, Volume 233, Issue 1, pp 89–97 | Cite as

Emotional traits predict individual differences in amphetamine-induced positive mood in healthy volunteers

  • Matthew G. Kirkpatrick
  • Nicholas I. Goldenson
  • Nahel Kapadia
  • Christopher W. Kahler
  • Harriet de Wit
  • Robert M. Swift
  • John E. McGeary
  • Steve Sussman
  • Adam M. Leventhal
Original Investigation



Previous research on emotional correlates of individual differences in subjective responses to d-amphetamine has focused on relatively broad personality traits. Yet, emotional functioning is best characterized by several narrow subcomponents, each of which may contribute uniquely to amphetamine response. Here, we examine several specific subdomains of emotional functioning in relation to acute amphetamine response.


At a baseline session, healthy stimulant-naive volunteers (N = 97) completed measures of several subdomains of baseline trait emotional functioning and then completed two counterbalanced experimental sessions during which they received a single oral dose of 20 mg d-amphetamine or placebo. Acute subjective drug response measures were completed at repeated intervals before and after drug administration. Data from subjective measures that were significantly modulated by amphetamine were reduced using principal component analysis (amphetamine or placebo) into three higher-order factors of “positive mood,” “arousal,” and “drug high.” Amphetamine did not significantly alter any “negative” subjective states. Separate multiple regression analyses were conducted regressing these three drug factors on baseline trait emotional functioning scales.


The combined set of trait emotional functioning indicators accounted for approximately 22 % of the variance in acute amphetamine-induced positive mood changes. Greater anticipatory pleasure and greater anxious distress each uniquely predicted greater amphetamine-induced positive mood. Trait emotional functioning did not significantly predict amphetamine-induced changes in arousal or drug high.


Emotional traits appear to moderate drug-induced positive mood but not other dimensions of amphetamine effects. Different facets of emotional functioning may differentially modulate amphetamine’s subjective effect profile.


Amphetamine Emotion Human Subjective effects 



This research was supported with a grant from the National Institute on Drug Abuse (K08-DA025041: PI Leventhal).


