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.
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References
Abramson HA (1967). The use of LSD in psychotherapy and alcoholism. edn. [s.n.]: Indianapolis.
Barber TX (1995). Hypnosis: a scientific approach. edn. J. Aronson: Northvale, N.J.;; London.
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):84–108
Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571
Blazhenkova O, Kozhevnikov M (2010) Visual-object ability: a new dimension of non-verbal intelligence. Cognition 117(3):276–301
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):2007–2019
Braffman W, Kirsch I (1999) Imaginative suggestibility and hypnotizability: an empirical analysis. J Pers Soc Psychol 77(3):578–587
Carhart-Harris R (2013) Is the brainstem really sufficient for a consciousness that would have interested Freud? Neuropsychoanal 15(1):29–32
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):1265–1283
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 25:1562–67
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):238–244
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 8:20
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):1497–1508
Cohen S (1964) The beyond within; the LSD story, 1st edn. Atheneum, New York
Crawford HJ, Knebel T, Vendemia JMC (1998) The nature of hypnotic analgesia: neurophysiological foundation and evidence. Contemporary Hypnosis 15:24–35
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):2550–2560
Dienes Z, Hutton S (2013) Understanding hypnosis metacognitively: rTMS applied to left DLPFC increases hypnotic susceptibility. Cortex 49:386–392
Dienes Z, Brown E, Hutton S, Kirsch I, Mazzoni G, Wright DB (2009) Hypnotic suggestibility, cognitive inhibition, and dissociation. Consciousness and cognition 18(4):837–847
Eysenck HJ, Furneaux WD (1945) Primary and secondary suggestibility; an experimental and statistical study. J Exp Psychol 35:485–503
Fabing HD (1955) New blocking agent against the development of LSD-25 psychosis. Science 121(3137):208–210
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):513–20
Gelade GA (1997) Creativity in conflict: the personality of the commercial creative. J Genet Psychol 158(1):67–78
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):317–326
Glennon RA, Titeler M, McKenney JD (1984) Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sci 35(25):2505–2511
Griffiths RR, Grob CS (2010) Hallucinogens as medicine. Sci Am 303(6):76–79
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):71–78
Grof S (1980) LSD Psychotherapy. Hunter House, US
Gudjonsson GH (1983) Suggestibility, intelligence, memory recall and personality: an experimental study. Br J Psychiatr: J Mental Sci 142:35–37
Gudjonsson G (2003) The psychology of interrogations and confessions. Wiley, New York
Halberstadt AL, Geyer MA (2011) Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens. Neuropharmacology 61(3):364–381
Harvey JA (2003) Role of the serotonin 5-HT(2A) receptor in learning. Learn Mem 10(5):355–362
Hilgard ER (1986) Divided consciousness: multiple controls in human thought and action. Am J Psychol 91(3):545–547
Hofmann A (1980) LSD: my problem child. McGraw-Hill, New York
Hull CL (1933). Hypnosis and suggestibility: an experimental approach. edn. Appleton: [S.l.].
