Skip to main content
SpringerLink
Log in

Thermoregulatory effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans

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

Abstract

Rationale

Although 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) has been reported to cause fatal hyperthermia, few studies of the effects of MDMA on core body temperature in humans have been conducted demonstrating increased body temperature. In rats, MDMA causes hyperthermia at warm ambient temperatures but hypothermia at cold ones.

Objectives

In this study, the physiological and subjective effects of MDMA in humans were determined at cold (18°C) and warm (30°C) ambient temperatures in a temperature and humidity-controlled laboratory.

Methods

Ten healthy volunteers who were recreational users of MDMA were recruited. Four laboratory sessions were conducted in a 2×2 design [i.e., two sessions at 30°C and two at 18°C, two during MDMA (2 mg/kg, p.o.) and two during placebo, in double-blind fashion]. Core body temperature (ingested radiotelemetry pill), skin temperature (four weighted sites), heart rate, blood pressure, metabolic rate (indirect calorimetry), shivering (electromyogram levels), and sweat rate (capacitance hygrometry) were measured as well as subjective effects for several time periods following capsule ingestion.

Results

MDMA produced significant elevations in core body temperature and metabolic rate in both warm and cold conditions. MDMA also produced significant elevations in blood pressure and heart rate and significantly increased several ratings of subjective effects similar to those previously reported. There were no differences related to ambient temperature for any of the subjective effects, except that ratings of cold and warm were appropriate to the ambient temperature and were not influenced by MDMA.

Conclusions

Unlike findings in rats, MDMA increased core body temperature regardless of ambient temperature in humans. These increases appeared related to increases in metabolic rate, which were substantial. These findings warrant further investigations on the role of MDMA and other stimulants in altering metabolism and thermogenesis.

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

Similar content being viewed by others

References

  • Crandall CG, Vongpatanasin W, Victor RG (2002) Mechanism of cocaine-induced hyperthermia in humans. Ann Intern Med 136:785–791

    PubMed  CAS  Google Scholar 

  • Dafters RI (1995) Hyperthermia following MDMA administration in rats: effects of ambient temperature, water consumption and chronic dosing. Physiol Behav 58:877–882

    Article  PubMed  CAS  Google Scholar 

  • Dafters RI, Lynch E (1998) Persistent loss of thermoregulation in the rat induced by 3, 4-methylenedioxymethamphetamine (MDMA or “Ecstasy”) but not by fenfluramine. Psychopharmacology (Berl) 138:207–212

    Article  CAS  Google Scholar 

  • Dar KJ, McBrien ME (1996) MDMA induced hyperthermia: report of a fatality and review of current therapy. Intensive Care Med 22:995–996

    Article  PubMed  CAS  Google Scholar 

  • Fantegrossi WE, Godlewski T, Karabenick RL, Stephens JM, Ullrich T, Rice KC, Woods JH (2003) Pharmacological characterization of the effects of 3,4-methylenedioxymethamphetamine (“ecstasy”) and its enantiomers on lethality, core temperature, and locomotor activity in singly housed and crowded mice. Psychopharmacology (Berl) 166(3):202–211

    CAS  Google Scholar 

  • Ferrie R, Loveland RC (2000) Bilateral gluteal compartment syndrome after ‘ecstasy’ hyperpyrexia. J R Soc Med 93:260

    PubMed  CAS  Google Scholar 

  • First MB, Spitzer RL, Gibbon M, Williams JBW (1996) Structured clinical interview of DSM-IV axis I disorders—patient edition (SCID I/P, version 2). NY State Psychiatric Institute, New York, NY

    Google Scholar 

  • Fisher M, Paolone V, Rosene J, Drury D, Van Dyke A, Moroney D (1999) The effect of submaximal exercise on recovery hermodynamics and thermoregulation in men and women. Res Q Exerc Sport 70:361–368

    PubMed  CAS  Google Scholar 

  • Freedman RR, Krell W (1999) Reduced thermoregulatory null zone in postmenopausal women with hot flashes. Am J Obstet Gynecol 181:66–70

    Article  PubMed  CAS  Google Scholar 

  • Gleeson M (1998) Temperature regulation during exercise. Int J Sports Med 19(Suppl 2):S96–S99

    Article  PubMed  Google Scholar 

  • Gonzales LP (1993) Cocaine alters body temperature and behavioral thermoregulatory responses. Neuroreport 4:106–108

    Article  PubMed  Google Scholar 

  • Gordon CJ, Watkinson WP, O'Callaghan JP, Miller DB (1991) Effects of 3, 4-methylenedioxymethamphetamine on autonomic thermoregulatory responses of the rat. Pharmacol Biochem Behav 38(2):339–344

    Article  PubMed  CAS  Google Scholar 

  • Gouzoulis-Mayfrank E, Thelen B, Habermeyer E, Kunert HJ, Kovar KA, Lindenblatt H, Hermle L, Spitzer M, Sass H (1999) Psychopathological, neuroendocrine and autonomic effects of 3,4-methylenedioxyethylamphetamine (MDE), psilocybin and d-methamphetamine in healthy volunteers. Psychopharmacology (Berl) 142:41–50

    Article  CAS  Google Scholar 

  • Green AR, Mechan AO, Elliott JM, O'Shea E, Colado MI (2003) The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”). Pharmacol Rev 55:463–508

    Article  PubMed  CAS  Google Scholar 

  • Green AR, O'Shea E, Colado MI (2004) A review of the mechanisms involved in the acute MDMA (ecstasy)-induced hyperthermic response. Eur J Pharmacol 500(1–3):3–13

