The paradoxical psychological effects of lysergic acid diethylamide (LSD)

Psychological Medicine

Volumn 46, Issue 7, 2016, Pages 1379-1390

  Carhart Harris, R L ^a   Kaelen, M ^a   Bolstridge, M ^a   Williams, T M ^b   Williams, L T ^a   Underwood, R ^c   Feilding, A ^d   Nutt, D J ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY OF BRISTOL   (United Kingdom)

^c KING'S COLLEGE LONDON   (United Kingdom)

^d THE BECKLEY FOUNDATION   (United Kingdom)

Author keywords

LSD; mood; psychedelics; psychosis; serotonin

Indexed keywords

LYSERGIDE; PSYCHEDELIC AGENT; SEROTONIN 2A RECEPTOR;

ADULT; AFFECT; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DRUG EFFECTS; HUMAN; MIDDLE AGED; SATISFACTION; YOUNG ADULT;

ADULT; AFFECT; CROSS-OVER STUDIES; HALLUCINOGENS; HUMANS; LYSERGIC ACID DIETHYLAMIDE; MIDDLE AGED; PERSONAL SATISFACTION; RECEPTOR, SEROTONIN, 5-HT2A; YOUNG ADULT;

EID: 84957612008     PISSN: 00332917     EISSN: 14698978     Source Type: Journal    
DOI: 10.1017/S0033291715002901     Document Type: Article

References (77)

1. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961). An inventory for measuring depression. Archives of General Psychiatry 4, 561-571.
2. Bhagwagar Z, Hinz R, Taylor M, Fancy S, Cowen P, Grasby P (2006). Increased 5-HT2A receptor binding in euthymic, medication-free patients recovered from depression: a positron emission study with [11C]MDL 100,907. American Journal of Psychiatry 163, 1580-1587.
3. Bogenschutz MP, Forcehimes AA, Pommy JA, Wilcox CE, Barbosa P, Strassman RJ (2015). Psilocybin-Assisted treatment for alcohol dependence: a proof-of-concept study. Journal of Psychopharmacology 29, 289-299.
4. 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. Neuropsychopharmacology 33, 2007-2019.
5. 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, e42421.
6. Bouso JC, Palhano-Fontes F, Rodríguez-Fornells A, Ribeiro S, Sanches R, Crippa JA, Hallak JE, De Araujo DB, Riba J (2015). Long-term use of psychedelic drugs is associated with differences in brain structure and personality in humans. European Neuropsychopharmacology 25, 483-492.
7. Branchi I (2011). The double edged sword of neural plasticity: increasing serotonin levels leads to both greater vulnerability to depression and improved capacity to recover. Psychoneuroendocrinology 36, 339-351.
8. Carhart-Harris R, Brugger S, Nutt D, Stone J (2013). Psychiatry's next top model: cause for a re-think on drug models of psychosis and other psychiatric disorders. Journal of Psychopharmacology 27, 771-778.
9. Carhart-Harris R, Kaelen M, Whalley M, Bolstridge M, Feilding A, Nutt D (2014a). LSD enhances suggestibility in healthy volunteers. Psychopharmacology (Berlin) 232, 785-794.
10. 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 (2012). Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proceedings of the National Academy of Sciences USA 109, 2138-2143.
11. Carhart-Harris RL, Leech R, Hellyer PJ, Shanahan M, Feilding A, Tagliazucchi E, Chialvo DR, Nutt D (2014b). The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs. Frontiers in Human Neuroscience 8, 20.
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 (Berlin) 195, 415-424.
13. Carver CS, Scheier MF (2014). Dispositional optimism. Trends in Cognitive Science 18, 293-299.
14. Cohen S, Ditman KS (1962). Complications associated with lysergic acid diethylamide (LSD-25). JAMA 181, 161-162.
15. Costa PT Jr., McCrae RR (1995). Domains and facets: hierarchical personality assessment using the Revised NEO Personality Inventory. Journal of Personality Assessment 64, 21-50.
16. Dolder PC, Schmid Y, Haschke M, Rentsch KM, Liechti ME (2015). Pharmacokinetics and concentration-effect relationship of oral LSD in humans. International Journal of Neuropsychopharmacology. Published online 24 June 2015. doi:10.1093/ijnp/pyv072.
17. Floyd M, Scogin F, Chaplin WF (2004). The Dysfunctional Attitudes Scale: factor structure, reliability, and validity with older adults. Aging and Mental Health 8, 153-160.
18. Frecska E, More CE, Vargha A, Luna LE (2012). Enhancement of creative expression and entoptic phenomena as aftereffects of repeated ayahuasca ceremonies. Journal of Psychoactive Drugs 44, 191-199.
19. Frokjaer VG, Mortensen EL, Nielsen FA, Haugbol S, Pinborg LH, Adams KH, Svarer C, Hasselbalch SG, Holm S, Paulson OB, Knudsen GM (2008). Frontolimbic serotonin 2A receptor binding in healthy subjects is associated with personality risk factors for affective disorder. Biological Psychiatry 63, 569-576.
20. Gasser P, Holstein D, Michel Y, Doblin R, Yazar-Klosinski B, Passie T, Brenneisen R (2014). Safety and efficacy of lysergic acid diethylamide-Assisted psychotherapy for anxiety associated with life-threatening diseases. Journal of Nervous and Mental Diseases 202, 513-520.
21. Glaesmer H, Rief W, Martin A, Mewes R, Brahler E, Zenger M, Hinz A (2012). Psychometric properties and populationbased norms of the Life Orientation Test Revised (LOT-R). British Journal of Health Psychology 17, 432-445.
22. Glennon RA, Titeler M, Mckenney JD (1984). Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sciences 35, 2505-2511.
23. Gouzoulis-Mayfrank E, Heekeren K, Neukirch A, Stoll M, Stock C, Obradovic M, Kovar KA (2005). Psychological effects of (S)-ketamine and N,N-dimethyltryptamine (DMT): a double-blind, cross-over study in healthy volunteers. Pharmacopsychiatry 38, 301-311.
24. Griffiths R, Richards W, Johnson M, McCann U, Jesse R (2008). Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. Journal of Psychopharmacology 22, 621-632.
25. Griffiths RR, Richards WA, McCann U, Jesse R (2006). Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology (Berlin) 187, 268-283, discussion 284-292.
26. Grinspoon L, Bakalar JB (1979). Psychedelic Drugs Reconsidered. Basic Books: New York.
