Mephedrone and Alcohol Interactions in Humans

Mephedrone and Alcohol Interactions After Single-dose Administration in Humans

The purposes of this study are 1) to evaluate the pharmacological effects after oral coadministration of mephedrone and alcohol and 2) determine the pharmacokinetics changes of mephedrone and alcohol concentrations after oral coadministration of mephedrone and alcohol.

Study Overview

• Status: Completed
• Conditions: Alcohol-Related Disorders; Amphetamine-Related Disorders
• Intervention / Treatment: Drug: Mephedrone and alcohol; Drug: Mephedrone; Drug: Alcohol; Drug: Placebo

Detailed Description

Mephedrone (4-methylmetcathinone, 4-MMC) is a new psychoactive substance (NPS). Mephedrone is frequently used in combination with alcohol. At present, the effects of the interaction between mephedrone and alcohol in humans have not been previously evaluated in randomized controlled clinical trials.

The aims of this study are 1) to evaluate the pharmacological effects after oral coadministration of mephedrone and alcohol and 2) determine the pharmacokinetics changes of mephedrone and alcohol concentrations after oral coadministration of mephedrone and alcohol.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08003
    • Institut Hospital del Mar d'Investigacions Mèdiques-IMIM. Parc de Salut Mar.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Understanding and accepting the study procedures and signing the informed consent.
• Male adults volunteers (18-45 years old).
• Clinical history and physical examination demonstrating no organic or psychiatric disorders.
• The ECG and general blood and urine laboratory tests performed before the study should be within normal ranges. Minor or occasional changes from normal ranges are accepted if, in the investigator's opinion, considering the current state of the art, they are not clinically significant, are not life-threatening for the subjects and do not interfere with the product assessment. These changes and their non-relevance will be justified in writing specifically.
• Recreational use of amphetamines, ecstasy and hallucinogen derivate, mephedrone or other cathinone on at least 6 occasions (two in the previous year) without any adverse reactions.
• Recreational use of alcohol (ethanol). Previous experience in acute alcohol intoxication.
• Extensive metabolizer or intermediate metabolizer phenotype for cytochrome P-450-2D6 (CYP2D6) activity determined using dextromethorphan as a selective probe drug.
• The weight does not exceed 15% of ideal weight that applies according to size and will be between 60 and 100 Kg. Minor variations will be accepted as normal limits, if the researchers considered it clinically insignificant.

Exclusion Criteria:

