Caffeine provokes adverse interactions with 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’) and related psychostimulants: mechanisms and mediators
Natacha Vanattou‐saïfoudine, Ruth Mcnamara, Andrew Harkin
British Journal of Pharmacology June 1, 2012 DOI: 10.1111/j.1476-5381.2012.02065.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | MDMA Serotonin |
| Keywords | Caffeine Pharmacology Hallucinogen Drug Dextroamphetamine Adverse effect Dopamine |
| Citations | 60 |
| Key findings | Caffeine co-administration with MDMA in rats profoundly enhances acute toxicity (high core body temperature, tachycardia, increased mortality) and long-term serotonergic neurotoxicity. |
Abstract
Concomitant consumption of caffeine with recreational psychostimulant drugs of abuse can provoke severe acute adverse reactions in addition to longer term consequences. The mechanisms by which caffeine increases the toxicity of psychostimulants include changes in body temperature regulation, cardiotoxicity and lowering of the seizure threshold. Caffeine also influences the stimulatory, discriminative and reinforcing effects of psychostimulant drugs. In this review, we consider our current understanding of such caffeine‐related drug interactions, placing a particular emphasis on an adverse interaction between caffeine and the substituted amphetamine, 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’), which has been most recently described and characterized. Co‐administration of caffeine profoundly enhances the acute toxicity of MDMA in rats, as manifested by high core body temperature, tachycardia and increased mortality. In addition, co‐administration of caffeine enhances the long‐term serotonergic neurotoxicity induced by MDMA. Observations to date support an interactive model of drug‐induced toxicity comprising MDMA‐related enhancement of dopamine release coupled to a caffeine‐mediated antagonism of adenosine receptors in addition to inhibition of PDE. These experiments are reviewed together with reports of caffeine‐related drug interactions with cocaine, d‐amphetamine and ephedrine where similar mechanisms are implicated. Understanding the underlying mechanisms will guide appropriate intervention strategies for the management of severe reactions and potential for increased drug‐related toxicity, resulting from concomitant caffeine consumption.
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 20
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- The preclinical pharmacology of mephedrone; not justMDMAby another name British Journal of Pharmacology March 24, 2014
- MDMA/ecstasy use and psilocybin use are associated with lowered odds of psychological distress and suicidal thoughts in a sample of US adults Journal of Psychopharmacology 2022
- Qualitative Research of Online Drug Misuse Communities with Reference to the Novel Psychoactive Substances University of Hertfordshire Research Archive May 29, 2013
and 15 more in the library
Cites 11
- A review of acute effects of 3,4-methylenedioxymethamphetamine in healthy volunteers Journal of Psychopharmacology March 1, 2006
- Agony and ecstasy: a review of MDMA effects and toxicity European Psychiatry August 1, 2000
- Studies on the effect of MDMA (‘ecstasy’) on the body temperature of rats housed at different ambient room temperatures British Journal of Pharmacology July 4, 2005
- Mechanisms mediating the ability of caffeine to influence MDMA (‘Ecstasy’)‐induced hyperthermia in rats British Journal of Pharmacology May 24, 2010
- MDMA and Seizures: A Dangerous Liaison? Annals of the New York Academy of Sciences August 1, 2006
and 6 more in the library