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Abuse Liability and Human Pharmacology of Mephedrone

Phase 1
Completed
Conditions
Amphetamine-Related Disorders
Interventions
Registration Number
NCT02232789
Lead Sponsor
Parc de Salut Mar
Brief Summary

The purposes of this study are 1) to evaluate the abuse liability and human pharmacology of mephedrone after oral administration and 2) to compare the pharmacological effects of mephedrone with those obtained after administration of oral 3,4-methylenedioxymethamphetamine (MDMA, ecstasy).

Detailed Description

Mephedrone is a new psychoactive substance (NPS). At present, there are no randomized controlled trials evaluating the effects of mephedrone in humans. The current body of knowledge regarding the acute effects of mephedrone is based on anecdotal, self-reported effects (e.g. internet forums), case reports, and emergency room series and fatalities.

The aims of this study are 1) to evaluate the abuse liability and human pharmacology of mephedrone after oral administration and 2) to compare the pharmacological effects of mephedrone with those obtained after administration of oral 3,4-methylenedioxymethamphetamine (MDMA, ecstasy).

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
12
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 derivatives, mephedrone or other cathinone on at least 6 occasions (two in the previous year) without serious adverse reactions.
  • 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

.

  • 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). Subjects with 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 derivatives, 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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
LactosePlaceboPlacebo, single dose, oral administration
MephedroneMephedroneMephedrone 200 mg, single dose, oral administration
3,4-methylenedioxymethamphetamine3,4-methylenedioxymethamphetamine3,4-methylenedioxymethamphetamine (MDMA) 100 mg, single dose, oral administration
Primary Outcome Measures
NameTimeMethod
Changes in blood pressureFrom pre-dose (baseline) to 4h post-dose

Systolic and diastolic blood pressure

Secondary Outcome Measures
NameTimeMethod
Changes in heart rateFrom pre-dose (baseline) to 4h post-dose

Measure of heart rate (pulse)

Changes in euphoria-good effectsFrom pre-dose (baseline) to 4h post-dose

Euphoria-good effects effects will be measured using rating 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

Area Under the Concentration-Time Curve (AUC 0-24h)From baseline (pre-dose, 0h) to 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24h post-dose

Calculation of AUC of the concentrations of mephedrone and MDMA and its metabolites in blood, urine, oral fluid and sweat.

Elimination half-lifeFrom baseline to 24h post-dose

Calculation of elimination hal-life from concentrations of mephedrone, MDMA and its metabolites in plasma-blood, urine, oral fluid and sweat.

Changes in pupil diameterFrom pre-dose (baseline) to 4h post-dose

Measure of pupil diameter and capacity of convergence (esophoria) using a pupillometer

Number of Participants with Serious and Non-Serious Adverse Events7 days after each substance administration

Collection of adverse effects spontaneously reported by the participants and/or observed by the investigators

Changes in oral temperatureFrom pre-dose (baseline) to 4h post-dose

Measure of temperature in mouth using automatic thermometer

Trial Locations

Locations (1)

Institut Hospital del Mar d'Investigacions Mèdiques-IMIM. Parc de Salut Mar.

🇪🇸

Barcelona, Spain

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