Skip to main content
SpringerLink
Log in

Effects of stress on responses to methamphetamine in humans

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Studies with laboratory animals indicate that acute stress can modify both the direct effects of drugs of abuse and the tendency to self-administer drugs. Similarly, stress may also alter the acute subjective effects of drugs or the tendency to seek and consume drugs in humans.

Objectives

This laboratory-based study was designed to determine whether an acute social stressor (Trier Social Stress Test; TSST) alters subjective responses to a low oral dose of methamphetamine (METH; 10 mg) in humans.

Methods

The study utilized a mixed within- and between-subjects design. Healthy young men (n=28) participated in two sessions, one with stress and the other without. They were randomly assigned to two groups who received either METH (n=16) or placebo (n=12) on both sessions. On each session, subjects underwent the TSST or no TSST, and then ingested a beverage containing drug (10 mg METH) or placebo (PLAC). Over the next 1.5 h various self-reported mood measures and physiological measures, including salivary cortisol levels, were obtained at regular intervals.

Results

Both acute stress and METH produced mood-altering and physiological effects. Stress increased ratings of anxiety immediately after the stressful task, and increased salivary cortisol levels 20 min later. METH increased feelings of stimulation, and decreased fatigue and sedation, beginning about 20 min after drug administration and peaking at 60 and 90 min. Stress dampened the early responses to METH (i.e. at 20 min), but not the later effects (60 or 90 min).

Conclusions

These results demonstrate that acute stress can dampen subjective responses to a low dose of METH, but these effects are short-lived. It remains to be determined what mechanisms mediate this effect.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
Fig. 6.

Similar content being viewed by others

References

  • American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), 4th edn. American Psychiatric Association, Washington D.C.

  • Barbaccia ML, Concas A, Serra M, Biggio G (1998) Stress and neurosteroids in adult and aged rats. Exp Gerontol 33:697–712

    CAS  PubMed  Google Scholar 

  • Barbaccia ML, Affricano D, Trabucchi M, Purdy RH, Colombo G, Agabio R, Gessa GL (1999) Ethanol markedly increases "GABAergic" neurosteroids in alcohol-preferring rats. Eur J Pharmacol 19:R1–R2

    Google Scholar 

  • Barbaccia ML, Serra M, Purdy H, Biggio G (2001) Stress and neuroactive steroids. Int Rev Neurobiol 46:243–272

    CAS  PubMed  Google Scholar 

  • Barrot M, Vallée M, Gingras MA, Le Moal M, Mayo W, Piazza PV (1999) The neurosteroid pregnanolone sulphate increases dopamine release and the dopaminergic response to morphine in the rat nucleus accumbens. Eur J Neurosci 11:3757–3760

    Article  CAS  PubMed  Google Scholar 

  • Breslin FC, Hayward M, Baum A (1994) Effects of stress on perceived intoxication and the blood alcohol curve in men and women. Health Psychol 13:479–487

    Article  CAS  PubMed  Google Scholar 

  • Cador M, Dulluc J, Mormède P (1993) Modulation of the locomotor response to amphetamine by corticosterone. Neuroscience 56:981–988

    Google Scholar 

  • Caggiula AR, Donny EC, Epstein LH, Syed AF, Knopf S, Rose C, McAllister CG, Antelman SM, Perkins KC (1998) The role of corticosteroids in nicotine's physiological and behavioral effects. Psychoneuroendocrinology 23:143–159

    Article  CAS  PubMed  Google Scholar 

  • Conley KM, Toledano AY, Apfelbaum JL, Zacny JP (1997) Modulating effects of a cold water stimulus on opioid effects in volunteers. Psychopharmacology 131:313–320

    Article  CAS  PubMed  Google Scholar 

  • Deminière JM, Piazza PV, Le Moal M, Simon H (1989) Experimental approach to individual vulnerability to psychostimulant addiction. Neurosci Biobehav Rev 13:141–147

    PubMed  Google Scholar 

  • Deroche V, Piazza PV, Deminiere JM, Le Moal M, Simon H (1993) Rats orally self-administer corticosterone. Brain Res 622:315–320

    CAS  PubMed  Google Scholar 

  • Deroche V, Marinelli M, Maccari S, Le Moal M, Simon H, Piazza PV (1995) Stress-induced sensitization and glucocorticoids. I. Sensitization of dopamine-dependent locomotor effects of amphetamine and morphine depends on stress-induced corticosterone secretion. J Neurosci 15:7181–7188

    CAS  PubMed  Google Scholar 

  • Deroche V, Marinelli M, Le Moal M, Piazza PV (1997) Glucocorticoids and behavioral effects of psychostimulants. II: Cocaine intravenous self-administration and reinstatement depend on glucocorticoid levels. J Pharmacol Exp Ther 281:1401–1407

    CAS  PubMed  Google Scholar 

  • Derogatis L (1983) SCL-90-R manual II. Clinical Psychometric Research, Towson, Md.

