Chronic tolerance to recreational MDMA (3,4-methylenedioxymethamphetamine) or Ecstasy
Journal of Psychopharmacology 2005 DOI: 10.1177/0269881105048900 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Population | Recreational Ecstasy users |
| Topics | MDMA |
| Keywords | Recreational drug Hallucinogen Recreational use Pharmacology |
| Citations | 241 |
| Key findings | There is extensive evidence for chronic pharmacodynamic tolerance to recreational MDMA, but the underlying mechanisms are unclear, with serotonergic neurotoxicity as a possible contributing factor. |
Abstract
This review of chronic tolerance to MDMA (3,4-methylenedioxymetamphetamine) covers the empirical data on dosage escalation, reduced subjective efficacy and bingeing in recreational Ecstasy users. Novice users generally take a single Ecstasy tablet, regular users typically take 2-3 tablets, whereas the most experienced users may take 10-25 tablets in a single session. Reduced subjective efficacy following repeated usage is typically described, with many users subjectively reporting the development of tolerance. Intensive self-administration or bingeing is often noted by experienced users. This can comprise ‘stacking’ on several tablets together, and ‘boosting’ on successive doses over an extended period. Some experienced users snort Ecstasy powder nasally, whereas a small minority inject MDMA. Chronic tolerance and bingeing are statistically linked to higher rates of drug-related psychobiological problems. In terms of underlying mechanisms, neuroadaptive processes are certainly involved, but there is a paucity of evidence on hepatic and behavioural mechanisms. Further studies specifically designed to investigate chronic tolerance, involving low intermittent dose regimens, are required. Most animal research has involved intensive MDMA dosing regimens designed to engender serotonergic neurotoxicity, and this may comprise another underlying mechanism. If distal serotonin axon terminal loss was also developing in recreational users, it may help to explain why reducing subjective efficacy, dosage escalation and increasing psychobiological problems often develop in parallel. In conclusion, there is extensive evidence for chronic pharmacodynamic tolerance to recreational Ecstasy/MDMA, but the underlying mechanisms are currently unclear. Several traditional processes are probably involved, but one of the possible causes is a novel mechanism largely unique to the ring substituted amphetamine derivatives, namely serotonergic neurotoxicity.
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 103
- Clinical applications of hallucinogens: A review. Experimental and Clinical Psychopharmacology August 1, 2016
- Human psychobiology of MDMA or ‘Ecstasy’: an overview of 25 years of empirical research Human Psychopharmacology: Clinical and Experimental July 1, 2013
- Decreased cerebral cortical serotonin transporter binding in ecstasy users: a positron emission tomography/[11C]DASB and structural brain imaging study Brain May 17, 2010
- Mood, cognition and serotonin transporter availability in current and former ecstasy (MDMA) users: the longitudinal perspective Journal of Psychopharmacology March 1, 2006
- MDMA in humans: factors which affect the neuropsychobiological profiles of recreational ecstasy users, the integrative role of bioenergetic stress Journal of Psychopharmacology March 1, 2006
and 98 more in the library
Cites 56
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and 51 more in the library