  1. Baroni A, Castellanos FX (2015) Neuroanatomic and cognitive abnormalities in attention-deficit/hyperactivity disorder in the era of ‘high definition’ neuroimaging. Curr Opin Neurobiol 30:1–8PubMedCrossRefGoogle Scholar
  2. Berridge KC, Robinson TE (1998) What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Res Rev 28(3):309–369PubMedCrossRefGoogle Scholar
  3. Bremner JD, Krystal JH, Southwick SM, Charney DS (1996) Noradrenergic mechanisms in stress and anxiety: II. Clinical studies. Synapse 23(1):39–51PubMedCrossRefGoogle Scholar
  4. Buckner JD, Heimberg RG, Ecker AH, Vinci C (2013) A biopsychosocial model of social anxiety and substance use. Depression Anxiety 30(3):276–284PubMedCrossRefGoogle Scholar
  5. Campbell DG, Felker BL, Liu CF, Yano EM, Kirchner JE, Chan D, Chaney EF (2007) Prevalence of depression–PTSD comorbidity: implications for clinical practice guidelines and primary care-based interventions. J Gen Intern Med 22(6):711–718PubMedPubMedCentralCrossRefGoogle Scholar
  6. Charney DS, Woods SW, Heninger GR (1989) Noradrenergic function in generalized anxiety disorder: effects of yohimbine in healthy subjects and patients with generalized anxiety disorder. Psychiatry Res 27(2):173–182PubMedCrossRefGoogle Scholar
  7. Clark LA, Watson D (1991) Tripartite model of anxiety and depression: psychometric evidence and taxonomic implications. J Abnorm Psychol 100(3):316PubMedCrossRefGoogle Scholar
  8. Comer SD, Bickel WK, Yi R et al (2010) Human behavioral pharmacology, past, present, and future: symposium presented at the 50th annual meeting of the Behavioral Pharmacology Society. Behav Pharmacol 21:251–277PubMedPubMedCentralCrossRefGoogle Scholar
  9. Conway KP, Compton W, Stinson FS, Grant BF (2006) Lifetime comorbidity of DSM-IV mood and anxiety disorders and specific drug use disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Journal of Clinical PsychiatryGoogle Scholar
  10. Crabbe JC, Jarvik LF, Liston EH et al (1983) Behavioral responses to amphetamines in identical twins. Acta Genet Med Gemellol (Roma) 32:139–149Google Scholar
  11. Cuthbert BN, Insel TR (2013) Toward the future of psychiatric diagnosis: the seven pillars of RDoC. BMC Med 11(1):126PubMedPubMedCentralCrossRefGoogle Scholar
  12. Darke S, Kaye S, McKetin R, Duflou J (2008) Major physical and psychological harms of methamphetamine use. Drug Alcohol Rev 27:253–262Google Scholar
  13. Darke S, Torok M, McKetin R, Kaye S, Ross J (2011) Patterns of psychological distress related to regular methamphetamine and opioid use. Addict Res Theory 19:121–127Google Scholar
  14. De Graaf R, Bijl RV, Spijker J, Beekman ATF, Vollebergh WAM (2003) Temporal sequencing of lifetime mood disorders in relation to comorbid anxiety and substance use disorders. Soc Psychiatry Psychiatr Epidemiol 38(1):1–11PubMedCrossRefGoogle Scholar
  15. de Wit H, Phillips TJ (2012) Do initial responses to drugs predict future use or abuse? Neurosci Biobehav Rev 36:1565–1576PubMedPubMedCentralCrossRefGoogle Scholar
  16. Depue RA, Luciana M, Arbisi P et al (1994) Dopamine and the structure of personality: relation of agonist-induced dopamine activity to positive emotionality. J Pers Soc Psychol 67:485–498PubMedCrossRefGoogle Scholar
  17. First MB, Spitzer RL, Gibbon M, Williams JBW (2002) Structured clinical interview for DSM-IV-TR Axis I Disorders, Research Version, Non-Patient Edition (SCID-I/NP). Biometrics Research, New York State Psychiatric Institute, New YorkGoogle Scholar
  18. Fischman MW, Foltin RW (1991) Utility of subjective-effects measurements in assessing abuse liability of drugs in humans. Br J Addict 86(12):1563–1570PubMedCrossRefGoogle Scholar
  19. Gard DE, Gard MG, Kring AM, John OP (2006) Anticipatory and consummatory components of the experience of pleasure: a scale development study. J Res Pers 40(6):1086–1102CrossRefGoogle Scholar
  20. Geracioti TD Jr, Baker DG, Kasckow JW, Strawn JR, Jeffrey Mulchahey J, Dashevsky BA, Ekhator NN (2008) Effects of trauma-related audiovisual stimulation on cerebrospinal fluid norepinephrine and corticotropin-releasing hormone concentrations in post-traumatic stress disorder. Psychoneuroendocrinology 33(4):416–424PubMedCrossRefGoogle Scholar