• Not meeting the inclusion criteria.
• Daily consumption >20 cigarettes and >4 standard units of ethanol.
• Regular use of any drug in the month prior to the study sessions. The treatment with single or limited doses of symptomatic medicinal products in the week prior to the study sessions will not be a reason for exclusion if it is calculated that it has been cleared completely the day of the experimental session.
• Presence of major psychiatric disorders.
• Present history of abuse or drug dependence (except for nicotine dependence).
• Past history of drug dependence (except for nicotine dependence). Past history of drug abuse could be included.
• Having suffered any organic disease or major surgery in the three months prior to the study start.
• Blood donation 12 weeks before or participation in other clinical trials with drugs in the previous 4 weeks.
• Subjects with intolerance or serious adverse reactions to drugs or amphetamines, ecstasy and hallucinogen derivate, mephedrone or other cathinone.
• History or clinical evidence of gastrointestinal, liver, renal or other disorders which may lead to suspecting a disorder in drug absorption, distribution, metabolism or excretion, or that suggest gastrointestinal irritation due to drugs.
• Subjects unable to understand the nature, consequences of the study and the procedures requested to be followed.
• Subjects with positive serology to Hepatitis B, C or HIV.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mephedrone and alcohol; Mephedrone 200 mg, single dose, oral administration Alcohol 0.8g/kg diluted in lemon-flavoured water (350 ml), single dose, oral administration	Drug: Mephedrone and alcohol; Single oral dose mephedrone Single oral dose alcohol; Other Names: 4-methylmetcathinone; 4-MMC; Alcohol
Active Comparator: Mephedrone; Mephedrone 200 mg, single dose, oral administration Lemon-flavoured water (350 ml), single dose, oral administration	Drug: Mephedrone; Single oral dose mephedrone; Other Names: 4-methylmetcathinone; 4-MMC
Active Comparator: Alcohol; Lactose 200 mg, single dose, oral administration Alcohol 0.8g/kg diluted in lemon-flavoured water (350 ml), single dose, oral administration	Drug: Alcohol; Single oral dose alcohol
Placebo Comparator: Placebo; Lactose 200 mg, single dose, oral administration Lemon-flavoured water (350 ml), single dose, oral administration	Drug: Placebo; Single oral dose placebo; Other Names: Non-active treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in drunkenness and drowsiness and effects	Drunkenness and drowsiness effects will be measured using rate scales (visual analogue scales).	From pre-dose (baseline, 0h) to 6h post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in other subjective effects	Subjective effects will be measured using rate scales (visual analogue scales, the Addiction Research Center Inventory and the Evaluation of the Subjective Effects of Substances with Abuse Potential Questionnaires). All these instruments include measures of euphoria-good effects and other feelings induced by psychostimulants and alcohol.	From pre-dose (baseline, 0h) to 6h post-dose
Change in blood pressure	Systolic and diastolic blood pressure	From pre-dose (baseline, 0h) to 6h post-dose
Change in psychomotor function	Psychomotor function will be measured using Critical tracking task (CTT) and Divided Attention Task (DAT).	From pre-dose (baseline, 0h) to 1, 1.5 and 4h post-dose
Change in memory function	Memory function will be measured using Spatial Memory Task (SMT).	From pre-dose (baseline, 0h) to 1, 1.5 and 4h post-dose
Area Under the Concentration-Time Curve (AUC 0-24h)	Calculation of AUC of the concentrations of mephedrone and its metabolites in blood and urine.	From pre-dose (baseline, 0h) to 0.15, 0.3, 0.45, 1, 1.5, 2, 3, 4, 6, 8, and 10h post-dose
Area Under the Concentration-Time Curve (AUC 0-10h)	Calculation of AUC of the concentrations of alcohol in blood.	From pre-dose (baseline, 0h) to 0.45, 1, 1.5, 2, 3, 4, 6, 8, and 10h post-dose
Number of Participants with Serious and Non-Serious Adverse Events	Collection of adverse effects spontaneously reported by the participants and/or observed by the investigators.	7 days after each
Elimination hal-life	Calculation of elimination hal-life from concentrations of mephedrone and its metabolites in blood and urine.	From pre-dose (baseline, 0h) to 0.15, 0.30, 0.45, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24h post-dose
Elimination hal-life	Calculation of elimination hal-life from concentrations of alcohol in blood.	From pre-dose (baseline, 0h) to 0.45, 1, 1.5, 2, 3, 4, 6, 8, an 10h post-dose
Change in heart rate	Measure of heart rate	From pre-dose (baseline, 0h) to 6h post-dose
Change in pupil diameter	Measure of pupil diameter	From pre-dose (baseline, 0h) to 6h post-dose
Change in oral temperature	Measure of oral temperature	From pre-dose (baseline, 0h) to 6h post-dose

Collaborators and Investigators

• Sponsor: Parc de Salut Mar
• Collaborators: Instituto de Salud Carlos III
• Investigators: Principal Investigator: Magí Farré, MD, PhD, Institut Hospital del Mar d'Investigacions Mèdiques-IMIM. Parc

Publications and helpful links

General Publications

• Papaseit E, Perez-Mana C, de Sousa Fernandes Perna EB, Olesti E, Mateus J, Kuypers KP, Theunissen EL, Fonseca F, Torrens M, Ramaekers JG, de la Torre R, Farre M. Mephedrone and Alcohol Interactions in Humans. Front Pharmacol. 2020 Jan 28;10:1588. doi: 10.3389/fphar.2019.01588. eCollection 2019.

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: November 17, 2014
• First Submitted That Met QC Criteria: November 17, 2014
• First Posted (Estimate): November 19, 2014

Study Record Updates

• Last Update Posted (Estimate): October 8, 2015
• Last Update Submitted That Met QC Criteria: October 7, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Substance-Related Disorders; Disease; Alcohol-Related Disorders; Amphetamine-Related Disorders; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents, Local; Anti-Infective Agents; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Sympathomimetics; Adrenergic Uptake Inhibitors; Ethanol; Methamphetamine
• Other Study ID Numbers: IMIMFTCL/MEF/2