Abuse Liability and Human Pharmacology of Mephedrone

Sponsor

Parc de Salut Mar (Other)

Overall Status

Completed

CT.gov ID

NCT02232789

Collaborator

Instituto de Salud Carlos III (Other)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Amphetamine-Related Disorders	Drug: Mephedrone Drug: 3,4-methylenedioxymethamphetamine Drug: Placebo	Phase 1

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).

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Official Title:

Abuse Liability and Human Pharmacology of Mephedrone (4-methylmethcathinone,4-MMC)

Study Start Date :

Sep 1, 2014

Actual Primary Completion Date :

Dec 1, 2014

Actual Study Completion Date :

Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mephedrone Mephedrone 200 mg, single dose, oral administration	Drug: Mephedrone Single oral dose mephedrone Other Names: 4-methylmethcathinone 4-MMC
Active Comparator: 3,4-methylenedioxymethamphetamine 3,4-methylenedioxymethamphetamine (MDMA) 100 mg, single dose, oral administration	Drug: 3,4-methylenedioxymethamphetamine Single oral dose MDMA Other Names: MDMA Ecstasy
Placebo Comparator: Lactose Placebo, single dose, oral administration	Drug: Placebo Single oal dose placebo Other Names: Non active treatment

Arm

Intervention/Treatment

Experimental: Mephedrone

Mephedrone 200 mg, single dose, oral administration

Drug: Mephedrone

Single oral dose mephedrone

Other Names:

4-methylmethcathinone

4-MMC

Active Comparator: 3,4-methylenedioxymethamphetamine

3,4-methylenedioxymethamphetamine (MDMA) 100 mg, single dose, oral administration

Drug: 3,4-methylenedioxymethamphetamine

Single oral dose MDMA

Other Names:

MDMA

Ecstasy

Placebo Comparator: Lactose

Placebo, single dose, oral administration

Drug: Placebo

Single oal dose placebo

Other Names:

Non active treatment

Outcome Measures

Primary Outcome Measures

Changes in blood pressure [From pre-dose (baseline) to 4h post-dose]
Systolic and diastolic blood pressure

Secondary Outcome Measures

Changes in euphoria-good effects [From 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.
Number of Participants with Serious and Non-Serious Adverse Events [7 days after each substance administration]
Collection of adverse effects spontaneously reported by the participants and/or observed by the investigators
Elimination half-life [From 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 heart rate [From pre-dose (baseline) to 4h post-dose]
Measure of heart rate (pulse)
Changes in pupil diameter [From pre-dose (baseline) to 4h post-dose]
Measure of pupil diameter and capacity of convergence (esophoria) using a pupillometer
Changes in oral temperature [From pre-dose (baseline) to 4h post-dose]
Measure of temperature in mouth using automatic thermometer

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

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.