridge
  • A. Feilding
  • D. J. Nutt
Original Investigation

Abstract

Rationale

Lysergic acid diethylamide (LSD) has a history of use as a psychotherapeutic aid in the treatment of mood disorders and addiction, and it was also explored as an enhancer of mind control.

Objectives

The present study sought to test the effect of LSD on suggestibility in a modern research study.

Methods

Ten healthy volunteers were administered with intravenous (i.v.) LSD (40–80 μg) in a within-subject placebo-controlled design. Suggestibility and cued mental imagery were assessed using the Creative Imagination Scale (CIS) and a mental imagery test (MIT). CIS and MIT items were split into two versions (A and B), balanced for ‘efficacy’ (i.e. A≈B) and counterbalanced across conditions (i.e. 50 % completed version ‘A’ under LSD). The MIT and CIS were issued 110 and 140 min, respectively, post-infusion, corresponding with the peak drug effects.

Results

Volunteers gave significantly higher ratings for the CIS (p = 0.018), but not the MIT (p = 0.11), after LSD than placebo. The magnitude of suggestibility enhancement under LSD was positively correlated with trait conscientiousness measured at baseline (p = 0.0005).

Conclusions

These results imply that the influence of suggestion is enhanced by LSD. Enhanced suggestibility under LSD may have implications for its use as an adjunct to psychotherapy, where suggestibility plays a major role. That cued imagery was unaffected by LSD implies that suggestions must be of a sufficient duration and level of detail to be enhanced by the drug. The results also imply that individuals with high trait conscientiousness are especially sensitive to the suggestibility-enhancing effects of LSD.

Keywords

Serotonin Hallucinogens Psychedelics LSD Suggestibility Hypnosis 

Supplementary material

213_2014_3714_MOESM1_ESM.docx (29 kb)
ESM 1(DOCX 29 kb)