Jamieson G (1987). The structure and meaning of absorption: Phd thesis
Johnson M, Richards W, Griffiths R (2008) Human hallucinogen research: guidelines for safety. J Psychopharmacol 22(6):603–620
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 York
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):419–426
Kirsch I, Low CB (2013) Suggestion in the treatment of depression. Am J Clin Hypn 55(3):221–229
Krebs TS, Johansen PO (2012) Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. J Psychopharmacol 26(7):994–1002
Marks J (1979). The search for the “Manchurian candidate”: the CIA and mind control. edn. Norton, 1991: New York;; London
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):265–277
McCrae RR, Costa PT Jr (1987) Validation of the five-factor model of personality across instruments and observers. J Pers Soc Psychol 52(1):81–90
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):277–280
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):15171–15183
Nichols DE (2004) Hallucinogens. Pharmacol Ther 101(2):131–181
Nutt DJ, King LA, Nichols DE (2013) Effects of schedule I drug laws on neuroscience research and treatment innovation. Nat Rev Neurosci 14(8):577–585
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):29–32
Paddock JR, Terranova S (2001) Guided visualization and suggestibility: effect of perceived authority on recall of autobiographical memories. J Genet Psychol 162(3):347–356
Panksepp J, Solms M (2012) What is neuropsychoanalysis? Clinically relevant studies of the minded brain. Trends Cogn Sci 16(1):6–8
Patterson DR, Jensen MP (2003) Hypnosis and clinical pain. Psychological Bulletin 129(4):495–521
Raz A, Shapiro T, Fan J, Posner MI (2002) Hypnotic suggestion and the modulation of Stroop interference. Arch Gen Psychiatry 59(12):1155–1161
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):441–448
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
Rosen GM, Sageman M, Loftus E (2004) A historical note on false traumatic memories. J Clin Psychol 60:137–9
Sandison RA, Whitelaw JD (1957) Further studies in the therapeutic value of lysergic acid diethylamide in mental illness. J Mental Sci 103(431):332–343
Savage C (1957) The resolution and subsequent remobilization of resistance by LSD in psychotherapy. J Nerv Ment Dis 125(3):434–437
Semmens-Wheeler R, Dienes Z, Duka T (2013) Alcohol increases hypnotic susceptibility. Consciousness and Cognition 22:1082–1091
Sessa B (2005) Can psychedelics have a role in psychiatry once again? Brit J Psychiatr 186:457–458
Sheehan PW (1967) A shortened form of Betts’ questionnaire upon mental imagery. J Clin Psychol 23(3):386–389
Sjoberg BM Jr, Hollister LE (1965) The effects of psychotomimetic drugs on primary suggestibility. Psychopharmacologia 8(4):251–262
Spanos NP (1986) Hypnotic behaviour: a social-psychological interpretation of amnesia, analgesia, and ‘trance logic’. Behavioural and Brain Sciences 9:449–502
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):1055–1057
Stevens J (1987). Storming heaven: LSD and the American dream. edn. Paladin, 1989: London
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):85–97
Studerus E, Gamma A, Kometer M, Vollenweider FX (2012) Prediction of psilocybin response in healthy volunteers. PLoS ONE 7(2):e30800
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:1405.6466
Tellegen A, Atkinson G (1974) Openness to absorbing and self-altering experiences (“absorption”), a trait related to hypnotic susceptibility. J Abnorm Psychol 83(3):268–277
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):1456–1458
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):2785–2795
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):357–372
Weitzenhoffer AM (1980) Hypnotic susceptibility revisited. Am J Clin Hypn 22(3):130–146
Weitzenhoffer AM, Hilgard ER (1959) Stanford hypnotic susceptibility scale, for use in research investigations in the field of hypnotic phenomena. Consulting Psychologists, Palo Alto
Whalley MG, Brooks GB (2009) Enhancement of suggestibility and imaginative ability with nitrous oxide. Psychopharmacology 203(4):745–752
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):235–249
Woody E, Sadler P (1998) On re-integrating dissociated theories: comment on Kirsch and Lynn. Psychological Bulletin 123:192–197
Acknowledgments
This research received financial and intellectual support from the Beckley Foundation and was conducted as part of a wider Beckley-Imperial research programme. This report presents independent research carried out at the NIHR/Wellcome Trust Imperial Clinical Research Facility. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The authors are grateful to Devin Terhune, David Luke and Jamie Ward for advising on the inclusion of the MODTAS and OSIVQ and to Neiloufar Family for her help with managing the research.
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Carhart-Harris, R.L., Kaelen, M., Whalley, M.G. et al. LSD enhances suggestibility in healthy volunteers. Psychopharmacology 232, 785–794 (2015). https://doi.org/10.1007/s00213-014-3714-z
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DOI: https://doi.org/10.1007/s00213-014-3714-z