    Article  PubMed  CAS  Google Scholar 

  • Grob CS, Poland RE, Chang L, Ernst T (1996) Psychobiologic effects of 3, 4-methylenedioxymethamphetamine in humans: methodological considerations and preliminary observations. Behav Brain Res 73:103–107

    Article  PubMed  CAS  Google Scholar 

  • Henry JA (2000) Metabolic consequences of drug misuse. Br J Anaesth 85:136–142

    Article  PubMed  CAS  Google Scholar 

  • Hoeks J, van Baak MA, Hesselink MK, Hul GB, Vidal H, Saris WH, Schrauwen P (2003) Effect of beta1- and beta2-adrenergic stimulation on energy expenditure, substrate oxidation, and UCP3 expression in humans. Am J Physiol Endocrinol Metab 285:E775–E781

    PubMed  CAS  Google Scholar 

  • Johanson CE, Uhlenhuth EH (1980) Drug preference and mood in humans: d-amphetamine. Psychopharmacology (Berl) 71:275–279

    Article  CAS  Google Scholar 

  • Lester SJ, Baggott M, Welm S, Schiller NB, Jones RT, Foster E, Mendelson J (2000) Cardiovascular effects of 3,4-methylenedioxymethamphetamine. Ann Intern Med 133:969–973

    PubMed  CAS  Google Scholar 

  • Malberg JE, Seiden LS (1998) Small changes in ambient temperature cause large changes in 3, 4-methylenedioxymethamphetamine (MDMA)-induced serotonin neurotoxicity and core body temperature in the rat. J Neurosci 18(13):5086–5094

    PubMed  CAS  Google Scholar 

  • Mallick A, Bodenham AR (1997) MDMA induced hyperthermia: a survivor with an initial body temperature of 42.9 degrees C. J Accid Emerg Med 14:336–338

    PubMed  CAS  Google Scholar 

  • Martin WR, Sloan JW, Sapira JD, Jasinski DR (1971) Physiologic, subjective and behavioral effects of amphetamine, ephedrine, phemetrazine, and methylphenidate in man. Clin Pharmacol Ther 12:245–258

    PubMed  CAS  Google Scholar 

  • Mas M, Farré M, De La Torre R, Roset PN, Ortuño J, Segura J, Camí J (1999) Cardiovascular and neuroendocrine effects and pharmacokinetics of 3, 4-methylenedioxymethamphetamine in humans. J Pharmacol Exp Ther 290:136–145

    PubMed  CAS  Google Scholar 

  • McNair DM, Lorr M, Droppleman LF (1971) Manual for the profile of mood states. Educational and Industrial Testing Service, San Diego

    Google Scholar 

  • Pedersen NP, Blessing WW (2001) Cutaneous vasoconstriction contributes to hyperthermia induced by 3,4-methylenedioxymethamphetamine (ecstasy) in conscious rabbits. J Neurosci 21:8648–8654

    PubMed  CAS  Google Scholar 

  • Schiffelers SL, Saris WH, Boomsma F, van Baak MA (2001) Beta(1)- and beta(2)-adrenoceptor-mediated thermogenesis and lipid utilization in obese and lean men. J Clin Endocrinol Metab 86:2191–2199

    Article  PubMed  CAS  Google Scholar 

  • Schmidt CJ, Black CK, Abbate GM, Taylor VL (1990) Methylenedioxymethamphetamine-induced hyperthermia and neurotoxicity are independently mediated by 5-HT2 receptors. Brain Res 529:85–90

    Article  PubMed  CAS  Google Scholar 

  • Tancer M, Johanson CE (2003) Reinforcing, subjective, and physiological effects of MDMA in humans: a comparison with d-amphetamine and mCPP. Drug Alcohol Depend 72:33–44

    Article  PubMed  CAS  Google Scholar 

  • Tucker GT, Lennard MS, Ellis SW, Woods HF, Cho AK, Lin LY, Hiratsuka A, Schmitz DA, Chu TY (1994) The demethylenation of methylenedioxymethamphetamine (“ecstasy”) by debrisoquine hydroxylase (CYP2D6). Biochem Pharmacol 47:1151–1156

    Article  PubMed  CAS  Google Scholar 

  • Vollenweider FX, Gamma A, Liechti M, Huber T (1998) Psychological and cardiovascular effects and short-term sequelae of MDMA (“ecstasy”) in MDMA-naïve healthy volunteers. Neurophychopharmacology 19(4):241–251

    Article  CAS  Google Scholar 

  • Zachary R (1986) Manual for the Revised Shipley Institute of Living Scale. Western Psychological Services, Los Angeles

    Google Scholar 

Download references

Acknowledgements

Supported by RO1 DA-14874 from the National Institute on Drug Abuse (P.I. Tancer) and Joe Young, Sr. funds from the state of Michigan. The authors would like to thank James Granneman for his input on issues of thermogenesis.

Author information

Authors and Affiliations

  1. Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, 48201, USA

    Robert R. Freedman, Chris-Ellyn Johanson & Manuel E. Tancer

  2. C.S. Mott Center, 275 E. Hancock Avenue, Detroit, MI, 48201, USA

    Robert R. Freedman

Authors
  1. Robert R. Freedman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chris-Ellyn Johanson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Manuel E. Tancer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert R. Freedman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Freedman, R.R., Johanson, CE. & Tancer, M.E. Thermoregulatory effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans. Psychopharmacology 183, 248–256 (2005). https://doi.org/10.1007/s00213-005-0149-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-005-0149-6

Keywords

Search

Navigation