  • Fahlke C, Engel JA, Eriksson CJP, Hård E, Söderpalm B (1994a) Involvement of corticosterone in the modulation of ethanol consumption in the rat. Alcohol 11:195–202

    CAS  PubMed  Google Scholar 

  • Fahlke C, Hård E, Thomasson R, Engel JA, Hansen S (1994b) Metyrapone-induced suppression of corticosterone synthesis reduces ethanol consumption in high-preferring rats. Pharmacol Biochem Behav 48:977–981

    CAS  PubMed  Google Scholar 

  • Fahlke C, Hård E, Eriksson CPJ, Engel JA, Hansen S (1995) Consequence of long-term exposure to corticosterone or dexamethasone on ethanol consumption in the adrenalectomized rat, and the effect of type I and type II corticosterone receptor antagonists. Psychopharmacology 117:216–224

    CAS  PubMed  Google Scholar 

  • Finn DA, Phillips TJ, Okorn DM, Chester JA, Cunnigham CL (1997) Rewarding effect of the neuroactive steroid 3α-hydroxy-5α-pregnan-20-one in mice. Pharmacol Biochem Behav 56:261–264

    CAS  PubMed  Google Scholar 

  • Fischman M, Foltin RW (1991) Utility of subjective-effects measurements in assessing abuse liability of drugs in humans. Br J Addict 86:1563–1570

    CAS  PubMed  Google Scholar 

  • Folstein MF, Luria R (1973) Reliability, validity, and clinical application of the Visual Analogue Mood Scale. Psychol Med 3:479–486

    CAS  PubMed  Google Scholar 

  • Fox HM, Gifford S (1953) Psychological responses to ACTH and cortisone. Psychosom Med 15:614–631

    Google Scholar 

  • Freeman EW, Purdy RH, Coutifaris C, Rickels K, Paul SM (1993) Anxiolytic metabolites of progesterone: correlation with mood and performance measures following oral progesterone administration in healthy female volunteers. Clin Neuroendocrinol 58:478–484

    Google Scholar 

  • Garlind T, Goldberg L, Graf L, Perman ES, Strandell T, Strom G (1960) Effect of ethanol on circulatory, metabolic and neurohormonal function during muscular work in men. Acta Pharmacol Toxiol 17:106–114

    CAS  Google Scholar 

  • Gerra G, Zaimovic A, Mascetti GG, Gardini S, Zambelli U, Timpano M, Raggi MA, Brambilla F (2001) Neuroendocrine responses to experimentally induced psychological stress in healthy humans. Psychoneuroendocrinology 26:91–107

    Article  CAS  PubMed  Google Scholar 

  • Goeders NE, Guerin GF (1994) Non-contingent electric footshock facilities the acquisition of intravenous cocaine self-administration in rats. Psychopharmacology 114:63–70

    CAS  PubMed  Google Scholar 

  • Goeders NE, Guerin GF (1996) Role of corticosterone in intravenous cocaine self-administration in rats. Neuroendocrinology 64:337–348

    CAS  PubMed  Google Scholar 

  • Goolker P, Shein J (1953) Psychic effects of ACTH and cortisone. Psychosom Med 15:589–613

    Google Scholar 

  • Haney M, Maccari S, Le Moal M, Simon H, Piazza PV (1995) Social stress increases the acquisition of cocaine self-administration in male and female rats. Brain Res 698:46–52

    CAS  PubMed  Google Scholar 

  • Hansen S, Fahlke C, Söderpalm AHV, Hård E (1995) Adrenal corticosteroid secretion for the food restriction-induced enhancement of alcohol drinking in the rat. Psychopharmacology 121:213–221

    Google Scholar 

  • Harris DS, Mendelson JE, Wolkowitz OM, Reus VI, Jones RT (2001) Effects of cortisol on human methamphetamine response: preliminary results. Drug Alcohol Depend 63:243

    Google Scholar 

  • Higgins RL, Marlatt GA (1975) Fear of interpersonal evaluation as a determinant of alcohol consumption in male social drinkers. J Abnorm Psychol 84:644–651

    CAS  PubMed  Google Scholar 

  • Hull JG, Young RD (1983) Self-consciousness, self-esteem, and success-failure as determinants of alcohol consumption in male social drinkers. J Person Soc Psychol 44:1097–1109

