Abuse Liability and Human Pharmacology of Mephedrone

• ClinicalTrials.gov Identifier: NCT02232789
• Recruitment Status: Completed
• First Posted: September 5, 2014
• Last Update Posted: December 4, 2014
• Sponsor: Parc de Salut Mar
• Collaborator: Instituto de Salud Carlos III
• Information provided by (Responsible Party): Parc de Salut Mar

Tracking Information

• First Submitted Date: August 29, 2014
• First Posted Date: September 5, 2014
• Last Update Posted Date: December 4, 2014
• Study Start Date: September 2014
• Actual Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 2, 2014)

Changes in blood pressure [ Time Frame: From pre-dose (baseline) to 4h post-dose ]

Systolic and diastolic blood pressure

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 2, 2014)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Abuse Liability and Human Pharmacology of Mephedrone
• Official Title: Abuse Liability and Human Pharmacology of Mephedrone (4-methylmethcathinone,4-MMC)
• 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).

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Investigator)
• Condition: Amphetamine-Related Disorders

Intervention

• Drug: Mephedrone
  Single oral dose mephedrone
  Other Names:

  • 4-methylmethcathinone
  • 4-MMC
• Drug: 3,4-methylenedioxymethamphetamine
  Single oral dose MDMA
  Other Names:

  • MDMA
  • Ecstasy
• Drug: Placebo
  Single oal dose placebo
  Other Name: Non active treatment

Study Arms

• Experimental: Mephedrone
  Mephedrone 200 mg, single dose, oral administration
  Intervention: Drug: Mephedrone
• Active Comparator: 3,4-methylenedioxymethamphetamine
  3,4-methylenedioxymethamphetamine (MDMA) 100 mg, single dose, oral administration
  Intervention: Drug: 3,4-methylenedioxymethamphetamine
• Placebo Comparator: Lactose
  Placebo, single dose, oral administration
  Intervention: Drug: Placebo

• Publications *: Papaseit E, Pérez-Mañá C, Mateus JA, Pujadas M, Fonseca F, Torrens M, Olesti E, de la Torre R, Farré 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 2, 2014): 12
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 2014
• Actual Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years to 45 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT02232789
• Other Study ID Numbers: IMIMFTCL/MEF/1
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Parc de Salut Mar
• Study Sponsor: Parc de Salut Mar
• Collaborators: Instituto de Salud Carlos III

Investigators

• Principal Investigator: Magi Farre, MD, PhD; Parc de Salut Mar

• PRS Account: Parc de Salut Mar
• Verification Date: December 2014