References

  1. Abramson HA (1967). The use of LSD in psychotherapy and alcoholism. edn. [s.n.]: Indianapolis.Google Scholar
  2. Barber TX (1995). Hypnosis: a scientific approach. edn. J. Aronson: Northvale, N.J.;; London.Google Scholar
  3. Barber TX, Wilson SC (1978) The Barber Suggestibility Scale and the Creative Imagination Scale: experimental and clinical applications. Am J Clin Hypn 21(2–3):84–108PubMedCrossRefGoogle Scholar
  4. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571PubMedCrossRefGoogle Scholar
  5. Blazhenkova O, Kozhevnikov M (2010) Visual-object ability: a new dimension of non-verbal intelligence. Cognition 117(3):276–301PubMedCrossRefGoogle Scholar
  6. Boulougouris V, Glennon JC, Robbins TW (2008) Dissociable effects of selective 5-HT2A and 5-HT2C receptor antagonists on serial spatial reversal learning in rats. Neuropsychopharmacol : Off Publ Am Coll Neuropsychopharmacol 33(8):2007–2019CrossRefGoogle Scholar
  7. Braffman W, Kirsch I (1999) Imaginative suggestibility and hypnotizability: an empirical analysis. J Pers Soc Psychol 77(3):578–587PubMedCrossRefGoogle Scholar
  8. Carhart-Harris R (2013) Is the brainstem really sufficient for a consciousness that would have interested Freud? Neuropsychoanal 15(1):29–32CrossRefGoogle Scholar
  9. Carhart-Harris RL, Friston KJ (2010) The default-mode, ego-functions and free-energy: a neurobiological account of Freudian ideas. Brain : J Neurol 133(Pt 4):1265–1283CrossRefGoogle Scholar
  10. Carhart-Harris RL, Williams TM, Sessa B, Tyacke RJ, Rich AS et al (2011) The administration of psilocybin to healthy, hallucinogen-experienced volunteers in a mock-functional magnetic resonance imaging environment: a preliminary investigation of tolerability. J Psychopharmacol 25:1562–67PubMedCrossRefGoogle Scholar
  11. Carhart-Harris RL, Leech R, Williams TM, Erritzoe D, Abbasi N, Bargiotas T et al (2012) Implications for psychedelic-assisted psychotherapy: functional magnetic resonance imaging study with psilocybin. Br J Psychiatr: J Mental Sci 200(3):238–244CrossRefGoogle Scholar
  12. Carhart-Harris RL, Leech R, Tagliazucchi E, Hellyer PJ, Chialvo DR, Feilding A et al (2014) The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs. Front Hum Neurosci 8:20PubMedCentralPubMedCrossRefGoogle Scholar
  13. Carter OL, Burr DC, Pettigrew JD, Wallis GM, Hasler F, Vollenweider FX (2005) Using psilocybin to investigate the relationship between attention, working memory, and the serotonin 1A and 2A receptors. J Cogn Neurosci 17(10):1497–1508PubMedCrossRefGoogle Scholar
  14. Cohen S (1964) The beyond within; the LSD story, 1st edn. Atheneum, New YorkGoogle Scholar
  15. Crawford HJ, Knebel T, Vendemia JMC (1998) The nature of hypnotic analgesia: neurophysiological foundation and evidence. Contemporary Hypnosis 15:24–35Google Scholar
  16. de Araujo DB, Ribeiro S, Cecchi GA, Carvalho FM, Sanchez TA, Pinto JP et al (2012) Seeing with the eyes shut: neural basis of enhanced imagery following ayahuasca ingestion. Hum Brain Mapp 33(11):2550–2560PubMedCrossRefGoogle Scholar
  17. Dienes Z, Hutton S (2013) Understanding hypnosis metacognitively: rTMS applied to left DLPFC increases hypnotic susceptibility. Cortex 49:386–392Google Scholar
  18. Dienes Z, Brown E, Hutton S, Kirsch I, Mazzoni G, Wright DB (2009) Hypnotic suggestibility, cognitive inhibition, and dissociation. Consciousness and cognition 18(4):837–847Google Scholar
  19. Eysenck HJ, Furneaux WD (1945) Primary and secondary suggestibility; an experimental and statistical study. J Exp Psychol 35:485–503PubMedCrossRefGoogle Scholar
  20. Fabing HD (1955) New blocking agent against the development of LSD-25 psychosis. Science 121(3137):208–210PubMedCrossRefGoogle Scholar
  21. Gasser P, Holstein D, Michel Y, Doblin R, Yazar-Klosinski B, Passie T, et al. (2014). Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases. J Nerv Mental Dis 202(7):513–20Google Scholar
  22. Gelade GA (1997) Creativity in conflict: the personality of the commercial creative. J Genet Psychol 158(1):67–78PubMedCrossRefGoogle Scholar
  23. 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(2):317–326PubMedCrossRefGoogle Scholar
  24. Glennon RA, Titeler M, McKenney JD (1984) Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sci 35(25):2505–2511PubMedCrossRefGoogle Scholar
  25. Griffiths RR, Grob CS (2010) Hallucinogens as medicine. Sci Am 303(6):76–79CrossRefGoogle Scholar