    CAS  Google Scholar 

  • Kirschbaum C, Wüst S, Hellhammer DH (1992) Consistent sex differences in cortisol response to psychological stress. Psychosom Med 54:648–657

    CAS  PubMed  Google Scholar 

  • Kirschbaum C, Pirke K-M, Hellhammer DH (1993a) The "Trier Social Stress Test"—a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology 28:76–81

    CAS  PubMed  Google Scholar 

  • Kirschbaum C, Strasburger J, Hellhammer DH (1993b) Attenuated cortisol responses to psychological stress but not to corticotropin-releasing hormone or bicycle ergometry in young habitual smokers. Pharmacol Biochem Behav 44:527–531

    CAS  PubMed  Google Scholar 

  • Kirschbaum C, Pirke K-M, Hellhammer DH (1995) Preliminary evidence for reduced cortisol responsivity to psychological stress in women using oral contraceptive medication. Psychoneuroendocrinology 20:509–514

    Article  CAS  PubMed  Google Scholar 

  • Koob GF (1992) Drugs of abuse: anatomy, pharmacology and function of reward pathways. Trends Pharmacol Sci 13:177–184

    PubMed  Google Scholar 

  • Majewaska MD, Harrison NL, Schwartz RD, Barker JL, Paul SM (1986) Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science 232:1004–1007

    CAS  PubMed  Google Scholar 

  • Marinelli M, Rougè-Pont F, De Jesus-Oliveira C, Le Moal M, Piazza PV (1997a) Acute blockade of corticosterone secretion decreases the psychomotor stimulant effects of cocaine. Neuropsychopharmacology 16:156–161

    Google Scholar 

  • Marinelli M, Rouge-Pont F, Deroche V, Barrot M, De Jesus-Oliveira C, Le Moal M, Piazza PV (1997b) Glucocorticoids and behavioral effects of psychostimulants. I: locomotor response to cocaine depends on basal levels of glucocorticoids. J Pharmacol Exp Ther 281:1392–1400

    CAS  PubMed  Google Scholar 

  • Marlatt GA, Kosturn CF, Lang AR (1975) Provocation to anger and opportunity for retaliation as determinants of alcohol consumption in social drinkers. J Abnorm Psychol 84:652–659

    CAS  PubMed  Google Scholar 

  • 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 12:245–258

    CAS  PubMed  Google Scholar 

  • Miczek KA, Mutschler NH (1996) Activational effects of social stress on IV cocaine self-administration in rats. Psychopharmacology 128:256–264

    CAS  PubMed  Google Scholar 

  • Morrow AL, Janis GC, VanDoren MJ, Matthews DB, Samson HH, Janak PH, Grant KA (1999) Neurosteroids mediate pharmacological effects of ethanol: a new mechanism of ethanol action? Alcohol Clin Exp Res 23:1933–1940

    Google Scholar 

  • Paul SM, Purdy RH (1992) Neuroactive steroids. FASEB J 6:2311–2322

    CAS  PubMed  Google Scholar 

  • Perkins KA, Grobe JE (1992) Increased desire to smoke during acute stress. Br J Addict 87:1037–1040

    CAS  PubMed  Google Scholar 

  • Piazza PV, Le Moal M (1998) The role of stress in drug self-administration. Trends Pharmacol Sci 19:67–74

    CAS  PubMed  Google Scholar 

  • Piazza PV, Deminiere JM, Le Moal M, Simon H (1990) Stress- and pharmacologically-induced behavioral sensitization increases vulnerability to acquisition of amphetamine self-administration. Brain Res 514:22–26

    CAS  PubMed  Google Scholar 

  • Piazza PV, Maccari S, Deminiere JM, Le Moal M, Mormede P, Simon H (1991) Corticosterone levels determine individual vulnerability to amphetamine self-administration. Proc Natl Acad Sci USA 88:2088–2092

    CAS  PubMed  Google Scholar 

  • Piazza PV, Deroche V, Deminier J-M, Maccari S, Le Moal M, Simon H (1993) Corticosterone in the range of stress induced levels possess reinforcing properties: implications for sensation seeking behaviors. Proc Natl Acad Sci USA 90 11738–11742

    Google Scholar 

  • Piazza PV, Marinelli M, Jodogne C, Deroche V, Rougè-Pont F, Maccari S, Le Moal M, Simon H (1994) Inhibition of corticosterone synthesis by metyrapone decreases cocaine-induced locomotion and relapse of cocaine self-administration. Brain Res 658:259–264

    CAS  PubMed  Google Scholar 

  • Plihal W, Krug R, Pietrowsky R, Fehm HL, Born J (1996) Corticosteroid receptor mediated effects on mood in humans. Psychoneuroendocrinology 21:515–523