27. Grob CS, Danforth AL, Chopra GS, Hagerty M, McKay CR, Halberstadt AL, Greer GR (2011). Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Archives of General Psychiatry 68, 71-78.
28. Harvey JA (2003). Role of the serotonin 5-HT2A receptor in learning. Learning and Memory 10, 355-362.
29. Harvey JA, Quinn JL, Liu R, Aloyo VJ, Romano AG (2004). Selective remodeling of rabbit frontal cortex: relationship between 5-HT2A receptor density and associative learning. Psychopharmacology (Berlin) 172, 435-442.
30. Hendricks PS, Thorne CB, Clark CB, Coombs DW, Johnson MW (2015). Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. Journal of Psychopharmacology 29, 280-288.
31. Hintzen A, Passie T (2010). The Pharmacology of LSD: A Critical Review. Oxford University Press: Oxford.
32. Hirt ER, Devers EE, Mccrea SM (2008). I want to be creative: exploring the role of hedonic contingency theory in the positive mood-cognitive flexibility link. Journal of Personality and Social Psychology 94, 214-230.
33. Hodgues WF, Spielberger CD (1969). An indicant of trait or state anxiety? Journal of Consultancy and Clinical Psychology 33, 430-434.
34. Hofmann A (1980). LSD: My Problem Child. McGraw-Hill: New York.
35. Johnson M, Richards W, Griffiths R (2008). Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology 22, 603-620.
36. Johnson MW, Garcia-Romeu A, Cosimano MP, Griffiths RR (2014). Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. Journal of Psychopharmacology 28, 983-992.
37. Kaelen M, Barrett FS, Roseman L, Lorenz R, Family N, Bolstridge M, Curran HV, Feilding A, Nutt DJ, Carhart-Harris RL (2015). LSD enhances the emotional response to music. Psychopharmacology (Berlin) 232, 3607-3614.
38. Kaiser S, Heekeren K, Simon JJ (2011). The negative symptoms of schizophrenia: category or continuum? Psychopathology 44, 345-353.
39. King AR, Martin IL, Seymour KA (1972). Reversal learning facilitated by a single injection of lysergic acid diethylamide (LSD 25) in the rat. British Journal of Pharmacology 45, 161P-162P.
40. Kometer M, Schmidt A, Bachmann R, Studerus E, Seifritz E, Vollenweider FX (2012). Psilocybin biases facial recognition, goal-directed behavior, and mood state toward positive relative to negative emotions through different serotonergic subreceptors. Biological Psychiatry 72, 898-906.
41. Krebs TS, Johansen PO (2013). Psychedelics and mental health: a population study. PLOS ONE 8, e63972.
42. Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, Heninger GR, Bowers MB Jr., Charney DS (1994). Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Archives of General Psychiatry 51, 199-214.
43. Lin WL, Tsai PH, Lin HY, Chen HC (2014). How does emotion influence different creative performances? The mediating role of cognitive flexibility. Cognition and Emotion 28, 834-844.
44. Lebedev AV, Lovden M, Rosenthal G, Feilding A, Nutt DJ, Carhart-Harris RL (2015). Finding the self by losing the self: neural correlates of ego-dissolution under psilocybin. Human Brain Mapping 36, 3137-3153.
45. Maclean KA, Johnson MW, Griffiths RR (2011). Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness. Journal of Psychopharmacology 25, 1453-1461.
46. Mason O, Morgan CJ, Dhiman SK, Patel A, Parti N, Curran HV (2009). Acute cannabis use causes increased psychotomimetic experiences in individuals prone to psychosis. Psychological Medicine 39, 951-956.
47. Mason O, Wakerley D (2012). The psychotomimetic nature of dreams: an experimental study. Schizophrenia Research Treatment 2012, 872307.
48. Mason OJ, Morgan CJ, Stefanovic A, Curran HV (2008). The Psychotomimetic States Inventory (PSI): measuring psychotic-type experiences from ketamine and cannabis. Schizophrenia Research 103, 138-142.
49. Meyer JH, McMain S, Kennedy SH, Korman L, Brown GM, Dasilva JN, Wilson AA, Blak T, Eynan-Harvey R, Goulding VS, Houle S, Links P (2003). Dysfunctional attitudes and 5-HT2 receptors during depression and selfharm. American Journal of Psychiatry 160, 90-99.
50. Moreno FA, Wiegand CB, Taitano EK, Delgado PL (2006). Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. Journal of Clinical Psychiatry 67, 1735-1740.
51. Morrison PD, Zois V, Mckeown DA, Lee TD, Holt DW, Powell JF, Kapur S, Murray RM (2009). The acute effects of synthetic intravenous Δ9-tetrahydrocannabinol on psychosis, mood and cognitive functioning. Psychological Medicine 39, 1607-1616.
52. Muthukumaraswamy SD, Carhart-Harris RL, Moran RJ, Brookes MJ, Williams TM, Errtizoe D, Sessa B, Papadopoulos A, Bolstridge M, Singh KD, Feilding A, Friston KJ, Nutt DJ (2013). Broadband cortical desynchronization underlies the human psychedelic state. Journal of Neuroscience 33, 15171-15183.