  26. Grob CS, Danforth AL, Chopra GS, Hagerty M, McKay CR, Halberstadt AL et al (2011) Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry 68(1):71–78PubMedCrossRefGoogle Scholar
  27. Grof S (1980) LSD Psychotherapy. Hunter House, USGoogle Scholar
  28. Gudjonsson GH (1983) Suggestibility, intelligence, memory recall and personality: an experimental study. Br J Psychiatr: J Mental Sci 142:35–37CrossRefGoogle Scholar
  29. Gudjonsson G (2003) The psychology of interrogations and confessions. Wiley, New YorkGoogle Scholar
  30. Halberstadt AL, Geyer MA (2011) Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens. Neuropharmacology 61(3):364–381PubMedCentralPubMedCrossRefGoogle Scholar
  31. Harvey JA (2003) Role of the serotonin 5-HT(2A) receptor in learning. Learn Mem 10(5):355–362PubMedCentralPubMedCrossRefGoogle Scholar
  32. Hilgard ER (1986) Divided consciousness: multiple controls in human thought and action. Am J Psychol 91(3):545–547Google Scholar
  33. Hofmann A (1980) LSD: my problem child. McGraw-Hill, New YorkGoogle Scholar
  34. Hull CL (1933). Hypnosis and suggestibility: an experimental approach. edn. Appleton: [S.l.].Google Scholar
  35. Jamieson G (1987). The structure and meaning of absorption: Phd thesisGoogle Scholar
  36. Johnson M, Richards W, Griffiths R (2008) Human hallucinogen research: guidelines for safety. J Psychopharmacol 22(6):603–620PubMedCentralPubMedCrossRefGoogle Scholar
  37. Josiah Macy JF, Abramson HA (1960) The Use of LSD in Psychotherapy. Transactions of a conference on d-lysergic acid diethylamide, LSD-25, April 22, 23 and 24, 1959. Princeton, N.J. Edited by Harold A. Abramson. edn. New YorkGoogle Scholar
  38. King AR, Martin IL, Melville KA (1974) Reversal learning enhanced by lysergic acid diethylamide (LSD): concomitant rise in brain 5-hydroxytryptamine levels. Br J Pharmacol 52(3):419–426PubMedCentralPubMedCrossRefGoogle Scholar
  39. Kirsch I, Low CB (2013) Suggestion in the treatment of depression. Am J Clin Hypn 55(3):221–229PubMedCrossRefGoogle Scholar
  40. Krebs TS, Johansen PO (2012) Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. J Psychopharmacol 26(7):994–1002PubMedCrossRefGoogle Scholar
  41. Marks J (1979). The search for the “Manchurian candidate”: the CIA and mind control. edn. Norton, 1991: New York;; LondonGoogle Scholar
  42. McConkey KM, Sheehan PW, White KD (1979) Comparison of the Creative Imagination Scale and the Harvard Group Scale of Hypnotic Susceptibility, form A. Int J Clin Exp Hypn 27(3):265–277PubMedCrossRefGoogle Scholar
  43. McCrae RR, Costa PT Jr (1987) Validation of the five-factor model of personality across instruments and observers. J Pers Soc Psychol 52(1):81–90PubMedCrossRefGoogle Scholar
  44. Middlefell R (1967) The effects of LSD on body sway suggestibility in a group of hospital patients. Br J Psychiatr : J Mental Sci 113(496):277–280CrossRefGoogle Scholar
  45. Muthukumaraswamy SD, Carhart-Harris RL, Moran RJ, Brookes MJ, Williams TM, Errtizoe D et al (2013) Broadband cortical desynchronization underlies the human psychedelic state. J Neurosci : Off J Soc Neurosci 33(38):15171–15183CrossRefGoogle Scholar
  46. Nichols DE (2004) Hallucinogens. Pharmacol Ther 101(2):131–181PubMedCrossRefGoogle Scholar
  47. Nutt DJ, King LA, Nichols DE (2013) Effects of schedule I drug laws on neuroscience research and treatment innovation. Nat Rev Neurosci 14(8):577–585PubMedCrossRefGoogle Scholar
  48. Ott U, Reuter M, Hennig J, Vaitl D (2005) Evidence for a common biological basis of the absorption trait, hallucinogen effects, and positive symptoms: epistasis between 5-HT2a and COMT polymorphisms. Am J Med Genet B Neuropsychiatr Genet : Off Publ Int Soc Psychiatr Genet 137B(1):29–32CrossRefGoogle Scholar
  49. Paddock JR, Terranova S (2001) Guided visualization and suggestibility: effect of perceived authority on recall of autobiographical memories. J Genet Psychol 162(3):347–356PubMedCrossRefGoogle Scholar
  50. Panksepp J, Solms M (2012) What is neuropsychoanalysis? Clinically relevant studies of the minded brain. Trends Cogn Sci 16(1):6–8PubMedCrossRefGoogle Scholar
  51. Patterson DR, Jensen MP (2003) Hypnosis and clinical pain. Psychological Bulletin 129(4):495–521Google Scholar
  52. Raz A, Shapiro T, Fan J, Posner MI (2002) Hypnotic suggestion and the modulation of Stroop interference. Arch Gen Psychiatry 59(12):1155–1161PubMedCrossRefGoogle Scholar
  53. Romano AG, Quinn JL, Li L, Dave KD, Schindler EA, Aloyo VJ et al (2010) Intrahippocampal LSD accelerates learning and desensitizes the 5-HT(2A) receptor in the rabbit, Romano et al. Psychopharmacology 212(3):441–448PubMedCrossRefGoogle Scholar