    Article  CAS  PubMed  Google Scholar 

  • Pomerleau OF, Pomerleau CS (1990) Behavioural studies in humans: anxiety, stress and smoking. In: The biology of nicotine dependence. CIBA Foundation Symposium 152:225–239

    CAS  PubMed  Google Scholar 

  • Robinson TE, Berridge KC (1993) The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Rev 18:247–291

    CAS  PubMed  Google Scholar 

  • Rome HP, Braceland F (1952) The psychological response to ACTH, cortisone, hydrocortisone, and related steroid substances. Am J Psychiatry 108:641–651

    Google Scholar 

  • Rose JE, Ananda S, Jarvik ME (1983) Cigarette smoking during anxiety-provoking and monotonous tasks. Addict Behav 8:353–359

    Article  CAS  PubMed  Google Scholar 

  • Schenk S, Lacelle G, Gorman K, Amit Z (1987) Cocaine self-administration in rats influenced by environmental conditions: implications for the etiology of drug abuse. Neurosci Lett 81 227–231

    Google Scholar 

  • Selzer ML (1971) The Michigan alcoholism screening test: the quest for a new diagnostic instrument. Am Psychiatry 127:1653–1658

    CAS  Google Scholar 

  • Sinha R (2001) How does stress increase risk of drug abuse and relapse? Psychopharmacology 158:343–359

    Google Scholar 

  • Sinha R, Catapano D, O'Malley S (1999) Stress-induced craving and stress response in cocaine dependent individuals. Psychopharmacology 142:343–351

    CAS  PubMed  Google Scholar 

  • Söderpalm AHV, de Wit H (2002) Effects of stress and alcohol on subjective state in humans. Alcohol Clin Exp Res 26:818–826

    PubMed  Google Scholar 

  • Söderpalm AHV, Hansen S (1999) Alcohol alliesthesia: food restriction increases the palatability of alcohol through a corticosterone dependent mechanism. Physiol Behav 67:409–415

    Article  PubMed  Google Scholar 

  • Stone EA, Lin Y, Suckow RF, Quartermain D (2002) Stress-induced subsensitivity to modafinil and its prevention by corticosteroids. Pharmacol Biochem Behav 73:971–978

    Article  CAS  PubMed  Google Scholar 

  • Tidey JW, Miczek KA (1997) Acquisition of cocaine self-administration after social stress: role of accumbens dopamine. Psychopharmacology 130:203–212

    CAS  PubMed  Google Scholar 

  • Wachtel S, de Wit H (2001) Lack of effect of intravenous hydrocortisone on mood in humans: a preliminary study. Behav Pharmacol 12:373–376

    CAS  PubMed  Google Scholar 

  • Wachtel S, Charnot A, de Wit H (2001) Acute hydrocortisone does not affect subjective responses to d-amphetamine in humans. Psychopharmacology 153:380–388

    Article  CAS  PubMed  Google Scholar 

  • Wachtel S, Ortengren A, de Wit H (2002) The effects of acute haloperidol or risperidone on subjective responses to methamphetamine in healthy volunteers. Drug Alcohol Depend 68:23–33

    Article  CAS  PubMed  Google Scholar 

  • Wolff HG, Hardy JD, Goddell H (1942) Studies on pain: Measurement of the effect of ethyl alcohol on the pain threshold and on the "alarm" reaction. J Pharmacol Exp Ther 75:28–49

    Google Scholar 

  • Zacny JP, McKay MA, Toledano AY, Marks S, Young CJ, Klock A, Apfelbaum JL (1996) The effects of a cold-water immersion stressor on the reinforcing and subjective effects of fentanyl in healthy volunteers. Drug Alcohol Depend 42:133–142

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank B. Frank Mackey and Elizabeth Young for technical assistance of the study. This study was supported by grants from the National Institute on Drug Abuse (RO1 DA02812; T32 DA07255), the General Clinical Research Center (USPHS MO1RR00055), and the Swedish Foundation for International Cooperation and in Research and Higher Education (STINT).

Author information

Authors and Affiliations

  1. Department of Psychiatry, MC3077, The University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, USA

    Anna Söderpalm, Lilia Nikolayev & Harriet de Wit

Authors
  1. Anna Söderpalm
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lilia Nikolayev
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Harriet de Wit
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Harriet de Wit.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Söderpalm, A., Nikolayev, L. & de Wit, H. Effects of stress on responses to methamphetamine in humans. Psychopharmacology 170, 188–199 (2003). https://doi.org/10.1007/s00213-003-1536-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-003-1536-5

Keywords

Search

Navigation