Mephedrone and Alcohol Interactions in Humans

Esther Papaseit, Clara Pérez-Mañá, Elizabeth B de Sousa Fernandes Perna, Eulalia Olesti, Julian Mateus, Kim Pc Kuypers, Eef L Theunissen, Francina Fonseca, Marta Torrens, Jan G Ramaekers, Rafael de la Torre, Magí Farré, Esther Papaseit, Clara Pérez-Mañá, Elizabeth B de Sousa Fernandes Perna, Eulalia Olesti, Julian Mateus, Kim Pc Kuypers, Eef L Theunissen, Francina Fonseca, Marta Torrens, Jan G Ramaekers, Rafael de la Torre, Magí Farré

Abstract

Mephedrone (4-MMC, mephedrone) is a synthetic cathinone derivative included in the class of new psychoactive substances. It is commonly used simultaneously with alcohol (ethanol). The aim of the present study was to evaluate the interactions on subjective, cardiovascular and hormone effects and pharmacokinetics between mephedrone and alcohol in humans. Eleven male volunteers participated as outpatients in four experimental sessions in a double-blind, randomized, cross-over, and placebo-controlled clinical trial. Participants received a single oral dose of 200 mg of mephedrone plus 0.8 g/kg of alcohol (combination condition); 200 mg of mephedrone plus placebo alcohol (mephedrone condition); placebo mephedrone plus 0.8 g/kg of ethanol (alcohol condition); and placebo mephedrone plus placebo alcohol (placebo condition). Outcome variables included physiological (blood pressure, heart rate, temperature, and pupil diameter), psychomotor (Maddox wing), subjective (visual analogue scales, Addiction Research Center Inventory 49 item short form, and Valoración de los Efectos Subjetivos de Sustancias con Potencial de Abuso questionnaire), and pharmacokinetic parameters (mephedrone and ethanol concentrations). The study was registered in ClinicalTrials.gov, number NCT02294266. The mephedrone and alcohol combination produced an increase in the cardiovascular effects of mephedrone and induced a more intense feeling of euphoria and well-being in comparison to the two drugs alone. Mephedrone reduced the sedative effects produced by alcohol. These results are similar to those obtained when other psychostimulants such as amphetamines and 3,4-methylenedioxymethamphetamine are combined simultaneously with alcohol. The abuse liability of mephedrone combined with alcohol is greater than that induced by mephedrone alone.

Keywords: 4-methylmethcathinone (mephedrone); alcohol (ethanol); interaction; new psychoactive substance; pharmacokinetics; pharmacologic effects.

Copyright © 2020 Papaseit, Pérez-Mañá, de Sousa Fernandes Perna, Olesti, Mateus, Kuypers, Theunissen, Fonseca, Torrens, Ramaekers, de la Torre and Farré.

Figures

Figure 1
Figure 1
Time course of drug effects (n = 11, mean, standard error) on physiological and psychomotor performance (differences from baseline). □ mephedrone + alcohol; ○ mephedrone; ◊ alcohol; Δ placebo; Significant differences between mephedrone vs mephedrone + alcohol (a: p

Figure 2

Time course of drug effects…

Figure 2

Time course of drug effects (n = 11, mean, standard error) on subjective…

Figure 2
Time course of drug effects (n = 11, mean, standard error) on subjective effects (differences from baseline). □ mephedrone + alcohol; ○ mephedrone; ◊ alcohol; Δ placebo; Significant differences between mephedrone vs mephedrone + alcohol (a: p

Figure 3

Plasma concentration over time curves…

Figure 3

Plasma concentration over time curves of mephedrone (left) and ethanol (right) (n =…

Figure 3
Plasma concentration over time curves of mephedrone (left) and ethanol (right) (n = 11, mean, standard error). ○ mephedrone; ◊ alcohol; □ mephedrone + alcohol.
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References
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Figure 2
Figure 2
Time course of drug effects (n = 11, mean, standard error) on subjective effects (differences from baseline). □ mephedrone + alcohol; ○ mephedrone; ◊ alcohol; Δ placebo; Significant differences between mephedrone vs mephedrone + alcohol (a: p

Figure 3

Plasma concentration over time curves…

Figure 3

Plasma concentration over time curves of mephedrone (left) and ethanol (right) (n =…

Figure 3
Plasma concentration over time curves of mephedrone (left) and ethanol (right) (n = 11, mean, standard error). ○ mephedrone; ◊ alcohol; □ mephedrone + alcohol.
Figure 3
Figure 3
Plasma concentration over time curves of mephedrone (left) and ethanol (right) (n = 11, mean, standard error). ○ mephedrone; ◊ alcohol; □ mephedrone + alcohol.

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