  21. Glasner‐Edwards S, Mooney LJ, Marinelli‐Casey P, Hillhouse M, Ang A, Rawson R (2010) Anxiety disorders among methamphetamine dependent adults: association with post-treatment functioning. Am J Addict 19(5):385–390PubMedPubMedCentralCrossRefGoogle Scholar
  22. Grant BF, Stinson FS, Dawson DA, Chou SP, Dufour MC, Compton W, Kaplan K (2004) Prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry 61(8):807–816PubMedCrossRefGoogle Scholar
  23. Halkitis PN, Fischgrund BN, Parsons JT (2005) Explanations for methamphetamine use among gay and bisexual men in New York City. Subst Use Misuse 40:1331–1345PubMedCrossRefGoogle Scholar
  24. Hall W, Hando J, Darke S, Ross J (1996) Psychological morbidity and route of administration among amphetamine users in Sydney, Australia. Addiction 91(1):81–87PubMedCrossRefGoogle Scholar
  25. Hart AB, Engelhardt BE, Wardle MC, Sokoloff G, Stephens M, de Wit H, Palmer AA (2012) Genome-wide association study of d-amphetamine response in healthy volunteers identifies putative associations, including cadherin 13 (CDH13). PLoS One 7(8):e42646PubMedPubMedCentralCrossRefGoogle Scholar
  26. Insel T, Cuthbert B, Garvey M, Heinssen R, Pine DS, Quinn K, Wang P (2010) Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am J Psychiatr 167(7):748–751PubMedCrossRefGoogle Scholar
  27. Jasinski DR (1991) History of abuse liability testing in humans. Br J Addict 86:1559–1562PubMedCrossRefGoogle Scholar
  28. Johanson CE, Uhlenhuth EH (1980) Drug preference and mood in humans: d-amphetamine. Psychopharmacology 71(3):275–27PubMedCrossRefGoogle Scholar
  29. Kelly BC, Parsons JT, Wells BE (2006) Prevalence and predictors of club drug use among club-going young adults in New York City. J Urban Health 83:884–895PubMedPubMedCentralCrossRefGoogle Scholar
  30. Kessler RC, Adler L, Barkley R, Biederman J, Conners CK, Demler O, Zaslavsky AM (2006) The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry 163(4):716–723PubMedPubMedCentralCrossRefGoogle Scholar
  31. Kirkpatrick MG, Johanson CE, de Wit H (2013) Personality and the acute subjective effects of d-amphetamine in humans. J Psychopharmacol 27(3):256–264PubMedPubMedCentralCrossRefGoogle Scholar
  32. Leventhal AM, Brightman M, Ameringer KA, Greenberg J, Mickens L, Ray LA, Sun P, Sussman S (2010) Anhedonia associated with stimulant use and dependence in a population-based sample of American adults. Exp Clin Psychopharmacol 18(6):562–569PubMedPubMedCentralCrossRefGoogle Scholar
  33. Martin WR, Sloan JW, Sapira JD, Jasinski DR (1971) Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methylphenidate in man. Clin Pharmacol Ther 12:245–258PubMedGoogle Scholar
  34. McNair DM, Lorr M, Droppleman LF (1971) Profile of mood states (manual). Educational and Industrial Testing Services, San DiegoGoogle Scholar
  35. Newton TF, Kalechstein AD, De La Garza R II, Cutting DJ, Ling W (2005) Apathy predicts hedonic but not craving response to cocaine. Pharmacol Biochem Behav 82(1):236–240PubMedCrossRefGoogle Scholar
  36. Rector NA, Szacun-Shimizu K, Leybman M (2007) Anxiety sensitivity within the anxiety disorders: disorder-specific sensitivities and depression comorbidity. Behav Res Ther 45(8):1967–1975PubMedCrossRefGoogle Scholar
  37. Rodgers J, Buchanan T, Pearson C, Parrott AC, Ling J, Hefferman TM, Scholey AB (2006) Differential experiences of the psychobiological sequelae of ecstasy use: quantitative and qualitative data from an Internet study. J Psychopharmacol 20:437–446PubMedCrossRefGoogle Scholar
  38. Ross HE, Glaser FB, Germanson T (1988) The prevalence of psychiatric disorders in patients with alcohol and other drug problems. Arch Gen Psychiatry 45(11):1023–1031PubMedCrossRefGoogle Scholar
  39. Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS (2001) Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse 39(1):32–41PubMedCrossRefGoogle Scholar
  40. Ruhé HG, Mason NS, Schene AH (2007) Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies. Mol Psychiatry 12(4):331–359PubMedCrossRefGoogle Scholar