  54. Roseman L, Leech R, Nutt DJ, Feilding A, Carhart-Harris RL (2014). The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers. Front Hum Neurosci 8:204. doi:10.3389/fnhum.2014.00204
  55. Rosen GM, Sageman M, Loftus E (2004) A historical note on false traumatic memories. J Clin Psychol 60:137–9PubMedCrossRefGoogle Scholar
  56. Sandison RA, Whitelaw JD (1957) Further studies in the therapeutic value of lysergic acid diethylamide in mental illness. J Mental Sci 103(431):332–343Google Scholar
  57. Savage C (1957) The resolution and subsequent remobilization of resistance by LSD in psychotherapy. J Nerv Ment Dis 125(3):434–437PubMedCrossRefGoogle Scholar
  58. Semmens-Wheeler R, Dienes Z, Duka T (2013) Alcohol increases hypnotic susceptibility. Consciousness and Cognition 22:1082–1091Google Scholar
  59. Sessa B (2005) Can psychedelics have a role in psychiatry once again? Brit J Psychiatr 186:457–458CrossRefGoogle Scholar
  60. Sheehan PW (1967) A shortened form of Betts’ questionnaire upon mental imagery. J Clin Psychol 23(3):386–389PubMedCrossRefGoogle Scholar
  61. Sjoberg BM Jr, Hollister LE (1965) The effects of psychotomimetic drugs on primary suggestibility. Psychopharmacologia 8(4):251–262PubMedCrossRefGoogle Scholar
  62. Spanos NP (1986) Hypnotic behaviour: a social-psychological interpretation of amnesia, analgesia, and ‘trance logic’. Behavioural and Brain Sciences 9:449–502Google Scholar
  63. Spitzer M, Thimm M, Hermle L, Holzmann P, Kovar KA, Heimann H et al (1996) Increased activation of indirect semantic associations under psilocybin. Biol Psychiatry 39(12):1055–1057PubMedCrossRefGoogle Scholar
  64. Stevens J (1987). Storming heaven: LSD and the American dream. edn. Paladin, 1989: LondonGoogle Scholar
  65. Strassman RJ, Qualls CR (1994) Dose-response study of N, N-dimethyltryptamine in humans. I. Neuroendocrine, autonomic, and cardiovascular effects. Arch Gen Psychiatry 51(2):85–97PubMedCrossRefGoogle Scholar
  66. Studerus E, Gamma A, Kometer M, Vollenweider FX (2012) Prediction of psilocybin response in healthy volunteers. PLoS ONE 7(2):e30800PubMedCentralPubMedCrossRefGoogle Scholar
  67. Tagliazucchi E, Carhart-Harris R, Leech R, Nutt D, Chialvo DR (2014). Enhanced repertoire of brain dynamical states during the psychedelic experience. arXiv preprint arXiv:1405.6466Google Scholar
  68. Tellegen A, Atkinson G (1974) Openness to absorbing and self-altering experiences (“absorption”), a trait related to hypnotic susceptibility. J Abnorm Psychol 83(3):268–277PubMedCrossRefGoogle Scholar
  69. Turecki G, Briere R, Dewar K, Antonetti T, Lesage AD, Seguin M et al (1999) Prediction of level of serotonin 2A receptor binding by serotonin receptor 2A genetic variation in postmortem brain samples from subjects who did or did not commit suicide. Am J Psychiatry 156(9):1456–1458PubMedGoogle Scholar
  70. 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 : Off J Soc Neurosci 17(8):2785–2795Google Scholar
  71. 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. Neuropsychopharmacol : Off Publ Am Coll Neuropsychopharmacol 16(5):357–372CrossRefGoogle Scholar
  72. Weitzenhoffer AM (1980) Hypnotic susceptibility revisited. Am J Clin Hypn 22(3):130–146PubMedCrossRefGoogle Scholar
  73. Weitzenhoffer AM, Hilgard ER (1959) Stanford hypnotic susceptibility scale, for use in research investigations in the field of hypnotic phenomena. Consulting Psychologists, Palo AltoGoogle Scholar
  74. Whalley MG, Brooks GB (2009) Enhancement of suggestibility and imaginative ability with nitrous oxide. Psychopharmacology 203(4):745–752PubMedCrossRefGoogle Scholar
  75. Wilson SC, Barber TX (1978) The creative imagination scale as a measure of hypnotic responsiveness: applications to experimental and clinical hypnosis. Am J Clin Hypn 20(4):235–249PubMedCrossRefGoogle Scholar
  76. Woody E, Sadler P (1998) On re-integrating dissociated theories: comment on Kirsch and Lynn. Psychological Bulletin 123:192–197Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • R. L. Carhart-Harris
    • 1
  • M. Kaelen
    • 1
  • M. G. Whalley
    • 3
  • M. Bolstridge
    • 1
  • A. Feilding
    • 2
  • D. J. Nutt
    • 1
  1. 1.Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of MedicineImperial College LondonLondonUK
  2. 2.The Beckley FoundationOxfordUK
  3. 3.Berkshire NHS Foundation TrustReadingUK

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