The risky cocktail: what combination effects can we expect between ecstasy and other amphetamines?

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Diana Dias da Silva (Author) Other; Helena Carmo (Author) FFUP; Elisabete Silva (Author) Other

Journal

Title: Archives of Toxicology

Vol. 87

Pages: 111-122

ISSN: 0340-5761

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 12 Citations

ISI Web of Science

Scopus - 16 Citations

Pubmed / Medline

Scientific classification

FOS: Medical and Health sciences > Basic medicine

CORDIS: Health sciences > Pharmacological sciences > Toicology

Other information

Authenticus ID: P-002-20V

DOI: 10.1007/s00204-012-0929-9

Abstract (EN): The recreational and illicit use of amphetaminic designer compounds, specially 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy), is of concern worldwide. Such psychostimulating drugs are frequently present as complex mixtures in 'rave' pills, making concomitant polysubstance use a common trend. However, the understanding of possible combination effects with these substances is still scarce. The present study was aimed at predicting the cytotoxic effects of mixtures of four amphetaminic derivatives: MDMA, methamphetamine, 4-methylthioamphetamine and d-amphetamine in a human hepatoma cell line. Concentration-response curves for all single-mixture components were recorded by the MTT assay. Data obtained for individual agents were then used to compute the additivity expectations for mixtures of definite composition, using the pharmacological models of concentration addition (CA) and independent action. By comparing the predicted calculations with the experimentally observed effects, we concluded that CA accurately predicts the combination of amphetamines, which act together to generate additive effects over a large range of concentrations. Notably, we observed substantial mixture effects even when each drug was present at low concentrations, which individually produced unnoticeable effects. Nonetheless, for all tested mixtures, a small deviation from additivity was observed towards higher concentrations, particularly at high effect levels. A possible metabolic interaction, which could explain such deviation, was investigated, and it was observed that at higher mixture concentrations increased MDMA metabolism could be contributing to divergences from additivity. In conclusion, the present work clearly demonstrates that potentially harmful interactions among amphetaminic drugs are expected when these drugs are taken concomitantly.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12