  41. Schott BH, Minuzzi L, Krebs RM, Elmenhorst D, Lang M, Winz OH, Bauer A (2008) Mesolimbic functional magnetic resonance imaging activations during reward anticipation correlate with reward-related ventral striatal dopamine release. J Neurosci 28(52):14311–14319PubMedCrossRefGoogle Scholar
  42. Schultz W, Apicella P, Scarnati E, Ljungberg T (1992) Neuronal activity in monkey ventral striatum related to the expectation of reward. J Neurosci 12(12):4595–4610PubMedGoogle Scholar
  43. Sevy S, Papadimitriou GN, Surmont DW, Goldman S, Mendiewicz J (1989) Noradrenergic function in generalized anxiety disorder, major depressive disorder, and healthy subjects. Biol Psychiatry 25(2):141–152PubMedCrossRefGoogle Scholar
  44. Shafer AB (2006) Meta-analysis of the factor structures of four depression questionnaires: Beck, CES-D, Hamilton, and Zung. J Clin Psychol 62(1):123–146PubMedCrossRefGoogle Scholar
  45. Shaffer HJ, Eber GB (2002) Temporal progression of cocaine dependence symptoms in the US National Comorbidity Survey. Addiction 97(5):543–554PubMedCrossRefGoogle Scholar
  46. Silberman EK, Reus VI, Jimerson DC et al (1981) Heterogeneity of amphetamine response in depressed patients. Am J Psychiatry 138:1302–1307PubMedCrossRefGoogle Scholar
  47. Snaith RP, Hamilton M, Morley S, Humayan A, Hargreaves D, Trigwell P (1995) A scale for the assessment of hedonic tone the Snaith-Hamilton Pleasure Scale. Br J Psychiatry 167(1):99–103PubMedCrossRefGoogle Scholar
  48. Southwick SM, Bremner JD, Rasmusson A, Morgan CA III, Arnsten A, Charney DS (1999) Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder. Biol Psychiatry 46(9):1192–1204PubMedCrossRefGoogle Scholar
  49. Tremblay LK, Naranjo CA, Cardenas L, Herrmann N, Busto UE (2002) Probing brain reward system function in major depressive disorder: altered response to dextroamphetamine. Arch Gen Psychiatry 59(5):409–416PubMedCrossRefGoogle Scholar
  50. Tremblay LK, Naranjo CA, Graham SJ, Herrmann N, Mayberg HS, Hevenor S, Busto UE (2005) Functional neuroanatomical substrates of altered reward processing in major depressive disorder revealed by a dopaminergic probe. Arch Gen Psychiatry 62(11):1228–1236PubMedCrossRefGoogle Scholar
  51. Watson D, Clark LA, Carey G (1988a) Positive and negative affectivity and their relation to anxiety and depressive disorders. J Abnorm Psychol 97(3):346PubMedCrossRefGoogle Scholar
  52. Watson D, Clark LA, Tellegen A (1988b) Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol 54(6):1063PubMedCrossRefGoogle Scholar
  53. Watson D, Weber K, Assenheimer JS, Clark LA, Strauss ME, McCormick RA (1995) Testing a tripartite model: I. Evaluating the convergent and discriminant validity of anxiety and depression symptom scales. J Abnorm Psychol 104:3–14PubMedCrossRefGoogle Scholar
  54. White TL, Justice AJ, de Wit H (2002) Differential subjective effects of D-amphetamine by gender, hormone levels and menstrual cycle phase. Pharmacol Biochem Behav 73(4):729–741PubMedCrossRefGoogle Scholar
  55. White TL, Lott DC, de Wit H (2006) Personality and the subjective effects of acute amphetamine in healthy volunteers. Neuropsychopharmacology 31(5):1064–1074PubMedCrossRefGoogle Scholar
  56. Wise RA (1982) Neuroleptics and operant behavior: the anhedonia hypothesis. Behav Brain Sci 5(01):39–53CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Matthew G. Kirkpatrick
    • 1
  • Nicholas I. Goldenson
    • 1
  • Nahel Kapadia
    • 1
  • Christopher W. Kahler
    • 2
  • Harriet de Wit
    • 3
  • Robert M. Swift
    • 2
    • 4
  • John E. McGeary
    • 2
    • 4
  • Steve Sussman
    • 1
  • Adam M. Leventhal
    • 1
  1. 1.Department of Preventive Medicine, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA
  2. 2.Center for Alcohol and Addiction StudiesBrown University School of Public HealthProvidenceUSA
  3. 3.Department of Psychiatry and Behavioral NeuroscienceUniversity of ChicagoChicagoUSA
  4. 4.Providence VA Medical CenterProvidenceUSA

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