The role of monoamines in the changes in body temperature induced by 3,4‐methylenedioxymethamphetamine (MDMA, ecstasy) and its derivatives
British Journal of Pharmacology March 3, 2010 DOI: 10.1111/j.1476-5381.2010.00722.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | MDMA |
| Keywords | Hyperthermia Hypothermia Pharmacology Thermoregulation Dopamine Hallucinogen Norepinephrine Anesthesia |
| Citations | 88 |
| Key findings | MDMA-induced hyperthermia involves complex interactions among serotonin, dopamine, and noradrenaline systems, and no single pharmaceutical agent is likely to reverse it, making body cooling the principal clinical approach. |
Abstract
Hyperthermia is probably the most widely known acute adverse event that can follow ingestion of 3,4‐methylenedioxymethamphetamine (MDMA, ecstasy) by recreational users. The effect of MDMA on body temperature is complex because the drug has actions on all three major monoamine neurotransmitters [5‐hydroxytryptamine (5‐HT), dopamine and noradrenaline], both by amine release and by direct receptor activation. Hyperthermia and hypothermia can be induced in laboratory animals by MDMA, depending on the ambient temperature, and involve both central thermoregulation and peripheral changes in blood flow and thermogenesis. Acute 5‐HT release is not directly responsible for hyperthermia, but 5‐HT receptors are involved in modulating the hyperthermic response. Impairing 5‐HT function with a neurotoxic dose of MDMA or p ‐chlorophenylalanine alters the subsequent MDMA‐induced hyperthermic response. MDMA also releases dopamine, and evidence suggests that this transmitter is involved in both the hyperthermic and hypothermic effects of MDMA in rats. The noradrenergic system is also involved in the hyperthermic response to MDMA. MDMA activates central α 2A ‐adrenoceptors and peripheral α 1 ‐adrenoceptors to produce cutaneous vasoconstriction to restrict heat loss, and β 3 ‐adrenoceptors in brown adipose tissue to increase heat generation. The hyperthermia occurring in recreational users of MDMA can be fatal, but data reviewed here indicate that it is unlikely that any single pharmaceutical agent will be effective in reversing the hyperthermia, so careful body cooling remains the principal clinical approach. Crucially, educating recreational users about the potential dangers of hyperthermia and the control of ambient temperature should remain key approaches to prevent this potentially fatal problem.
Comparable studies
Other narrative reviews on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Human Pharmacology of MDMA | 2004 | Review | |
| Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research | 2001 | Review | |
| 3,4‐Methylenedioxymethamphetamine (MDMA, “Ecstasy”): pharmacology and toxicology in animals and humans | 1994 | Review | |
| (±)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-Induced Serotonin Neurotoxicity: Studies in Animals | 2000 | Review | |
| Amphetamine toxicities | 2010 | Review |
Citations in the library
Cited by 30
- Pharmacological profile of novel psychoactive benzofurans British Journal of Pharmacology March 13, 2015
- Genetic Deletion of Trace Amine 1 Receptors Reveals Their Role in Auto-Inhibiting the Actions of Ecstasy (MDMA) Journal of Neuroscience November 23, 2011
- 3,4-methylenedioxymethamphetamine (MDMA): current perspectives Substance Abuse and Rehabilitation November 1, 2013
- Multiple MDMA (Ecstasy) Overdoses at a Rave Event Journal of Intensive Care Medicine May 28, 2012
- Carvedilol inhibits the cardiostimulant and thermogenic effects of MDMA in humans British Journal of Pharmacology March 8, 2012
and 25 more in the library
Cites 49
- Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin Synapse 2000
- Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Journal of Neuroscience July 1, 1998
- 'Eve' and 'Ecstasy'. A report of five deaths associated with the use of MDEA and MDMA JAMA March 27, 1987
- Chronic tolerance to recreational MDMA (3,4-methylenedioxymethamphetamine) or Ecstasy Journal of Psychopharmacology 2005
- The pharmacology of the acute hyperthermic response that follows administration of 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’) to rats British Journal of Pharmacology 2002
and 44 more in the library