Mephedrone and Alcohol Interactions in Humans

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Mephedrone and Alcohol Interactions After Single-dose Administration in Humans

Conditions
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Amphetamine-Related Disorders, Alcohol-Related Disorders

Intervention / Treatment
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* Drug: Mephedrone and alcohol
* Drug: Mephedrone
* Drug: Alcohol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 |