Reinforcing, subjective, and physiological effects of MDMA in humans: A comparison with d-amphetamine and mCPP
Abstract
3,4-methylenedioxymethamphetamine (MDMA) is a widely used drug of abuse chemically related to both the amphetamines and mescaline. Laboratory animal studies have shown that MDMA is a potent re-uptake inhibitor and releaser of dopamine and serotonin. Although the subjective and physiological effects of MDMA have been compared to d-amphetamine in humans, no direct comparison with a serotonin releasing agent has been reported and reinforcing effects have not been evaluated. In this paper we report a direct comparison of the reinforcing, subjective, and physiological effects of MDMA (1 and 2 mg/kg) to d-amphetamine (10 and 20 mg), to metachlorophenylpiperazine (mCPP--a serotonin releasing agent (0.5 and 0.75 mg/kg)), and to placebo using a within-subject design in 12 volunteers with moderate MDMA experience. Both the high dose of d-amphetamine and MDMA showed significant reinforcing effects as indicated by high cross-over values on the multiple choice procedure compared to all other treatments. All three drugs showed dose-dependent changes in subjective effects whereas physiological effects were most pronounced for MDMA with almost no changes seen with mCPP. The subjective effects of MDMA were similar both to those of mCPP and d-amphetamine, suggesting that both dopamine and serotonin systems are involved in mediating these effects. In contrast, only the dopaminergic agents, d-amphetamine and MDMA, had reinforcing effects.
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Earlier controlled lab work suggests MDMA raises self-reported states tied to empathy and social ease, but findings are mixed.
“These studies indicate that MDMA increases feelings related to empathy and sociability, including self-rated friendliness [7–8], extroversion [9–10], closeness to others [11], sociability [7, 12], talkativeness [7–8], amicability, and gregariousness [13], although some of these effects are inconsistent [14–16].”
From Is Ecstasy an “Empathogen”? Effects of +/- 3,4-Methylenedioxymethamphetamine on Prosocial Feelings and Identification of Emotional States in Others (2010) · cites this paper as [7]
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- Authors
- Tancer, M., & Johanson, C.-E.
- Affiliations
- Wayne State University (US)
- Corresponding author
- Tancer, Manuel
- Venue
- Drug and Alcohol Dependence
- Publisher
- Elsevier BV
- Published
- 2003-10
- Volume
- 72
- Issue
- 1
- Pages
- 33-44
- ISSN
- 0376-8716 (ISSN-L)
- OpenAlex
- W2127854642
- Cited by
- 153
- References
- 58
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 5 · 2023: 2 · 2022: 1 · 2021: 8 · 2020: 3 · 2019: 6 · 2018: 12 · 2017: 8 · 2016: 7 · 2015: 5 · 2014: 13 · 2013: 7 · 2012: 10
- FWCI
- 8.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drug and Alcohol Dependence (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k08da000370-05)
- National Institute on Drug Abuse (5 K08 DA00370)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
- Keywords
- MDMA, 3,4-methylenedioxymethamphetamine, d-amphetamine, mCPP, serotonin release, dopamine release, drug reinforcement, subjective effects, physiological effects, dose dependence
- MeSH terms
- Adolescent, Adult, Affect, Dextroamphetamine, Female, Hallucinogens, Humans, Hydrocortisone, Male, Piperazines, Surveys and Questionnaires, Reinforcement, Psychology, Severity of Illness Index, Serotonin Receptor Agonists, Dopamine Agonists, Cross-Over Studies, N-Methyl-3,4-methylenedioxyamphetamine, Substance-Related Disorders
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