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MDMA, Methylone, and MDPV: Drug-Induced Brain Hyperthermia and Its Modulation by Activity State and Environment

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Neuropharmacology of New Psychoactive Substances (NPS)

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 32))

Abstract

Psychomotor stimulants are frequently used by humans to intensify the subjective experience of different types of social interactions. Since psychomotor stimulants enhance metabolism and increase body temperatures, their use under conditions of physiological activation and in warm humid environments could result in pathological hyperthermia, a life-threatening symptom of acute drug intoxication. Here, we will describe the brain hyperthermic effects of MDMA, MDPV, and methylone, three structurally related recreational drugs commonly used by young adults during raves and other forms of social gatherings. After a short introduction on brain temperature and basic mechanisms underlying its physiological fluctuations, we will consider how MDMA, MDPV, and methylone affect brain and body temperatures in awake freely moving rats. Here, we will discuss the role of drug-induced heat production in the brain due to metabolic brain activation and diminished heat dissipation due to peripheral vasoconstriction as two primary contributors to the hyperthermic effects of these drugs. Then, we will consider how the hyperthermic effects of these drugs are modulated under conditions that model human drug use (social interaction and warm ambient temperature). Since social interaction results in brain and body heat production, coupled with skin vasoconstriction that impairs heat loss to the external environment, these physiological changes interact with drug-induced changes in heat production and loss, resulting in distinct changes in the hyperthermic effects of each tested drug. Finally, we present our recent data, in which we compared the efficacy of different pharmacological strategies for reversing MDMA-induced hyperthermia in both the brain and body. Specifically, we demonstrate increased efficacy of the centrally acting atypical neuroleptic compound clozapine over the peripherally acting vasodilator drug, carvedilol. These data could be important for understanding the potential dangers of MDMA in humans and the development of pharmacological tools to alleviate drug-induced hyperthermia – potentially saving the lives of highly intoxicated individuals.

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Abbreviations

ip:

Intraperitoneal

iv:

Intravenous

MDMA:

3,4-Methylenedioxymethamphetamine (Ecstasy)

MDPV:

3,4-Methylenedioxypyrovalerone

METH:

Methamphetamine

methylone:

3,4-Methylenedioxymethcathinone

NAc:

Nucleus accumbens

sc:

Subcutaneous

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Acknowledgements

This work was supported by the National Institute on Drug Abuse, Intramural Research Program (DA000445-14).

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No potential conflicts of interest are disclosed.

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Authors and Affiliations

  1. Behavioral Neuroscience Branch, National Institute on Drug Abuse – Intramural Research Program, NIH, 333 Cassell Drive, Baltimore, MD, 21224, USA

    Eugene A. Kiyatkin & Suelynn E. Ren

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  1. Eugene A. Kiyatkin
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  2. Suelynn E. Ren
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Correspondence to Eugene A. Kiyatkin .

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Editors and Affiliations

  1. Designer Drug Research Unit (DDRU), National Institute on Drug Abuse, Baltimore, MD, USA

    Michael H. Baumann

  2. Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, USA

    Richard A. Glennon

  3. RTI International, Research Triangle Park, NC, USA

    Jenny L. Wiley

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Kiyatkin, E.A., Ren, S.E. (2016). MDMA, Methylone, and MDPV: Drug-Induced Brain Hyperthermia and Its Modulation by Activity State and Environment. In: Baumann, M.H., Glennon, R.A., Wiley, J.L. (eds) Neuropharmacology of New Psychoactive Substances (NPS). Current Topics in Behavioral Neurosciences, vol 32. Springer, Cham. https://doi.org/10.1007/7854_2016_35

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