Clinical trial NCT02294266: Mephedrone and Alcohol Interactions in Humans
Official title: Mephedrone and Alcohol Interactions After Single-dose Administration in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Amphetamine-Related Disorders
Alcohol-Related Disorders
Lead sponsor: Parc de Salut Mar
Sponsor class: OTHER
Collaborators: name: Instituto de Salud Carlos III
First posted: 2014-11-19
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in drunkenness and drowsiness and effects
timeFrame: From pre-dose (baseline, 0h) to 6h post-dose
Secondary outcomes:
measure: Change in other subjective effects
timeFrame: From pre-dose (baseline, 0h) to 6h post-dose
measure: Change in blood pressure
timeFrame: From pre-dose (baseline, 0h) to 6h post-dose
measure: Change in psychomotor function
timeFrame: From pre-dose (baseline, 0h) to 1, 1.5 and 4h post-dose
measure: Change in memory function
timeFrame: From pre-dose (baseline, 0h) to 1, 1.5 and 4h post-dose
measure: Area Under the Concentration-Time Curve (AUC 0-24h)
timeFrame: From pre-dose (baseline, 0h) to 0.15, 0.3, 0.45, 1, 1.5, 2, 3, 4, 6, 8, and 10h post-dose
measure: Area Under the Concentration-Time Curve (AUC 0-10h)
timeFrame: From pre-dose (baseline, 0h) to 0.45, 1, 1.5, 2, 3, 4, 6, 8, and 10h post-dose
measure: Number of Participants with Serious and Non-Serious Adverse Events
timeFrame: 7 days after each
measure: Elimination hal-life
timeFrame: 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
measure: Elimination hal-life
timeFrame: From pre-dose (baseline, 0h) to 0.45, 1, 1.5, 2, 3, 4, 6, 8, an 10h post-dose
measure: Change in heart rate
timeFrame: From pre-dose (baseline, 0h) to 6h post-dose
measure: Change in pupil diameter
timeFrame: From pre-dose (baseline, 0h) to 6h post-dose
measure: Change in oral temperature
timeFrame: From pre-dose (baseline, 0h) to 6h post-dose
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Institut Hospital del Mar d'Investigacions Mèdiques-IMIM. Parc de Salut Mar.
Study officials:
affiliation: Institut Hospital del Mar d'Investigacions Mèdiques-IMIM. Parc
name: Magí Farré, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.