MDMA, Methylone, and MDPV: Drug-Induced Brain Hyperthermia and Its Modulation by Activity State and Environment.
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.
Behavioral Neuroscience Branch, National Institute on Drug Abuse - Intramural Research Program, NIH, 333 Cassell Drive, Baltimore, MD, 21224, USA. ekiyatki@intra.nida.nih.gov.
Eugene A
EA
Kiyatkin
Behavioral Neuroscience Branch, National Institute on Drug Abuse - Intramural Research Program, NIH, 333 Cassell Drive, Baltimore, MD, 21224, USA.
Suelynn E
SE
Ren
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D052117:Benzodioxoles / Q000009:adverse effects* / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D002227:Carbazoles / Q000494:pharmacology / Q000627:therapeutic use; D000077261:Carvedilol; D000697:Central Nervous System Stimulants / Q000009:adverse effects* / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology / Q000627:therapeutic use; D004777:Environment; D005334:Fever / Q000139:chemically induced* / Q000188:drug therapy; D006801:Humans; D007398:Interpersonal Relations; D008694:Methamphetamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects* / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology / Q000627:therapeutic use; D011759:Pyrrolidines / Q000009:adverse effects* / Q000494:pharmacology; D051381:Rats; D012919:Social Behavior; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use; D000094982:Synthetic Cathinone
D014150:Antipsychotic Agents; D052117:Benzodioxoles; D002227:Carbazoles; D000697:Central Nervous System Stimulants; D011412:Propanolamines; D011759:Pyrrolidines; D014665:Vasodilator Agents; D000077261:Carvedilol; D008694:Methamphetamine; D003024:Clozapine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; C400939:methylone; D000094982:Synthetic Cathinone
Active ingredients of “bath salts”; Brain metabolism; Cerebral heat production; Drug-induced intoxication; Drugs of abuse; MDMA (Ecstasy); Psychomotor stimulants; Rave parties; Vasoconstriction
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