Abstract
Background
Ketamine has previously been shown to induce delusion-like or referential beliefs, both acutely in healthy volunteers and naturalistically among nonintoxicated users of the drug. Delusions are theoretically underpinned by increased superstitious conditioning or the erroneous reinforcement of random events.
Materials and methods
Using a novel and objectively measured superstitious conditioning task, experiment 1 assessed healthy volunteers before and during placebo (n = 16), low-dose (n = 15), and high-dose ketamine (n = 16) under randomized and double-blind conditions. Experiment 2 used the same task to compare ketamine users (n = 18), polydrug controls (n = 19), and nondrug-using controls (n = 17).
Results
In experiment 1, ketamine produced dose-dependent psychotomimetic effects but did not cause changes in superstitious conditioning. Experiment 2 found increased levels of superstitious conditioning among ketamine users compared to polydrug and nondrug-using controls, respectively, as evidenced by both objective task responses and subjective beliefs following the task.
Conclusions
Results indicate that chronic but not acute exposure to ketamine may increase the propensity to adopt superstitious conditioning. These findings are discussed in terms of acute and chronic ketamine models of delusion-like belief formation in schizophrenia.
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References
Aeschleman SR, Rosen CC, Williams MR (2003) The effect of non-contingent negative and positive reinforcement operations on the acquisition of superstitious behaviors. Behav Processes 61:37–45
Baddeley A, Emslie H, Nimmo-Smith I (1993) The spot the word test: a robust estimate of verbal intelligence based on lexical decision. Br J Clin Psychol 32:55–65
Bloom CM, Venard J, Harden M, Seetharaman S (2007) Non-contingent positive and negative reinforcement schedules of superstitious behaviors. Behav Processes 75:8–13
Bowdle TA, Radant AD, Cowley DS, Kharasch ED, Strassman RJ, Roy-Byrne PP (1998) Psychedelic effects of ketamine in healthy volunteers: relationship to steady-state plasma concentrations. Anesthesiology 88:82–88
Brugger P, Dowdy MA, Graves RE (1994) From superstitious behavior to delusional thinking: the role of the hippocampus in misattributions of causality. Med Hypotheses 43:397–402
Clements JA, Nimmo WS (1981) Pharmacokinetics and analgesic effect of ketamine in man. Br J Anaesth 53:27–30
Cohen JD, McClure SM, Yu AJ (2007) Should I stay or should I go? How the human brain manages the trade-off between exploitation and exploration. Phil Trans R Soc B 362:933–942
Corlett PR, Honey GD, Aitken MR, Dickinson A, Shanks DR, Absalom AR, Lee M, Pomarol-Clotet E, Murray GK, McKenna PJ, Robbins TW, Bullmore ET, Fletcher PC (2006) Frontal responses during learning predict vulnerability to the psychotogenic effects of ketamine: linking cognition, brain activity, and psychosis. Arch Gen Psychiatry 63:611–621
Corlett PR, Honey GD, Fletcher PC (2007) From prediction error to psychosis: ketamine as a pharmacological model of delusions. J Psychopharmacol 21:238–252
Cubells JF, Feinn R, Pearson D, Burda J, Tang Y, Farrer LA, Gelernter J, Kranzler HR (2005) Rating the severity and character of transient cocaine-induced delusions and hallucinations with a new instrument, the Scale for Assessment of Positive Symptoms for Cocaine-Induced Psychosis (SAPS-CIP). Drug Alcohol Depend 80:23–33
Curran HV (2000) Is MDMA (‘Ecstasy’) neurotoxic in humans? An overview of evidence and of methodological problems in research. Neuropsychobiology 42:34–41
Curran HV, Monaghan L (2001) In and out of the K-hole: a comparison of the acute and residual effects of ketamine in frequent and infrequent ketamine users. Addiction 96:749–760
Curran HV, Morgan CJA (2000) Cognitive, dissociative and psychotogenic effects of ketamine on recreational users on the night of drug use and 3 days later. Addiction 95:575–590
Jensen J, Smith AJ, Willeit M, Crawley AP, Mikulis DJ, Vitcu I, Kapur S (2007) Separate brain regions code for salience vs. valence during reward prediction in humans. Hum Brain Mapp 28:294–302
Jentsch JD, Roth RH (1999) The neuropsychopharmacology of phencyclidine: from NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia. Neuropsychopharmacology 30:201–225
Jentsch JD, Taylor JR, Roth RH (1998) Subchronic phencyclidine administration increases mesolimbic dopaminergic system responsivity and augments stress- and psychostimulant-induced hyperlocomotion. Neuropsychopharmacology 19:105–113
Jorgensen P (1998) Schizophrenic delusions: the detection of warning signals. Schizophr Res 32:17–22
Kapur S (2003) Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. Am J Psychiatry 160:13–23
Kim H, Lee D, Shin YM, Chey J (2007) Impaired strategic decision making in schizophrenia. Brain Res 1180:90–100
King R, Barchas JD, Huberman BA (1984) Chaotic behavior in dopamine neurodynamics. Proc Natl Acad Sci U S A 81:1244–1247
Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, Heninger GR, Bowers MB, Charney DS (1994) Subanesthetic effects of the non-competitive NMDA-antagonist, ketamine, in humans. Arch Gen Psychiatry 51:199–214
Lahti AC, Weiler MA, Tamara Michaelidis BA, Parwani A, Tamminga CA (2001) Effects of ketamine in normal and schizophrenic volunteers. Neuropsychopharmacology 25:455–467
Malhotra AK, Pinals DA, Weingartner H, Sirocco K, Missar CD, Pickar D, Breier A (1996) NMDA receptor function and human cognition: the effects of ketamine in healthy volunteers. Neuropsychopharmacology 14:301–307
Mason O, Linney Y, Claridge G (2005) Short scales for measuring schizotypy. Schizophr Res 78:293–296
Mason O, Morgan CJA, Stefanovic A, Curran HV (2008) The Psychotomimetic States Inventory: A new measure of psychotic-type experiences. Schizophr Res Psychol Med 19:1–6
Matute H (1994) Learned helplessness and superstitious behavior as opposite effects of uncontrollable reinforcement in humans. Learn Motiv 25:216–232
Montoya AG, Sorrentino R, Lukas SE, Price BH (2002) Long-term neuropsychiatric consequences of "ecstasy" (MDMA): a review. Harv Rev Psychiatry 10:212–220
Moore TH, Zammit S, Lingford-Hughes A, Barnes TR, Jones PB, Burke M, Lewis G (2007) Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 370:319–328
Morgan CJ, Curran HV (2006) Acute and chronic effects of ketamine upon human memory: a review. Psychopharmacology (Berl) 188:408–424
Morgan CJA, Monaghan L, Curran HV (2004) Beyond the K-hole: a 3-year longitudinal investigation of the cognitive and subjective effects of ketamine in recreational users who have substantially reduced their use of the drug. Addiction 99:1450–1461
Morgan CJ, Muetzelfeldt L, Curran HV (2009) Ketamine use, cognition and psychological wellbeing: a comparison of frequent, infrequent and ex-users with polydrug and non-using controls. Addiction 104:77–87
Mouri A, Noda Y, Enomoto T, Nabeshima T (2007) Phencyclidine animal models of schizophrenia: approaches from abnormality of glutamatergic neurotransmission and neurodevelopment. Neurochem Int 51:173–184
Murray GK, Corlett PR, Clark L, Pessiglione M, Blackwell AD, Honey G, Jones PB, Bullmore ET, Robbins TW, Fletcher PC (2008) Substantia nigra/ventral tegmental reward prediction error disruption in psychosis. Mol Psychiatry 13:239267–239276
Nelson HE (1982) National Adult Reading Test (NART): test manual. NFER, Nelson, Windsor
Newcomer JW, Farber NB, Jevtovic-Todorovic V, Selke G, Melson AK, Hershey T, Craft S, Olney JW (1999) Ketamine-Induced NMDA receptor hypofunction as a model of memory impairment and psychosis. Neuropsychopharmacology 20:106–118
Nunn JA, Rizza F, Peters ER (2001) The incidence of schizotypy among cannabis and alcohol users. J Nerv Ment Dis 189:741–748
Ono K (1987) Superstitious behavior in humans. J Exp Anal Behav 47:261–271
Overall JE, Gorham DR (1962) The brief psychiatric rating scale. Psychol Rep 10:799–812
Peters ER, Joseph SA, Garety PA (1999) Measurement of delusional ideation in the normal population: introducing the PDI (Peters et al. Delusions Inventory). Schizophr Bull 25:553–576
Pomarol-Clotet E, Honey GD, Murray GK, Corlett PR, Absalom AR, Lee M, McKenna PJ, Bullmore ET, Fletcher PC (2006) Psychological effects of ketamine in healthy volunteers. Phenomenological study. Br J Psychiatry 189:173–179
Roiser JP, Stephan KE, den Ouden HE, Barnes TR, Friston KJ, Joyce EM (2009) Do patients with schizophrenia exhibit aberrant salience? Psychol Med 39:199–209
Rudski J (2001) Competition, superstition and illusion of control. Curr Psychol 20:68–84
Schafer SL, Vervel JR, Aziz N, Scott JC (1990) Pharmacokinetics of fentanyl administered by computer controlled infusion pump. Anaesthesiology 73:1091–1102
Shaner A (1999) Delusions, superstitious conditioning and chaotic dopamine neurodynamics. Med Hypotheses 52:119–123
Skinner BF (1948) Superstition in the pigeon. J Exp Psychol 38:168–172
Solowij N, Hall W, Lee N (1992) Recreational MDMA use in Sydney: a profile of "Ecstasy" users and their experience with the drug. Br J Addict 87:1161–1172
Stefanovic A, Brandner B, Klassen E, Cregg R, Nagaratnam M, Bromley L, Das RK, Rossell SL, Morgan C, Curran HV (2009) Acute and chronic effects of ketamine on semantic priming: modelling schizophrenia? J Clin Psychopharmacol 29(2):124–133
Uhlhaas PJ, Millard I, Muetzelfeldt L, Curran HV, Morgan CJ (2007) Perceptual organization in ketamine users: preliminary evidence of deficits on night of drug use but not 3 days later. J Psychopharmacol 21:347–352
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Freeman, T.P., Morgan, C.J.A., Klaassen, E. et al. Superstitious conditioning as a model of delusion formation following chronic but not acute ketamine in humans. Psychopharmacology 206, 563–573 (2009). https://doi.org/10.1007/s00213-009-1564-x
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DOI: https://doi.org/10.1007/s00213-009-1564-x