Clinical trial NCT02232789: Abuse Liability and Human Pharmacology of Mephedrone
Official title: Abuse Liability and Human Pharmacology of Mephedrone (4-methylmethcathinone,4-MMC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Amphetamine-Related Disorders
Keywords: Mephedrone
3,4-methylenedioxymethamphetamine
Abuse liability
Human Pharmacology
Lead sponsor: Parc de Salut Mar
Sponsor class: OTHER
Collaborators: name: Instituto de Salud Carlos III
First posted: 2014-09-05
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 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).

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 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.

Primary outcomes:
measure: Changes in blood pressure
timeFrame: From pre-dose (baseline) to 4h post-dose
Secondary outcomes:
measure: Changes in euphoria-good effects
timeFrame: From pre-dose (baseline) to 4h post-dose
measure: Area Under the Concentration-Time Curve (AUC 0-24h)
timeFrame: 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
measure: Number of Participants with Serious and Non-Serious Adverse Events
timeFrame: 7 days after each substance administration
measure: Elimination half-life
timeFrame: From baseline to 24h post-dose
measure: Changes in heart rate
timeFrame: From pre-dose (baseline) to 4h post-dose
measure: Changes in pupil diameter
timeFrame: From pre-dose (baseline) to 4h post-dose
measure: Changes in oral temperature
timeFrame: From pre-dose (baseline) to 4h 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: Parc de Salut Mar
name: Magi Farre, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Papaseit E, Perez-Mana C, Mateus JA, Pujadas M, Fonseca F, Torrens M, Olesti E, de la Torre R, Farre M. Human Pharmacology of Mephedrone in Comparison with MDMA. Neuropsychopharmacology. 2016 Oct;41(11):2704-13. doi: 10.1038/npp.2016.75. Epub 2016 May 20.