53. Osmond H, Smythies J (1952). Schizophrenia: a new approach. Journal of Mental Science 98, 309-315.
54. 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. American Journal of Medical Genetics. Part B, Biological Neuropsychiatric Genetics 137B, 29-32.
55. Peters ER, Joseph SA, Garety PA (1999). Measurement of delusional ideation in the normal population: introducing the PDI (Peters et al. Delusions Inventory). Schizophrenia Bulletin 25, 553-576.
56. Petri G, Expert P, Turkheimer F, Carhart-Harris R, Nutt D, Hellyer PJ, Vaccarino F (2014). Homological scaffolds of brain functional networks. Journal of the Royal Society Interface 11, 20140873.
57. Petrovsky N, Ettinger U, Hill A, Frenzel L, Meyhofer I, Wagner M, Backhaus J, Kumari V (2014). Sleep deprivation disrupts prepulse inhibition and induces psychosis-like symptoms in healthy humans. Journal of Neuroscience 34, 9134-9140.
58. Reich P, Hepps RB (1972). Homicide during a psychosis induced by LSD. JAMA 219, 869-871.
59. Roelofs J, Muris P, Huibers M, Peeters F, Arntz A (2006). On the measurement of rumination: a psychometric evaluation of the ruminative response scale and the rumination on sadness scale in undergraduates. Journal of Behavior Therapy and Experimental Psychiatry 37, 299-313.
60. Romano AG, Quinn JL, Li L, Dave KD, Schindler EA, Aloyo VJ, Harvey JA (2010). Intrahippocampal LSD accelerates learning and desensitizes the 5-HT2A receptor in the rabbit, Romano et al. Psychopharmacology (Berlin) 212, 441-448.
61. Roseman L, Leech R, Nutt DJ, Feilding A, Carhart-Harris RL (2014). The effects of psilocybin and MDMA on betweennetwork resting state functional connectivity in healthy volunteers. Frontiers in Human Neuroscience 8, 204.
62. Rush AJ, Trivedi MH, Ibrahim HM, Carmody TJ, Arnow B, Klein DN, Markowitz JC, Ninan PT, Kornstein S, Manber R, Thase ME, Kocsis JH, Keller MB (2003). The 16-item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biological Psychiatry 54, 573-583.
63. Scheier MF, Carver CS, Bridges MW (1994). Distinguishing optimism from neuroticism (and trait anxiety, self-mastery, and self-esteem): a reevaluation of the Life Orientation Test. Journal of Personality and Social Psychology 67, 1063-1078.
64. Schmid Y, Enzler F, Gasser P, Grouzmann E, Preller KH, Vollenweider FX, Brenneisen R, Muller F, Borgwardt S, Liechti ME (2014). Acute effects of lysergic acid diethylamide in healthy subjects. Biological Psychiatry 78, 544-553.
65. Stokes PR, Mehta MA, Curran HV, Breen G, Grasby PM (2009). Can recreational doses of THC produce significant dopamine release in the human striatum? NeuroImage 48, 186-190.
66. Studerus E, Gamma A, Vollenweider FX (2010). Psychometric evaluation of the altered states of consciousness rating scale (OAV). PLoS ONE 5, e12412.
67. 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. Journal of Psychopharmacology 25, 1434-1452.
68. Tagliazucchi E, Carhart-Harris R, Leech R, Nutt D, Chialvo DR (2014). Enhanced repertoire of brain dynamical states during the psychedelic experience. Human Brain Mapping 35, 5442-5456.
69. Tellegen A, Atkinson G (1974). Openness to absorbing and self-Altering experiences ("absorption"), a trait related to hypnotic susceptibility. Journal of Abnormal Psychology 83, 268-277.
70. Turecki G, Briere R, Dewar K, Antonetti T, Lesage AD, Seguin M, Chawky N, Vanier C, Alda M, Joober R, Benkelfat C, Rouleau GA (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. American Journal of Psychiatry 156, 1456-1458.
71. Umbricht D, Vollenweider FX, Schmid L, Grubel 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, 170-181.
72. Van Wel JH, Kuypers KP, Theunissen EL, Bosker WM, Bakker K, Ramaekers JG (2012). Effects of acute MDMA intoxication on mood and impulsivity: role of the 5-HT2 and 5-HT1 receptors. PLOS ONE 7, e40187.
73. 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, 1876-1887.
74. Vollenweider FX, Vollenweider-Scherpenhuyzen MF, Babler A, Vogel H, Hell D (1998). Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Neuroreport 9, 3897-3902.
75. Weisstaub NV, Zhou M, Lira A, Lambe E, Gonzalez-Maeso J, Hornung JP, Sibille E, Underwood M, Itohara S, Dauer WT, Ansorge MS, Morelli E, Mann JJ, Toth M, Aghajanian G, Sealfon SC, Hen R, Gingrich JA (2006). Cortical 5-HT2A receptor signaling modulates anxiety-like behaviors in mice. Science 313, 536-540.
76. Williams GV, Rao SG, Goldman-Rakic PS (2002). The physiological role of 5-HT2A receptors in working memory. Journal of Neuroscience 22, 2843-2854.
77. Zarate CA Jr., Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK (2006). A randomized trial of an N-methyl-D-Aspartate antagonist in treatment-resistant major depression. Archives of General Psychiatry 63, 856-864.